Regular readers will likely remember that I take part, time to time, in a series of panels on Myeloma hosted by the wonderful people at Cure Talk, with help from Priya Menon who has done a remarkable job of assembling this program.
At 5PM Eastern on February 26th, there will be a panel discussing "Cure vs. Control" and featuring noted Myeloma expert Dr. S. Vincent Rajkumar of Mayo, Rochester.
This is of particular interest to me for two reasons. First, Dr. Rajkumar took part in a very thoughtful debate with my doctor a few years ago, and this debate can be found on youtube here (this is part 1 of 4). I'm looking forward to learning if Dr. Rajkumar, in light of the progress made in the last two years and the announcement of the Black Swan initiative by the IMF, has reconsidered his stance that the disease is not curable.
Second, and probably more important to me personally, is that Dr. Rajkumar was the author of the paper that discussed the presence of transient monoclonal protein after transplant being a good thing. I'm interested in learning why we are just now observing this (when for years we knew that oligoclonal bands appear during immune system recovery), what difference if any there is between the two types of bands appearing post-treatment, and what impact it this might have on assessing the effectiveness of treatment. Since I exhibited both oligoclonal and -- much later -- monoclonal bands during recovery, I'm particularly intrigued.
For instructions on how to participate on the call, including the opportunity to ask a question of the panel or Dr. Rajkumar, click here.
You can also post a comment here with a question for me to ask the good doctor!
Monday, February 10, 2014
...and why cure matters
The cure versus control debate has been gaining steam in the past few years.
I've been accused of favoring Arkansas in the past, so I will be careful to make the below claims with appropriate caveats and considering all I've learned, and the contributions of others. For example, I claimed that Barlogie was the first to use Velcade in up-front therapy. Evidently others began at or around the same time. It doesn't matter, really, to the argument I'm making.
When I was diagnosed in October of 2008, there may have been other voices in the wilderness talking about a cure, but UAMS was the only center openly discussing it as the objective of their therapy, and touting that Total Therapy was curing people. Many did not believe them then; many still do not believe them now. And many of the non-believers are very smart people, and many of them are learned doctors.
The startling statement of being curative was just one of several aspects of Arkansas' approach that led some others to call it "crazy" (whether in that word or a more polite variant thereof).
In addition to the fact that common wisdom said the disease was incurable, here are a few other things that common wisdom said:
- Velcade should be reserved for relapsed patients. Barlogie used it up front.
- Revlimid should be reserved for relapsed patients. Barlogie used it up front.
- Maintenance therapy did not make a difference in outcome. Barlogie has had it as a mainstay of his protocols for 20 years.
- Complete Remission doesn't matter; there's no real difference between a minimal M spike and the absence thereof. Barlogie, in contrast, uses CR as a prognostic precursor to cure.
- Tandem transplants won't make a difference in outcome. Barlogie has used them from the outset -- it's not about the transplant iself, it's about administering more melphalan.
- Focal lesions do not resolve and are meaningless as a prognostic factor once no longer active for cancer. Meanwhile Barlogie has maintained they resolve, though it can take years -- and believes that until they are resolved they can represent microenvironments where cancer can lurk, awaiting recurrence.
Now, fast forward five years.
- Velcade is the standard of care for newly-diagnosed patients
- Revlimid is the standard of care for newly-diagnosed patients
- More and more evidence exists (I'm not going to research the publications right now -- there are too many now and can be found via a google search) that maintenance prolongs overall survival as well as progression free survival and it is becoming the standard of care if it isn't already
- Complete remission is being recognized as an important marker with more advanced tests designed to investigate for the traces of any remaining disease
- I've seen at least one study that confirms the superior outcomes of tandem transplants
- My own focal lesions continue to resolve. I had at least 10 (I think 12?) and all but four are now gone.
- The IMF has announced the Black Swan Initiative, which at a minimum is a tacit acknowledgement that some patients are being cured
- More doctors are admitting that some patients are likely cured. I'm not going to "out" them, here, but they exist.
This is not about a "neener neener, I was right / my doctor was right." This isn't about bragging rights.
This is first and foremost about giving patients as many options as possible.
But this is also about getting on with life as normal for a good subset of patients who have families that depend on them.
Some people phrase it as "isn't a long remission as good as a cure?"
The answer, for me at least, is no.
Long remission doesn't let you buy life insurance.
Long remission doesn't let you buy disability insurance.
Long remission introduces questions like "will this person hire me if they believe I have incurable cancer?" I'm not sure of the legality of this -- but common sense dictates that it's a concern.
With other cancers, after five years of remission, you're considered free and clear. But until such time as enough of the medical community agrees that Myeloma is curable, that window will not be available for those of us with this disease.
I want to be very clear on my perspective here:
* Each person's biology is different. I have enjoyed a favorable response (thus far) to a curative approach. That doesn't mean other people will. The most aggressive claims of Arkansas acknowledge that 15-20% of newly diagnosed patients have dire prognoses despite the success of Total Therapy with other patients. Most might not be cured regardless -- although time will tell.
* Each person's choice is their own. Some people don't want to sacrifice quality of life for quantity of life. Some people simply don't want aggressive therapy and are prepared to accept a different set of odds as a result. Some people don't believe in the Arkansas protocol -- and it could certainly be proved wrong. This is not about asserting Arkansas being right over anybody else's choice.
* That said, patients need to be aware of their options, and make their own choice about their own treatment based on a fully informed perspective, understanding the pros and cons of each alternative.
Arkansas and Total Therapy are not for everybody, for a variety of reasons: age, health, philosophy, individual disease biology, etc. But patients should be informed enough to know that this treatment approach exists. Because cure, in many cases, does matter.
I've been accused of favoring Arkansas in the past, so I will be careful to make the below claims with appropriate caveats and considering all I've learned, and the contributions of others. For example, I claimed that Barlogie was the first to use Velcade in up-front therapy. Evidently others began at or around the same time. It doesn't matter, really, to the argument I'm making.
When I was diagnosed in October of 2008, there may have been other voices in the wilderness talking about a cure, but UAMS was the only center openly discussing it as the objective of their therapy, and touting that Total Therapy was curing people. Many did not believe them then; many still do not believe them now. And many of the non-believers are very smart people, and many of them are learned doctors.
The startling statement of being curative was just one of several aspects of Arkansas' approach that led some others to call it "crazy" (whether in that word or a more polite variant thereof).
In addition to the fact that common wisdom said the disease was incurable, here are a few other things that common wisdom said:
- Velcade should be reserved for relapsed patients. Barlogie used it up front.
- Revlimid should be reserved for relapsed patients. Barlogie used it up front.
- Maintenance therapy did not make a difference in outcome. Barlogie has had it as a mainstay of his protocols for 20 years.
- Complete Remission doesn't matter; there's no real difference between a minimal M spike and the absence thereof. Barlogie, in contrast, uses CR as a prognostic precursor to cure.
- Tandem transplants won't make a difference in outcome. Barlogie has used them from the outset -- it's not about the transplant iself, it's about administering more melphalan.
- Focal lesions do not resolve and are meaningless as a prognostic factor once no longer active for cancer. Meanwhile Barlogie has maintained they resolve, though it can take years -- and believes that until they are resolved they can represent microenvironments where cancer can lurk, awaiting recurrence.
Now, fast forward five years.
- Velcade is the standard of care for newly-diagnosed patients
- Revlimid is the standard of care for newly-diagnosed patients
- More and more evidence exists (I'm not going to research the publications right now -- there are too many now and can be found via a google search) that maintenance prolongs overall survival as well as progression free survival and it is becoming the standard of care if it isn't already
- Complete remission is being recognized as an important marker with more advanced tests designed to investigate for the traces of any remaining disease
- I've seen at least one study that confirms the superior outcomes of tandem transplants
- My own focal lesions continue to resolve. I had at least 10 (I think 12?) and all but four are now gone.
- The IMF has announced the Black Swan Initiative, which at a minimum is a tacit acknowledgement that some patients are being cured
- More doctors are admitting that some patients are likely cured. I'm not going to "out" them, here, but they exist.
This is not about a "neener neener, I was right / my doctor was right." This isn't about bragging rights.
This is first and foremost about giving patients as many options as possible.
But this is also about getting on with life as normal for a good subset of patients who have families that depend on them.
Some people phrase it as "isn't a long remission as good as a cure?"
The answer, for me at least, is no.
Long remission doesn't let you buy life insurance.
Long remission doesn't let you buy disability insurance.
Long remission introduces questions like "will this person hire me if they believe I have incurable cancer?" I'm not sure of the legality of this -- but common sense dictates that it's a concern.
With other cancers, after five years of remission, you're considered free and clear. But until such time as enough of the medical community agrees that Myeloma is curable, that window will not be available for those of us with this disease.
I want to be very clear on my perspective here:
* Each person's biology is different. I have enjoyed a favorable response (thus far) to a curative approach. That doesn't mean other people will. The most aggressive claims of Arkansas acknowledge that 15-20% of newly diagnosed patients have dire prognoses despite the success of Total Therapy with other patients. Most might not be cured regardless -- although time will tell.
* Each person's choice is their own. Some people don't want to sacrifice quality of life for quantity of life. Some people simply don't want aggressive therapy and are prepared to accept a different set of odds as a result. Some people don't believe in the Arkansas protocol -- and it could certainly be proved wrong. This is not about asserting Arkansas being right over anybody else's choice.
* That said, patients need to be aware of their options, and make their own choice about their own treatment based on a fully informed perspective, understanding the pros and cons of each alternative.
Arkansas and Total Therapy are not for everybody, for a variety of reasons: age, health, philosophy, individual disease biology, etc. But patients should be informed enough to know that this treatment approach exists. Because cure, in many cases, does matter.
Why I love my doctor...
Here it comes: an end to the initials of those involved with Arkansas.
There are going to be three posts from me today, I think, broken up for easier digestion. Each is related, but each also has its own little piece of the message.
The first is a bit about why I love Dr. (B)art (B)arlogie and his team.
In the interest of not putting off people that chose a different therapeutic path, I've generally backed off any kind of zealous proselytization of Total Therapy in the past few years, however for these next few posts I'm going to be a bit more assertive.
Some people that have disparaged Arkansas refer to adherents of its program as "cult members" because of the faith that we place in Total Therapy and/or the larger-than-life personality of Dr. Barlogie. One of the most vocal online denigrators of this dynamic has actually become a valued friend of mine -- and though I respect this person and acknowledge that this person's individual disease characteristics make Total Therapy much less appealing for them than for others, I nevertheless must disagree with this person about the "cult" commentary and about this person's overall opinion of Barlogie.
Those who are passionate about UAMS, Barlogie and Total Therapy are thus because (1) we believe it works and that a meaningful proportion (call it 50%) of newly diagnosed patients can be cured of this disease through this protocol, (2) our doctor ENCOURAGES patients to become educated about their disease, their therapy, their biology, etc. and (3) we are passionate just as our doctor is passionate. If we strongly encourage a newly diagnosed person to learn about the Arkansas program, it's because we believe there is a better way than just saying "well, the disease can't be cured, it will always come back and I'm eventually going to die from it unless a cure is found." I realize that's a little like an Evangelical Christian wanting to force the "Good News" on others in order to save their soul...but even the most spiritually minded among us have to recognize that our mortal life is a bit more tangible than our soul. Extending our life is knowable and measurable.
I will address the issues of curability and being an informed patient in my next post, but I want to talk about my doctor's passion and knowledge here.
I have developed a privileged relationship with Dr. Barlogie, his wonderful wife Kathy, his awesome son Bart Jr., and his amazing chief of staff Bonnie Jenkins over the years. When I go back to Arkansas for regular visits, I usually try to get together with as many of them as possible for a drink or dinner. Often, one or more of them is traveling or (particularly in the case of Dr. Barlogie) too busy. But this last week, I was very fortunate. I had dinner with Bart Sr., Kathy and Bonnie three nights in a row, and Bart Jr. was able to join for two of them.
On the first night, Bart was at the clinic until after 9PM. It was another routine 12+ hour day for him and it would continue after dinner. He was late because he was personally editing FIFTEEN articles that were about to be submitted to ASCO (the American Society of Clinical Oncology) for potential publication. Dr. Barlogie is approaching 70 years old, but still sees between 15-25 patients a day including around 20 new patients a week. His dedication is tireless.
I often speak of the need for people to see a specialist. Virtually all of Dr. Barlogie's patients have Myeloma (a few may have related diseases like Waldenstrom's Macroglobulinemia or the like) and this has been the case for 30 years. He has likely seen more Myeloma than any practicing physician in the world.
Because of this, he knows the disease as well or better than any practicing Myeloma physician in the world. And that takes nothing away from the many learned physicians including a dozen or so absolutely brilliant specialists (this is my estimation only) who I am sure Dr. Barlogie fully considers his peers. He may not be smarter than other top doctors -- though he certainly is brilliant -- but he's simply seen more of the disease. If your car is mangled in a wreck, do you take it to a brilliant mechanic who has worked on 500 cars, or a brilliant mechanic who has worked on 5,000 of the same make and model?
I spoke with Dr. Barlogie at dinner this first night for two hours about the disease: why he believes it responds the way it does to some kinds of therapies and not others; why he feels the new classes of immunotherapy agents (e.g., elotuzimab, daritumimab -- both of which are receiving a lot of press now) are not ready for prime time and not as effective for Myeloma as similar agents are for lymphoma; why he feels the disease is curable. And why he believes Total Therapy works. As he ultimately put it to me:
This is not to say that Total Therapy works for everybody. It does not. As I have always noted, 15-20% of patients have high risk characteristics -- or, if you prefer, have a biology which Arkansas' Gene Array test indicates will not be cured by Total Therapy. Then, of the remaining 80-85%, only about 80% or so are likely to be cured according to UAMS. However, those are compelling statistics for a supposedly "incurable" disease. Even if they are off by a factor of two, it's still 30% of low-risk patients being cured.
Included in the 20% that Arkansas recognizes will not be cured by TT despite low-risk biology are those who have standard risk disease (or, if one prefers, disease which has attributes that, according to Arkansas' Gene Array test, are likely to respond well to Total Therapy) but who lose remission. These are sad cases, because often times the disease returns with very aggressive characteristics and prognosis is not good.
One such case is a friend of mine, and I was discussing this person with Dr. Barlogie over dinner (within the confines of patient confidentiality as appropriate). Where other doctors would say "well, we could try X, or Y" Dr. Barlogie shared with me that he had researched additional therapies that work on a specific cellular level since this patient didn't have trouble reaching remission, but had difficulty remaining on therapy due to his blood counts (white cells and platelets) being knocked out by the therapy. So Barlogie's new therapeutic choice for this individual was to select chemo agents that work at a stem cell level and don't damage mature cells, so that the counts would not be as impacted. Barlogie not only knows what to do, he knows WHY he is doing it.
When he sees a patient that has been heavily treated elsewhere -- and I have personally referred patients from Los Angeles to Canada who were told by their supposed experts that they would be dead in three months only to be given a new lease on life in Arkansas -- Barlogie knows what the options are and why. This can include experimentation, particularly in those that have received all the common treatments before. But when one can either update one's will and sign up for hospice, or sign up for experimentation and live 18 months to who knows how long, that's a meaningful choice to have, even for those who choose the first path.
As another example, because he has seen so many patients, Barlogie knows that certain procedures ENCOURAGE plasma cells and Myeloma. In patients that are not in remission, something as simple as removing a central line (a catheter placed subcutaneously for infusions, and which requires an incision) can sometimes cause the eruption of plasmacytomas at the incision site. Patients with serious disease might even experience this at the site of simple injections. Doctors that haven't seen thousands of patients and haven't observed this phenomenon dozens if not hundreds of times simply won't know this is happening.
Similarly, I have friends that receive radiation. Radiation can possibly cause the same thing -- plasma cells rush to the area that experiences the radiation. This could strengthen the Myeloma over the long haul. This is why my doctor favors "melting tumors" with chemotherapy. A doctor that hasn't seen this many times over might be quick to radiate something that won't help the situation.
Now, some of this is theory -- and some of it is likely the age-old difference between chemotherapists and radiologists whom, I am told, haven't always gotten along well (this is not specific at all to UAMS, where the departments work well together). But a lot of this is experience. Experience that few doctors in the world have.
Over the course of the next two nights, I had other conversations with Bart, his family, and Bonnie. About the disease, about what we learn from going through it, about their own lives and families as well as my own. Bart and his family become profoundly emotionally involved in the outcome of Bart's patients. Some may say this is a bad thing -- they prefer a doctor that is detached and unemotional. I can understand that -- but there's also something about having a specialist being emotionally invested in one's case and wanting that person to beat the disease. Not to qualify for more funding, not to validate or invalidate a particular drug's efficacy -- but because Bart hates this disease and loves his patients.
That is not a cult. That is a family of care.
I've seen an unfortunate few of those in Bart's care -- both newly diagnosed who arrive full of hope, and those who have been treated elsewhere that aren't able to hope for a cure through Total Therapy because being pre-treated means the TT approach isn't as effective -- die. These people are not bitter. Uniformly, they are at peace. Because they know that they have been seen by the best and there could not have been a better outcome. That, too, is not a cult. That is the result of a dignified grace conferred at least in part by confidence in one's medical team. I am not certain I would experience such grace in the face of imminent mortality. I hope I never need to find out. The UAMS people don't sugar-coat things...Bonnie once told me "I can help you beat this disease, but should the time come, I can also help you prepare to die from it." That's both awful and pretty remarkable at the same time.
I have a privileged relationship with Bart and his family, as I've said in the past and said earlier in this article. He doesn't visit everybody in the hospital, as he did with me (and did with my friend who experienced relapse, whom I mentioned above). Kathy, who doesn't even work at UAMS, doesn't visit everybody in the hospital either -- yet I remember when I was basically in a coma from Dilaudid, I opened my eyes once to see her sitting there holding the hand of my terrified wife. Yet this privileged relationship didn't come from anything special and isn't unique to me. I reciprocate and invest in it, because it's good for my care clinically but mostly because I love these people. This privileged relationship arises for me and others BECAUSE of the commitment that Bart and his team give to their patients.
If that collectively means I'm part of a cult, then sign me up. So long as it doesn't involve purple jumpsuits or Kool-Aid. :)
As to curability and why it matters, that's coming up next.
P.S. As part of being in the cult, I provide free advertising for associated businesses. :) If you are in Little Rock, make sure to check out The Fold, which is Bart Jr'.s restaurant featuring farm-to-table, high-end tacos and other small plates. Calling them tacos is a bit of an understatement. It's a very relaxed, reasonably priced and cool place with a wide variety of good eats. I've now put it in my rotation along with certain BBQ and pizza places when I go my weeks in Little Rock.
There are going to be three posts from me today, I think, broken up for easier digestion. Each is related, but each also has its own little piece of the message.
The first is a bit about why I love Dr. (B)art (B)arlogie and his team.
In the interest of not putting off people that chose a different therapeutic path, I've generally backed off any kind of zealous proselytization of Total Therapy in the past few years, however for these next few posts I'm going to be a bit more assertive.
Some people that have disparaged Arkansas refer to adherents of its program as "cult members" because of the faith that we place in Total Therapy and/or the larger-than-life personality of Dr. Barlogie. One of the most vocal online denigrators of this dynamic has actually become a valued friend of mine -- and though I respect this person and acknowledge that this person's individual disease characteristics make Total Therapy much less appealing for them than for others, I nevertheless must disagree with this person about the "cult" commentary and about this person's overall opinion of Barlogie.
Those who are passionate about UAMS, Barlogie and Total Therapy are thus because (1) we believe it works and that a meaningful proportion (call it 50%) of newly diagnosed patients can be cured of this disease through this protocol, (2) our doctor ENCOURAGES patients to become educated about their disease, their therapy, their biology, etc. and (3) we are passionate just as our doctor is passionate. If we strongly encourage a newly diagnosed person to learn about the Arkansas program, it's because we believe there is a better way than just saying "well, the disease can't be cured, it will always come back and I'm eventually going to die from it unless a cure is found." I realize that's a little like an Evangelical Christian wanting to force the "Good News" on others in order to save their soul...but even the most spiritually minded among us have to recognize that our mortal life is a bit more tangible than our soul. Extending our life is knowable and measurable.
I will address the issues of curability and being an informed patient in my next post, but I want to talk about my doctor's passion and knowledge here.
I have developed a privileged relationship with Dr. Barlogie, his wonderful wife Kathy, his awesome son Bart Jr., and his amazing chief of staff Bonnie Jenkins over the years. When I go back to Arkansas for regular visits, I usually try to get together with as many of them as possible for a drink or dinner. Often, one or more of them is traveling or (particularly in the case of Dr. Barlogie) too busy. But this last week, I was very fortunate. I had dinner with Bart Sr., Kathy and Bonnie three nights in a row, and Bart Jr. was able to join for two of them.
On the first night, Bart was at the clinic until after 9PM. It was another routine 12+ hour day for him and it would continue after dinner. He was late because he was personally editing FIFTEEN articles that were about to be submitted to ASCO (the American Society of Clinical Oncology) for potential publication. Dr. Barlogie is approaching 70 years old, but still sees between 15-25 patients a day including around 20 new patients a week. His dedication is tireless.
I often speak of the need for people to see a specialist. Virtually all of Dr. Barlogie's patients have Myeloma (a few may have related diseases like Waldenstrom's Macroglobulinemia or the like) and this has been the case for 30 years. He has likely seen more Myeloma than any practicing physician in the world.
Because of this, he knows the disease as well or better than any practicing Myeloma physician in the world. And that takes nothing away from the many learned physicians including a dozen or so absolutely brilliant specialists (this is my estimation only) who I am sure Dr. Barlogie fully considers his peers. He may not be smarter than other top doctors -- though he certainly is brilliant -- but he's simply seen more of the disease. If your car is mangled in a wreck, do you take it to a brilliant mechanic who has worked on 500 cars, or a brilliant mechanic who has worked on 5,000 of the same make and model?
I spoke with Dr. Barlogie at dinner this first night for two hours about the disease: why he believes it responds the way it does to some kinds of therapies and not others; why he feels the new classes of immunotherapy agents (e.g., elotuzimab, daritumimab -- both of which are receiving a lot of press now) are not ready for prime time and not as effective for Myeloma as similar agents are for lymphoma; why he feels the disease is curable. And why he believes Total Therapy works. As he ultimately put it to me:
"I was counseling one of our new doctors. He had seen a patient and based on his previous training, had suggested a course of action that involved a few well known drugs in small doses, but not the newest drugs, and not a widespread group of drugs that would attack all pathways. He said to me that he was saving the best for recurrence. I told him you don't get it, son...we use the best we have NOW, so that there will BE no recurrence."This falls somewhere between philosophy and treatment reality. But Bart knows too much about why things work and do not work for this to be written off as a stab in the dark. I have too many friends with Myeloma who went for non-aggressive approaches and are now relapsing and having dire outcomes. I have seen too many friends with doctors that are supposed specialists guessing at what to do next, disagreeing with other doctors and with patients, and not having any real plan other than picking some agents that might work and throwing it at the disease and hoping it sticks. Having a doctor that has a plan, can articulate it, and knows why it works and when it doesn't is a HUGE asset as a patient.
This is not to say that Total Therapy works for everybody. It does not. As I have always noted, 15-20% of patients have high risk characteristics -- or, if you prefer, have a biology which Arkansas' Gene Array test indicates will not be cured by Total Therapy. Then, of the remaining 80-85%, only about 80% or so are likely to be cured according to UAMS. However, those are compelling statistics for a supposedly "incurable" disease. Even if they are off by a factor of two, it's still 30% of low-risk patients being cured.
Included in the 20% that Arkansas recognizes will not be cured by TT despite low-risk biology are those who have standard risk disease (or, if one prefers, disease which has attributes that, according to Arkansas' Gene Array test, are likely to respond well to Total Therapy) but who lose remission. These are sad cases, because often times the disease returns with very aggressive characteristics and prognosis is not good.
One such case is a friend of mine, and I was discussing this person with Dr. Barlogie over dinner (within the confines of patient confidentiality as appropriate). Where other doctors would say "well, we could try X, or Y" Dr. Barlogie shared with me that he had researched additional therapies that work on a specific cellular level since this patient didn't have trouble reaching remission, but had difficulty remaining on therapy due to his blood counts (white cells and platelets) being knocked out by the therapy. So Barlogie's new therapeutic choice for this individual was to select chemo agents that work at a stem cell level and don't damage mature cells, so that the counts would not be as impacted. Barlogie not only knows what to do, he knows WHY he is doing it.
When he sees a patient that has been heavily treated elsewhere -- and I have personally referred patients from Los Angeles to Canada who were told by their supposed experts that they would be dead in three months only to be given a new lease on life in Arkansas -- Barlogie knows what the options are and why. This can include experimentation, particularly in those that have received all the common treatments before. But when one can either update one's will and sign up for hospice, or sign up for experimentation and live 18 months to who knows how long, that's a meaningful choice to have, even for those who choose the first path.
As another example, because he has seen so many patients, Barlogie knows that certain procedures ENCOURAGE plasma cells and Myeloma. In patients that are not in remission, something as simple as removing a central line (a catheter placed subcutaneously for infusions, and which requires an incision) can sometimes cause the eruption of plasmacytomas at the incision site. Patients with serious disease might even experience this at the site of simple injections. Doctors that haven't seen thousands of patients and haven't observed this phenomenon dozens if not hundreds of times simply won't know this is happening.
Similarly, I have friends that receive radiation. Radiation can possibly cause the same thing -- plasma cells rush to the area that experiences the radiation. This could strengthen the Myeloma over the long haul. This is why my doctor favors "melting tumors" with chemotherapy. A doctor that hasn't seen this many times over might be quick to radiate something that won't help the situation.
Now, some of this is theory -- and some of it is likely the age-old difference between chemotherapists and radiologists whom, I am told, haven't always gotten along well (this is not specific at all to UAMS, where the departments work well together). But a lot of this is experience. Experience that few doctors in the world have.
Over the course of the next two nights, I had other conversations with Bart, his family, and Bonnie. About the disease, about what we learn from going through it, about their own lives and families as well as my own. Bart and his family become profoundly emotionally involved in the outcome of Bart's patients. Some may say this is a bad thing -- they prefer a doctor that is detached and unemotional. I can understand that -- but there's also something about having a specialist being emotionally invested in one's case and wanting that person to beat the disease. Not to qualify for more funding, not to validate or invalidate a particular drug's efficacy -- but because Bart hates this disease and loves his patients.
That is not a cult. That is a family of care.
I've seen an unfortunate few of those in Bart's care -- both newly diagnosed who arrive full of hope, and those who have been treated elsewhere that aren't able to hope for a cure through Total Therapy because being pre-treated means the TT approach isn't as effective -- die. These people are not bitter. Uniformly, they are at peace. Because they know that they have been seen by the best and there could not have been a better outcome. That, too, is not a cult. That is the result of a dignified grace conferred at least in part by confidence in one's medical team. I am not certain I would experience such grace in the face of imminent mortality. I hope I never need to find out. The UAMS people don't sugar-coat things...Bonnie once told me "I can help you beat this disease, but should the time come, I can also help you prepare to die from it." That's both awful and pretty remarkable at the same time.
I have a privileged relationship with Bart and his family, as I've said in the past and said earlier in this article. He doesn't visit everybody in the hospital, as he did with me (and did with my friend who experienced relapse, whom I mentioned above). Kathy, who doesn't even work at UAMS, doesn't visit everybody in the hospital either -- yet I remember when I was basically in a coma from Dilaudid, I opened my eyes once to see her sitting there holding the hand of my terrified wife. Yet this privileged relationship didn't come from anything special and isn't unique to me. I reciprocate and invest in it, because it's good for my care clinically but mostly because I love these people. This privileged relationship arises for me and others BECAUSE of the commitment that Bart and his team give to their patients.
If that collectively means I'm part of a cult, then sign me up. So long as it doesn't involve purple jumpsuits or Kool-Aid. :)
As to curability and why it matters, that's coming up next.
P.S. As part of being in the cult, I provide free advertising for associated businesses. :) If you are in Little Rock, make sure to check out The Fold, which is Bart Jr'.s restaurant featuring farm-to-table, high-end tacos and other small plates. Calling them tacos is a bit of an understatement. It's a very relaxed, reasonably priced and cool place with a wide variety of good eats. I've now put it in my rotation along with certain BBQ and pizza places when I go my weeks in Little Rock.
Saturday, February 8, 2014
A good checkup
I will post more on this soon, but here are the highlights:
* The monoclonal signature in the blood is gone. Which means all along it was the secondary MGUS phenomenon that Mayo research indicated is a good thing. Hurray!
* Bone marrow is negative for Myeloma, minimal residual disease test looked at 2.1 mil "events" (not sure if this is a cell or a receptor on a cell) and found no Myeloma.
* Formerly active focal lesion at my 12th thoracic vertebrae is gone. Formerly active lesion at T10 remains but is slightly smaller.
Unchanged lesions remain at T2, T3 and T4. These lesions were too difficult to aspirate with a fine needle so I thankfully only had two holes dug in my hip (one for marrow, one for gene array) and none in my spine.
So now we are down to four lesions. Stay the course.
I will post more detail soon, but a spoiler: I love my doctor and I am utterly convinced that this aggressive approach is by far the best one to use. I would urge any newly diagnosed patients who come across this blog to go to Arkansas for treatment.
Oh, and just to prove the old dog can learn a new trick, my doctor now thinks curcumin "can't hurt." :)
* The monoclonal signature in the blood is gone. Which means all along it was the secondary MGUS phenomenon that Mayo research indicated is a good thing. Hurray!
* Bone marrow is negative for Myeloma, minimal residual disease test looked at 2.1 mil "events" (not sure if this is a cell or a receptor on a cell) and found no Myeloma.
* Formerly active focal lesion at my 12th thoracic vertebrae is gone. Formerly active lesion at T10 remains but is slightly smaller.
Unchanged lesions remain at T2, T3 and T4. These lesions were too difficult to aspirate with a fine needle so I thankfully only had two holes dug in my hip (one for marrow, one for gene array) and none in my spine.
So now we are down to four lesions. Stay the course.
I will post more detail soon, but a spoiler: I love my doctor and I am utterly convinced that this aggressive approach is by far the best one to use. I would urge any newly diagnosed patients who come across this blog to go to Arkansas for treatment.
Oh, and just to prove the old dog can learn a new trick, my doctor now thinks curcumin "can't hurt." :)
Friday, January 31, 2014
Insurance...
I consider myself very lucky that I've never had to complain about insurance, until now.
Since BB is an outlier in his efforts to cure the disease, his protocols and testing are more rigorous than many. He uses MRI to track disease eradication, and he uses PET for the same thing as well as to provide measurements for precise bone marrow biopsies called fine needle aspirations.
I've just learned that my insurance company has rejected these tests, which means I either have to do without, or go out of pocket for several thousand (!!) dollars. I know this because I found out in arrears that they rejected the last batch and I need to come up with several thousand for that go-round.
It had been a pretty consistent dance over the years. BB orders advanced imaging. Insurance company refuses to approve. Somebody from the clinic does a "peer to peer" review with the insurance company and convinces them. They approve.
This time -- and last -- they did not approve.
Not sure if that's because of a change in policy or a change in personnel.
The reality is, whomever is the "peer" on the insurance end of the phone doesn't know this disease. That's why they are working as a minor administrative official in an insurance company, effectively stamping forms, instead of practicing medicine and treating disease.
As of now, the plan is go proceed with PET because that will highlight the presence of any lesions and can be used to guide the fine needle aspirations. I may or may not also get limited MRIs of my hip and spine, depending on what the PET says, I guess.
What a pain.
I have -- with a smidgen of effort, I must admit -- resisted the urge to make any political commentary so I would ask those of you kind enough to comment to also refrain from doing so. :)
Since BB is an outlier in his efforts to cure the disease, his protocols and testing are more rigorous than many. He uses MRI to track disease eradication, and he uses PET for the same thing as well as to provide measurements for precise bone marrow biopsies called fine needle aspirations.
I've just learned that my insurance company has rejected these tests, which means I either have to do without, or go out of pocket for several thousand (!!) dollars. I know this because I found out in arrears that they rejected the last batch and I need to come up with several thousand for that go-round.
It had been a pretty consistent dance over the years. BB orders advanced imaging. Insurance company refuses to approve. Somebody from the clinic does a "peer to peer" review with the insurance company and convinces them. They approve.
This time -- and last -- they did not approve.
Not sure if that's because of a change in policy or a change in personnel.
The reality is, whomever is the "peer" on the insurance end of the phone doesn't know this disease. That's why they are working as a minor administrative official in an insurance company, effectively stamping forms, instead of practicing medicine and treating disease.
As of now, the plan is go proceed with PET because that will highlight the presence of any lesions and can be used to guide the fine needle aspirations. I may or may not also get limited MRIs of my hip and spine, depending on what the PET says, I guess.
What a pain.
I have -- with a smidgen of effort, I must admit -- resisted the urge to make any political commentary so I would ask those of you kind enough to comment to also refrain from doing so. :)
Monday, January 27, 2014
Big week for tests coming up
So next week is a little more than the usual "poke 'n' prod" as I've taken to calling it.
To sum up where I am these days, at the risk of repeating material I've presented over the past several months:
* I have had a signature in my blood in the past, which is no longer present under LA lab tests but was present under Arkansas labs even when not present in LA labs, which is either a sign of an immune system rebuilding itself or a sign of disease return.
* Other lab tests would point in the direction of good news, but BB and team have not seen this particular signature before -- or at least don't know what to make of it. This is in contrast to research from Mayo. And the uncertainty is troubling to me, since BB sees more of this than Mayo and treats more aggressively than them and thus would likely see more evidence of profound disease suppression / eradication than they would.
* I have been waiting for more than two years for resolution of lingering spots in my spine that used to be hot spots for cancer but have been dormant for some time. Several others formerly active lesions in my body have gone away completely. It's interesting that most doctors don't believe these lesions resolve. My doctor believes they do. And they have in me. Which makes me feel like my confidence in my doctor -- iconoclastic though he may be in some respects -- we well placed.
* If my disease comes back after the treatment I've been through, it may likely come back in an aggressive form which would have dire implications.
Next week, then, we'll have the usual complements of tests: PET/CT, MRI, blood work, bone marrow biopsy, etc. I'll also have the fairly recently introduced test for minimal residual disease, which tests literally millions of cells rather than the 40 that are typically looked at in bone marrow.
However, in addition to this, if the signature remains in my blood, we will try to devise a means of comparing that with the original protein. This may not be possible, however, as I am told that a precise comparison requires bone marrow and my bone marrow is currently clean. If I have Myeloma in my bone marrow, then we have our answer and it is not a good one. If I don't, then they would need to compare my current blood against a sample that was originally taken (I think) and they may not be able to do this.
The other non-standard test they are doing are fine needle aspirations of the remaining lesions in my spine. These are essentially precisely targeted bone marrow biopsies of the exact spots that used to be active for cancer. It is BB's theory that if there are any cancer cells lingering, these spots are likely where they are hiding. These will not be pleasant as they are deep in the spine and my bones are hard from multiple courses of the bone-strengthening agent Zometa. I'm endeavoring right now to ensure I will be knocked out when these do these. As barbaric as it sounds, normally one is conscious when this happens. But I tried that once before -- for a comparatively innocuous FNA in my hip -- as it didn't work out well. So now, I make them knock me out.
The best outcome here is for the blood and bone marrow biopsy to be clean and the lesions to be gone. If that's the case, then the strange signature in the blood was in fact what Mayo believes it to be -- a good sign. QED. I won't need the FNAs done if this is the case as there This outcome might even result in BB telling me I'm cured.
If the blood is clean and the lesions are still there, the next best outcome is for them to be negative for MRD under the fine needle aspiration. If that's the case, BB will probably continue to watch and see, but the belief will likely be that they are "shadows" rather than things to be actively worried about. This keeps the sword of Damocles hanging, but essentially indicates that the twine that holds it remains relatively sturdy.
Anything else is pretty much a disaster so...I'll not even enumerate those outcomes.
Fingers and toes crossed. Will likely update from Arkansas next week, which I gather is going to be one chilly trip!
To sum up where I am these days, at the risk of repeating material I've presented over the past several months:
* I have had a signature in my blood in the past, which is no longer present under LA lab tests but was present under Arkansas labs even when not present in LA labs, which is either a sign of an immune system rebuilding itself or a sign of disease return.
* Other lab tests would point in the direction of good news, but BB and team have not seen this particular signature before -- or at least don't know what to make of it. This is in contrast to research from Mayo. And the uncertainty is troubling to me, since BB sees more of this than Mayo and treats more aggressively than them and thus would likely see more evidence of profound disease suppression / eradication than they would.
* I have been waiting for more than two years for resolution of lingering spots in my spine that used to be hot spots for cancer but have been dormant for some time. Several others formerly active lesions in my body have gone away completely. It's interesting that most doctors don't believe these lesions resolve. My doctor believes they do. And they have in me. Which makes me feel like my confidence in my doctor -- iconoclastic though he may be in some respects -- we well placed.
* If my disease comes back after the treatment I've been through, it may likely come back in an aggressive form which would have dire implications.
Next week, then, we'll have the usual complements of tests: PET/CT, MRI, blood work, bone marrow biopsy, etc. I'll also have the fairly recently introduced test for minimal residual disease, which tests literally millions of cells rather than the 40 that are typically looked at in bone marrow.
However, in addition to this, if the signature remains in my blood, we will try to devise a means of comparing that with the original protein. This may not be possible, however, as I am told that a precise comparison requires bone marrow and my bone marrow is currently clean. If I have Myeloma in my bone marrow, then we have our answer and it is not a good one. If I don't, then they would need to compare my current blood against a sample that was originally taken (I think) and they may not be able to do this.
The other non-standard test they are doing are fine needle aspirations of the remaining lesions in my spine. These are essentially precisely targeted bone marrow biopsies of the exact spots that used to be active for cancer. It is BB's theory that if there are any cancer cells lingering, these spots are likely where they are hiding. These will not be pleasant as they are deep in the spine and my bones are hard from multiple courses of the bone-strengthening agent Zometa. I'm endeavoring right now to ensure I will be knocked out when these do these. As barbaric as it sounds, normally one is conscious when this happens. But I tried that once before -- for a comparatively innocuous FNA in my hip -- as it didn't work out well. So now, I make them knock me out.
The best outcome here is for the blood and bone marrow biopsy to be clean and the lesions to be gone. If that's the case, then the strange signature in the blood was in fact what Mayo believes it to be -- a good sign. QED. I won't need the FNAs done if this is the case as there This outcome might even result in BB telling me I'm cured.
If the blood is clean and the lesions are still there, the next best outcome is for them to be negative for MRD under the fine needle aspiration. If that's the case, BB will probably continue to watch and see, but the belief will likely be that they are "shadows" rather than things to be actively worried about. This keeps the sword of Damocles hanging, but essentially indicates that the twine that holds it remains relatively sturdy.
Anything else is pretty much a disaster so...I'll not even enumerate those outcomes.
Fingers and toes crossed. Will likely update from Arkansas next week, which I gather is going to be one chilly trip!
Wednesday, January 8, 2014
A short but purposeful post
When I reference this blog in some MM communities online, the reference will pull up the latest graphic and that gets inserted next to whatever I've typed.
For months, this was a bottle of that magnesium rocket fuel laxative.
Now, it's the ridiculous "Madame" puppet photo.
So PURELY so I don't look like a complete weirdo, I'm putting another picture up here.
My doctor. Looking a little less avant garde than usual, without his leather pants and motorcycle jacket!
For months, this was a bottle of that magnesium rocket fuel laxative.
Now, it's the ridiculous "Madame" puppet photo.
So PURELY so I don't look like a complete weirdo, I'm putting another picture up here.
My doctor. Looking a little less avant garde than usual, without his leather pants and motorcycle jacket!
A little observation, not specific to my own biology
Happy New Year, all.
No news to update, while I wait to schedule an upcoming trip to Arkansas for a significant series of tests including multiple bone marrow biopsies (assuming the former lesions in my spine still exist).
I'm beginning to come around on the notion of this M protein being benign, actually. Although I note that in the Mayo research the majority of these faint signals resolve on their own after a median of six months. It's been about that long for me, give or take, so I wouldn't mind seeing it go away. If it hasn't, I may have more significant issues.
So best case is the lesions have all fully resolved with healthy new bone tissue (I've had a few courses of Zometa over the past few months to help this process, although I'd been on that before and it didn't finish the job and BB discontinued it before resuming it this time, so who knows...probably guesswork at this point). If that happens, and the M protein is gone, and the MRD (minimal residual disease) test is negative, then I may be celebrating soon.
Worst case (other than disease return) is the lesions haven't resolved, M protein still there, but MRD is still negative including all the marrow analyzed from those lesions, in which case we still watch and wait and maybe consider treating more aggressively.
An added bonus to lesion resolution is they won't need to do more than one bone marrow. We'll have to see.
Wow, for a post that wasn't supposed to be about my biology, it sure has turned into that...
Anyhow, what I was ORIGINALLY going to post follows. I posted this elsewhere (in a comment on a post on Pat Killingsworth's blog) but I thought it was a good thing to keep in mind in the spirit of New Years Resolutions. Essentially: when someone you know -- even if only a little -- is facing a tragedy or a terrible event in their life, err on the side of reaching out. It may be more helpful than you know.
No news to update, while I wait to schedule an upcoming trip to Arkansas for a significant series of tests including multiple bone marrow biopsies (assuming the former lesions in my spine still exist).
I'm beginning to come around on the notion of this M protein being benign, actually. Although I note that in the Mayo research the majority of these faint signals resolve on their own after a median of six months. It's been about that long for me, give or take, so I wouldn't mind seeing it go away. If it hasn't, I may have more significant issues.
So best case is the lesions have all fully resolved with healthy new bone tissue (I've had a few courses of Zometa over the past few months to help this process, although I'd been on that before and it didn't finish the job and BB discontinued it before resuming it this time, so who knows...probably guesswork at this point). If that happens, and the M protein is gone, and the MRD (minimal residual disease) test is negative, then I may be celebrating soon.
Worst case (other than disease return) is the lesions haven't resolved, M protein still there, but MRD is still negative including all the marrow analyzed from those lesions, in which case we still watch and wait and maybe consider treating more aggressively.
An added bonus to lesion resolution is they won't need to do more than one bone marrow. We'll have to see.
Wow, for a post that wasn't supposed to be about my biology, it sure has turned into that...
Anyhow, what I was ORIGINALLY going to post follows. I posted this elsewhere (in a comment on a post on Pat Killingsworth's blog) but I thought it was a good thing to keep in mind in the spirit of New Years Resolutions. Essentially: when someone you know -- even if only a little -- is facing a tragedy or a terrible event in their life, err on the side of reaching out. It may be more helpful than you know.
I remember I always used to wonder, when a friend or loved one faced some sort of tragedy or crisis, whether or not they wouldn't want to be bothered by a call to check in on them -- or whether I didn't know somebody well enough to intrude on a private experience. When I was going through my own diagnosis and initial aggressive treatment, the calls and emails that touched me most were from people that I wasn't in regular contact with, or whom I didn't know particularly well, but who just wanted to let me know they were thinking of me. I found these remarkably uplifting. Perhaps it's because it's a reminder of how many lives we touch -- more than we think. In any case: when in doubt, call someone, email someone, send them a note and let them know you are thinking of them. The worst it will do is nothing -- and it might significantly brighten their day.
Tuesday, December 17, 2013
Hmm...partial answers from Dr. FVR from UAMS
So I was on this panel today with Dr. Van Rhee, who did an admirable job of explaining the total therapy philosophy.
I told him I was a fervent believer in their approach, thanked him and his colleagues for saving my life, and then told him I was going to ask him tough questions.
I pointed out that the "cure curve" presentations that had formerly been featured on the UAMS site were now down, and that BB is now looking at administering Revlimid post therapy to see if there is a difference in outcome. I wanted to know what the cure curves looked like now -- how long until a plateau is reached and what percent of patients under TT3 look like they will exit in a "cured" state. I mean, look -- it's disturbing that the folks who have been saying they can cure this condition are (a) removing their formerly strongly-worded documents to this effect from their website, and (b) doing a test to see if medicine should really be stopped after three years of maintenance. There could be very legitimate reasons for both of these things (for example, the papers are now 4 and 6 years old, respectively, and the ongoing maintenance could be a test to demonstrate that the existing maintenance already does as good a job as possible). However it is disconcerting.
I'm looking back at my copies of these papers, starting with one called "The Myth of Incurability" that was published in 2007. The original data on TT3 -- ignoring projections for the moment -- was that low-risk patients had a event free survival rate of about 80% and things looked like they were flattening out at that point -- meaning that if you made it to four years without a recurrence, you were highly likely to sustain remission. High risk patients, unfortunately, are not so fortunate -- only about 35% of these folks were still alive, and only about 20% of them had maintained remission. There is no claim of cure for high risk MM through Total Therapy (or any other therapy).
Based on this performance, the first projected "continuous complete remission" for both low risk and high risk combined was forecasted and showed what looked to be a 35% cure rate for both cohorts (low and high risk). If we assume 15% are high risk that are not cured, this implies about 50% of low-risk patients being cured overall. Bear in mind, these figures includes deaths from everything -- if somebody gets diagnosed at 68 years old and lives for 8 years and dies of heart disease, they fall off the graph. So the cure rates are likely understated for that reason.
Moreover, performance is better for low risk patients that achieved complete remission. Here, the forecast was for ">60% 10-year continuous complete remission" for both cohorts. Again, if we assume that high risk patients representing 15% of diagnoses are unable to achieve 10-year continuous complete remission, that implies about 70% of low risk patients achieve 10-year continuous complete remission. And since not all patients achieve complete remission in the first place, the implication is that a very high percentage of low risk patients that achieve complete remission are projected to be cured. In fact, looking at another chart, it looks like of the total TT3 cohort of 303 patients (including both low and high risk) about 52% achieved complete remission, taking an average of one year (based on the median of this group) but up to 30 months to get there. Meanwhile, the relapse rate of those who achieved complete remission fell to zero, basically, after about three years. So if we say 18 months to get to complete remission and three years of remission to get through the time period where there is a risk of relapse, then somewhere between four and five years out people can be confident they are cured.
Fast forward now to 2009, and a follow-up paper called "Modeling for the Cure." This paper I can't even find, unfortunately, although I'm sure I have it somewhere (probably at my office -- I may update all of this later today). In this paper, I remember clearly the forecast was that low-risk patients that achieve complete remission have an 87.6% chance of being cured, and that by the end of four years, the plateau has been reached. In other words, the 13.4% chance of relapse exists at the beginning of remission and is slowly reduced over four years to the point of it being basically nothing. This seemed to tie to the earlier data. All good, right?
I should be able to breathe easy.
Except this paper has now vanished. It's not referenced anywhere any longer and it's as though it's ceased to exist.
I pressed Dr. van Rhee on this, and he said that the plateau now appeared to be at "7-8 years." I'm not sure whether or not this means 7-8 years from the achievement of remission (unlikely) or 7-8 years from the commencement of therapy (more likely, and obviously better since it takes a while to get into remission). If the plateau is reached at 7-8 years from the start of therapy -- let's say 8 years to be on the safe side -- then I've got three more years to go.
He also said that the rate of patients still in complete remission at that point was about 50%. Now again, this includes high risk patients as well, and it includes death from other sources. If we make the adjustment to remove the high risk patients once again, we are back to around 60% of low risk patients being cured (the number is probably higher, again, if we consider deaths from other causes as well as the fact that patients achieving complete remission is higher). Nonetheless, worst case, 60%. And if we assume an even "failure rate" of remission over the total eight years from therapy, I'm now just about 5/8 of the way through. Which would imply that I've got an 85% chance of being cured, which should increase steadily over the next three years until eventually, I can rest easy.
This is all rough math based on numbers from different sources, often interpolated and extrapolated to provide approximations for numbers I don't know. So it's far from perfect, but it's something. It's more than a 50% chance I'm cured, and it's less than the 100% that I expected by now.
All this estimating is almost enough to make my head explode -- which, if taken literally rather than figuratively, would convolute my own statistics due to morbidity from something other than Myeloma! :)
Which brings me to my second question for Dr. Van Rhee -- that of the monoclonal light chain under immunofixation that I have had in my blood for several months. Is this the harbinger of remission loss? Or is it a sign of deep response to therapy that would be consistent with significantly extended survival if not cure? The bottom line is: he doesn't know. He seemed to be somewhat familiar with the Mayo paper that observed this, but said they hadn't observed this "secondary MGUS" at UAMS. He did reference to a sub-population of low-risk patients that had MGUS likely before it became Myeloma, and were treated for Myeloma, and did fine (as in no return of the disease for many if not most of them) post therapy, but who retained the original MGUS. I'm not sure I fall into this camp -- my monoclonal signature now may not be the same protein. If it *is* the same protein, then maybe I have this "cure with MGUS" hope, per that cohort of patients. If it is *not* the same protein, then it seems more likely that this is consistent with the Mayo interpretation of an immune system repairing itself.
I've written to BB asking this question more directly, and we will discuss it when I have my next follow-up in a few weeks (early February) if not before.
Ugh. I'd love to be able to close the door on this chapter but the Myeloma has its food wedged in there pretty firmly. Let's fight another day at a time, shall we?
Meanwhile, I want to have a shout-out here to my friend MAdAM (funny, that really is the acronym, but I'm not referring to this puppet
(As an aside, per my Google search that came up with this picture, it's provenance was an auction site that had "authentic Madame puppet with fainting couch" as the listing -- yikes, the mind boggles).
Anyhow, I digress. My friend MAdAM was being treated in LA by an anti-transplant doctor of renown and was told he'd run out of options for her, she had a good run, get her affairs in order. That was several months ago. MAdAM went to BB and just came out of her transplant in remission, and has a plan with plenty of options going forward. Will she live another 2 years? Another 10? Long enough to find a definitive cure? Let's hope so. One thing is for sure -- she's a lot better off now than she was a few months ago. So for whatever long-term questions I have about the final cure fraction of TT, it remains highly effective against Myeloma.
So ONWARD, BB and team!
I told him I was a fervent believer in their approach, thanked him and his colleagues for saving my life, and then told him I was going to ask him tough questions.
I pointed out that the "cure curve" presentations that had formerly been featured on the UAMS site were now down, and that BB is now looking at administering Revlimid post therapy to see if there is a difference in outcome. I wanted to know what the cure curves looked like now -- how long until a plateau is reached and what percent of patients under TT3 look like they will exit in a "cured" state. I mean, look -- it's disturbing that the folks who have been saying they can cure this condition are (a) removing their formerly strongly-worded documents to this effect from their website, and (b) doing a test to see if medicine should really be stopped after three years of maintenance. There could be very legitimate reasons for both of these things (for example, the papers are now 4 and 6 years old, respectively, and the ongoing maintenance could be a test to demonstrate that the existing maintenance already does as good a job as possible). However it is disconcerting.
I'm looking back at my copies of these papers, starting with one called "The Myth of Incurability" that was published in 2007. The original data on TT3 -- ignoring projections for the moment -- was that low-risk patients had a event free survival rate of about 80% and things looked like they were flattening out at that point -- meaning that if you made it to four years without a recurrence, you were highly likely to sustain remission. High risk patients, unfortunately, are not so fortunate -- only about 35% of these folks were still alive, and only about 20% of them had maintained remission. There is no claim of cure for high risk MM through Total Therapy (or any other therapy).
Based on this performance, the first projected "continuous complete remission" for both low risk and high risk combined was forecasted and showed what looked to be a 35% cure rate for both cohorts (low and high risk). If we assume 15% are high risk that are not cured, this implies about 50% of low-risk patients being cured overall. Bear in mind, these figures includes deaths from everything -- if somebody gets diagnosed at 68 years old and lives for 8 years and dies of heart disease, they fall off the graph. So the cure rates are likely understated for that reason.
Moreover, performance is better for low risk patients that achieved complete remission. Here, the forecast was for ">60% 10-year continuous complete remission" for both cohorts. Again, if we assume that high risk patients representing 15% of diagnoses are unable to achieve 10-year continuous complete remission, that implies about 70% of low risk patients achieve 10-year continuous complete remission. And since not all patients achieve complete remission in the first place, the implication is that a very high percentage of low risk patients that achieve complete remission are projected to be cured. In fact, looking at another chart, it looks like of the total TT3 cohort of 303 patients (including both low and high risk) about 52% achieved complete remission, taking an average of one year (based on the median of this group) but up to 30 months to get there. Meanwhile, the relapse rate of those who achieved complete remission fell to zero, basically, after about three years. So if we say 18 months to get to complete remission and three years of remission to get through the time period where there is a risk of relapse, then somewhere between four and five years out people can be confident they are cured.
Fast forward now to 2009, and a follow-up paper called "Modeling for the Cure." This paper I can't even find, unfortunately, although I'm sure I have it somewhere (probably at my office -- I may update all of this later today). In this paper, I remember clearly the forecast was that low-risk patients that achieve complete remission have an 87.6% chance of being cured, and that by the end of four years, the plateau has been reached. In other words, the 13.4% chance of relapse exists at the beginning of remission and is slowly reduced over four years to the point of it being basically nothing. This seemed to tie to the earlier data. All good, right?
I should be able to breathe easy.
Except this paper has now vanished. It's not referenced anywhere any longer and it's as though it's ceased to exist.
I pressed Dr. van Rhee on this, and he said that the plateau now appeared to be at "7-8 years." I'm not sure whether or not this means 7-8 years from the achievement of remission (unlikely) or 7-8 years from the commencement of therapy (more likely, and obviously better since it takes a while to get into remission). If the plateau is reached at 7-8 years from the start of therapy -- let's say 8 years to be on the safe side -- then I've got three more years to go.
He also said that the rate of patients still in complete remission at that point was about 50%. Now again, this includes high risk patients as well, and it includes death from other sources. If we make the adjustment to remove the high risk patients once again, we are back to around 60% of low risk patients being cured (the number is probably higher, again, if we consider deaths from other causes as well as the fact that patients achieving complete remission is higher). Nonetheless, worst case, 60%. And if we assume an even "failure rate" of remission over the total eight years from therapy, I'm now just about 5/8 of the way through. Which would imply that I've got an 85% chance of being cured, which should increase steadily over the next three years until eventually, I can rest easy.
This is all rough math based on numbers from different sources, often interpolated and extrapolated to provide approximations for numbers I don't know. So it's far from perfect, but it's something. It's more than a 50% chance I'm cured, and it's less than the 100% that I expected by now.
All this estimating is almost enough to make my head explode -- which, if taken literally rather than figuratively, would convolute my own statistics due to morbidity from something other than Myeloma! :)
Which brings me to my second question for Dr. Van Rhee -- that of the monoclonal light chain under immunofixation that I have had in my blood for several months. Is this the harbinger of remission loss? Or is it a sign of deep response to therapy that would be consistent with significantly extended survival if not cure? The bottom line is: he doesn't know. He seemed to be somewhat familiar with the Mayo paper that observed this, but said they hadn't observed this "secondary MGUS" at UAMS. He did reference to a sub-population of low-risk patients that had MGUS likely before it became Myeloma, and were treated for Myeloma, and did fine (as in no return of the disease for many if not most of them) post therapy, but who retained the original MGUS. I'm not sure I fall into this camp -- my monoclonal signature now may not be the same protein. If it *is* the same protein, then maybe I have this "cure with MGUS" hope, per that cohort of patients. If it is *not* the same protein, then it seems more likely that this is consistent with the Mayo interpretation of an immune system repairing itself.
I've written to BB asking this question more directly, and we will discuss it when I have my next follow-up in a few weeks (early February) if not before.
Ugh. I'd love to be able to close the door on this chapter but the Myeloma has its food wedged in there pretty firmly. Let's fight another day at a time, shall we?
Meanwhile, I want to have a shout-out here to my friend MAdAM (funny, that really is the acronym, but I'm not referring to this puppet
(As an aside, per my Google search that came up with this picture, it's provenance was an auction site that had "authentic Madame puppet with fainting couch" as the listing -- yikes, the mind boggles).
Anyhow, I digress. My friend MAdAM was being treated in LA by an anti-transplant doctor of renown and was told he'd run out of options for her, she had a good run, get her affairs in order. That was several months ago. MAdAM went to BB and just came out of her transplant in remission, and has a plan with plenty of options going forward. Will she live another 2 years? Another 10? Long enough to find a definitive cure? Let's hope so. One thing is for sure -- she's a lot better off now than she was a few months ago. So for whatever long-term questions I have about the final cure fraction of TT, it remains highly effective against Myeloma.
So ONWARD, BB and team!
Friday, December 13, 2013
Myeloma panel with Dr. van Rhee of UAMS next Monday
Next Monday I am participating as a patient panelist on another Cure Talk call, hosted by the wonderful Priya Menon and the Cure Talk organization, which will feature Dr. van Rhee who is BB's head of research.
As of now, I plan on asking him about the current cure curves for TT3 and TT4 -- TT3 data is now 10 years out so the low risk patients should have achieved a true plateau is there is one. The last data that was routinely spoken about was in a 2009 publication called "modeling for the cure" but that data has been pulled down. Is this because the data did not hold up to longer-term study? Or for a less distressing reason? This reporter wants to know!
I'll also be asking very specifically about the monoclonal light chain that is believed by some to be a sign of disease eradication but could also be disease return.
It should be an interesting conversation -- all of the ones in which I've participated have been very enlightening.
The call is December 16th at 3PM pacific time, 6PM EST. Registration and dial-in information is below for those interested.
Have a great weekend!
As of now, I plan on asking him about the current cure curves for TT3 and TT4 -- TT3 data is now 10 years out so the low risk patients should have achieved a true plateau is there is one. The last data that was routinely spoken about was in a 2009 publication called "modeling for the cure" but that data has been pulled down. Is this because the data did not hold up to longer-term study? Or for a less distressing reason? This reporter wants to know!
I'll also be asking very specifically about the monoclonal light chain that is believed by some to be a sign of disease eradication but could also be disease return.
It should be an interesting conversation -- all of the ones in which I've participated have been very enlightening.
The call is December 16th at 3PM pacific time, 6PM EST. Registration and dial-in information is below for those interested.
Have a great weekend!
Registration link: http://curepanel.carefeed.net/event/rsvp/12/
Dial-in: 718-664-6574
Wednesday, December 11, 2013
No longer suffering from chemo brain
I went to a neurological oncologist to get a "new baseline" for my cognitive abilities. I wanted to make sure that I had survived chemo brain. Frankly, I went through a period in my job where I wasn't thinking as adroitly as I was accustomed to and lacked a lot of energy. It impacted my performance and career prospects, and frankly was something that I had heard existed but didn't really understand. I'll say this -- it's difficult to self-diagnose when you have it.
Essentially, high dose chemo of any kind bathes your brain in chemicals and there's an impact on executive function -- attention, memory, focus, energy, decision-making, etc. These are the types of things that executives (duh) rely upon in their jobs. It usually takes around four years, it turns out, for these effects to subside. The amount of chemo I received would indicate that I should have this worse than most, but my age and general mental acuity before all of it would indicate that I would fare better than most.
Anyhow, I'm relieved to report that I scored off the charts on most of the stuff including the areas that were once impacted. My IQ is 98-99th percentile (140+) and executive function is intact, as are memory and attention. I'm under a tremendous amount of emotional stress right now due to everything from the overall cancer situation, the M protein signature that has appeared, the car, my job (stressful on the best day), and other things and that's depleting energy so I've got to find a way to deal with that, but the core intellect and processing power is back. So onward!
Essentially, high dose chemo of any kind bathes your brain in chemicals and there's an impact on executive function -- attention, memory, focus, energy, decision-making, etc. These are the types of things that executives (duh) rely upon in their jobs. It usually takes around four years, it turns out, for these effects to subside. The amount of chemo I received would indicate that I should have this worse than most, but my age and general mental acuity before all of it would indicate that I would fare better than most.
Anyhow, I'm relieved to report that I scored off the charts on most of the stuff including the areas that were once impacted. My IQ is 98-99th percentile (140+) and executive function is intact, as are memory and attention. I'm under a tremendous amount of emotional stress right now due to everything from the overall cancer situation, the M protein signature that has appeared, the car, my job (stressful on the best day), and other things and that's depleting energy so I've got to find a way to deal with that, but the core intellect and processing power is back. So onward!
Thursday, November 28, 2013
Enough already! Or, be thankful and hugs your kids.
So here I am, busy not dying from cancer, when I almost died from an auto accident.
Near as I can tell (because I couldn't see anything) a truck with a flatbed / auto carrier ran into my left rear quarter panel hard enough to severely bend my rear axel, wreck the wheel and tire, activate the side air bag (which exploded with a force and sound that immediately deafened me) and spun my car counter-clockwise. So I went from moving along no problem to being deaf and having the car spinning wildly out of control before I had any idea what was going on. Then, as I was spinning, part of the same truck (near as I can tell) rammed full force into the passenger side of my car with enough force to knock me across three lanes of freeway traffic to come to rest facing the wrong way in the slow lane on the freeway. All of this at 45 MPH, mind you.
Somehow, I walked away from this unscathed, other than deafness (hopefully temporary) in my left ear from the airbag going off and first degree burns on the back of my left arm and on my left side from the same airbag.
I might add, had the car flipped (which it certainly could have) I would have tumbled off this stretch of freeway over an 80 foot drop-off.
Then the driver of the truck -- which was the only other vehicle involved since no other cars were struck, miraculously -- drove away. Nice guy.
Look, I realize my great great grandmother back in the old country spit in the eye of the village witch and invited a curse upon the family but ENOUGH ALREADY WITH THE NEAR DEATH EXPERIENCES!!! I'm not gonna beat supposedly incurable cancer just to die in a car accident, for Pete's sake!
Happy Thanksgiving to you all. Not gonna lie, I'm half in the bag here already from a few mimosa and I envision spending the rest of the day in a bit of a haze so...this reporter is signing off. : )
Near as I can tell (because I couldn't see anything) a truck with a flatbed / auto carrier ran into my left rear quarter panel hard enough to severely bend my rear axel, wreck the wheel and tire, activate the side air bag (which exploded with a force and sound that immediately deafened me) and spun my car counter-clockwise. So I went from moving along no problem to being deaf and having the car spinning wildly out of control before I had any idea what was going on. Then, as I was spinning, part of the same truck (near as I can tell) rammed full force into the passenger side of my car with enough force to knock me across three lanes of freeway traffic to come to rest facing the wrong way in the slow lane on the freeway. All of this at 45 MPH, mind you.
Somehow, I walked away from this unscathed, other than deafness (hopefully temporary) in my left ear from the airbag going off and first degree burns on the back of my left arm and on my left side from the same airbag.
I might add, had the car flipped (which it certainly could have) I would have tumbled off this stretch of freeway over an 80 foot drop-off.
Then the driver of the truck -- which was the only other vehicle involved since no other cars were struck, miraculously -- drove away. Nice guy.
Look, I realize my great great grandmother back in the old country spit in the eye of the village witch and invited a curse upon the family but ENOUGH ALREADY WITH THE NEAR DEATH EXPERIENCES!!! I'm not gonna beat supposedly incurable cancer just to die in a car accident, for Pete's sake!
Happy Thanksgiving to you all. Not gonna lie, I'm half in the bag here already from a few mimosa and I envision spending the rest of the day in a bit of a haze so...this reporter is signing off. : )
Tuesday, November 26, 2013
Past and future Myeloma panels
Hello folks.
I had the opportunity to participate in another Myeloma Panel hosted by Cure Talk and the wonderful Priya Menon. Last week's guest was Dr. Asher Chanan-Khan of Mayo in Jacksonville.
Dr. Chanan-Khan was speaking about monoclonal antibodies (elotuzimab, daratumumab, etc.) which are emerging therapies that didn't exist even a few years ago. They're exciting because most of the developments in Myeloma over the past five years -- chiefly Carfilzomib and Pomalyst -- have been continuations of existing families of drugs. Carfilzomib is a proteasome inhibitor, like Velcade, and is essentially a more effective version of the same drug. Pomalyst is next generation Revlimid, which itself was next generation Thalidomide -- all immunomodulatory drugs. And like Carfilzomib vis-a-vis Velcade, it's more effective and is easier to tolerate. Because Velcade and Relimid are themselves so effective against Myeloma, and because Carfilzomib and Pomalyst / Pomalidomide are effective in patients that have MM with resistance to Velcade and Revlimid, Car and Pom are usually used as "salvage" therapy to extend the lives of people who have otherwise run out of options. This is all good and fine, and 18 months may be a lot of time to somebody who is otherwise looking at packing bags (not to be overly morbid).
But 18 months isn't long enough for somebody that wants to live many years. And so new drugs that are whole new ways of attacking MM have special interest. There are others (believe it or not, one is called a hedgehog inhibitor) but the ones that are now "in market" so to speak (meaning in Phase III trials) are monoclonal antibodies.
I knew very little of these prior to the call, so I was excited to learn a bit about them.
Essentially, myeloma cells express certain proteins -- these have names like CD138, CD38, CD27, CD45, etc (the CD stands for, I think, "cluster designation" since the proteins are in clusters). Monoclonal antibodies attach themselves to these proteins and allow the body's immune system to attack them, killing or weakening the cells. Consequently, these are effective both on their own and in conjunction with other therapy (e.g., Velcade, Revlimid, etc.) that kill cells. As a result, adding an antibody to treatment with Velcade can reduce drug-resistance to Velcade.
Because not all MM cells express these proteins, and because the key is still getting a weakened immune system that wasn't particularly good at getting rid of MM in the first place to respond and kill the targeted cells, this is not a perfect therapy and it's not a cure. But it does represent an advancement and, combined with other therapies, could make a significant impact.
Looking at my MRD test, UAMS tested for the presence of seven proteins in my marrow (CD138, CD38, CD45, CD56, CD81, CD27, CD20 and CD19, for those playing the home game). Of the 3,562,010 cells analyzed, none exhibited any of these proteins. That sounds good!
On December 16th, there will be another panel conversation and the guest physician will be Dr. FVR, who works for BB. I will have some specific questions for him about the current "cure curves" for Total Therapy 3 and 4, now that there has been 10 years of follow up for the first group and five for the second. I will also be asking about residual monoclonal protein, per my last post.
If any of you have other questions, feel free to post them in response to this, or email me and I'll see if we can't get some of them answered.
Meanwhile, for those that celebrate the holiday, let me extend a hearty Happy Thanksgiving to you and your families!
I had the opportunity to participate in another Myeloma Panel hosted by Cure Talk and the wonderful Priya Menon. Last week's guest was Dr. Asher Chanan-Khan of Mayo in Jacksonville.
Dr. Chanan-Khan was speaking about monoclonal antibodies (elotuzimab, daratumumab, etc.) which are emerging therapies that didn't exist even a few years ago. They're exciting because most of the developments in Myeloma over the past five years -- chiefly Carfilzomib and Pomalyst -- have been continuations of existing families of drugs. Carfilzomib is a proteasome inhibitor, like Velcade, and is essentially a more effective version of the same drug. Pomalyst is next generation Revlimid, which itself was next generation Thalidomide -- all immunomodulatory drugs. And like Carfilzomib vis-a-vis Velcade, it's more effective and is easier to tolerate. Because Velcade and Relimid are themselves so effective against Myeloma, and because Carfilzomib and Pomalyst / Pomalidomide are effective in patients that have MM with resistance to Velcade and Revlimid, Car and Pom are usually used as "salvage" therapy to extend the lives of people who have otherwise run out of options. This is all good and fine, and 18 months may be a lot of time to somebody who is otherwise looking at packing bags (not to be overly morbid).
But 18 months isn't long enough for somebody that wants to live many years. And so new drugs that are whole new ways of attacking MM have special interest. There are others (believe it or not, one is called a hedgehog inhibitor) but the ones that are now "in market" so to speak (meaning in Phase III trials) are monoclonal antibodies.
I knew very little of these prior to the call, so I was excited to learn a bit about them.
Essentially, myeloma cells express certain proteins -- these have names like CD138, CD38, CD27, CD45, etc (the CD stands for, I think, "cluster designation" since the proteins are in clusters). Monoclonal antibodies attach themselves to these proteins and allow the body's immune system to attack them, killing or weakening the cells. Consequently, these are effective both on their own and in conjunction with other therapy (e.g., Velcade, Revlimid, etc.) that kill cells. As a result, adding an antibody to treatment with Velcade can reduce drug-resistance to Velcade.
Because not all MM cells express these proteins, and because the key is still getting a weakened immune system that wasn't particularly good at getting rid of MM in the first place to respond and kill the targeted cells, this is not a perfect therapy and it's not a cure. But it does represent an advancement and, combined with other therapies, could make a significant impact.
Looking at my MRD test, UAMS tested for the presence of seven proteins in my marrow (CD138, CD38, CD45, CD56, CD81, CD27, CD20 and CD19, for those playing the home game). Of the 3,562,010 cells analyzed, none exhibited any of these proteins. That sounds good!
On December 16th, there will be another panel conversation and the guest physician will be Dr. FVR, who works for BB. I will have some specific questions for him about the current "cure curves" for Total Therapy 3 and 4, now that there has been 10 years of follow up for the first group and five for the second. I will also be asking about residual monoclonal protein, per my last post.
If any of you have other questions, feel free to post them in response to this, or email me and I'll see if we can't get some of them answered.
Meanwhile, for those that celebrate the holiday, let me extend a hearty Happy Thanksgiving to you and your families!
Tuesday, November 19, 2013
More research on the new protein
As I suspected, Mayo was not willing to let me have a phone conversation about this particular topic. So rather than contemplate flying to Rochester, MN in winter for what will amount to a 10 minute conversation, I'm going to see if BB will be kind enough to arrange a scheduled call with Dr. K or Dr. VR when I next visit UAMS, if not sooner. My local guy could also call one of them -- but I'm sorry to say I'm not sure they would take his call, as busy as they are.
In the meantime, I've done more digging.
The prevailing wisdom as of 2006 -- as agreed upon by a host of doctors, including BB, VR and several others with whom I have consulted (GT, KA, PR) or mentioned here -- was that any return of protein under immunofixation constitutes disease relapse. That would be bad.
In 2008, however, this study, published in the British Journal of Haematology, noted that people with a "high degree of response" to therapy exhibit "atypical serum immunofixation patterns." They go on to say that this is "not associated with new clonal plasma cells or other lymphoproliferative processes, and molecular remissions were documented." Molecular remission is no longer the state of the art but it does mean that people in complete remission can exhibit monoclonal proteins under IFE. In fact, in their study of 72 patients, these patterns were seen in 71% of those who achieved complete remission under their protocol, versus in 23% of people that did not, and they were seen in 100% of those who exhibited some response to therapy. Now these include those with oligoclonal protein, which I had as well -- not everybody had monoclonal secondary MGUS. This study is one of the ones referenced by the Mayo paper yeterday. The other is quite old, and didn't have much to add.
In this British study, they had a couple of observations. The first is that while they used to see this in post-transplant patients, they now see it in people that DIDN'T have a transplant as well. They take that as a sign that novel drugs alone are able to achieve the same depth of response as transplants, and they anticipate seeing more of these proteins as therapies are more effective.
The second piece of information is rather interesting. Their hypothesis on what causes it is roughly as follows:
* The spectrum of proteins in our immune system is like a cup of water that must always remain full. The cup itself may get larger or smaller (consider this the total protein number) but regardless of the size of the cup, it must be full of water (the individual proteins).
* With myeloma, the monoclonal protein crowds out the normal protein and results in a non-functioning immune system. As M protein goes up, it displaces the regular part of the immune system.
* When the myeloma is beaten down, the immune system gradually returns in order to fill the cup back up.
* If the myeloma is treated particularly well, there is so much myeloma gone before the immune system can fill the glass back up properly that the water that's in the cup looks around and says "oh crap, we better make more of ourselves" but that results in some non-cancerous duplication since there isn't enough "original" water to keep the cup full.
The more medically correct (and jargon-filled) version of this is as follows:
Once again, though, what's important is to be sure that the new protein is NOT the same as the original protein. So I'm back where I started, kinda: if this is the old protein, I'm in deep doo-doo. If it's a new protein, it's probably consistent with profound remission or cure.
I *must* get that blood immunophenotyped.
In the meantime, I've done more digging.
The prevailing wisdom as of 2006 -- as agreed upon by a host of doctors, including BB, VR and several others with whom I have consulted (GT, KA, PR) or mentioned here -- was that any return of protein under immunofixation constitutes disease relapse. That would be bad.
In 2008, however, this study, published in the British Journal of Haematology, noted that people with a "high degree of response" to therapy exhibit "atypical serum immunofixation patterns." They go on to say that this is "not associated with new clonal plasma cells or other lymphoproliferative processes, and molecular remissions were documented." Molecular remission is no longer the state of the art but it does mean that people in complete remission can exhibit monoclonal proteins under IFE. In fact, in their study of 72 patients, these patterns were seen in 71% of those who achieved complete remission under their protocol, versus in 23% of people that did not, and they were seen in 100% of those who exhibited some response to therapy. Now these include those with oligoclonal protein, which I had as well -- not everybody had monoclonal secondary MGUS. This study is one of the ones referenced by the Mayo paper yeterday. The other is quite old, and didn't have much to add.
In this British study, they had a couple of observations. The first is that while they used to see this in post-transplant patients, they now see it in people that DIDN'T have a transplant as well. They take that as a sign that novel drugs alone are able to achieve the same depth of response as transplants, and they anticipate seeing more of these proteins as therapies are more effective.
The second piece of information is rather interesting. Their hypothesis on what causes it is roughly as follows:
* The spectrum of proteins in our immune system is like a cup of water that must always remain full. The cup itself may get larger or smaller (consider this the total protein number) but regardless of the size of the cup, it must be full of water (the individual proteins).
* With myeloma, the monoclonal protein crowds out the normal protein and results in a non-functioning immune system. As M protein goes up, it displaces the regular part of the immune system.
* When the myeloma is beaten down, the immune system gradually returns in order to fill the cup back up.
* If the myeloma is treated particularly well, there is so much myeloma gone before the immune system can fill the glass back up properly that the water that's in the cup looks around and says "oh crap, we better make more of ourselves" but that results in some non-cancerous duplication since there isn't enough "original" water to keep the cup full.
The more medically correct (and jargon-filled) version of this is as follows:
Recent reports demonstrate that in normal bone marrow, there is a plasma cell compartment that has a capped, or finite, population of cells. In order for new, normal, plasma cells to occupy this bone marrow niche after antigenic stimulation, older plasma cells must be replaced (Odendahl et al., 2005;Radbruch et al., 2006). It may be possible that BiRD therapy (or high-dose chemotherapy) clears the bone marrow of malignant plasma cells in such a rapid and complete manner that an environment is created that allows benign plasma cells to expand within the predefined niche without competition. Certainly, the wide spectrum and variability of the ASIP protein isotypes, the recent confirmation that normal plasma cells express the inhibitory FcγRIIb receptor which suppresses normal polyclonal Ig expression, and the finding that administration of tetanus toxoid vaccine after stem cell transplantation induces oligoclonal banding patterns, all support the theory of rapid oligoclonal plasma cell expansion after the clearance MM cells as a potential cause for ASIP generation (Gerritsen et al., 1994; Xiang et al., 2007).
Once again, though, what's important is to be sure that the new protein is NOT the same as the original protein. So I'm back where I started, kinda: if this is the old protein, I'm in deep doo-doo. If it's a new protein, it's probably consistent with profound remission or cure.
I *must* get that blood immunophenotyped.
Monday, November 18, 2013
New energy to get to the bottom of this new M protein
Howdy folks.
So I got my monthly tests back last week and saw that "faint monoclonal lambda light chain" present under IFE. Still nothing under SPEP. But this isn't noise -- it's not going away on its own.
I need to get to the bottom of this. It's not like me to sit back and just let this happen without thoroughly understanding it and taking appropriate action. I think I was occupied with the first order question -- is this bad? -- and then when information was (as with everything with Myeloma) equivocal, I reverted to trusting in BB to see what happens in January. And I do trust BB.
But this isn't proactive enough for me.
I first took a look more thoroughly at the work that is out there on this topic. The most direct reference is from work done by Mayo, Minnesota, published in 2011. The full article can be found here.
First, secondary MGUS refers to a new monoclonal protein, distinct from the original protein. We will need to determine whether or not the protein I exhibit now under IFE is different from the one I originally presented with. This can be done -- hopefully -- through a process called immunophenotyping. A bunch of antibody tests are done on the blood to help triangulate it. I have asked BB to have this done when I next visit UAMS in January, although I would like it done sooner. Like, now, basically. I asked BJ (BB's right arm) to look into this for me last week, but as UAMS is planning for the ASH conference in two weeks it's probably fallen between the cracks. I will gently prod.
Anyhow, back to the Mayo article.
The highlights:
* They looked at almost 2,000 patients
* 6.6% of these patients had a secondary MGUS
* A good portion of these were in complete remission for the primary Myeloma at the time they developed the secondary MGUS
* Among the population that received a stem-cell transplant (about 25% of these patients -- 458 of them) 104, or 22.7%, were identified as having secondary MGUS. Among patients who were followed at least 8 times over two years (248 of this 458) the incidence rose to 36.2%. So of people that transplanted and were monitored regularly, over a third of them exhibited a secondary MGUS.
* It has been hypothesized that secondary MGUS is the result of "recapitulation of early B-cell ontogeny following stem-cell transplant." I am informed by an online dictionary that ontogeny is the development of an organism. So this is the immune system reasserting itself. Sounds like good news -- but it's just a hypothesis.
* "Overall survival was significantly superior in MM patients who developed secondary MGUS compared with the rest of the cohort -- 73 months versus 38 months." This is plainly good news.
* "The occurrence of a secondary MGUS 6 months after transplant was associated with better OS, median 102 months versus 68 months." This, too, is good news. Median survival of 9 years.
* In conclusion, "secondary MGUS is a favorable prognostic factor for OS, independent of year of diagnosis, age, stage and renal function." Again, good news.
HOWEVER...nothing is this simple.
If I look at some of the key citations referenced in this article, there are qualifications.
* The statement right after that conclusion is "this is consistent with findings from other studies." However, following that citation leads me to Dr. GT, who told me that he needed to know more about the protein before we can breathe easy (this goes back to the need to immunophenotype that protein as noted at the top of this posting).
* We need to look for spontaneous resolution of this secondary MGUS, because the failure of it to do so "may effect OS, but this needs further study." So I need to monitor those labs. Maybe it will go away. Spontaneous implies without treatment, so there's that to consider.
And then there are the lingering questions:
* Mayo does single transplantation, without aggressive pre-transplant chemo or consolidation chemo. What do they think -- if anything -- the implications of secondary MGUS would be for someone who went through Total Therapy? If it's the immune system rebuilding, then there should be no difference -- but if it's something else, there could be a difference.
* I've spoken so far with two doctors about this, other than BB. GT says I should discontinue Velcade as whatever is left is resistant to it, and that he doesn't know if this protein is bad and needs to learn more first. Dr. PR, a colleague of Dr. KA and a very prominent doctor, says I should resume Velcade and Revlimid (he modified this after I explained my secondary cancer) and had no opinion on the protein. Disconcerting that neither could assuage my concerns, and disconcerting that they had opposite perspectives on resuming Velcade.
* Most disconcerting: BB's comment that he doesn't know what this means.
There is more research to be done. Two papers referenced in the Mayo paper are key. The first is from 2010 and published by a group of doctors with whom I'm unfamiliar and its title ends with "...a matter of undetermined significance." Their attempt at a clever self-referential play on words doesn't help resolve my unease. The second paper is much older -- from 1989. It is likely overtaken by more recent research, but it may be at such a fundamental level that it could be useful. It is titled "Monoclonal and oligoclonal gammopathy after bone marrow transplantation." We know (and BB is confident) that oligoclonal gammopathy is a positive thing -- if monoclonal gammopathy in that same content is a positive thing, it will be helpful. But again -- why is BB not seeing this at UAMS, with all his transplant patients?
That's enough hardcore science for the day.
I've requested a phone consult with Dr. VR at Mayo, who was one of the authors of the study. In my limited experience, Mayo doesn't do phone consults but as this is such a specific question, perhaps they will make an exception.
Onward. I have renewed focus!
So I got my monthly tests back last week and saw that "faint monoclonal lambda light chain" present under IFE. Still nothing under SPEP. But this isn't noise -- it's not going away on its own.
I need to get to the bottom of this. It's not like me to sit back and just let this happen without thoroughly understanding it and taking appropriate action. I think I was occupied with the first order question -- is this bad? -- and then when information was (as with everything with Myeloma) equivocal, I reverted to trusting in BB to see what happens in January. And I do trust BB.
But this isn't proactive enough for me.
I first took a look more thoroughly at the work that is out there on this topic. The most direct reference is from work done by Mayo, Minnesota, published in 2011. The full article can be found here.
First, secondary MGUS refers to a new monoclonal protein, distinct from the original protein. We will need to determine whether or not the protein I exhibit now under IFE is different from the one I originally presented with. This can be done -- hopefully -- through a process called immunophenotyping. A bunch of antibody tests are done on the blood to help triangulate it. I have asked BB to have this done when I next visit UAMS in January, although I would like it done sooner. Like, now, basically. I asked BJ (BB's right arm) to look into this for me last week, but as UAMS is planning for the ASH conference in two weeks it's probably fallen between the cracks. I will gently prod.
Anyhow, back to the Mayo article.
The highlights:
* They looked at almost 2,000 patients
* 6.6% of these patients had a secondary MGUS
* A good portion of these were in complete remission for the primary Myeloma at the time they developed the secondary MGUS
* Among the population that received a stem-cell transplant (about 25% of these patients -- 458 of them) 104, or 22.7%, were identified as having secondary MGUS. Among patients who were followed at least 8 times over two years (248 of this 458) the incidence rose to 36.2%. So of people that transplanted and were monitored regularly, over a third of them exhibited a secondary MGUS.
* It has been hypothesized that secondary MGUS is the result of "recapitulation of early B-cell ontogeny following stem-cell transplant." I am informed by an online dictionary that ontogeny is the development of an organism. So this is the immune system reasserting itself. Sounds like good news -- but it's just a hypothesis.
* "Overall survival was significantly superior in MM patients who developed secondary MGUS compared with the rest of the cohort -- 73 months versus 38 months." This is plainly good news.
* "The occurrence of a secondary MGUS 6 months after transplant was associated with better OS, median 102 months versus 68 months." This, too, is good news. Median survival of 9 years.
* In conclusion, "secondary MGUS is a favorable prognostic factor for OS, independent of year of diagnosis, age, stage and renal function." Again, good news.
HOWEVER...nothing is this simple.
If I look at some of the key citations referenced in this article, there are qualifications.
* The statement right after that conclusion is "this is consistent with findings from other studies." However, following that citation leads me to Dr. GT, who told me that he needed to know more about the protein before we can breathe easy (this goes back to the need to immunophenotype that protein as noted at the top of this posting).
* We need to look for spontaneous resolution of this secondary MGUS, because the failure of it to do so "may effect OS, but this needs further study." So I need to monitor those labs. Maybe it will go away. Spontaneous implies without treatment, so there's that to consider.
And then there are the lingering questions:
* Mayo does single transplantation, without aggressive pre-transplant chemo or consolidation chemo. What do they think -- if anything -- the implications of secondary MGUS would be for someone who went through Total Therapy? If it's the immune system rebuilding, then there should be no difference -- but if it's something else, there could be a difference.
* I've spoken so far with two doctors about this, other than BB. GT says I should discontinue Velcade as whatever is left is resistant to it, and that he doesn't know if this protein is bad and needs to learn more first. Dr. PR, a colleague of Dr. KA and a very prominent doctor, says I should resume Velcade and Revlimid (he modified this after I explained my secondary cancer) and had no opinion on the protein. Disconcerting that neither could assuage my concerns, and disconcerting that they had opposite perspectives on resuming Velcade.
* Most disconcerting: BB's comment that he doesn't know what this means.
There is more research to be done. Two papers referenced in the Mayo paper are key. The first is from 2010 and published by a group of doctors with whom I'm unfamiliar and its title ends with "...a matter of undetermined significance." Their attempt at a clever self-referential play on words doesn't help resolve my unease. The second paper is much older -- from 1989. It is likely overtaken by more recent research, but it may be at such a fundamental level that it could be useful. It is titled "Monoclonal and oligoclonal gammopathy after bone marrow transplantation." We know (and BB is confident) that oligoclonal gammopathy is a positive thing -- if monoclonal gammopathy in that same content is a positive thing, it will be helpful. But again -- why is BB not seeing this at UAMS, with all his transplant patients?
That's enough hardcore science for the day.
I've requested a phone consult with Dr. VR at Mayo, who was one of the authors of the study. In my limited experience, Mayo doesn't do phone consults but as this is such a specific question, perhaps they will make an exception.
Onward. I have renewed focus!
Thursday, November 14, 2013
Well, well, well...five years passes.
Yesterday was the five year anniversary of my diagnosis.
I had had my bloodwork come back and the doctor had said that "everything is pointing to MGUS" since I had proper red, white, and platelet counts, calcium was okay, B2M was okay, albumin was okay. Other than the M spike which elevated my protein, it looked like it wasn't Myeloma.
My dear friend Dr. BM had told me that people die of Myeloma and this was a terrible thing and even MGUS was bad. Dr. SH, the hematologist, had laughed this off and said not to worry and don't be silly and all that good stuff. So I wasn't as concerned as I might have been.
I had met at UCLA with the Director of the Jules Stein Eye Institute earlier that day. My daughter has a genetic condition with her retina that has left her with poor vision that cannot be corrected with glasses and I was trying to get involved in some capacity. A friend who has some influence with that organization made the introduction and I was thinking I would go there to discuss being on the Board of Directors for the Eye Institute.
The Director there didn't see it the same way (no pun intended but hey, that's pretty funny). I left there with his suggestion to drive around bad neighborhoods in LA in the "Vision Van" and encourage gun-toting gang members to get their eyes checked once every two years.
This was not what I had in mind.
I left in a rather poor mood, having wasted my time and been somewhat humiliated in the process. I was driving to my house. It was a sunny afternoon. A graduating student from Harvard Business School was being recruited by Disney, and my colleague EP and I were on the phone with him convincing him to join our group when my call waiting kicked in. I saw it was Dr. SH's office. My heart started racing, and I dropped off the work call with my apologies. I said a quick little prayer and picked up the call.
Dr. SH said "I have the bone marrow results back, and it looks like you have Myeloma."
I was shocked. Numb. This was supposed to be MGUS. I can't remember if I asked if it needed to be rechecked, but I think I did ask. It did not need to be rechecked.
"Am I going to be alive in five years?"
"That's a difficult question to answer."
REALLY?!?!?! Two days earlier it was a joke when I relayed my friend's concern, and now all of a sudden he can't tell me if I'm going to be alive in five years?!?!?!?
He continued. "I want you to come in on Friday [the 15th, I believe]. You will be my last patient of the day so we will have plenty of time to discuss options."
I called my wife. We were both in hysterics.
And that began this journey in earnest.
I considered posting yesterday -- but I thought not posting would send a message. Yeah, it's been five years. Yeah, I'm past the point where that particular doctor couldn't confidently say I'd still be alive. Yeah, I'm still in complete or near-complete remission. All good stuff.
So to drop everything and post yesterday would have been acknowledging too much to the disease.
I still have to respect it, unfortunately. I still can't confidently dance around, laughing in its face. It could still come back and if it comes back, the results have not been good.
BUT...I found a doctor that believes he can cure the disease. I went through aggressive treatment. The disease has been gone for over four years. My recent tests, while inconclusive on blood, are highly promising on bone marrow. We'll see where we are in January. I also want to have a conversation with Dr. R at Mayo, who wrote about this "secondary MGUS" condition that it appears I have. In their research, they don't understand causality or the prognistic value, but they have seen the late-emerging secondary MGUS is associated with significantly greater OS. At it was seen in about 15% of the people they studied. It bothers me that Dr. BB hasn't seen enough of it to immediately recognize it in my biology and to assuage my concerns -- but we'll tackle that when we can.
Meanwhile, I'm here. I've adjusted to the "new normal." Yes, there are issues -- I'm not sure I'll ever get 8 hours of sleep on a consistent basis again. My GI tract doesn't work as well as it did before I got cancer. I'm missing a chunk of fingernail (and a bit of finger) from the tip of my right index finger and it's unpleasantly numb when it touches something, like somewhere between a foot falling asleep and a funny-bone being hit. And I tire more easily than I used to. And then, I must admit, there's chemo-brain...which has had more of an impact on my career than the rest of my life but which has been an issue.
All this said, as I pointed out, I'm still here.
And that, really, is what matters.
So on this five year anniversary plus one day, to the newly diagnosed: there is hope. In fact there is even more hope today than there was five years ago. To BB and company, THANK YOU THANK YOU THANK YOU for saving my life. To SH, my diagnosis hematologist, THANK YOU THANK YOU THANK YOU for being open-minded enough to mention BB to me. I'd like to also thank my caregiver and wife, Jill, the other doctors that have weighed in with their opinions and help (both formal and informal) over the years, and to the wonderful friends and followers I have on this blog, and my fellow patients in a broader sense.
And as far as five-year anniversary comments to the disease...well, Myeloma, you can go !*&&)(*!@#! yourself. :)
I had had my bloodwork come back and the doctor had said that "everything is pointing to MGUS" since I had proper red, white, and platelet counts, calcium was okay, B2M was okay, albumin was okay. Other than the M spike which elevated my protein, it looked like it wasn't Myeloma.
My dear friend Dr. BM had told me that people die of Myeloma and this was a terrible thing and even MGUS was bad. Dr. SH, the hematologist, had laughed this off and said not to worry and don't be silly and all that good stuff. So I wasn't as concerned as I might have been.
I had met at UCLA with the Director of the Jules Stein Eye Institute earlier that day. My daughter has a genetic condition with her retina that has left her with poor vision that cannot be corrected with glasses and I was trying to get involved in some capacity. A friend who has some influence with that organization made the introduction and I was thinking I would go there to discuss being on the Board of Directors for the Eye Institute.
The Director there didn't see it the same way (no pun intended but hey, that's pretty funny). I left there with his suggestion to drive around bad neighborhoods in LA in the "Vision Van" and encourage gun-toting gang members to get their eyes checked once every two years.
This was not what I had in mind.
I left in a rather poor mood, having wasted my time and been somewhat humiliated in the process. I was driving to my house. It was a sunny afternoon. A graduating student from Harvard Business School was being recruited by Disney, and my colleague EP and I were on the phone with him convincing him to join our group when my call waiting kicked in. I saw it was Dr. SH's office. My heart started racing, and I dropped off the work call with my apologies. I said a quick little prayer and picked up the call.
Dr. SH said "I have the bone marrow results back, and it looks like you have Myeloma."
I was shocked. Numb. This was supposed to be MGUS. I can't remember if I asked if it needed to be rechecked, but I think I did ask. It did not need to be rechecked.
"Am I going to be alive in five years?"
"That's a difficult question to answer."
REALLY?!?!?! Two days earlier it was a joke when I relayed my friend's concern, and now all of a sudden he can't tell me if I'm going to be alive in five years?!?!?!?
He continued. "I want you to come in on Friday [the 15th, I believe]. You will be my last patient of the day so we will have plenty of time to discuss options."
I called my wife. We were both in hysterics.
And that began this journey in earnest.
I considered posting yesterday -- but I thought not posting would send a message. Yeah, it's been five years. Yeah, I'm past the point where that particular doctor couldn't confidently say I'd still be alive. Yeah, I'm still in complete or near-complete remission. All good stuff.
So to drop everything and post yesterday would have been acknowledging too much to the disease.
I still have to respect it, unfortunately. I still can't confidently dance around, laughing in its face. It could still come back and if it comes back, the results have not been good.
BUT...I found a doctor that believes he can cure the disease. I went through aggressive treatment. The disease has been gone for over four years. My recent tests, while inconclusive on blood, are highly promising on bone marrow. We'll see where we are in January. I also want to have a conversation with Dr. R at Mayo, who wrote about this "secondary MGUS" condition that it appears I have. In their research, they don't understand causality or the prognistic value, but they have seen the late-emerging secondary MGUS is associated with significantly greater OS. At it was seen in about 15% of the people they studied. It bothers me that Dr. BB hasn't seen enough of it to immediately recognize it in my biology and to assuage my concerns -- but we'll tackle that when we can.
Meanwhile, I'm here. I've adjusted to the "new normal." Yes, there are issues -- I'm not sure I'll ever get 8 hours of sleep on a consistent basis again. My GI tract doesn't work as well as it did before I got cancer. I'm missing a chunk of fingernail (and a bit of finger) from the tip of my right index finger and it's unpleasantly numb when it touches something, like somewhere between a foot falling asleep and a funny-bone being hit. And I tire more easily than I used to. And then, I must admit, there's chemo-brain...which has had more of an impact on my career than the rest of my life but which has been an issue.
All this said, as I pointed out, I'm still here.
And that, really, is what matters.
So on this five year anniversary plus one day, to the newly diagnosed: there is hope. In fact there is even more hope today than there was five years ago. To BB and company, THANK YOU THANK YOU THANK YOU for saving my life. To SH, my diagnosis hematologist, THANK YOU THANK YOU THANK YOU for being open-minded enough to mention BB to me. I'd like to also thank my caregiver and wife, Jill, the other doctors that have weighed in with their opinions and help (both formal and informal) over the years, and to the wonderful friends and followers I have on this blog, and my fellow patients in a broader sense.
And as far as five-year anniversary comments to the disease...well, Myeloma, you can go !*&&)(*!@#! yourself. :)
Thursday, November 7, 2013
Five years ago today, my first detailed blood test for Myeloma
I remember going to the hematologist, who had told me that I could have MGUS or Myeloma but that it was very unlikely that somebody my age would have the latter.
He told me I needed to have a bone marrow biopsy done, and I didn't want to do it that day. It was a Friday, and I scheduled it for Monday. Little did I know that would be the last weekend that I didn't worry about this stuff. How silly that seems -- to have not worried! But at the time, both my primary care doctor and this hematologist downplayed the likelihood that I had Myeloma, and downplayed its severity. No need to be alarmist, I suppose...
He told me I needed to have a bone marrow biopsy done, and I didn't want to do it that day. It was a Friday, and I scheduled it for Monday. Little did I know that would be the last weekend that I didn't worry about this stuff. How silly that seems -- to have not worried! But at the time, both my primary care doctor and this hematologist downplayed the likelihood that I had Myeloma, and downplayed its severity. No need to be alarmist, I suppose...
Tuesday, October 29, 2013
Five years...the first of several posts on the topic
I'm sitting at my desk right now. It's a sunny October day in southern California and the sun in streaming in. The desk is a pipe of papers. The scene is very much like it was five years ago.
Five years ago, essentially to the day, my primary care physician called me to tell me that he observed high protein in my blood. I had no idea what it meant. I'd been on a moderately high protein diet for some time, was that what he meant? No, he said.
I'd been on Lipitor for some time for genetically high cholesterol. I don't like needles (irony alert) so I'd avoided the required blood test for about a year. Lipitor is hard on the liver and to make sure everything is still working, they want blood every 90 days. I'd avoided it as long as I could, when my primary care doctor told me I had to man up and get the blood drawn or he wouldn't renew the prescription.
I went in, they did bloodwork.
Two days later he called me back to give more blood, only saying he wanted to run one test over.
Two days later he called me back to tell me about this protein.
He said it was unlikely, but it could be one of two things. One is called MGUS. And he said it was VERY unlikely but that it could also possibly be something called Myeloma.
I said "anything that ends in Oma is bad."
He chuckled. He said "it's a malignancy of the blood, but not like Leukemia or anything like that." To rule that out and just confirm that this was nothing (or MGUS at worst) he wanted me to see a Hematologist. I made an appointment.
I was still blissfully unaware.
That night I called my longtime best friend Dr. BM, who was considerably more concerned. He said people die from Myeloma. That didn't sound very good at all. But I wasn't worried.
Silly me.
More to come.
But...five years later, here I am. In complete remission (we think...that stupid marker in my blood has me nervous even though there is other data that says I shouldn't be). Surviving. I've been through a lot. The treatment has derailed my career, if only (hopefully) temporarily. It's left me tired, poked, prodded, and more familiar with the inside of a MRI machine. It's gotten me up close and personal with those needles I didn't care for -- and still don't. I've learned what I can from it. I'm still here. But all in all, this has really, really sucked.
I guess we call that perspective qualified optimism. It's the best I can muster. My frame of mind relative to pre-diagnosis is hard to put a brave face on. My frame of mind relative to diagnosis and prognosis, I assure you, will be more positive.
Interesting reflections. And more to come.
Five years ago, essentially to the day, my primary care physician called me to tell me that he observed high protein in my blood. I had no idea what it meant. I'd been on a moderately high protein diet for some time, was that what he meant? No, he said.
I'd been on Lipitor for some time for genetically high cholesterol. I don't like needles (irony alert) so I'd avoided the required blood test for about a year. Lipitor is hard on the liver and to make sure everything is still working, they want blood every 90 days. I'd avoided it as long as I could, when my primary care doctor told me I had to man up and get the blood drawn or he wouldn't renew the prescription.
I went in, they did bloodwork.
Two days later he called me back to give more blood, only saying he wanted to run one test over.
Two days later he called me back to tell me about this protein.
He said it was unlikely, but it could be one of two things. One is called MGUS. And he said it was VERY unlikely but that it could also possibly be something called Myeloma.
I said "anything that ends in Oma is bad."
He chuckled. He said "it's a malignancy of the blood, but not like Leukemia or anything like that." To rule that out and just confirm that this was nothing (or MGUS at worst) he wanted me to see a Hematologist. I made an appointment.
I was still blissfully unaware.
That night I called my longtime best friend Dr. BM, who was considerably more concerned. He said people die from Myeloma. That didn't sound very good at all. But I wasn't worried.
Silly me.
More to come.
But...five years later, here I am. In complete remission (we think...that stupid marker in my blood has me nervous even though there is other data that says I shouldn't be). Surviving. I've been through a lot. The treatment has derailed my career, if only (hopefully) temporarily. It's left me tired, poked, prodded, and more familiar with the inside of a MRI machine. It's gotten me up close and personal with those needles I didn't care for -- and still don't. I've learned what I can from it. I'm still here. But all in all, this has really, really sucked.
I guess we call that perspective qualified optimism. It's the best I can muster. My frame of mind relative to pre-diagnosis is hard to put a brave face on. My frame of mind relative to diagnosis and prognosis, I assure you, will be more positive.
Interesting reflections. And more to come.
Monday, October 21, 2013
Interesting publication on benefits of transplant
I rarely re-post other articles -- there are other blogs for that sort of thing. But this one struck me as important.
There has been considerable debate about whether or not novel drugs alone versus novel drugs plus transplant would achieve the same outcomes. Dr. Berenson in Los Angeles, to name one vocal proponent, believes this to be the case and that there is no benefit from transplantation.
I've not dug into this study other than to read the abstract, but it does show that overall survival and progression-free survival were both superior when transplantation was part of the regimen.
Bear in mind, as well, this was a single transplant. Tandem transplantation should be superior still, if in fact this data is accurate.
Food for thought.
Note: some considerations with respect to the study: we don't know if the non-transplant patients were transplant-eligible, we don't know if the type of disease (IgX, kappa vs. lambda, and most importantly risk assessment) was evenly distributed, etc.
Still, while maybe not as statistically significant as we'd like, it's at least a data point, even if anecdotal.
I will likely ask Dr. Paul Richardson about this on this week's CurePanel talk on the 24th of this month, where the topic is "To Transplant or Not to Transplant." If you have any questions you'd like me to ask, please let me know!
There has been considerable debate about whether or not novel drugs alone versus novel drugs plus transplant would achieve the same outcomes. Dr. Berenson in Los Angeles, to name one vocal proponent, believes this to be the case and that there is no benefit from transplantation.
I've not dug into this study other than to read the abstract, but it does show that overall survival and progression-free survival were both superior when transplantation was part of the regimen.
Bear in mind, as well, this was a single transplant. Tandem transplantation should be superior still, if in fact this data is accurate.
Food for thought.
Note: some considerations with respect to the study: we don't know if the non-transplant patients were transplant-eligible, we don't know if the type of disease (IgX, kappa vs. lambda, and most importantly risk assessment) was evenly distributed, etc.
Still, while maybe not as statistically significant as we'd like, it's at least a data point, even if anecdotal.
I will likely ask Dr. Paul Richardson about this on this week's CurePanel talk on the 24th of this month, where the topic is "To Transplant or Not to Transplant." If you have any questions you'd like me to ask, please let me know!
Wednesday, October 9, 2013
The Strep That Wouldn't Die, and other stories. Or other story. Or question, really.
So after being symptom free for a few days I woke up yesterday with a painful sore throat again. Took a Vicodin immediately, and a Tamiflu, and a Keflex. Went to my morning workout.
Then I felt nauseous.
Great, I says to myself, I says.
I called my primary care doctor and told him what was up. I didn't know if I got the same thing AGAIN, or if I didn't get rid of it the first time, or what. I got in to see my doctor a few hours later. Supporters of the ACA, remember that sentence in a couple of years -- you probably won't see it ever again.
I digress.
Anyhow, the doctor thought because of the stomach issues I originally had that it was probably a virus, but he did a swab for strep anyway. Told me to see what happens and go back on the Keflex. He was surprised that it had responded as quickly as it had before, and this, too, led him to believe it was a virus.
Long-story short, it was strep. Probably stuck around because I didn't take the full course of antibiotics. Stupid me, took about three days worth and when the symptoms ended, I figured I didn't need any more. THIS WAS DUMB. Take the full course of antibiotics. I feel like a putz because (a) I didn't get all-the-way better, and (b) those superbugs that are resistant to all antibiotics and will eat through steel and become sentient and take control of the world's nuclear weaponry and hold us all hostage unless we come up with money are being strengthened by (1) the use of very powerful antibiotics to treat stuff that would respond to less powerful stuff, and (2) people like me who stop using something before it's all the way gone. I'm sorry world: I vow to do my part from here on out.
As for the nausea, that was likely just taking those drugs on an empty stomach and then working out. I usually don't need food to take stuff but I think the combo of the three may have been enough to tweak my innards. Blech. Anyhow, false alarm, thankfully. After two solid days last week of projectile vomiting that would have impressed William Friedkin, I'm glad that didn't come back. Although I was kinda looking forward to dropping these last five pounds...
God bless the good people of Arkansas, including BB and BJ, who responded to my email immediately and were prepared to sync up with my doctor out here. I also got a long list of tests to run on my blood which attests (no pun intended) to UAMS' thoroughness and emphasis on prolific testing, which I love. As it turns out, they weren't needed in this instance. But I was ready to get tested for everything from Parvo (sounds gross) to salmonella to feline distemper to Gumbo Limbo virus. The last two are not serious. In fact that last one came from a google search I just did for "funny sounding virus names." Turns out there are a LOOOOOOT of viruses out there, folks. See for yourself if you are astonishingly bored.
Now, as for the other story / question. My friend EW commented in the last post that I should get a flu shot. My primary care doctor suggested this, too. The traditional wisdom from UAMS is that a flu shot in my current state (or perhaps recent stake) is useless as my immune system won't mount an immune response, and that was probably true for a while. But my CD4 count is 510 now, which means it might actually do something, and my PCP said "better to have a muted immune response than no immune response." So I guess when flu season starts up, I'll get a shot.
Maybe.
I still like Purell and Tamiflu, personally.
Wednesday, October 2, 2013
How a simple cold turns into hell with a compromised immune system
Hello friends.
So there's been a little bug going around. Seems some people have a sore throat which then turns into a cold in some people if they haven't fought off the sore throat part.
That's what happens for people with healthy immune systems, that is.
Me, not so much.
I report this not for sympathy but because it could be of value to people assessing the response of their own post-SCT immune system.
I have been enjoying a pretty healthy last few years -- I don't think I've had a cold lasting more than a day or two in two years time. I attribute this to taking Tamiflu the second I feel a tickle in my throat. 90% of the time, if I feel this coming on and get in front of it, the feeling is gone the next morning. Maybe twice in two years (if that) it's turned into a cold that has gone away in a couple of days. If I feel a tickle in my chest, I take an antibiotic (usually Amoxy-Clavicin) designed to wipe out respiratory infections. I do this because when I first had my SCT, any sniffle turned into six weeks of bronchitis. I spent my first year sick probably 60% of the time since it took so damn long to recover and as soon as I did, I'd get sick two weeks later.
Anyhow, through use of Tamilu, Amoxy-Clavicin and more importantly Purell, I've been pretty healthy for the last couple of years. Enough where I must have gotten complacent.
I flew up to San Francisco last weekend to celebrate my mother's 91st birthday. I didn't use Purell and came into contact with the germs of whatever parade of deranged, disease-ridden folks had used the airline seat before me. Without thinking, I probably ate peanuts or pretzels on the flight which means germs went from the arm-rest to my hand to the peanuts to my mouth. That's how colds get spread.
Sure enough, Thursday night I felt a tickle. I sourced some Tamiflu from a local pharmacy and popped a pill. Friday morning I felt okay, maybe the same tickle. I figured worst case it would go away in a day or two.
Oops.
Saturday morning I got up to have breakfast and after two bites of an innocent egg white omelette, went to the bathroom for some violent vomiting for about 10 minutes. I was supposed to meet an old college roommate for a lunch or a drink so I trudged along, sat down, had an innocuous mimosa (so I thought) and a small fruit plate. Bad idea. More violent vomiting.
Maybe some fresh air would help. I had a sip of water (no more food or anything else, I finally determined) and walked for a bit. Bad idea. More violent vomiting. On the street. I felt like a heroin addict.
Got a car back to my hotel. Went up to my room. You guessed it: more violent vomiting.
About the time that I realized this was stomach flu and not just food poisoning is around the time that my throat felt like it was being slashed with a straight razor every time I swallowed. I'd had that feeling before once or twice in my life...strep throat.
Yep. A simple bug that wouldn't be anything went to town on me and manifested as stomach flu PLUS strep. I flew home and got into bed immediatley, and tried Levaquin -- a carpet-bombing antibiotic -- and that didn't seem to help. I was having to take a strong Vicodin (the 10mg of the good stuff plus 325mg of acetominophen) every two hours just to take the edge off the pain. I was actually considering dipping into my remaining Dilaudid -- the pain was THAT bad -- and because I was worried about the amount of acetominophen on my liver. Before doing that, though, I called my PCP who told me that Levaquin is a great general use antibiotic but isn't great for strep throat. He put me on Keflex and about eight hours later the pain in the throat finally abated. This was, lessee...Monday. I went from probably ten Vicodin on Sunday to two on Monday to none on Tuesday (I'm not addicted to opiates, thank God -- was very easy for me to not take it). As of now, things are downgraded to a mild chest cold with no symptoms other than coughing and respiratory congestion that will clear up in a few days, I'm sure.
Not a lot of fun.
The moral of the story: be ever vigilant, and use Purell!
So there's been a little bug going around. Seems some people have a sore throat which then turns into a cold in some people if they haven't fought off the sore throat part.
That's what happens for people with healthy immune systems, that is.
Me, not so much.
I report this not for sympathy but because it could be of value to people assessing the response of their own post-SCT immune system.
I have been enjoying a pretty healthy last few years -- I don't think I've had a cold lasting more than a day or two in two years time. I attribute this to taking Tamiflu the second I feel a tickle in my throat. 90% of the time, if I feel this coming on and get in front of it, the feeling is gone the next morning. Maybe twice in two years (if that) it's turned into a cold that has gone away in a couple of days. If I feel a tickle in my chest, I take an antibiotic (usually Amoxy-Clavicin) designed to wipe out respiratory infections. I do this because when I first had my SCT, any sniffle turned into six weeks of bronchitis. I spent my first year sick probably 60% of the time since it took so damn long to recover and as soon as I did, I'd get sick two weeks later.
Anyhow, through use of Tamilu, Amoxy-Clavicin and more importantly Purell, I've been pretty healthy for the last couple of years. Enough where I must have gotten complacent.
I flew up to San Francisco last weekend to celebrate my mother's 91st birthday. I didn't use Purell and came into contact with the germs of whatever parade of deranged, disease-ridden folks had used the airline seat before me. Without thinking, I probably ate peanuts or pretzels on the flight which means germs went from the arm-rest to my hand to the peanuts to my mouth. That's how colds get spread.
Sure enough, Thursday night I felt a tickle. I sourced some Tamiflu from a local pharmacy and popped a pill. Friday morning I felt okay, maybe the same tickle. I figured worst case it would go away in a day or two.
Oops.
Saturday morning I got up to have breakfast and after two bites of an innocent egg white omelette, went to the bathroom for some violent vomiting for about 10 minutes. I was supposed to meet an old college roommate for a lunch or a drink so I trudged along, sat down, had an innocuous mimosa (so I thought) and a small fruit plate. Bad idea. More violent vomiting.
Maybe some fresh air would help. I had a sip of water (no more food or anything else, I finally determined) and walked for a bit. Bad idea. More violent vomiting. On the street. I felt like a heroin addict.
Got a car back to my hotel. Went up to my room. You guessed it: more violent vomiting.
About the time that I realized this was stomach flu and not just food poisoning is around the time that my throat felt like it was being slashed with a straight razor every time I swallowed. I'd had that feeling before once or twice in my life...strep throat.
Yep. A simple bug that wouldn't be anything went to town on me and manifested as stomach flu PLUS strep. I flew home and got into bed immediatley, and tried Levaquin -- a carpet-bombing antibiotic -- and that didn't seem to help. I was having to take a strong Vicodin (the 10mg of the good stuff plus 325mg of acetominophen) every two hours just to take the edge off the pain. I was actually considering dipping into my remaining Dilaudid -- the pain was THAT bad -- and because I was worried about the amount of acetominophen on my liver. Before doing that, though, I called my PCP who told me that Levaquin is a great general use antibiotic but isn't great for strep throat. He put me on Keflex and about eight hours later the pain in the throat finally abated. This was, lessee...Monday. I went from probably ten Vicodin on Sunday to two on Monday to none on Tuesday (I'm not addicted to opiates, thank God -- was very easy for me to not take it). As of now, things are downgraded to a mild chest cold with no symptoms other than coughing and respiratory congestion that will clear up in a few days, I'm sure.
Not a lot of fun.
The moral of the story: be ever vigilant, and use Purell!
Thursday, September 19, 2013
An idiot's guide to cytogenetic abnormalities.
This will be a curious post in some ways, because it will provide partial answers and half-truths. Not in the sense that I'm keeping anything or being intentionally misleading, but in the sense that my understanding is not fully formed.
In keeping with the philosophy of this blog, I report things as they occur, to record my understanding of events as they happen. Other blogs will fully research something and present it in a way that is clinically correct, but may be less penetrable and will be less personal.
So the upshot of this is to give you a glimpse into a complex topic in a way that reflects my own limited understanding at this time. It can be seen (I hope, anyhow!) as an invitation to other MM patients to learn more about their own condition -- and also as a platform for correction and further illumination.
So without further ado...
Cytogenetic abnormalities refer to tweaked (highly clinical word there) chromosomes within one's cells (in this case, myelomic plasma cells). A normal cell has 46 chromosomes (23 "diploids" which consist of 23 from the mother and 23 from the father).
The severity of one's Myeloma can be impacted by both the number of cytogenetic abnormalities, and the type of cytogenetic abnormalities. Typically, these abnormalities take the place of either an extra copy of a chromosome (which results in a "hyperdiploid" -- too many chromosomes -- characteristic to the cell), the deletion of a chromosome ("hypodiploid"), or a translocation of chromosome pairs (like let's say the 4th chromosome of one pair has gone off and paired up with the 14th chromosome of another pair and vice-versa, resulting in what's called translocation (4;14).
Some of the more well-known cytogenetic abormalities include del 13 (deletion of the 13th chromosome, which used to be perceived as a high-risk trait), del 17 (which remains a high-risk trait), translocation (4;14) as noted (formerly high-risk but responsive to Velcade), etc. Additionally, a "hyperdiploid" diagnosis (too many chromosomes) is generally a better factor than a "hypodiploid" diagnosis. I have no idea why this is -- others may be able to inform. Particularly SuzieRose who again knows more about this stuff than any other patient I've encountered.
I was aware that I was hyperdiploid, but didn't ever really know the extent of my cytogenetic abnormalities. How many did I have? They are "nearly universal" in Myeloma cells -- in fact I'm not sure how one could have Myeloma without any.
At any rate, when I was last in Arkansas, I dug through my file and took a photo of the result of the marrow analysis that was done at "baseline" -- before treatment started.
Here's what it looks like.
54,XY,+2,der(2)t(2;2)(p11.1;q21),der(2;3)(p10;q10),+3,der(4)t(1;4)(q12;p16),+5,+6,+9,+11,+15,+18,+19[cp22]/46,XY[cp8]
Yikes! It's a miracle I wasn't staggering into the emergency room with smoke pouring out of my butt with that much wrong with me.
(pause for laughter...thank you, thank you)
I refer back to part of BB's recent dictation when he commented, in reference to my current (normal) marrow, "flow cytometry [the test through which this is assessed] was negative, and originally had shown rather profound hyperdiploid lambda light chain restricted disease."
By "rather profound" he probably means that's a long string of gobbeldygook up above, versus a short string.
I recognized only a few things in here, and I was able to determine a few things on my own, but to really make sense of this without calling a microbiologist, I reached out to SuzieRose to see if she could help decipher it. She was kind enough to invest some time in doing so, noting that every lab reports this stuff differently.
My sole contributions to the deciphering were (1) to note that the "cp" refers to "cell population." By looking at the two numbers, there were 30 cells analyzed, of which 22 had all the crap wrong with them that is delineated, and 8 of them were nice, pretty, 46 chromosome cells that had their act together; and (2) that the 54 referred to the number of chromosomes, so I had 8 extra copies somewhere versus a normal cell.
As a quick aside, subsequent bone marrow analyses show that after one cycle of VDT-PACE, in a 20 cell sample, I had 3 goofy looking ones exactly like the ones above, and 17 normal ones. After my first transplant, I had only normal ones.
So, to the goofiness.
Of the 22 messed up cells, here's how SuzieRose helped me decipher it.
* When there are translocations, they leave a piece of the chromosome behind at the site of the translocation. This is said to be a "derivative" of the chromosome that was translocated and is appreviated "der". So in my case, I had a derivative of chromosome 2, and a derivative of chromosome 4
* Whey they catalogue the chromosome changes they pinpoint them to a specific "address" on the cell, and in this case the changes occurred at 2p11.1 and 2q21, as well as 2p10 and 3q10. I also had a translocation of chromosomes 1 and 4 that occurred at 1q12 and 4p16, respectively.
I don't know what p and q refer to -- perhaps they are the two strings where the pairs of chromosomes are supposed to align? I don't know. I suppose I haven't...wait for it...been minding my P's and Q's.
(pause for groan...these are the jokes, people -- they can't all be gems).
I continue.
I gather that the first marker in a pair is the "long arm" and the second is the "short arm." So Suzierose said I have a translocation of chromosome 2 on the long arm of p at band 11.1 and on the short arm of q at band 21.
All those plusses refer to trisomies -- an extra copy of the chromosome. I had nine of them, of chromosomes 2, 3, 5, 6, 9, 11, 15, 18 and 19.
What does all this mean?
Not much, to me, anyhow.
UAMS uses more advanced genetic analysis to determine risk characteristics of Myeloma. So this is interesting information insofar as it shows how mangled my marrow was and shows the impact of therapy (significant reduction after one cycle of induction) -- and if there were any high-risk signs (for example, del 17p, del 1p, gain 1q) it would be valuable to know. But in Arkansas, the real value is from the gene array that draws upon thousands of marrow samples and can assign risk based on a profile of characteristics from studying 80 different genes.
Maybe I'll take a picture of my gene array analysis next time and try to figure that one out! : )
Special thanks again to SuzieRose -- or maybe I should call her SuzieRosettaStone. : )
In keeping with the philosophy of this blog, I report things as they occur, to record my understanding of events as they happen. Other blogs will fully research something and present it in a way that is clinically correct, but may be less penetrable and will be less personal.
So the upshot of this is to give you a glimpse into a complex topic in a way that reflects my own limited understanding at this time. It can be seen (I hope, anyhow!) as an invitation to other MM patients to learn more about their own condition -- and also as a platform for correction and further illumination.
So without further ado...
Cytogenetic abnormalities refer to tweaked (highly clinical word there) chromosomes within one's cells (in this case, myelomic plasma cells). A normal cell has 46 chromosomes (23 "diploids" which consist of 23 from the mother and 23 from the father).
The severity of one's Myeloma can be impacted by both the number of cytogenetic abnormalities, and the type of cytogenetic abnormalities. Typically, these abnormalities take the place of either an extra copy of a chromosome (which results in a "hyperdiploid" -- too many chromosomes -- characteristic to the cell), the deletion of a chromosome ("hypodiploid"), or a translocation of chromosome pairs (like let's say the 4th chromosome of one pair has gone off and paired up with the 14th chromosome of another pair and vice-versa, resulting in what's called translocation (4;14).
Some of the more well-known cytogenetic abormalities include del 13 (deletion of the 13th chromosome, which used to be perceived as a high-risk trait), del 17 (which remains a high-risk trait), translocation (4;14) as noted (formerly high-risk but responsive to Velcade), etc. Additionally, a "hyperdiploid" diagnosis (too many chromosomes) is generally a better factor than a "hypodiploid" diagnosis. I have no idea why this is -- others may be able to inform. Particularly SuzieRose who again knows more about this stuff than any other patient I've encountered.
I was aware that I was hyperdiploid, but didn't ever really know the extent of my cytogenetic abnormalities. How many did I have? They are "nearly universal" in Myeloma cells -- in fact I'm not sure how one could have Myeloma without any.
At any rate, when I was last in Arkansas, I dug through my file and took a photo of the result of the marrow analysis that was done at "baseline" -- before treatment started.
Here's what it looks like.
54,XY,+2,der(2)t(2;2)(p11.1;q21),der(2;3)(p10;q10),+3,der(4)t(1;4)(q12;p16),+5,+6,+9,+11,+15,+18,+19[cp22]/46,XY[cp8]
Yikes! It's a miracle I wasn't staggering into the emergency room with smoke pouring out of my butt with that much wrong with me.
(pause for laughter...thank you, thank you)
I refer back to part of BB's recent dictation when he commented, in reference to my current (normal) marrow, "flow cytometry [the test through which this is assessed] was negative, and originally had shown rather profound hyperdiploid lambda light chain restricted disease."
By "rather profound" he probably means that's a long string of gobbeldygook up above, versus a short string.
I recognized only a few things in here, and I was able to determine a few things on my own, but to really make sense of this without calling a microbiologist, I reached out to SuzieRose to see if she could help decipher it. She was kind enough to invest some time in doing so, noting that every lab reports this stuff differently.
My sole contributions to the deciphering were (1) to note that the "cp" refers to "cell population." By looking at the two numbers, there were 30 cells analyzed, of which 22 had all the crap wrong with them that is delineated, and 8 of them were nice, pretty, 46 chromosome cells that had their act together; and (2) that the 54 referred to the number of chromosomes, so I had 8 extra copies somewhere versus a normal cell.
As a quick aside, subsequent bone marrow analyses show that after one cycle of VDT-PACE, in a 20 cell sample, I had 3 goofy looking ones exactly like the ones above, and 17 normal ones. After my first transplant, I had only normal ones.
So, to the goofiness.
Of the 22 messed up cells, here's how SuzieRose helped me decipher it.
* When there are translocations, they leave a piece of the chromosome behind at the site of the translocation. This is said to be a "derivative" of the chromosome that was translocated and is appreviated "der". So in my case, I had a derivative of chromosome 2, and a derivative of chromosome 4
* Whey they catalogue the chromosome changes they pinpoint them to a specific "address" on the cell, and in this case the changes occurred at 2p11.1 and 2q21, as well as 2p10 and 3q10. I also had a translocation of chromosomes 1 and 4 that occurred at 1q12 and 4p16, respectively.
I don't know what p and q refer to -- perhaps they are the two strings where the pairs of chromosomes are supposed to align? I don't know. I suppose I haven't...wait for it...been minding my P's and Q's.
(pause for groan...these are the jokes, people -- they can't all be gems).
I continue.
I gather that the first marker in a pair is the "long arm" and the second is the "short arm." So Suzierose said I have a translocation of chromosome 2 on the long arm of p at band 11.1 and on the short arm of q at band 21.
All those plusses refer to trisomies -- an extra copy of the chromosome. I had nine of them, of chromosomes 2, 3, 5, 6, 9, 11, 15, 18 and 19.
What does all this mean?
Not much, to me, anyhow.
UAMS uses more advanced genetic analysis to determine risk characteristics of Myeloma. So this is interesting information insofar as it shows how mangled my marrow was and shows the impact of therapy (significant reduction after one cycle of induction) -- and if there were any high-risk signs (for example, del 17p, del 1p, gain 1q) it would be valuable to know. But in Arkansas, the real value is from the gene array that draws upon thousands of marrow samples and can assign risk based on a profile of characteristics from studying 80 different genes.
Maybe I'll take a picture of my gene array analysis next time and try to figure that one out! : )
Special thanks again to SuzieRose -- or maybe I should call her SuzieRosettaStone. : )
Wednesday, September 18, 2013
An update, with help from a fellow patient
I have had the good fortune to connect with two fellow MM sufferers on a couple of different topics recently and would like to acknowledge both of them.
Today's thanks go to SuzieRose, aka Myeloma Cinderella. SuzieRose and I differ on our opinions of Arkansas, BB and Total Therapy but she is a remarkably educated patient and has been extremely kind to help "talk me off the ledge" with respect to the recent lab results, as well as digging into my cytogenetic abnormalities.
I'll be acknowledging the help of another friend, DC, in my next couple of posts. But I'd like to share what SuzieRose told me. By the way, she keeps her own blog, which can be found here. It can be rather technical, which may make it somewhat more challenging to approach at times, but it is incredibly well-researched.
Anyhow, in the wake of the last update, I emailed BB and told him I was concerned that he didn't know the significance of the Immunifixation results that showed a faint monoclonal band, noting that I had first reported this result several weeks ago and was told it was nothing to worry about but that it seemed this might have changed. I reminded him I was negative for MRD, but was concerned that we were no longer confident I remained in complete remission based on his carefully-worded letter. I asked if I should come back sooner than January for the fine needle aspirations of the persistent focal lesions in my vertebrae (again, these are not active lesions -- they are holes in the bone, essentially, where active lesions used to be).
BB and BJ both wrote back, assuring me that I shouldn't be concerned, and that they'd be reviewing my case with their colleagues to discuss, but that the MRD trumps the IFE test.
This was somewhat calming, but not as much as I'm sure they intended. After all, if your life depends on your car working, and there's a funny rattle, and the mechanic says "I'm not worried"...well, it's still a little worrisome.
Now, I'm no dummy when it comes to this disease. I'm a pretty smart guy and I've researched this as well as a non-biologist is generally able to do. But I don't hold a candle to SuzieRose in this area. She is the most informed patient I've ever come across. So I emailed her to ask her opinion about the biology of somebody who is MRD negative but IFE not-so-negative.
Her response was very helpful, citing research from three institutions that indicated that protein bands in the blood were a sign of successful treatment. Some of this research refers to oligoclonal bands -- multiple monoclonal bands that appeared in my blood in the months after my transplants and which BB at the time said were consistent with profound remission. However, my current bloodwork doesn't say that there are multiple monoclonal bands. It says there is a faint monoclonal band that may or may not be the original protein. So I wasn't going to get any comfort from that.
On the other hand, some of the research indicated that a "second MGUS" of sorts -- a single abnormal protein -- can also emerge after treatment. And further, this research notes that this cannot be interpreted as disease recurrence, but in fact may be consistent with "eradication" of the disease. I rather like that characterization.
So for others out there who may find this type of signature in your blood, take heart. I'm still spooked, of course, and probably will be until the remaining lesions have either fully resolved (more on this in a future update...some doctors don't think they ever resolve) or at least until the marrow from each is tested for MRD and is negative for myeloma.
That said, the research that SuzieRose pulled together for me that references the monoclonal bands was comforting, and is recounted here:
I'll post again on how SuzieRose helped me understand the incredibly complex lab report that described the cytogenetic abnormalities (i.e., things wrong with my cells) in my bone marrow at diagnosis.
Today's thanks go to SuzieRose, aka Myeloma Cinderella. SuzieRose and I differ on our opinions of Arkansas, BB and Total Therapy but she is a remarkably educated patient and has been extremely kind to help "talk me off the ledge" with respect to the recent lab results, as well as digging into my cytogenetic abnormalities.
I'll be acknowledging the help of another friend, DC, in my next couple of posts. But I'd like to share what SuzieRose told me. By the way, she keeps her own blog, which can be found here. It can be rather technical, which may make it somewhat more challenging to approach at times, but it is incredibly well-researched.
Anyhow, in the wake of the last update, I emailed BB and told him I was concerned that he didn't know the significance of the Immunifixation results that showed a faint monoclonal band, noting that I had first reported this result several weeks ago and was told it was nothing to worry about but that it seemed this might have changed. I reminded him I was negative for MRD, but was concerned that we were no longer confident I remained in complete remission based on his carefully-worded letter. I asked if I should come back sooner than January for the fine needle aspirations of the persistent focal lesions in my vertebrae (again, these are not active lesions -- they are holes in the bone, essentially, where active lesions used to be).
BB and BJ both wrote back, assuring me that I shouldn't be concerned, and that they'd be reviewing my case with their colleagues to discuss, but that the MRD trumps the IFE test.
This was somewhat calming, but not as much as I'm sure they intended. After all, if your life depends on your car working, and there's a funny rattle, and the mechanic says "I'm not worried"...well, it's still a little worrisome.
Now, I'm no dummy when it comes to this disease. I'm a pretty smart guy and I've researched this as well as a non-biologist is generally able to do. But I don't hold a candle to SuzieRose in this area. She is the most informed patient I've ever come across. So I emailed her to ask her opinion about the biology of somebody who is MRD negative but IFE not-so-negative.
Her response was very helpful, citing research from three institutions that indicated that protein bands in the blood were a sign of successful treatment. Some of this research refers to oligoclonal bands -- multiple monoclonal bands that appeared in my blood in the months after my transplants and which BB at the time said were consistent with profound remission. However, my current bloodwork doesn't say that there are multiple monoclonal bands. It says there is a faint monoclonal band that may or may not be the original protein. So I wasn't going to get any comfort from that.
On the other hand, some of the research indicated that a "second MGUS" of sorts -- a single abnormal protein -- can also emerge after treatment. And further, this research notes that this cannot be interpreted as disease recurrence, but in fact may be consistent with "eradication" of the disease. I rather like that characterization.
So for others out there who may find this type of signature in your blood, take heart. I'm still spooked, of course, and probably will be until the remaining lesions have either fully resolved (more on this in a future update...some doctors don't think they ever resolve) or at least until the marrow from each is tested for MRD and is negative for myeloma.
That said, the research that SuzieRose pulled together for me that references the monoclonal bands was comforting, and is recounted here:
MAYO:
... during the course of MM, new monoclonal gammopathies of an isotype (heavy and/or light chain) distinct from the original MM can emerge.17,18 This entity, termed secondary MGUS,17 has been hypothesized to be caused by recapitulation of early B-cell ontogeny after stem cell transplantation (SCT).18 Previous investigations suggest that the appearance of a secondary MGUS is associated with better outcome.19,20 We studied the frequency, characteristics, and natural history of secondary MGUS in MM.
"we have shown by ASO-PCR and sequencing that oligoclonal serum Igs post transplantation is not caused by myeloma related clonal B cells but rather by the regenerating B cell compartment, indicating that the oligoclonal serum Igs post transplantation can not be considered as a sign of relapse of the disease."
"Thus, the initial development of APB (abnormal protein band) appears to be associated with marked reduction in the malignant plasma cell clone as evidenced by the achievement of complete remission and may be a surrogate marker for myeloma eradication.In summary, the development of small APB post-transplant in patients with myeloma is common, appears to have no adverse clinical significance and cannot be considered a sign of disease relapse. "
I'll post again on how SuzieRose helped me understand the incredibly complex lab report that described the cytogenetic abnormalities (i.e., things wrong with my cells) in my bone marrow at diagnosis.
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