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. : )
Thursday, September 19, 2013
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.
Monday, September 16, 2013
From the Doctor's mouth...
Every time I think I don't need to worry, I find more to worry about.
In the wake of last week's little goof-up with the remission terminology, BJ wrote to advise me that the people filling out those forms don't know the difference between the two diagnoses and I shouldn't worry about it, but instead should focus on what BB says and does.
He did say, via text, that I had not lost remission.
Reading his clinical notes from my last visit, though, there's enough here to create low-grade unease.
As always, he dictates his notes in a letter addressed to all my doctors in LA on which I am copied (this is routine and a wonderful aspect of what BB does). I am reminded that my doctors in LA -- SF, GD and especially RV -- constitute a pretty darn good team as well, alongside BB. Anyhow...the salient points:
"I am reporting to you on nick who has IgG lamba myeloma in complete remission..." so far so good.
"Immunofixation analysis [this is sensitive blood work] suggested that the original IgG lambda band might still be present and I am going back to a March investigation when this was not hte case and I am not sure about the implications."
No longer very good.
This is the thing that I saw in my blood more than a month ago when I was told not to worry about it. By BB, BJ and CR. BJ again said not to worry about it when I asked her before leaving the clinic the other day. It seems like I'm "not sure" if it's a big deal or not...that's enough to justify a bit of worry.
Then, some good news.
"The bone marrow examination dated September 4, 2013 showed no morphological evidence of myeloma...No MDS changes [this is good: don't want MDS, which is pre-leukemia, essentially, and which Revlimid can impact]. The MRD, or minimal residual disease, test was again negative."
Fine and dandy.
"The DWIBS [a type of MRI] study by MRI showed again sub centimeter focal lesions remaining in thoracic spine and pelvis also noted on dedicated STIR weighted image analysis [another type of MRI] of the axial skeleton showing 1 cm lesions at T2-4, T10 and T12. No focal lesions in the pelvis."
These are a frustration, but by themselves would be no big deal. However, here's the upshot.
"Thus, the patient appears to continue in complete or near-complete remission of IgG lambda myeloma qualifying for MRD negativity with persistent FDG non-avid focal lesions on MRI."
Worried emphasis mine. These are not confident words, and BB chooses them carefully.
The clinical follow-through is as I have explained:
"I would like to see the patient back here in January 2014 when I would like to perform fine needle aspiration examination from at least 2 or 3 of the persistent focal lesions...and I would like to resume Zometa at 2 mg monthly."
I have had a couple of extraordinarily helpful email exchanges with two other patients, both of whom know a lot about the disease. The first conversation helped me dig into the abnormalities in my marrow at diagnosis. The second provided the perspective of another doctor (GT) on these persistent lesions, thyroid issues, cure fractions and that immunofixation test. I'll post about these topics over the next couple of days.
Lastly, for fellow patients or caregivers that follow along, I wanted to report that it's okay to have moments of despair. I am generally pretty strong, being mindful that it's easier to be strong when you are responding to therapy. I had a bit of a breakdown Saturday night when I read this letter for the first time. I felt a little like I was being told not to worry when in fact there is reason for concern. Normally BB is as straight a shooter as it comes...so I should perhaps take at face value his telling me not to worry, except that it does contradict the letter if not the spirit of this particular dictation.
Anyhow, it's okay to be weak. Once in a while, anyhow. Back to being strong for now.
In the wake of last week's little goof-up with the remission terminology, BJ wrote to advise me that the people filling out those forms don't know the difference between the two diagnoses and I shouldn't worry about it, but instead should focus on what BB says and does.
He did say, via text, that I had not lost remission.
Reading his clinical notes from my last visit, though, there's enough here to create low-grade unease.
As always, he dictates his notes in a letter addressed to all my doctors in LA on which I am copied (this is routine and a wonderful aspect of what BB does). I am reminded that my doctors in LA -- SF, GD and especially RV -- constitute a pretty darn good team as well, alongside BB. Anyhow...the salient points:
"I am reporting to you on nick who has IgG lamba myeloma in complete remission..." so far so good.
"Immunofixation analysis [this is sensitive blood work] suggested that the original IgG lambda band might still be present and I am going back to a March investigation when this was not hte case and I am not sure about the implications."
No longer very good.
This is the thing that I saw in my blood more than a month ago when I was told not to worry about it. By BB, BJ and CR. BJ again said not to worry about it when I asked her before leaving the clinic the other day. It seems like I'm "not sure" if it's a big deal or not...that's enough to justify a bit of worry.
Then, some good news.
"The bone marrow examination dated September 4, 2013 showed no morphological evidence of myeloma...No MDS changes [this is good: don't want MDS, which is pre-leukemia, essentially, and which Revlimid can impact]. The MRD, or minimal residual disease, test was again negative."
Fine and dandy.
"The DWIBS [a type of MRI] study by MRI showed again sub centimeter focal lesions remaining in thoracic spine and pelvis also noted on dedicated STIR weighted image analysis [another type of MRI] of the axial skeleton showing 1 cm lesions at T2-4, T10 and T12. No focal lesions in the pelvis."
These are a frustration, but by themselves would be no big deal. However, here's the upshot.
"Thus, the patient appears to continue in complete or near-complete remission of IgG lambda myeloma qualifying for MRD negativity with persistent FDG non-avid focal lesions on MRI."
Worried emphasis mine. These are not confident words, and BB chooses them carefully.
The clinical follow-through is as I have explained:
"I would like to see the patient back here in January 2014 when I would like to perform fine needle aspiration examination from at least 2 or 3 of the persistent focal lesions...and I would like to resume Zometa at 2 mg monthly."
I have had a couple of extraordinarily helpful email exchanges with two other patients, both of whom know a lot about the disease. The first conversation helped me dig into the abnormalities in my marrow at diagnosis. The second provided the perspective of another doctor (GT) on these persistent lesions, thyroid issues, cure fractions and that immunofixation test. I'll post about these topics over the next couple of days.
Lastly, for fellow patients or caregivers that follow along, I wanted to report that it's okay to have moments of despair. I am generally pretty strong, being mindful that it's easier to be strong when you are responding to therapy. I had a bit of a breakdown Saturday night when I read this letter for the first time. I felt a little like I was being told not to worry when in fact there is reason for concern. Normally BB is as straight a shooter as it comes...so I should perhaps take at face value his telling me not to worry, except that it does contradict the letter if not the spirit of this particular dictation.
Anyhow, it's okay to be weak. Once in a while, anyhow. Back to being strong for now.
Wednesday, September 11, 2013
Talk about false alarms! What a day I had yesterday...
Regular readers will know I encourage patients to learn as much as they can about their disease and their treatment. This is, generally, a good thing. But sometimes, when you know just enough to be dangerous, it can have unintended consequences.
Regular readers will also know that my aggressive treatment plan for the disease has been in pursuit of a cure. Looking back five years ago (I was diagnosed in October of 2008, so at this time five years ago I had a pain in my shoulder that was a tumor and I had raging disease but no idea) I had two options, really. Option one was to treat the disease sequentially, hoping for a good response to each successful drug cocktail, until I ran out of combinations that worked, at which point I would have drug-resistant disease and a poor prognosis. Option two was to clobber the disease with everything at once, hoping for a cure, and if it failed I would end up with drug-resistant disease and a poor prognosis.
I went for option two and I'm glad I did. While it has meant prolonged treatment, I have had four years of continuous complete remission this month. And while complete remission may not mean a cure in every case, there's no doubt that there can't be cure WITHOUT it so at the very least it's a positive sign that my remission is profound.
Nonetheless, if I *lose* remission, it's a dreadful thing. It's not the same thing as somebody who DIDN'T pursue a cure losing remission, because most people with low-risk disease that achieve complete remission in Total Therapy DON'T lose it. Most are cured (the exact percentage is debatable and will be proven out over time).
The downside is if remission *IS* lost, it means drug-resistant disease. And it often returns in a high-risk variant. Oh, sure, a couple of new drugs (Kyprolis/Carfilzomib and Pomalyst/Pomalidomide) have come out in the last five years and they can extend life by a little bit but at 45, I'm not looking for a little bit.
So every six months, when I check in and the remission has sustained, I'm closer to being confident that I'm cured. And if it's lost, then it's pretty dire.
So this dynamic, and my acute awareness of it, sets the stage for an episode of panic yesterday that thankfully has a benign ending.
After last week's visit when I wasn't able to meet with BB because his rounds had him later than usual, I was a little uneasy about those residual lesions not fully resolving yet, and the monoclonal signature in my blood which is either a sign of profound remission and recovering marrow, or a sign of return of the disease. The fact that my bone marrow was negative for residual disease was definitely encouraging and lends credence to the fact that the blood is a non-issue, but I'm still eager to have those damn lesions resolve so that I can feel confident I've beaten this thing once and for all.
I got my paperwork Monday via Fedex and perused it. Put me back on Zometa for bone strengthening. Come back in January for two fine needle aspirations (of the T10 and T12 vertebrae, for those playing along with the home version of the game). Seemed like low grade stress at most. All tests were negative.
Then yesterday morning a dear friend called and said he was sorry to hear the news. I thought he was taking yesterday's blog post a bit hard.
Then I found out that my wife had informed him I had lost remission.
I then calmly told my wife that wasn't the case.
Then she texted me a photo of something on the paperwork. A tiny little check-the-box thing that I hadn't even looked at because it has been so rote for the past four years. Of COURSE I'm in remission, right?
Except that's not what it said. Instead, it looked like this:
Forgive the rotation of the photo, but you get the point. The big circle around "without Remission" was the scary thing.
My wife had thought I was aware of this due to my consternation at the need for more bone marrow work and the mysterious blood results. So she hadn't said anything to me, thinking I already knew.
I texted BB (thank God I have a direct line) and said "Paperwork says I have lost remission. Is this true?"
I also texted his chief administrator BJ, and my PA who is named JA after my former PA (CR) moved on from UAMS to other pastures. Sorry for the overload of initials, by the way.
While I was waiting, it occurred to me that I thought there were other places that indicated with a check box what my diagnosis was. I called my wife and had her pore through the papers for it. We couldn't find it. The closest thing we could find was this, in indecipherable doctor script:
About all I can make out of that is...uh...nothing whatsoever. In the cold light of day today, GL probably means IgG Lambda. Then there's a symbol that could mean "with" or "without" followed by CR. Again, in the cold light of day, what I thought was GIRD with a weird symbol is really MRD negative. Then underneath it is a FL with a plus sign and in the cold light of day that probably means focal lesions still persist. So, dammit, I figured it all out, a day later. Except I still wouldn't know whether that symbol meant in complete remission or not. And even then, they wouldn't say that "complete remission" has been lost -- they would say "remission" has been lost. So any mention of CR has to be a positive thing.
No need to panic after all. This could have allayed my fears. However, dear reader, I can assure you that adrenaline was interfering with this simple analysis.
About 40 minutes after I sent my text to BB, he wrote back "Hell no." I do love that man. "Have I lost remission?" "Hell no."
He confirmed it was a transcription error. BJ later emailed me the same thing.
I was in a bit of a daze the rest of the day -- if the cancer doesn't get me, I might have a heart attack from that kind of stress! :)
There's probably a lesson here about just living each day and enjoying it for the gift that it is. That, too, is something that is easier to recognize when you aren't in the heat of it, believe me.
So for now, steady as she goes. I'll be back in January to have my spine poked and that will hopefully tell us more -- unless, of course, the Zometa helps those lesions resolve fully by then. It's worth noting that many doctors don't think these things ever go away...but then I didn't go to just any doctor. :)
Regular readers will also know that my aggressive treatment plan for the disease has been in pursuit of a cure. Looking back five years ago (I was diagnosed in October of 2008, so at this time five years ago I had a pain in my shoulder that was a tumor and I had raging disease but no idea) I had two options, really. Option one was to treat the disease sequentially, hoping for a good response to each successful drug cocktail, until I ran out of combinations that worked, at which point I would have drug-resistant disease and a poor prognosis. Option two was to clobber the disease with everything at once, hoping for a cure, and if it failed I would end up with drug-resistant disease and a poor prognosis.
I went for option two and I'm glad I did. While it has meant prolonged treatment, I have had four years of continuous complete remission this month. And while complete remission may not mean a cure in every case, there's no doubt that there can't be cure WITHOUT it so at the very least it's a positive sign that my remission is profound.
Nonetheless, if I *lose* remission, it's a dreadful thing. It's not the same thing as somebody who DIDN'T pursue a cure losing remission, because most people with low-risk disease that achieve complete remission in Total Therapy DON'T lose it. Most are cured (the exact percentage is debatable and will be proven out over time).
The downside is if remission *IS* lost, it means drug-resistant disease. And it often returns in a high-risk variant. Oh, sure, a couple of new drugs (Kyprolis/Carfilzomib and Pomalyst/Pomalidomide) have come out in the last five years and they can extend life by a little bit but at 45, I'm not looking for a little bit.
So every six months, when I check in and the remission has sustained, I'm closer to being confident that I'm cured. And if it's lost, then it's pretty dire.
So this dynamic, and my acute awareness of it, sets the stage for an episode of panic yesterday that thankfully has a benign ending.
After last week's visit when I wasn't able to meet with BB because his rounds had him later than usual, I was a little uneasy about those residual lesions not fully resolving yet, and the monoclonal signature in my blood which is either a sign of profound remission and recovering marrow, or a sign of return of the disease. The fact that my bone marrow was negative for residual disease was definitely encouraging and lends credence to the fact that the blood is a non-issue, but I'm still eager to have those damn lesions resolve so that I can feel confident I've beaten this thing once and for all.
I got my paperwork Monday via Fedex and perused it. Put me back on Zometa for bone strengthening. Come back in January for two fine needle aspirations (of the T10 and T12 vertebrae, for those playing along with the home version of the game). Seemed like low grade stress at most. All tests were negative.
Then yesterday morning a dear friend called and said he was sorry to hear the news. I thought he was taking yesterday's blog post a bit hard.
Then I found out that my wife had informed him I had lost remission.
I then calmly told my wife that wasn't the case.
Then she texted me a photo of something on the paperwork. A tiny little check-the-box thing that I hadn't even looked at because it has been so rote for the past four years. Of COURSE I'm in remission, right?
Except that's not what it said. Instead, it looked like this:
Forgive the rotation of the photo, but you get the point. The big circle around "without Remission" was the scary thing.
My wife had thought I was aware of this due to my consternation at the need for more bone marrow work and the mysterious blood results. So she hadn't said anything to me, thinking I already knew.
I texted BB (thank God I have a direct line) and said "Paperwork says I have lost remission. Is this true?"
I also texted his chief administrator BJ, and my PA who is named JA after my former PA (CR) moved on from UAMS to other pastures. Sorry for the overload of initials, by the way.
While I was waiting, it occurred to me that I thought there were other places that indicated with a check box what my diagnosis was. I called my wife and had her pore through the papers for it. We couldn't find it. The closest thing we could find was this, in indecipherable doctor script:
About all I can make out of that is...uh...nothing whatsoever. In the cold light of day today, GL probably means IgG Lambda. Then there's a symbol that could mean "with" or "without" followed by CR. Again, in the cold light of day, what I thought was GIRD with a weird symbol is really MRD negative. Then underneath it is a FL with a plus sign and in the cold light of day that probably means focal lesions still persist. So, dammit, I figured it all out, a day later. Except I still wouldn't know whether that symbol meant in complete remission or not. And even then, they wouldn't say that "complete remission" has been lost -- they would say "remission" has been lost. So any mention of CR has to be a positive thing.
No need to panic after all. This could have allayed my fears. However, dear reader, I can assure you that adrenaline was interfering with this simple analysis.
About 40 minutes after I sent my text to BB, he wrote back "Hell no." I do love that man. "Have I lost remission?" "Hell no."
He confirmed it was a transcription error. BJ later emailed me the same thing.
I was in a bit of a daze the rest of the day -- if the cancer doesn't get me, I might have a heart attack from that kind of stress! :)
There's probably a lesson here about just living each day and enjoying it for the gift that it is. That, too, is something that is easier to recognize when you aren't in the heat of it, believe me.
So for now, steady as she goes. I'll be back in January to have my spine poked and that will hopefully tell us more -- unless, of course, the Zometa helps those lesions resolve fully by then. It's worth noting that many doctors don't think these things ever go away...but then I didn't go to just any doctor. :)
Monday, September 9, 2013
Ruminations on last weeks' tests
I try not to overthink all this stuff, really, but it's a fine line between wanting to know everything I can about my condition and the likelihood that I'm cured and what can be done to ensure that outcome, versus obsessing about it. Generally speaking, I feel like I've done a very good job of managing this. I don't feel or live as though I have a Sword of Damocles hanging over my head. I don't think about cancer -- consciously -- all that much, all things considered. I hear about people who approach upcoming tests with dread and I don't really have that feeling. I have 10 minutes of eagerness reading through results on the day I'm to meet with BB, but other than that, I've got it under control most if not all of the time. And part of the reason I don't have that dread, I think, is because the tests are so frequent and I am sufficiently on top of things that the "unknown" part is kept pretty well managed.
For this reason, I'm permitting myself to indulge in some "what if" thinking at the moment, based on last week's test results.
At the end of the day, if I have a thyroid problem, that's controllable with pills. It might even explain some of the fatigue and GI issues.
Similarly, I'm not really worried about the presence of "small lymphocyte aggregates" in my marrow, because if it was something serious, they'd have told me instead of telling me not to worry about it. While I want to learn more about this, the little research I've done indicates that it's present in a benign form in much of the population. It's connected to lymphoma but I think it's correlation without causality and if I had other lymphoma markers, they'd be evident.
What I *am* worried about is the connection between the unresolved lesions in my bones, and the mysterious reappearance of the monoclonal signature in my blood under sensitive tests (normal tests still show that it's negative).
When they perform the fine needle aspirates of my spine and hip, they will pull marrow (assuming the sites are accessible) and analyze it for the presence of myeloma. They last did this a year ago during the "great MYC gene scare of 2012" and the one site they were able to access at that time was the hip, and it was negative.
They did not, at that time, have the ability to run an MRD test -- the Minimal Residual Disease test there is dozens of times more accurate (I seem to think 60X) than a standard bone marrow analysis. I haven't had the chance to speak with them about this but it's certainly possible that they may want to pull the marrow from there to run MRD tests on it.
The one marrow site they did access -- my hip, not where the lesion was but in one of the sites where the marrow is most prominent in the body -- was negative for MRD, and that's great. If I was MRD negative throughout the body, I'd be considered cured. The issue is that it's from one site, and marrow could be clean in one place and not-so-clean in another. BB told me he is working on developing a test that would perform MRD on the blood, rather than the marrow, which would tell all.
But we don't have that yet, so instead I will be pin-cushioned here once we get it scheduled.
The best case: the former lesion sites are all accessible, each is MRD negative, the marker in the blood is a sign of marrow recovery rather than returning disease, and BB tells me I'm cured and can go off meds.
The worst case: one or more lesion sites show residual disease, the marker in the blood is a sign of its return, and I need to determine whether or not to undergo aggressive chemo to keep on the potential cure path -- or accept that relapse is inevitable and join folks who are waiting for more treatments to come out of big pharma. After all, if I still have disease, it's resistant to Velcade at a minimum.
The likely case: not all lesion sites are accessible, the one or two that are are negative for MRD, we chalk the blood up to marrow recovery but deep down inside neither of us is all that confident in it, and I stay on Velcade and continue to wait out resolution of these lesions.
More news to come as events merit. Be well, all.
For this reason, I'm permitting myself to indulge in some "what if" thinking at the moment, based on last week's test results.
At the end of the day, if I have a thyroid problem, that's controllable with pills. It might even explain some of the fatigue and GI issues.
Similarly, I'm not really worried about the presence of "small lymphocyte aggregates" in my marrow, because if it was something serious, they'd have told me instead of telling me not to worry about it. While I want to learn more about this, the little research I've done indicates that it's present in a benign form in much of the population. It's connected to lymphoma but I think it's correlation without causality and if I had other lymphoma markers, they'd be evident.
What I *am* worried about is the connection between the unresolved lesions in my bones, and the mysterious reappearance of the monoclonal signature in my blood under sensitive tests (normal tests still show that it's negative).
When they perform the fine needle aspirates of my spine and hip, they will pull marrow (assuming the sites are accessible) and analyze it for the presence of myeloma. They last did this a year ago during the "great MYC gene scare of 2012" and the one site they were able to access at that time was the hip, and it was negative.
They did not, at that time, have the ability to run an MRD test -- the Minimal Residual Disease test there is dozens of times more accurate (I seem to think 60X) than a standard bone marrow analysis. I haven't had the chance to speak with them about this but it's certainly possible that they may want to pull the marrow from there to run MRD tests on it.
The one marrow site they did access -- my hip, not where the lesion was but in one of the sites where the marrow is most prominent in the body -- was negative for MRD, and that's great. If I was MRD negative throughout the body, I'd be considered cured. The issue is that it's from one site, and marrow could be clean in one place and not-so-clean in another. BB told me he is working on developing a test that would perform MRD on the blood, rather than the marrow, which would tell all.
But we don't have that yet, so instead I will be pin-cushioned here once we get it scheduled.
The best case: the former lesion sites are all accessible, each is MRD negative, the marker in the blood is a sign of marrow recovery rather than returning disease, and BB tells me I'm cured and can go off meds.
The worst case: one or more lesion sites show residual disease, the marker in the blood is a sign of its return, and I need to determine whether or not to undergo aggressive chemo to keep on the potential cure path -- or accept that relapse is inevitable and join folks who are waiting for more treatments to come out of big pharma. After all, if I still have disease, it's resistant to Velcade at a minimum.
The likely case: not all lesion sites are accessible, the one or two that are are negative for MRD, we chalk the blood up to marrow recovery but deep down inside neither of us is all that confident in it, and I stay on Velcade and continue to wait out resolution of these lesions.
More news to come as events merit. Be well, all.
Saturday, September 7, 2013
An update: the good, the bad, and the ugly...
Clint Eastwood:
* My MRD test (the most sensitive marrow test they have) tested more than twice as many cells as last time, owing to a better marrow sample. With around 3.5 million cells tested, not a single myeloma cell. From this part of my hip, at least, there is no disease remaining.
Lee Van Cleef:
* My bloodwork under Immunofixation says "the original IgG Lambda M Protein may be present. An in distinct monoclonal band is present in the lambda region.". This COULD, I am told, just be the product of recovering marrow. Of course it is also what it would look like should the disease return.
* My T4 thyroid count is very low. Not sure what this means but it requires more testing. T3 is normal but on the lower end of the normal range. T4 has dropped significantly.
* My marrow, while negative for myeloma and MDS, is reported as having a "significant hematologist abnormality" called a "small lymphoid aggregate.". BJ told me not to worry about this but anything that is a significant abnormality seems definitionally to be something to worry about. I don't yet know what it means although initial research indicates it may be present in up to 60 percent of the general population so I will see what I can learn.
Eli Wallach:
* The lesions in my spine and hip are unchanged. As they haven't made any move towards further resolution in two years, BB wants to stick needles into each of them and test the marrow from those spots. I suppose if they are all MRD negative, he might say I am cured regardless of the fact that they persist, but I don't know as he was running so late I didn't get to speak with him directly about this.
That means a return visit to Arkansas for more bone marrow biopsies sometime soon.
I am tired of this -- and yet mindful that many others with this disease have it far worse than do I.
On balance, then, I probably don't feel as crestfallen as Eli Wallach did when his agent called and said "they're considering you for a movie called 'The Good, the Bad and the Ugly'...the good and the bad parts are taken."
* My MRD test (the most sensitive marrow test they have) tested more than twice as many cells as last time, owing to a better marrow sample. With around 3.5 million cells tested, not a single myeloma cell. From this part of my hip, at least, there is no disease remaining.
Lee Van Cleef:
* My bloodwork under Immunofixation says "the original IgG Lambda M Protein may be present. An in distinct monoclonal band is present in the lambda region.". This COULD, I am told, just be the product of recovering marrow. Of course it is also what it would look like should the disease return.
* My T4 thyroid count is very low. Not sure what this means but it requires more testing. T3 is normal but on the lower end of the normal range. T4 has dropped significantly.
* My marrow, while negative for myeloma and MDS, is reported as having a "significant hematologist abnormality" called a "small lymphoid aggregate.". BJ told me not to worry about this but anything that is a significant abnormality seems definitionally to be something to worry about. I don't yet know what it means although initial research indicates it may be present in up to 60 percent of the general population so I will see what I can learn.
Eli Wallach:
* The lesions in my spine and hip are unchanged. As they haven't made any move towards further resolution in two years, BB wants to stick needles into each of them and test the marrow from those spots. I suppose if they are all MRD negative, he might say I am cured regardless of the fact that they persist, but I don't know as he was running so late I didn't get to speak with him directly about this.
That means a return visit to Arkansas for more bone marrow biopsies sometime soon.
I am tired of this -- and yet mindful that many others with this disease have it far worse than do I.
On balance, then, I probably don't feel as crestfallen as Eli Wallach did when his agent called and said "they're considering you for a movie called 'The Good, the Bad and the Ugly'...the good and the bad parts are taken."
Wednesday, September 4, 2013
Concern allayed
I had the pleasure of having dinner (and wine!!!) with BB, his lovely wife, his irrepressible chief of staff BJ and a colleague of theirs who has recently joined in a consulting role after years of doing this with the IMF.
Among the stories, laughter, jokes and discussion of all things Myeloma, I did speak with BB about the ending of the lite arm of my study. As it turns out, because the stated goal of the study was to reduce toxicity (mouth sores, most prominently) and because this wasn't achieved, the study was ended early by a review board. All patients now receive the standard arm. BB said that there were no meaningful differences in outcome and in fact depending on what cytogenetic abnormalities a given patient has, some patients fared better under the lite arm. He said they were working to try to understand why but did not have this figured out yet.
He also told me he is working with some colleagues on a new MRD test that will seek to overcome the imitations of the current one -- primarily that marrow from one individual site in the body could be free of cancer cells but there could be some elsewhere.
All good news.
Now we wait to see if the MRI is clean, if my MRD is negative in marrow, and if the bloodwork is clean and I can write off that mysterious monoclonal signature that showed up recently.
We should know on Friday.
Among the stories, laughter, jokes and discussion of all things Myeloma, I did speak with BB about the ending of the lite arm of my study. As it turns out, because the stated goal of the study was to reduce toxicity (mouth sores, most prominently) and because this wasn't achieved, the study was ended early by a review board. All patients now receive the standard arm. BB said that there were no meaningful differences in outcome and in fact depending on what cytogenetic abnormalities a given patient has, some patients fared better under the lite arm. He said they were working to try to understand why but did not have this figured out yet.
He also told me he is working with some colleagues on a new MRD test that will seek to overcome the imitations of the current one -- primarily that marrow from one individual site in the body could be free of cancer cells but there could be some elsewhere.
All good news.
Now we wait to see if the MRI is clean, if my MRD is negative in marrow, and if the bloodwork is clean and I can write off that mysterious monoclonal signature that showed up recently.
We should know on Friday.
Tuesday, September 3, 2013
An unnerving update from Arkansas
I have been in Little Rock for about 16 hours, and already managed to get my pizza fix in from the always-delicious Dam Goode Pies.
Sadly, that is the highlight of the trip so far.
After early morning MRIs, the scheduling snafus began. I am in the infusion center for my third attempt at getting labs done today. I mention this primarily because I think back to nearly five years ago when I was running around City of Hope. I have grown more tolerant of delays and scheduling mistakes -- I wonder how much is that I cut the good people of Arkansas slack given that they have hopefully saved my life, versus me just having mellowed. Perhaps a bit of both.
I met with the data manager, a usually innocuous meeting that involves me updating the center here on anything of merit (for example the endoscopy, side effects, etc.) and signing some consent forms once in a while. Velcade now has a small risk of some kind of horrible brain virus that kills ya dead. Very rare, I am told. Nobody has seen it here in Arkansas, but it must exist.
That wasn't what troubled me, however.
I was told that the "lite arm" of Total Therapy 4 had been discontinued. The lite arm involved one less cycle of induction (pre-transplant) chemo, and one less cycle of consolidation (post-transplant) chemo, and the transplant chemo spread out over more days versus the standard arm of the study. The goal of doing the two arms was to see if they could achieve the same clinical efficacy (ie cure rates) and achieve less toxicity.
I was told the lite arm would not result in any less efficacy of outcome or it wouldn't be studied as it would be unethical to do so if the doctor had any reason to believe the outcomes wouldn't be as good. So on we went and I was happy to get the lite arm as it meant less chemo.
In explaining why the study had been discontinued, the data manager said that it was because there was no difference in toxicity noted between the two arms, and the "gold standard" remained the standard arm so they didn't want to change it. That is one interpretation. The other is that the lite arm outcomes weren't as good. Sadly, my money is on this as the real reason.
It is very disturbing, to say the least.
I see BB on Thursday and will ask him abut it then, if I don't see him before then for a drink or dinner.
I better not have gone through all this to have a worse outcome than if I had done just a little more.
:(
Sadly, that is the highlight of the trip so far.
After early morning MRIs, the scheduling snafus began. I am in the infusion center for my third attempt at getting labs done today. I mention this primarily because I think back to nearly five years ago when I was running around City of Hope. I have grown more tolerant of delays and scheduling mistakes -- I wonder how much is that I cut the good people of Arkansas slack given that they have hopefully saved my life, versus me just having mellowed. Perhaps a bit of both.
I met with the data manager, a usually innocuous meeting that involves me updating the center here on anything of merit (for example the endoscopy, side effects, etc.) and signing some consent forms once in a while. Velcade now has a small risk of some kind of horrible brain virus that kills ya dead. Very rare, I am told. Nobody has seen it here in Arkansas, but it must exist.
That wasn't what troubled me, however.
I was told that the "lite arm" of Total Therapy 4 had been discontinued. The lite arm involved one less cycle of induction (pre-transplant) chemo, and one less cycle of consolidation (post-transplant) chemo, and the transplant chemo spread out over more days versus the standard arm of the study. The goal of doing the two arms was to see if they could achieve the same clinical efficacy (ie cure rates) and achieve less toxicity.
I was told the lite arm would not result in any less efficacy of outcome or it wouldn't be studied as it would be unethical to do so if the doctor had any reason to believe the outcomes wouldn't be as good. So on we went and I was happy to get the lite arm as it meant less chemo.
In explaining why the study had been discontinued, the data manager said that it was because there was no difference in toxicity noted between the two arms, and the "gold standard" remained the standard arm so they didn't want to change it. That is one interpretation. The other is that the lite arm outcomes weren't as good. Sadly, my money is on this as the real reason.
It is very disturbing, to say the least.
I see BB on Thursday and will ask him abut it then, if I don't see him before then for a drink or dinner.
I better not have gone through all this to have a worse outcome than if I had done just a little more.
:(
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