Hello,
Below are hubby's FISH results. He had a single plasmacytoma in July 13 (quickly broken T1 neck, surgery, radiation). His M-spike at the time was only 0.45 g/dL (4.5 g/L) and normal kappa-lambda ratio. He then progressed in only 12 months to multiple myeloma and currently has at least 2 large tumors (pelvis and hip).
His current M-spike is only 0.36 g/dL, kappa-lambda ratio 8, and very mild if any anemia. He started RVD (Revlimid, Velcade, and dex) after his FISH (see below). His tumors have seemed to be unusually aggressive and almost defying his good blood work in comparison, but the FISH results may explain that now.
He had to resort to a walker for 2 weeks and is able to walk the past few days. Doc has mentioned possibly adding radiation to shrink one of the tumors pressing on his sciatic, but hopefully that can be avoided with the improved walking the past 2 days.
Doc wants to proceed to an autologous stem cell transplant (ASCT) in September, but hubby wants to delay to next summer for work reasons. He would still collect stem cells, but not do transplant until later. Second opinion at Dana Farber thought that was reasonable, but his myeloma specialist at Norris Cotton Dartmouth does not agree. This was before we had the FISH results.
We are now wondering if it is even worth doing the ASCT following the FISH results with what we understand would be a likely short time before disease progression anyway?
Any insight into his FISH results and advice / experience with similar cytogenetics and ASCT or not would be greatly appreciated.
Karyotype
nuc ish (CDKN2Cx2,CKS1Bx3) [9/127] / (CDKN2Cx1,CKS1Bx3) [8/127] , (FGFR3,IGH)x2[127] ,(D13S319,LAMP1)x1[33/88] , (IGH,MAF)x2[65] , (TP53,D17Z1)x2[68]
Interpretation
Multiple myeloma FISH panel: ABNORMAL and consistent with 1q21/CKS1B gain alone in 7.1% of cells, 1q21/CKS1B and 1p32/CDKN2C deletion in 6.3% of cells, and monosomy 13 alone in 37.5% of cells.
NO EVIDENCE of IGH-FGFR3/t(4;14), IGH-MAF/t(14;16), or 17p13.1/TP53 deletion.
Interphase FISH analysis using the probes specific for the 1p32/CDKN2C and 1q21/CKS1B loci (Empire Genomics, Inc) showed a signal pattern consistent with both 1p32/CDKN2C deletion and 1q21/CKS1B gain in 6.3% of the cells. A signal pattern consistent with 1q21/CKS1B gain alone was noted in 7.1% of the cells. This was significantly above the normal limits (1q21/CKS1B gain: 0-3.1%). A total of 127 cells were scored for each of the probes. Thus, there was evidence of 1q21/CKS1B gain and 1p32/CDKN2C deletion.
Interphase FISH analysis using dual-color, dual-fusion probe for the IGH-FGFR3/t(4;14)(p16;q32) (Abbott Molecular, Inc) revealed a signal pattern consistent with IGH-FGFR3/t(4;14) in 0% of 127 cells analyzed. This was within the normal limits (0-2.3%). Therefore, there was no evidence of IGH-FGFR3/t(4;14).
Interphase FISH analysis using probes specific for 13q14.3/D13S319 and 13q34/LAMP1 (Abbott Molecular, Inc) revealed a signal pattern consistent with a loss of chromosome 13 (monosomy 13) in 37.5% of 88 cells. This was significantly above the normal limits (0-4.4%). Therefore, there was evidence of monosomy 13.
Interphase FISH analysis using dual-color, dual-fusion probes for IGH-MAF/t(14;16)(q32;q23) (Abbott Molecular, Inc) showed a signal pattern consistent with IGH-MAF/t(14;16) in 0% of 65 cells. This was within the normal limits (0-1.5%). Thus, there was no evidence of IGH-MAF/t(14;16).
Interphase FISH analysis using the probes specific for 17p13/TP53 (Abbott Molecular, Inc) showed a signal pattern consistent with 17p13/TP53 deletion in 1.5% of 68 cells. This was within the normal limits (0-7.9%). Therefore, there was no evidence of 17p13/TP53
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Re: ASCT or not with 1q+, del(1p), and monosomy 13 (FISH)?
Hello, Honeybear:
If you have not done so already, I would wade through the Mayo Clinic's guidelines, called MSmart. Although there are doctors whose approach diverge from that guideline, it is widely accepted and it is good to at least understand where you stand with respect to MSmart's protocol. Here is the link:
http://www.msmart.org/about.html
I am not 100% sure of your husband's FISH test, but it sounds like he is intermediate risk with respect to the cytogenetic abnormalities. MSmart does recommend early ASCT based on intermediate risk. More than the CA and the blood test numbers, your husband does have the tumors on the bone. I am thinking that is a factor in what they are recommending, separate and apart from the numbers and the FISH. Also, what your husband's PET scan might have said (assuming it was done to date).
If you are high-risk according to MSmart, then you are in the category where there is a high possibility of a fast relapse. The one of greatest concern is deletion(17p). Very interestingly, the test picked up a very low level of about 1%, but the statement said it was non-detect for 17p. I am not sure what that means, exactly. If it's negative for 17p, however, there is a better chance of the ASCT getting a decent response and an advantage over delayed ASCT (or no ASCT).
If 17p is positive, then the point you made is the same one I have heard some doctors make, namely that the ASCT might not be worth it, based on a small advantage compared to the "ordeal" of the ASCT process. Interestingly, MSmart does also select the early ASCT route for high risk (which is contrary to the idea you mentioned).
Best of luck to you in this challenging decision, either way you all go.
If you have not done so already, I would wade through the Mayo Clinic's guidelines, called MSmart. Although there are doctors whose approach diverge from that guideline, it is widely accepted and it is good to at least understand where you stand with respect to MSmart's protocol. Here is the link:
http://www.msmart.org/about.html
I am not 100% sure of your husband's FISH test, but it sounds like he is intermediate risk with respect to the cytogenetic abnormalities. MSmart does recommend early ASCT based on intermediate risk. More than the CA and the blood test numbers, your husband does have the tumors on the bone. I am thinking that is a factor in what they are recommending, separate and apart from the numbers and the FISH. Also, what your husband's PET scan might have said (assuming it was done to date).
If you are high-risk according to MSmart, then you are in the category where there is a high possibility of a fast relapse. The one of greatest concern is deletion(17p). Very interestingly, the test picked up a very low level of about 1%, but the statement said it was non-detect for 17p. I am not sure what that means, exactly. If it's negative for 17p, however, there is a better chance of the ASCT getting a decent response and an advantage over delayed ASCT (or no ASCT).
If 17p is positive, then the point you made is the same one I have heard some doctors make, namely that the ASCT might not be worth it, based on a small advantage compared to the "ordeal" of the ASCT process. Interestingly, MSmart does also select the early ASCT route for high risk (which is contrary to the idea you mentioned).
Best of luck to you in this challenging decision, either way you all go.
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JPC - Name: JPC
Re: ASCT or not with 1q+, del(1p), and monosomy 13 (FISH)?
JPC, I believe sMART as per Mayo puts him at Intermediate based on the 1q gain.
Some research studies, of the few I could find, mention the 1p deletion being adverse to ASCT. Yet Mayo doesn't seem to factor that in, only the 1q gain, and promotes early ASCT. This adds to my concern about doing the ASCT at all.
Interesting that there was mention of the 17p deletion but within normal range. I had ignored that until you brought it up. I do wonder if that means that is where his multiple myeloma is heading if it is low level now, or if it can be disregarded as a concern, risk-wise, if it is only within normal range now.
I appreciate your reasoning on doing ASCT early and we are pondering that for the reasons you mentioned. Thank you for responding. I am trying to encourage hubby to reconsider postponing, but I need all the reasons I can give him to help me if that is in fact the best route with the new info from his FISH.
P.S. Yes he has had PET scans done, which is how we know where his current tumors are and their size and rapid growth, despite blood work that would not have indicated such degree of bone damage.
Some research studies, of the few I could find, mention the 1p deletion being adverse to ASCT. Yet Mayo doesn't seem to factor that in, only the 1q gain, and promotes early ASCT. This adds to my concern about doing the ASCT at all.
Interesting that there was mention of the 17p deletion but within normal range. I had ignored that until you brought it up. I do wonder if that means that is where his multiple myeloma is heading if it is low level now, or if it can be disregarded as a concern, risk-wise, if it is only within normal range now.
I appreciate your reasoning on doing ASCT early and we are pondering that for the reasons you mentioned. Thank you for responding. I am trying to encourage hubby to reconsider postponing, but I need all the reasons I can give him to help me if that is in fact the best route with the new info from his FISH.
P.S. Yes he has had PET scans done, which is how we know where his current tumors are and their size and rapid growth, despite blood work that would not have indicated such degree of bone damage.
Re: ASCT or not with 1q+, del(1p), and monosomy 13 (FISH)?
This is an excellent question but hard to answer definitively.
Statistical analysis of patients with gain of 1q21 treated on the "total therapy" regimen at the University of Arkansas had inferior outcomes to patients without the gain of 1q21. This regimen does incorporate stem cell transplants.
However, from this data, I am not able to say that there is not at least some benefit to the transplant in these patients. There is a small study from the Czech Republic that again concluded that remission durations were shorter after transplant for patients with gain of 1q21 compared to those that did not have the gain of 1q21, but even with the gain of 1q21, statistical average remission was 14 months.
On the other side of this argument are data – also from Arkansas – that patients with "high risk" disease based on a bone marrow gene test called "MyPRS" do not seem to derive benefit from stem cell transplant therapy. There can be an argument made that patients who are "high risk" should not be subjected to transplant treatment – particularly if they are responding to standard treatments which can be continued on a long term basis.
In your husband's case, it will be very important to see what the response is to standard drug treatment by monitoring his bones for new lesions. It seems that his disease is incompletely evaluated by the blood and urine markers typically used for easier response assessment. If he is responding to the RVD, this can be continued long term with relative safety. The mSMART guidelines use maintenance Velcade after a year of the Velcade, Cytoxan, and dex regimen, but our center continues patients on the RVD for as much as 3 years before moving to maintenance. With the gain of 1q21, I would favor long term RVD if he is responding to this treatment. If transplant is performed, maintenance therapy after the transplant has to be a strong consideration as well.
Note: There is a National Clinical Trials Network clinical trial for patients with "high risk" disease that does include patients with gain of 1q21. This trial does not include transplant as part of the treatment, but uses ongoing treatment with VRD, with or without an investigational drug elotuzumab. Patients can still be enrolled if they have only had 1 cycle of treatment. You can find more information about the trial at its information page at clinicaltrials.gov (the page does not mention that patients with gain 1q21 can enroll in the trial, but they can).
Another note: There is no significance to the 1% del 17 picked up.
I hope this was all understandable. All the best to you and your husband.
Statistical analysis of patients with gain of 1q21 treated on the "total therapy" regimen at the University of Arkansas had inferior outcomes to patients without the gain of 1q21. This regimen does incorporate stem cell transplants.
However, from this data, I am not able to say that there is not at least some benefit to the transplant in these patients. There is a small study from the Czech Republic that again concluded that remission durations were shorter after transplant for patients with gain of 1q21 compared to those that did not have the gain of 1q21, but even with the gain of 1q21, statistical average remission was 14 months.
On the other side of this argument are data – also from Arkansas – that patients with "high risk" disease based on a bone marrow gene test called "MyPRS" do not seem to derive benefit from stem cell transplant therapy. There can be an argument made that patients who are "high risk" should not be subjected to transplant treatment – particularly if they are responding to standard treatments which can be continued on a long term basis.
In your husband's case, it will be very important to see what the response is to standard drug treatment by monitoring his bones for new lesions. It seems that his disease is incompletely evaluated by the blood and urine markers typically used for easier response assessment. If he is responding to the RVD, this can be continued long term with relative safety. The mSMART guidelines use maintenance Velcade after a year of the Velcade, Cytoxan, and dex regimen, but our center continues patients on the RVD for as much as 3 years before moving to maintenance. With the gain of 1q21, I would favor long term RVD if he is responding to this treatment. If transplant is performed, maintenance therapy after the transplant has to be a strong consideration as well.
Note: There is a National Clinical Trials Network clinical trial for patients with "high risk" disease that does include patients with gain of 1q21. This trial does not include transplant as part of the treatment, but uses ongoing treatment with VRD, with or without an investigational drug elotuzumab. Patients can still be enrolled if they have only had 1 cycle of treatment. You can find more information about the trial at its information page at clinicaltrials.gov (the page does not mention that patients with gain 1q21 can enroll in the trial, but they can).
Another note: There is no significance to the 1% del 17 picked up.
I hope this was all understandable. All the best to you and your husband.
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Dr. Jason Valent - Name: Jason Valent, M.D.
Beacon Medical Advisor
Re: ASCT or not with 1q+, del(1p), and monosomy 13 (FISH)?
Dr. Valent -
Thank you SO much for such a clear and specific response! I wish I could get such answers more often in real life that explain the "why" that leads to informed decisions. Your response will certainly help put my concerns at ease should hubby not proceed with the usual protocol, and I am bringing info of the trial you mentioned to our next appointment on Monday.
Thank you SO much for such a clear and specific response! I wish I could get such answers more often in real life that explain the "why" that leads to informed decisions. Your response will certainly help put my concerns at ease should hubby not proceed with the usual protocol, and I am bringing info of the trial you mentioned to our next appointment on Monday.
Re: ASCT or not with 1q+, del(1p), and monosomy 13 (FISH)?
Whether to do an ASCT or not is probably the single biggest decision a myeloma patient must confront. As the Beacon's numerous forums and discussions demonstrate, there is no consensus on the subject: good results can and have been achieved with, as well as without, the transplant.
I have often shared that, if I had the choice to make over, I might very possibly have decided against the procedure. I share that so that it's clear I am not in the "rah-rah" transplant camp.
That being said, I just celebrated my 2 year post-transplant "birthday". I have del(17p), and none of my doctors had expected me to survive my initial stay at the local hospital in December of 2012. Despite my reservations, and despite the ordeal that the transplant process was, it was an amazing success.
Admittedly, I represent a very clear exception to the rule. As my nurse practitioner in the oncology department says, I have responded better than any del(17p) patient she's seen in over 17 years.
My point here is that doing all the research, learning all that you can, asking all the questions that you can, getting second, third, and even fourth, opinions from specialists, is critical. None of this, however, really helps you (or your husband, obviously) decide what the best course of action is.
Left to my own devices, I would very possibly have foregone the transplant, and the results might have been favorable. I will never know. What I do know is that I got amazing results with the ASCT. I also have learned to really trust my gut and my body's reaction to any drug or protocol.
What I would say to your husband is that work-related issues are not and cannot be a valid reason to decide for or against an ASCT. Neither can they be a valid reason to postpone an ASCT if he's already decided for the procedure.
As compelling as financial concerns seem to the mind, they pale when the potential issue is really life or death.
Aloha
Daniel
I have often shared that, if I had the choice to make over, I might very possibly have decided against the procedure. I share that so that it's clear I am not in the "rah-rah" transplant camp.
That being said, I just celebrated my 2 year post-transplant "birthday". I have del(17p), and none of my doctors had expected me to survive my initial stay at the local hospital in December of 2012. Despite my reservations, and despite the ordeal that the transplant process was, it was an amazing success.
Admittedly, I represent a very clear exception to the rule. As my nurse practitioner in the oncology department says, I have responded better than any del(17p) patient she's seen in over 17 years.
My point here is that doing all the research, learning all that you can, asking all the questions that you can, getting second, third, and even fourth, opinions from specialists, is critical. None of this, however, really helps you (or your husband, obviously) decide what the best course of action is.
Left to my own devices, I would very possibly have foregone the transplant, and the results might have been favorable. I will never know. What I do know is that I got amazing results with the ASCT. I also have learned to really trust my gut and my body's reaction to any drug or protocol.
What I would say to your husband is that work-related issues are not and cannot be a valid reason to decide for or against an ASCT. Neither can they be a valid reason to postpone an ASCT if he's already decided for the procedure.
As compelling as financial concerns seem to the mind, they pale when the potential issue is really life or death.
Aloha
Daniel
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DanielR - Name: Daniel Riebow
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: 12/2012
- Age at diagnosis: 59
Re: ASCT or not with 1q+, del(1p), and monosomy 13 (FISH)?
Thank you Daniel for weighing in. I appreciate your input.
At this point it does not look like hubby is ready to proceed with ASCT.
At this point it does not look like hubby is ready to proceed with ASCT.
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