My doctor is recommending I get the high dosage of Cytoxan (cyclophosphamide) prior to the stem cell harvest because my M spike didn't hit 0.00 after 5 rounds of induction therapy (Revlimid, Velcade, and dexamethasone - RVD) . I have leveled off at 0.42 g/dL (4.2 g/L0 from the initial 1.20 g/dL at diagnosis.
I forgot to ask what takes place after the harvest. If the spike goes to zero as a result of the Cytoxan, do I still go to a maintenance therapy, or do I go to a wait and watch? Haven't decided on a transplant yet because my numbers have always been so low.
If I don't do the Cytoxan prior to the harvest, I know that I will be on maintenance therapy, so if either way I will be on maintenance therapy, then why do the Cytoxan, which has some unwanted side affects?
Is there a low dosage option with Cytoxan that can lower the spike and not cause all the side affects?
Is there really a difference between a 0.00 and a 0.40 g/dL M-spike in today's non-curable disease?
Sorry for the unorganized banter.
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Re: Should I have high-dose Cytoxan for stem cell harvest?
Hello F:
Recalling a little more than a year ago for my wife's stem cell harvest at Memorial Sloan Kettering Cancer Center (MSKCC), the standard approach there is that if the BMB results were 5% plasma cells or less, then no Cytoxan conditioning, otherwise, they do use it.
You did not quote your plasma cell percentage. The pre-transplant M-Spike was 0.4 g/dL in her case. So it sounds like you might be at the range where it is borderline, but to go with the extra Cytoxan conditioning (maybe to be safe), based only on the MSKCC approach.
Good luck to you.
Recalling a little more than a year ago for my wife's stem cell harvest at Memorial Sloan Kettering Cancer Center (MSKCC), the standard approach there is that if the BMB results were 5% plasma cells or less, then no Cytoxan conditioning, otherwise, they do use it.
You did not quote your plasma cell percentage. The pre-transplant M-Spike was 0.4 g/dL in her case. So it sounds like you might be at the range where it is borderline, but to go with the extra Cytoxan conditioning (maybe to be safe), based only on the MSKCC approach.
Good luck to you.
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JPC - Name: JPC
Re: Should I have high-dose Cytoxan for stem cell harvest?
At initial diagnosis, my bone marrow plasma cell percentage was 12%. I haven't had a bone marrow biopsy done since.
The doctor's recommendation to use the Cytoxan is because I had a plasmacytoma on my L3, which is how they found the multiple myeloma. So, even with my plasma cell percentage of 12% and my initial M-spike of 1.20 g/dL, both low numbers, I still developed a plasmacytoma.
I would love not to lose my hair, etc, with the Cytoxan, and was trying to research if my course of treatment is just an aggressive approach - or not. The combination of plasma cell percentage > 10% and the presence of an M-spike (1.20 g/dL) and a plasmacytoma pushed me into the multiple myeloma pool. I got rid of 100% of the plasmacytoma L3 with one round of targeted radiation followed by a kyphoplasty.
The doctor's recommendation to use the Cytoxan is because I had a plasmacytoma on my L3, which is how they found the multiple myeloma. So, even with my plasma cell percentage of 12% and my initial M-spike of 1.20 g/dL, both low numbers, I still developed a plasmacytoma.
I would love not to lose my hair, etc, with the Cytoxan, and was trying to research if my course of treatment is just an aggressive approach - or not. The combination of plasma cell percentage > 10% and the presence of an M-spike (1.20 g/dL) and a plasmacytoma pushed me into the multiple myeloma pool. I got rid of 100% of the plasmacytoma L3 with one round of targeted radiation followed by a kyphoplasty.
Re: Should I have high-dose Cytoxan for stem cell harvest?
I did quite a lot of research on stem cell mobilisation protocols before I had my harvest.
There are two quite separate issues here.
The first is ensuring the production of sufficient stems cells for the harvest. Cytoxan used to be fairly standard for that purpose because it produces rapid immunosuppression. A few days later, the immune system bounces back and in the process of doing so, releases stem cells into the bloodstream. So Cytoxan was used to stimulate that "bounce back".
However, in the modern era of GCSF and plerixafor (Mozobil), the case for using cytoxan as a means of stimluating the production and release of stem cells for harvest seems much weaker. As you say, it produces a whole load of adverse side effects. There was also a recent article in the News section suggesting that the quality of stem cells generated is poorer than those produced using GCSF so that recovery can take longer.
In fact, as far as I can tell, there are really only two reasons for using it for mobilization. The first is that it is cheap. The second is that, in people who have previously been treated with melphalan, there can be difficulties in obtaining sufficient stem cells using GCSF / plerixafor. In those cases, it may still be necessary to add it in order to obtain sufficient stem cells.
I did not fall into that category, but was still offered it - I think because it was just their standard treatment. I politely declined and just took GCSF, which was fine and produced sufficient cells for two transplants.
The second issue is the use of Cytoxan as a chemo to reduce the level of myeloma plasma cells prior to transplant. I can see that might make sense, but that has nothing to do with stem cell mobilization. It is purely a treatment question. I think what you need to ask is whether they would still be recommending the Cytoxan prior to transplant if you had already been previously mobilized. If yes, then take it. if not then I'd avoid it. You don't want to be taking any more alkylating drugs than are strictly necessary.
Good luck
David
There are two quite separate issues here.
The first is ensuring the production of sufficient stems cells for the harvest. Cytoxan used to be fairly standard for that purpose because it produces rapid immunosuppression. A few days later, the immune system bounces back and in the process of doing so, releases stem cells into the bloodstream. So Cytoxan was used to stimulate that "bounce back".
However, in the modern era of GCSF and plerixafor (Mozobil), the case for using cytoxan as a means of stimluating the production and release of stem cells for harvest seems much weaker. As you say, it produces a whole load of adverse side effects. There was also a recent article in the News section suggesting that the quality of stem cells generated is poorer than those produced using GCSF so that recovery can take longer.
In fact, as far as I can tell, there are really only two reasons for using it for mobilization. The first is that it is cheap. The second is that, in people who have previously been treated with melphalan, there can be difficulties in obtaining sufficient stem cells using GCSF / plerixafor. In those cases, it may still be necessary to add it in order to obtain sufficient stem cells.
I did not fall into that category, but was still offered it - I think because it was just their standard treatment. I politely declined and just took GCSF, which was fine and produced sufficient cells for two transplants.
The second issue is the use of Cytoxan as a chemo to reduce the level of myeloma plasma cells prior to transplant. I can see that might make sense, but that has nothing to do with stem cell mobilization. It is purely a treatment question. I think what you need to ask is whether they would still be recommending the Cytoxan prior to transplant if you had already been previously mobilized. If yes, then take it. if not then I'd avoid it. You don't want to be taking any more alkylating drugs than are strictly necessary.
Good luck
David
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Davidg - Name: David
- When were you/they diagnosed?: Feb 2015 - AL Amyloidosis
- Age at diagnosis: 53
Re: Should I have high-dose Cytoxan for stem cell harvest?
There is a further point.
You say you have not yet decided on transplant. That being so, it doesn't make much sense to take high dose cytoxan to reduce the bone marrow plasma cell percentage now - given that the transplant might not take place for many months or even years.
You say you have not yet decided on transplant. That being so, it doesn't make much sense to take high dose cytoxan to reduce the bone marrow plasma cell percentage now - given that the transplant might not take place for many months or even years.
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Davidg - Name: David
- When were you/they diagnosed?: Feb 2015 - AL Amyloidosis
- Age at diagnosis: 53
Re: Should I have high-dose Cytoxan for stem cell harvest?
Thanks for responding. I actually took the same stance with respect to why take Cytoxan now if I want to push off transplant, and the response had enough merit to sway me. I was told the Cytoxan will lower my current M-spike from 0.42 g/dL to close to 0. With this in mind, why not lower the M-spike as low as possible (maybe 0), which could keep me in remission longer, giving me more time before receiving an auto transplant.
Your points are well thought out and something I will research. Much Appreciated.
Your points are well thought out and something I will research. Much Appreciated.
Re: Should I have high-dose Cytoxan for stem cell harvest?
Hello again 
I did a bit of research into the use of single-agent high-dose cyclophosphamide as a treatment for multiple myeloma. This paper seems to pretty much summarise the state of play:
Rivell, GL, et al., "Effectiveness and safety of high-dose cyclophosphamide as salvage therapy for high-risk multiple myeloma and plasma cell leukemia refractory to new biological agents," American Journal of Hematology, May 2011 (full text)
The upshot is that particularly for patients who are refractory to biological agents, cyclo is useful as a further line of therapy. However, the responses in those patients are transient - a few months only. The author's conclusion was:
"We suggest therefore that cyclophosphamide can be used as a “bridge” strategy for more definitive therapy, particularly in patients needing immediate disease control."
You are not of course refractory to biological agents and you don't seem to require immediate disease control so it is unclear to what extent the findings in that paper would apply to you.
But on the basis of the findings in the paper (that cyclophosphamide produces a good response rate but the responses tend to be transient), then:
1. If you want to defer your stem cell transplant for just a few months, then it might well make sense.
2. But if you are looking to defer for a year or more, then it seems likely that any benefit from the cyclophosphamide will have worn off by the time of your transplant.
Maybe the thing to do is to ask the doctors how long they would expect any response from cyclophosphamide to last for?
Best wishes,
David
I did a bit of research into the use of single-agent high-dose cyclophosphamide as a treatment for multiple myeloma. This paper seems to pretty much summarise the state of play:
Rivell, GL, et al., "Effectiveness and safety of high-dose cyclophosphamide as salvage therapy for high-risk multiple myeloma and plasma cell leukemia refractory to new biological agents," American Journal of Hematology, May 2011 (full text)
The upshot is that particularly for patients who are refractory to biological agents, cyclo is useful as a further line of therapy. However, the responses in those patients are transient - a few months only. The author's conclusion was:
"We suggest therefore that cyclophosphamide can be used as a “bridge” strategy for more definitive therapy, particularly in patients needing immediate disease control."
You are not of course refractory to biological agents and you don't seem to require immediate disease control so it is unclear to what extent the findings in that paper would apply to you.
But on the basis of the findings in the paper (that cyclophosphamide produces a good response rate but the responses tend to be transient), then:
1. If you want to defer your stem cell transplant for just a few months, then it might well make sense.
2. But if you are looking to defer for a year or more, then it seems likely that any benefit from the cyclophosphamide will have worn off by the time of your transplant.
Maybe the thing to do is to ask the doctors how long they would expect any response from cyclophosphamide to last for?
Best wishes,
David
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Davidg - Name: David
- When were you/they diagnosed?: Feb 2015 - AL Amyloidosis
- Age at diagnosis: 53
Re: Should I have high-dose Cytoxan for stem cell harvest?
I had my stem cell harvest a few weeks ago. Prior to the harvest, my M-spike was a constant 0.50 - 0.60 g/dL throughout my induction therapy of Revlimid / dex / Velcade.
I took a high dose of Cytoxan (cyclophosphamide) a week before harvest to get my M-spike closer to zero. Well, the lowest it went was to 0.32, and now 3 weeks after harvest, it's back to 0.48. I haven't resumed a chemo regimen yet but will this week.
Very disappointing that my M-spike didn't go down to zero. I'm waiting to talk to my doctor about this but has anyone else not been able to get their M-spike to zero before harvest?
Was the harvest a waste?
I took a high dose of Cytoxan (cyclophosphamide) a week before harvest to get my M-spike closer to zero. Well, the lowest it went was to 0.32, and now 3 weeks after harvest, it's back to 0.48. I haven't resumed a chemo regimen yet but will this week.
Very disappointing that my M-spike didn't go down to zero. I'm waiting to talk to my doctor about this but has anyone else not been able to get their M-spike to zero before harvest?
Was the harvest a waste?
Re: Should I have high-dose Cytoxan for stem cell harvest?
In the original study investigating RVD as induction therapy for newly diagnosed myeloma patients, only 40 percent of the patients achieved a complete response or near complete response. There is absolutely no reason to assume that all, or even most, patients treated with RVD will reach a complete response.
There are other treatment regimens, involving either more drugs, or newer drugs, which are likely to get more patients to a complete response or better. But even those regimens do not get all patients to complete response.
Here is a link to the paper about RVD as induction therapy:
Richardson, PG, et al, "Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma," Blood, August 2010 (full text)
See table 4 in the paper for a summary of the responses people had.
Given the Cytoxan you received, you can think of your treatment regimen as being similar to Revlimid, Velcade, dexamethasone, and cyclophosphamide. This actually has been investigated as a possible induction regimen and the complete response rate was about 25 percent.
Kumar, S, et al, "Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma," Blood, May 2012 (full text)
Again, see table 4 for a summary of the responses patients had.
Good luck with your transplant!
There are other treatment regimens, involving either more drugs, or newer drugs, which are likely to get more patients to a complete response or better. But even those regimens do not get all patients to complete response.
Here is a link to the paper about RVD as induction therapy:
Richardson, PG, et al, "Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma," Blood, August 2010 (full text)
See table 4 in the paper for a summary of the responses people had.
Given the Cytoxan you received, you can think of your treatment regimen as being similar to Revlimid, Velcade, dexamethasone, and cyclophosphamide. This actually has been investigated as a possible induction regimen and the complete response rate was about 25 percent.
Kumar, S, et al, "Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma," Blood, May 2012 (full text)
Again, see table 4 for a summary of the responses patients had.
Good luck with your transplant!
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