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Allogeneic Stem Cell Transplant in ALL

Insights From:Stefan Faderl, MD, John Theurer Cancer Center; Raoul Tibes, MD, PhD, Mayo Clinic; Bijal D. Shah, MD, Moffitt Cancer Center
Published: Tuesday, Mar 29, 2016


Transcript:

Bijal D. Shah, MD:
At the Moffitt Cancer Center, our approach to allogeneic transplant in acute lymphoblastic leukemias is to approach all of our patients with the option. Now, it’s understood that if we have a 70- or 75-year-old patient, that they may not be the best candidates and ultimately may not make it to that stage, depending on their response to chemotherapy, their comorbidities, and so on. On the other hand, for young adults, I’m going to tell you that our practice is, conventionally, to try to take them to allogeneic transplant in first remission. Why? The problem has been what happens when they relapse. The outcome has been exceptionally poor. We know that from the ECOG 2993 study, and also from retrospective data at MD Anderson, that we’re talking about 10%-20% survival, at best, for patients who relapse with this disease. And that likelihood of survival actually decreases with each subsequent decade of age. We need to come up with a better mechanism for keeping patients in remission, and so our approach is to send patients for consideration of transplant from the get-go, meaning from day 1 of therapy. So we type them at presentation.

Now, whether we ultimately take them to transplant is going to depend on some of their risk factors and also how they respond and tolerate therapy. A good example, as I mentioned before, if someone is MRD-negative, I’m going to be much less apt to take them to an allogeneic transplant in first remission unless they have a perfect sibling donor or someone who’s perfectly matched by HLA typing. On the other hand, if someone has residual MRD, I’m going to be much less demanding. I may be more willing to take on the risks that come with a haplotype transplant or a match unrelated donor transplant, knowing the toxicity is going to be higher in that space.

Raoul Tibes, MD, PhD: The age limit for an allogeneic stem cell transplantation depends on the center, I would say. In some of the trials, patients are transplanted up to 55 or 60 years of age, and the outcome, like with many other diseases, goes down the older the patient is. We transplant patients with ALL up to the age of 65 or even 70. Or some patients, if they’re fit, even above the age of 70. But I would not say this is the standard practice at this point.

Stefan Faderl, MD: What patients would I send to transplant? Personally, I stick to patients with high-risk disease. These are patients with particular chromosome abnormalities, such as the Philadelphia translocation, even in the era of tyrosine kinase inhibitors, at least at that point. These are patients with some other chromosome abnormalities—for instance, those that have MLL gene arrangements—because they’re known to have a worse outcome as well. There are other more traditional prognostic factors, say patients who present with a very high white cell count; patients at a certain age, say above 30 or 35, where the prognosis gets worse; and patients with a very insufficient response to treatment (patients who need more than one cycle to complete remission). These are more classical, historical prognostic markers that help to make that decision as well. There is still some debate about high-risk versus standard risk, and you will find specialists in the field who would also have an opinion about sending patients with more standard risk features to stem cell transplant.

Now, I’m not a transplant person myself, so the question about an optimal conditioning regimen is a little bit difficult for me to answer from the literature. There isn’t one that is the best conditioning regimen. There are just many combinations between total body irradiation and chemotherapy drugs, be that cyclophosphamide or VP-16, ara-C, busulfan, or whatever other alkylator. But due to lack of randomized studies, it’s hard to say that there’s any combination that would be superior over, say, a more standard combination of cyclophosphamide and TBI [total body irradiation]. There’s also attempts to get rid of TBI altogether, as much as it does reduce the relapse rate and as much as it is active. But it also has a potential for toxicity, so there are also conditioning regimens that try to combine chemotherapy drugs that are heavily alkylator-based in that sense. But it’s hard to say that there’s one single best conditioning regimen for those patients.

Transcript Edited for Clarity
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Transcript:

Bijal D. Shah, MD:
At the Moffitt Cancer Center, our approach to allogeneic transplant in acute lymphoblastic leukemias is to approach all of our patients with the option. Now, it’s understood that if we have a 70- or 75-year-old patient, that they may not be the best candidates and ultimately may not make it to that stage, depending on their response to chemotherapy, their comorbidities, and so on. On the other hand, for young adults, I’m going to tell you that our practice is, conventionally, to try to take them to allogeneic transplant in first remission. Why? The problem has been what happens when they relapse. The outcome has been exceptionally poor. We know that from the ECOG 2993 study, and also from retrospective data at MD Anderson, that we’re talking about 10%-20% survival, at best, for patients who relapse with this disease. And that likelihood of survival actually decreases with each subsequent decade of age. We need to come up with a better mechanism for keeping patients in remission, and so our approach is to send patients for consideration of transplant from the get-go, meaning from day 1 of therapy. So we type them at presentation.

Now, whether we ultimately take them to transplant is going to depend on some of their risk factors and also how they respond and tolerate therapy. A good example, as I mentioned before, if someone is MRD-negative, I’m going to be much less apt to take them to an allogeneic transplant in first remission unless they have a perfect sibling donor or someone who’s perfectly matched by HLA typing. On the other hand, if someone has residual MRD, I’m going to be much less demanding. I may be more willing to take on the risks that come with a haplotype transplant or a match unrelated donor transplant, knowing the toxicity is going to be higher in that space.

Raoul Tibes, MD, PhD: The age limit for an allogeneic stem cell transplantation depends on the center, I would say. In some of the trials, patients are transplanted up to 55 or 60 years of age, and the outcome, like with many other diseases, goes down the older the patient is. We transplant patients with ALL up to the age of 65 or even 70. Or some patients, if they’re fit, even above the age of 70. But I would not say this is the standard practice at this point.

Stefan Faderl, MD: What patients would I send to transplant? Personally, I stick to patients with high-risk disease. These are patients with particular chromosome abnormalities, such as the Philadelphia translocation, even in the era of tyrosine kinase inhibitors, at least at that point. These are patients with some other chromosome abnormalities—for instance, those that have MLL gene arrangements—because they’re known to have a worse outcome as well. There are other more traditional prognostic factors, say patients who present with a very high white cell count; patients at a certain age, say above 30 or 35, where the prognosis gets worse; and patients with a very insufficient response to treatment (patients who need more than one cycle to complete remission). These are more classical, historical prognostic markers that help to make that decision as well. There is still some debate about high-risk versus standard risk, and you will find specialists in the field who would also have an opinion about sending patients with more standard risk features to stem cell transplant.

Now, I’m not a transplant person myself, so the question about an optimal conditioning regimen is a little bit difficult for me to answer from the literature. There isn’t one that is the best conditioning regimen. There are just many combinations between total body irradiation and chemotherapy drugs, be that cyclophosphamide or VP-16, ara-C, busulfan, or whatever other alkylator. But due to lack of randomized studies, it’s hard to say that there’s any combination that would be superior over, say, a more standard combination of cyclophosphamide and TBI [total body irradiation]. There’s also attempts to get rid of TBI altogether, as much as it does reduce the relapse rate and as much as it is active. But it also has a potential for toxicity, so there are also conditioning regimens that try to combine chemotherapy drugs that are heavily alkylator-based in that sense. But it’s hard to say that there’s one single best conditioning regimen for those patients.

Transcript Edited for Clarity
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