Integrating Newer Therapies into Management of Adult ALL - Episode 10

Role of Transplant in Older Adults With Acute Lymphoblastic Leukemia

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Richard M. Stone, MD: Let’s discuss older adults with ALL and the decision of transplant. If you have a patient that is 55 or older and you manage to achieve remission, MRD-negative or positive, do you transplant?

Jae Park, MD: If they’ve become MRD-negative, it’s not just based on age factors alone. If they are MRD-negative there are a number of factors in terms of decision making for the transplants, MRD positivity, or the high-risk genetic features, I will consider the transplant.

Richard M. Stone, MD: We did a retrospective analysis looking at this and transplant doesn’t seem to be a great idea for older patients because of the toxicity.

Ryan D. Cassaday, MD: I generally do not do a transplant for older patients. I still consider it for Ph-positive disease. The Fred Hutchinson Cancer Research Center’s experience with reduced-intensity conditioning for ALL has been primarily, but not exclusively, for Ph-positive disease. The data that we have with that approach is relatively good. The challenge is to be eligible for a reduced intensity transplant, you’ve got to be in deep remission and those are the patients that are going to do well regardless of what you do. Then you have to consider the fact that many of those patients end up on a TKI [tyrosine kinase inhibitor] post-transplant. How much the GVL [graft versus leukemia] effect is truly adding is unclear. For fit and motivated older adults with Ph-positive ALL, I will typically recommend they undergo a transplant in first remission. We would consider giving a myeloablative preparative regimen to someone in their upper 50s if they were in great shape. For Ph-negative patients, unless we could do a myeloablative transplant in the setting of high-risk disease features, I would generally not do it.

Richard M. Stone, MD: Data has shown that Philadelphia-negative ALL is not very responsive to immunological therapies other than the obvious ones like blinatumomab and inotuzumab. But in terms of transplant, that’s a tough one.

Bijal Shah, MD: We’re going to end up on some level thinking very critically on how we approach ALL in the older adult population. We’re probably going to end up adopting a schema like in DLBCL [diffuse large B-cell lymphoma] where there’s the fit, the unfit, and the frail. We have to decide based on that determination whether we approach them with curative therapy or palliative therapy. For the older adults, more often than not it’s palliative. We’re talking about upwards of a third of those patients who have TP53 aberration, there may not be a significant benefit to an allogeneic stem cell transplant in the TP53-mutant subgroup. Not to say we don’t do it in a younger patient where we’re worried about possible Li-Fraumeni syndrome … or even just hypodiploid ALL. It’s becoming clearer that those patients are exceptionally at a high risk of relapse after the allogeneic transplant, suggesting that this is just a group of patients for which there’s a strong unmet need.

Transcript Edited for Clarity