Uday R. Popat, MD, Discusses Rationale for Post-Transplant Cyclophosphamide as GVHD Prophylaxis in AML/MDS

Uday R. Popat, MD, spoke about the decision to use post-transplant cyclophosphamide vs tacrolimus plus methotrexate to prevent graft-vs-host disease.

During the 2022 Tandem Meeting, Uday R. Popat, MD, professor and deputy chair ad interim in the Department of Stem Cell Transplantation, Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center in Houston, spoke with CancerNetwork® about the rationale for using post-transplant cyclophosphamide vs tacrolimus plus methotrexate as prophylaxis for graft-vs-host disease (GVHD) in patients with acute myeloid leukemia and myelodysplastic syndrome who underwent matched donor hematopoietic cell transplantation. The treatment used in the trial (NCT02250937) helped to reduce severe GVHD and nonrelapse mortality and improved survival.


We have always wanted to develop a myeloablative conditioning regimen for older patients. It is well known that treatment intensity reduces relapse rate. The biggest challenge in older patients is that when you give higher intensity conditioning, they have higher treatment-related mortality and therefore it negates the outcomes of reduction in the relapse rate.

With that aim in mind, we started with a very simple idea. Traditionally, the chemotherapy regimen is given over a 4-day period. We [extended treatment] over a 2-to-3-week period and gave a third dose of busulfan, which is the main agent in this regimen.

To our surprise, we found that this resulted in a significant reduction in treatment-related mortality without increasing the relapse rate. To build upon and develop that idea, we added some other agents to our regimen—including cladribine and fludarabine-bulsufan—and conducted a phase 2 study, in which we randomized patients to 2 different ongoing regimens. About a quarter of the way through the study, we discovered that we were able to deliver [the regimen], but we still had significantly higher nonrelapse mortality of about over 20%. We said wanted to know if there was a way we could reduce this. It was at that time that there were good data that were being published about the use of post-transplant cyclophosphamide to reduce severe GVHD, which is a major cause of treatment-related mortality. We amended the protocol and [tried] post-transplant cyclophosphamide. What we showed [at the meeting] are the results of comparison between our traditional GVHD prophylaxis tacrolimus/methotrexate vs post-transplant cyclophosphamide with a longer fractionated bulsufan regimen.


Popat UR, Mehta Rs, Bassett R, et al. Post-transplant cyclophosphamide versus tacrolimus and methotrexate to prevent graft-versus-host-disease in recipients of matched donor transplantation: comparison of sequential cohorts in a prospective trial. Presented at the 2022 Tandem Meeting; Salt Lake City, Utah; April 23-26, 2022. Poster 379.

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