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Are we ready for post-transplant cyclophosphamide use in matched donor transplants?

Bone Marrow Transplantation volume 56, pages 1235–1237 (2021)Cite this article

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Post-transplant cyclophosphamide (PTCy) graft vs. host disease (GVHD) prophylaxis was initially developed in order to mitigate an excessive risk of acute and chronic GVHD associated with the use of haploidentical donor graft in allogeneic transplantation. Early approaches utilized bone marrow grafts and a reduced intensity regimen, with remarkable findings of significantly reduced rates of both severe acute and chronic GVHD [1]. There have now been multiple clinical studies of the use of PTCy in matched donor transplantation [2]. Apart from the potential to reduce rates of GVHD, other attractive features of PTCy include its ease of administration and its possible use as a platform for developing alternative GVHD prophylaxis regimens with reduced toxicity, such as a calcineurin inhibitor free regimen. The questions that remain to be answered include the development of optimal conditioning and graft type, to balance the risks of relapse and toxicity which includes GVHD, organ toxicity, and infection.

Some follow-up studies also utilized bone marrow harvest grafts, such as the study by Luznik et al. [3], which used a single agent PTCy for myeloablative conditioning (MAC) matched donor transplants, producing remarkable incidence of Grade III–IV acute GVHD of 10% and chronic GVHD of 10% with 43% of patients not requiring further immunosuppression. Most studies in matched donors, however, utilize peripheral blood stem cell grafts with variable rates of acute (17–27%) and chronic GVHD (7–28%) [4,5,6]. BMT-CTN 1203 study compared three GVHD prophylactic regimens to a group of contemporaneous patients receiving standard GVHD prophylaxis with Tacrolimus and Methotrexate (Tac/MTX) in patients receiving reduced intensity conditioning (RIC) transplants [6]. The incidence of III–IV acute GVHD (2%) and GVHD free survival (53%) in PTCy group was significantly improved compared to control group (13% and 37% correspondingly) with a trend toward improved chronic GVHD rates of 28% in PTCy group vs. 38% in the control group at 1 year follow up, and no overall survival (OS) difference. With a drawback of a non-randomized comparison group and a possibility of confounding due to center effect as well as higher comorbidity scores in the control group, an ongoing follow up BMT-CTN 1703 study is currently accruing, with randomization between GVHD prophylaxis of Tac/MTX and PTCy.

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  1. Assistant Professor, Stem Cell Transplantation, University of Virginia Medical Center, 1300 Jefferson Park Avenue, West Complex, rm 6243, Charlottesville, VA, 22908, USA

    Leonid Volodin

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Volodin, L. Are we ready for post-transplant cyclophosphamide use in matched donor transplants?. Bone Marrow Transplant 56, 1235–1237 (2021). https://doi.org/10.1038/s41409-020-01204-7

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