Posttransplant Cyclophosphamide for GVHD



Yi-Bin A. Chen, MD: The use of posttransplant cyclophosphamide-based regimens do prevent graft-versus-host disease. It’s one of the biggest advances in transplant over the past 2 decades. Popularized by our colleagues at The Johns Hopkins University, it was first shown to be effective in… haploidentical transplantation. The ability to engender engraftment as well as prevent graft-versus-host disease in this setting of a half-mashed related donor has been remarkable. And posttransplant Cytoxan has emerged as the standard platform to conduct haploidentical transplantation.

As if success was observed and then also generalized in many centers across the country and the world, it was only natural to expand this platform to other transplant settings. At [Massachusetts] Mass General Hospital we…use this as a standard platform for all of our haploidentical transplants. We have now started to use posttransplant Cytoxan for our mismatch-unrelated owner transplants as well. A recent registry study from the EBMT [European Society for Blood and Marrow Transplant] would suggest that these results using the posttransplant Cytoxan for mismatch-unrelated transplants are superior to what we’ve used in the past, confirming our practice.

Recently, clinical trials have also been conducted comparing posttransplant Cytoxan with our standard regimens that we’ve used for conventional transplants, such as match-related or match-unrelated transplants. BMT CTN 1203 was a 3-arm trial in the reduced intensity setting that compared 3 new regimens, including posttransplant Cytoxan, with a contemporaneous registry control of our standard tacrolimus and methotrexate.

The posttransplant Cytoxan and platform was the only 1 of those 3 regimens that suggested superiority. And the BMT CTN has now moved into an ongoing phase III trial comparing these 2 regimens, specifically posttransplant Cytoxan with our long-held control of tacrolimus and methotrexate.

Similarly, at this [American Society of Hematology Annual Meeting], the Dutch HOVON group will present an abstract on Sunday showing the results of their randomized trial in about 150 patients in a reduced intensity setting comparing posttransplant Cytoxan regimen with the control cyclosporine and mycophenolate mofetil. Their results suggest that patients who receive posttransplant Cytoxan have benefits not only in the prevention of severe acute and moderate to severe chronic graft-versus-host disease. But long-term have a superior graft-versus-host disease relapse-free survival, the composite end point that many of our trials are based on right now. We look forward to a long-term follow-up for that study as well as the results to the BMT CTN study.

One of the abstracts that we are presenting here involves the small series of 9 patients, but we felt it was important to include. These 9 patients actually do not have hematological malignancies, but have nonmalignant hematological diseases such aplastic anemia, PNH [paroxysmal nocturnal hemoglobinuria], or Diamond-Blackfan anemia. And these patients will often need hematopoietic cell transplantation, and these are the patients that we want to prevent graft-versus-host disease in the most, because they do not benefit from any graft-versus-malignancy effect.

Several years ago, we read the exciting report …John Hopkins…had published [about] their early experience in aplastic anemia. And we adopted the use of posttransplant Cytoxan for our nonmalignant hematological patients as well, given that posttransplant Cytoxan appeared to be the most potent regimen we had to prevent graft-versus-host disease.

Our 9-patient series showed remarkable and compelling safety. All patients had full donor hematopoiesis and very limited graft-versus-host disease. and patients who were after 12 months all were all systemic immunosuppression. And this has become our standard for that subset of patients.

In the future, we look forward to the results of the large trials comparing posttransplant Cytoxan [with] our standards to see if this might become our new standard moving forward.

Transcript Edited for Clarity

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