Cyclophosphamide plus tacrolimus and mycophenolate mofetil as posttransplant graft vs host disease (GVHD) prophylaxis improved GVHD-free, relapse-free survival (GFRFS) compared with the current standard of care, tacrolimus plus methotrexate, among patients undergoing an allogeneic hematopoietic stem cell transplant (HSCT).1

“The results of this study will have an immediate impact on the standard of care in adults who receive a fully-matched peripheral blood stem cell transplant after reduced intensity conditioning,” Javier Bolaños-Meade, MD, of Johns Hopkins and said study Co-Chair said in a press release.2 “PTCy/Tac/MMF should be considered the standard for GVHD-prevention for these patients.”

The results of this phase 3 trial were also considered “practice changing” by the Blood & Marrow Transplant Clinical Trials Network (BMT CTN), the Center for International Blood and Marrow Transplant Research (CIBMTR), and the National Marrow Donor Program (NMDP)/Be The Match.2,3

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The results were published in the New England Journal of Medicine.1 In the study ( identifier: NCT03959241), 420 patients undergoing HSCT were randomly assigned to receive cyclophosphamide-based prophylaxis or standard of care after transplantation. The primary endpoint was 1-year GFRFS, which included grade 3-4 acute GVHD, chronic GVHD requiring immunosuppression, disease relapse or progression, and death from any cause.

At baseline, the mean age was 64.3 and 60.3% of patients were male. The majority of patients were White at 87.9%, followed by 3.2% who were Asian, 3.0% who were Black, 0.2% who were of multiple races, and 5.3% with unknown race. There were 7.2% of patients who were Hispanic or Latino. The majority of patients had an unrelated donor with 8/8 HLA matching at 66.8%, and 29.7% had a related donor with 6/6 HLA-matching, and 3.5% with an unrelated donor with 7/8 matching.

GFRFS was significantly longer among patients treated with the cyclophosphamide-based prophylaxis, with a rate of 52.7% compared with 34.9% among patients treated with the standard of care (hazard ratio [HR], 0.64; 95% CI, 0.49-0.83; P =.001).

Grade 3 or 4 acute GVHD occurred less frequently in the cyclophosphamide group, with a cumulative incidence of 6.3% compared with 14.7% of patients in the standard of care group. Death related to acute GVHD occurred among 4% and 14% of patients in the cyclophosphamide and standard of care groups, respectively.

Chronic GVHD was also lower with cyclophosphamide-based prophylaxis, with a  cumulative incidence of 21.9% compared with 35.1% in the standard of care arm.

There was no significant difference in overall survival, with 77.0% and 72.2% of patients in the cyclophosphamide and standard of care arms, respectively, alive at 1 year. Disease-free survival was 67.0% and 62.4%, respectively.

Neutrophil engraftment at day 28 occurred in 90.3% of patients in the cyclophosphamide-based prophylaxis arm compared with 93.4% in the standard of care arm. Similarly, platelet recovery at day 100 occurred among 90.3% and 92.8% of patients in the cyclophosphamide or standard of care arms, respectively.


1. Bolaños-Meade J, Hamadani M, Wu J, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. New Engl J Med. 2023;388:2338-2348. doi: 10.1056/NEJMoa2215943

2. New England Journal Of Medicine Publishes Practice-changing GVHD Study By the Blood and Marrow Transplant Clinical Trials Network. News release. BMT CTN; June 22, 2023.

3. Phase III Clinical Trial Published in New England Journal Of Medicine Identifies New Standards for Prevention of Graft Versus Host Disease Following Transplant. News release. NMDP/Be The Match; June 22, 2023.