Clinical Summary: 

• Design/Population: This randomized phase 3 trial compared post-transplant cyclophosphamide with antithymocyte globulin for graft-versus-host disease (GVHD) prophylaxis in 640 adults undergoing unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia, myelodysplastic syndromes, or myelodysplastic/myeloproliferative neoplasms. 

• Key Outcomes: Post-transplant cyclophosphamide reduced rates of acute and chronic GVHD but was associated with higher non-relapse mortality and failed to demonstrate noninferiority for overall survival compared with antithymocyte globulin. 

• Clinical Relevance: These findings support continued use of antithymocyte globulin-based prophylaxis as the standard of care for HLA-compatible unrelated donor transplantation.

Results from a phase 3 trial demonstrated that post-transplant cyclophosphamide did not achieve noninferiority to anti–T-lymphocyte globulin for overall survival (OS) following unrelated donor allogeneic hematopoietic cell transplantation (alloHCT) among patients with high-risk myeloid malignancies.

These results were presented by Johannes Schetelig, MD, University Hospital TU Dresden, Dresden, Germany, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden.

In this multicenter study, 640 adults with acute myeloid leukemia, myelodysplastic syndromes, or myelodysplastic/myeloproliferative neoplasms undergoing peripheral blood stem cell transplantation from an HLA-matched or single-antigen/allele-mismatched unrelated donor were randomized 3:2 to receive graft-versus-host disease (GVHD) prophylaxis with either post-transplant cyclophosphamide (n = 383) or anti–T-lymphocyte globulin (n = 257). Both groups received tacrolimus and mycophenolate mofetil as additional immunosuppression. The primary end point was OS.

At 2 years, OS was 68% in the post-transplant cyclophosphamide arm and 75% in the anti–T-lymphocyte globulin arm (adjusted hazard ratio [HR], 1.34). Noninferiority of post-transplant cyclophosphamide was not demonstrated (P = .85), and exploratory testing suggested a trend favoring anti–T-lymphocyte globulin (P = .051).

The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 21% in the post-transplant cyclophosphamide arm and 26% in the anti–T-lymphocyte globulin arm (P = .03), while rates of grade 3 to 4 acute GVHD were 7% in both groups. The 1-year cumulative incidence of chronic GVHD was 24% and 40%, respectively (P < .001). Severe chronic GVHD occurred in 6% and 10% of patients, respectively.

The 2-year rate of GVHD- and relapse-free survival was 48% in the post-transplant cyclophosphamide arm and 40% in the anti–T-lymphocyte globulin arm (adjusted HR, 0.85; P = .16). The cumulative incidence of relapse at 2 years was 26% and 31%, respectively (adjusted HR, 0.86; P = .32).

The 2-year non-relapse mortality rate was 13% with post-transplant cyclophosphamide compared with 7% with anti–T-lymphocyte globulin (adjusted HR, 1.86; P = .02), primarily due to severe infections occurring in the absence of severe acute or chronic GVHD.

“Considering the potency of [post-transplant cyclophosphamide] to prevent chronic GVHD, options to improve immune reconstitution should be explored," concluded Dr Stelljes. 

Source: 

Stelljes M, Kunadt D, Schröder T, et al. GVHD prophylaxis including ATG remains standard of care for HLA-compatible unrelated donor hematopoietic cell transplantation: Results from a large randomized controlled trial comparing ATG and PTCY. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-7202.