Effect of Anti-thymocyte Globulin and Post-Transplant Cyclophosphamide on GvHD Outcomes in Female Donor-to-Male Recipient Matched Unrelated Donor Allogeneic Stem Cell Transplantation for Acute Leukemia.

Female-to-male (F→M) sex-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) is known to increase the risk of graft-versus-host disease (GvHD). We evaluated the impact of donor-recipient sex mismatch on GvHD incidence and assessed the efficacy of combined low-dose antithymocyte globulin (ATG) (2.5 mg/kg) and post-transplant cyclophosphamide (PTCy) as GvHD prophylaxis compared to calcineurin inhibitor-methotrexate/mycophenolate mofetil (CNI-MTX/MMF). We retrospectively analyzed 861 HSCT recipients, with AML as the predominant indication (82%). Among the cohort, 39% of transplants were sex-mismatched (M→F: 26%, F→M: 13%), while 61% were sex-matched (M→M: 42%, F→F: 19%). The primary outcomes were cumulative incidences of acute and chronic GvHD, relapse, and non-relapse mortality (NRM). F→M HSCT were associated with higher rates of grade II-IV acute GvHD at day +100 (42.2% vs. 27.0%, HR: 1.54; p<0.01) and chronic GvHD at 2 years (54.2% vs. 43.4%, HR: 1.33; p=0.05). In the overall cohort, ATG-PTCy was associated with a reduced risk of grade III-IV acute GvHD (HR: 0.42; p<0.01) and chronic GvHD (HR: 0.22; p<0.001) compared to CNI-MTX/MMF, without an increased risk of relapse (HR: 0.86, p=0.39) or NRM (HR: 0.59, p=0.35). A subgroup multivariable analysis of F→M recipients (n=114) confirmed a reduced risk of grade II-IV (HR: 0.48, p=0.05), grade III-IV acute GvHD (HR: 0.25; p=0.04), and chronic GvHD (HR: 0.33; p<0.01) with ATG-PTCy. F→M sex mismatch is associated with increased GvHD risk after HSCT. The combination of low-dose ATG and PTCy may help reduce GvHD in this high-risk group without an increase in disease relapse or NRM.