Post-Transplant Cyclophosphamide Combined with Anti-Thymocyte Globulin as Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

Background: Allogeneic hematopoietic cell transplantation (HCT) is curative for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) but with significant non-relapse mortality (NRM) and relapse. We compared the combination of anti-thymocyte globulin (ATG; 4.5 mg/kg) and post-transplant cyclophosphamide (PTCy; 50 mg/kg on day +3 and +4) with other graft-versus-host disease (GvHD) prophylaxis regimens used for these patients. Methods: We retrospectively analyzed 159 patients, aged 22–73 (median 56) years, having undergone transplantation for high-risk AML (n = 120) or MDS (n = 39). The donors were matched related (33%), unrelated (55%) and haploidentical (12%). Almost all patients used peripheral blood stem cells. Conditioning was myeloablative (34%) or reduced intensity (66%). ATG + PTCy was used in 69 patients (43%), and other GvHD prophylaxis regimens in 90 patients (57%). Results: Grade III–IV acute GvHD occurred in 4% of the ATG + PTCy patients versus 20% of those using other regimens (p = 0.004), and chronic GvHD in 19% of the ATG + PTCy patients versus 41% of those using other regimens (p = 0.003). Two-year GvHD-free relapse-free survival (GRFS) was 30% with ATG + PTCy versus 18% with other regimens (p = 0.04). Multivariable analysis demonstrated that while ATG + PTCy had no significant influence on overall survival, cumulative incidence of relapse or NRM, there was a significant influence on GRFS in favor of ATG + PTCy (HR = 0.69, 95% CI 0.45–0.99, p = 0.04). Conclusions: We conclude that the ATG + PTCy combination significantly improved GRFS in allogeneic HCT for high-risk AML and MDS without influencing other outcomes.