Impact of Graft-Versus-Host Disease Prophylaxis on Long-Term Outcomes in Patients Surviving Beyond Two Years After Allogeneic Transplantation

PURPOSE Post-transplant cyclophosphamide (PTCy) is increasingly used for graft-versus-host disease (GVHD) prophylaxis, but long-term outcomes remain incompletely defined. PATIENTS AND METHODS We analyzed 874 relapse-free survivors at 2 years from 2,046 patients who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) for hematologic malignancies between 2010 and 2022. GVHD prophylaxis included PTCy plus rabbit antithymocyte globulin (ATG) and a calcineurin inhibitor (CnI; Group I, n = 429) or alternative regimens (Group II, n = 445). RESULTS With an overall follow-up of 5,275 person-years after HSCT, overall survival (OS) 3 years after the landmark was 88.7% (95% CI, 86 to 91). Patients receiving ATG-PTCy-CnI had improved outcomes compared with those receiving alternative regimens, with OS of 93.2% versus 85.0% ( P < .001), and lower nonrelapse mortality (NRM; 3.4% v 10.8%; P < .001). On multivariable analysis, ATG-PTCy-CnI was independently associated with improved OS (hazard ratio [HR], 0.41; 95% CI, 0.21 to 0.79; P = .007) and lower NRM (HR, 0.34; 95% CI, 0.17 to 0.74; P = .006). Chronic GVHD remained the leading cause of late mortality; deaths from GVHD, infections, treatment-related toxicity, and second primary malignancies were all reduced with ATG-PTCy-CnI. The cumulative incidence of relapse was similar between groups. Standardized mortality ratios were 1.32 for ATG-PTCy-CnI and 2.06 for other regimens, corresponding to a 1.6-fold higher excess mortality with alternative prophylaxis ( P = .036). CONCLUSION Among patients alive and relapse-free at least 2 years after HSCT, long-term outcomes were excellent. The use of ATG-PTCy-CnI prophylaxis was associated with further improvements in survival through reductions in GVHD-related mortality and late complications.