Sociodemographic and Patient-Related Determinants of Outcomes after Unrelated Donor Hematopoietic Cell Transplantation Using Posttransplant Cyclophosphamide-Based GVHD Prophylaxis

Disease- and transplant-related factors strongly influence outcomes after allogeneic hematopoietic cell transplantation (allo-HCT), but sociodemographic and patient-related determinants may also play a key role. We evaluated their impact in unrelated allo-HCT with post-transplant cyclophosphamide (PT-Cy)-based graft-versus-host disease (GVHD) prophylaxis. We performed a retrospective multicenter analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry (P-5891, Shaffer et al.) from 2017–2021. Outcomes included overall survival (OS), relapse, non-relapse mortality (NRM), grade II–IV and III–IV acute GVHD (aGVHD), moderate/severe chronic GVHD (cGVHD), and GVHD-free relapse-free survival (GRFS). Predictors analyzed were recipient age, sex, race/ethnicity, graft source, disease type, disease risk index (DRI), donor age, donor-recipient CMV status, Karnofsky performance status (KPS), and HCT-comorbidity index (HCT-CI). Univariable and multivariable Cox regression were performed; hazard ratios (HR) with 95% confidence intervals (CI) are reported. We included 2,271 unrelated allo-HCT recipients. Mean age was 57.0 (SD 13.9) years, 56.1% were male. Graft source was bone marrow in 90% and peripheral blood in 10%. Primary diagnoses included AML (54%), MDS (29.5%), and ALL (16.5%). Race was Caucasian (87%), African American (4.8%), Asian/other (9%). Myeloablative conditioning was used in 39.8%. KPS was <90 in 44.8%, and HCT-CI was ≥3 in 53%. Median OS was 24 months (IQR 11.6–36). Grade II–IV aGVHD, grade III–IV aGVHD, moderate/severe cGVHD, relapse, and mortality occurred in 29.1%, 6.4%, 11.4%, 27.1%, and 36.9%. On multivariable analysis, predictors of inferior OS included older age [HR 1.01, p=0.003], KPS <90 [HR 1.20, p=0.013], higher HCT-CI [HR 1.11, p<0.001], and high/very high DRI. Lower relapse risk was observed in ALL [HR 0.71, p=0.014], while non-myeloablative conditioning increased relapse [HR 1.43, p=0.004]. Higher NRM was associated with older age [HR 1.03, p<0.001], KPS <90 [HR 1.27, p=0.025], ALL [HR 1.58, p=0.003], and HCT-CI [HR 1.15, p<0.001]. GRFS was worse with Black race [HR 1.38, p=0.016], higher HCT-CI [HR 1.08, p<0.001], older donor age [HR 1.008, p=0.042], reduced-intensity conditioning [HR 1.18, p=0.034], and high/very high DRI. Higher HCT-CI also predicted increased risk of grade III–IV aGVHD [HR 1.12, p=0.003]. Recipient age, KPS, comorbidity burden, disease type, DRI, and conditioning intensity consistently predicted outcomes in unrelated allo-HCT with PT-Cy. Donor age and race also influenced GRFS, while sex, graft source, CMV status, and ethnicity did not.