Sociodemographic and Patient-Related Determinants of Outcomes after Matched Sibling Donor Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based GvHD Prophylaxis

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for several hematologic disorders. While disease- and transplant-related factors significantly impact post-transplant outcomes, sociodemographic and patient-related determinants such as age, gender, ethnicity, donor age and gender, cytomegalovirus (CMV) status, frailty, and comorbidities play a crucial role in the success of allo-HCT. Furthermore, performance status and comorbidities also affect the outcomes. We aimed to investigate the influence of sociodemographic and patient-related determinants on outcomes after matched sibling donor (MSD) HCT using post-transplant cyclophosphamide (PT-Cy)-based graft-versus-host disease (GVHD) prophylaxis.

Methods: A retrospective multicenter analysis was conducted, including MSD HCT recipients with PT-Cy-based GVHD prophylaxis in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2012 to 2017 using P5737 data by Ustun et al. We evaluated the impact of recipient age, gender, and ethnicity, donor age and gender match, CMV status, Karnofsky's performance status (KPS), and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) on overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), grade II-IV acute GVHD, chronic GVHD, and GVHD-free relapse-free survival (GRFS). Patient-, disease- and transplant-related factors were compared between groups using the Chi-square test for categorical variables and the Wilcoxon two-sample test for continuous variables. The median follow-up duration was estimated using the reverse Kaplan-Meier method. Cox proportional hazards regression analyses were performed. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p-values <0.2 in univariable analysis and the clinically relevant variables were included in the multivariable models. Statistical analyses were conducted using Stata version 18, and significance was defined as p<0.05.

Results: We included 315 MSD HCT recipients receiving PT-Cy-based GVHD prophylaxis. The median age was 48.9 years, and 59% (n=187) were male. The graft source was peripheral blood in 70.5% (n=222) and bone marrow in 29.5% (n=93) of patients. The primary hematologic malignancies included acute myeloid leukemia (55%, n=169), acute lymphoblastic leukemia (25%, n=76), and myelodysplastic syndrome (20%, n=63). Ethnicities were Caucasian (65.5%, n=206), African American (16%, n=51), Hispanic (10.5%, n=33), and Asian and others (8%, n=25). The conditioning regimen was myeloablative in 52% (n=163) of patients. The KPS was 90% or higher in 55% (n=173) of patients. The HCT-CI of less than 3 was noted in 53% (n=166) of patients. The median follow-up time was 3.26 (95% CI 3.06-3.89) years. The median OS, DFS, and GRFS were 5.07 years (95% CI 2.45-not reached), 1.35 years (95% CI 0.79-1.96), and 0.29 years (95% CI 0.23-0.34). Grade II-IV acute GVHD, chronic GVHD, relapse, and mortality rates were 37% (n=117), 36.5% (n=115), 42.5% (n=134), and 54% (n=170). After adjusting for significant variables in multivariate regression analysis, female donor-male recipient predicted inferior OS (HR 1.79, 95% CI 1.01-3.18, p=0.046), CMV donor/recipient-negative (HR = 1.90, 95% CI, 1.07-3.40, p= 0.029) predicted a higher risk of relapse, and KPS of 90% or higher predicted lower incidence of grade II-IV acute GVHD (HR 0.49, 95% CI 0.27-0.90, p=0.022). We found no significant association between recipient age, gender, ethnicity, donor age, or HCT-CI with post-transplant outcomes.

Conclusion: In this multicenter analysis, we found that a female donor-male recipient mismatch was associated with an inferior overall survival. Conversely, a cytomegalovirus donor/recipient-negative match and a poor performance status were associated with a higher risk of relapse and acute graft-versus-host disease, respectively. Most sociodemographic and patient-related factors do not appear to influence outcomes after a matched sibling donor hematopoietic cell transplantation using post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis.