Sociodemographic and Patient-Related Determinants of Outcomes after Allogeneic Hematopoietic Cell Transplantation in Acute Leukemia and Myelodysplastic Syndromes

Background: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a curative therapy for several high-risk hematologic disorders. Sociodemographic determinants (age, gender, and ethnicity) and patient-related factors (frailty and comorbidities) significantly impact post-transplant outcomes. We aimed to investigate the impact of sociodemographic and patient-related factors on allo-HCT outcomes.

Methods: A retrospective multicenter analysis was conducted, including allo-HCT patients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2013 to 2018 using P5646 data by Ramathan et al. Cox regression was performed to compare overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), and platelet and neutrophil engraftment. Multivariate analyses were performed for recipient age, gender, ethnicity, Karnofsky's performance status (KPS), and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and adjusted for significant variables identified in the univariate analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p <0.05.

Results: We included 7545 allo-HCT recipients. The median age at the time of transplant was 56 years, and 58% were men. Ethnicities were Caucasian (76%), Hispanic (8%), African American (6%), Asian (5%), and others (5%). The primary disorders included acute myeloid leukemia (47.2%), myelodysplastic syndrome (34.4%), and acute lymphoblastic leukemia (18.4%). Myeloablative conditioning was used in 53% of patients. Donor types were matched unrelated (49.5%), matched related (34.1%), and cord blood (16.4%). Graft sources were peripheral blood stem cells (68%), umbilical cord blood (16%), and bone marrow (16%). GVHD prophylaxis regimens included tacrolimus or cyclosporine-based (87%), post-transplant cyclophosphamide-based (9%), CD34 selection (2%), and others (2%). The KPS was 90% or higher (57%), 80-89 (29%), and <80 (14%). The HCT-CI was 0 (20%), 1-2 (30%), 3-4 (31%), and five or higher (19%). In the multivariate analyses adjusted for all significant predictors identified in the univariate analyses, significant predictors of outcomes included - inferior OSwas predicted by older age (HR 1.01, 95% CI 1.01-1.10, p<0.001), male gender (HR 1.08, 95% CI 1.00-1.15, p=0.030), lower KPS (HR 1.33, 95% CI 1.20-1.46, p<0.001), and higher HCT-CI (HR 1.71, 95% CI 1.53-1.92, p<0.001); lower DFSwas predicted by older age (HR 1.013, 95% CI 1.010-1.016 p<0.001), lower KPS (HR 1.30,95% CI 1.12-1.50, p<0.00), and higher HCT-CI (HR 1.66, 95% CI 1.41-1.95, p<0.001); higher NRMwas predicted by older age (HR 1.01, 95% CI 1.01-1.02, p<0.001), male gender (HR 1.13, 95% CI 1.00-1.28), lower KPS (HR 1.23, 95% CI 1.04-1.46, p=0.018), and higher HCT-CI (HR 2.17, 95% CI 1.77-2.65, p<0.001); higher rate of relapsewas predicted by older age (HR 1.01, 95% CI 1.01-1.01, p<0.001), lower KPS (HR 1.23, 95% CI 1.10-1.38, p<0.001), and higher HCT-CI (HR 1.15, 95% CI 1.02-1.30, p=0.020); higher incidence of chronic GVHD was predicted by older age (p<0.001, HR 1.01, 95% CI=1.0008-1.012), male gender (HR 1.12, 95% CI 1.04-1.20, p=0.003), and lower KPS (HR 1.134, 95% CI 1.01-1.27, p=0.028); and delayed neutrophil engraftment was predicted by older age (HR 1.01, 95% CI 1.01-1.01, p<0.001). No other significant associations were observed between these factors and post-transplant outcomes.

Conclusion: The analyses identified sociodemographic factors (older age, male gender), frailty, and higher comorbidities as predictors of post-transplant outcomes, including inferior overall and disease-free survival, higher risk of relapse and non-relapse mortality, and increased incidence of chronic graft-versus-host disease in patients with acute leukemia and myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplantation. Our findings highlight the relevance of developing patient-centered interventions and a tailored selection of disease- and transplant-related factors to improve post-transplant outcomes.

Mushtaq:Iovance Biotherapeutics: Research Funding. Hamadani:Omeros: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; CRISPR: Consultancy; Forte Biosciences: Consultancy; Allovir: Consultancy; BMS: Consultancy; Spectrum Pharmaceuticals: Research Funding; Autolus: Consultancy; Genmab: Consultancy; Caribou: Consultancy; Astellas Pharma: Research Funding; AbbVie: Consultancy; Sanofi Genzyme: Speakers Bureau; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Byondis: Consultancy; CRISPR: Speakers Bureau; DMC, Inc: Speakers Bureau; Genentech: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; Takeda: Research Funding. McGuirk:Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; Sana technologies: Consultancy; Legend biotech: Consultancy; Allo Vir: Consultancy; NEKTAR therapeutics: Consultancy; Novartis: Consultancy; BMS: Consultancy; Kite: Consultancy; Autolus: Consultancy; Envision: Consultancy.