Sociodemographic Determinants of Allogeneic Hematopoietic Stem Cell Transplant Outcomes

Background: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a curative therapy for several high-risk hematologic disorders. While clinical factors significantly impact post-transplant outcomes, socio-demographic determinants such as age, gender, and ethnicity 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 socio-demographic determinants on allo-HCT outcomes.

Methods: For this retrospective single-center study, we included all patients undergoing matched unrelated donor (MUD) and haploidentical (haplo) allo-SCT at the University of Kanas Medical Center from August 2016 to July 2021. Cox regression analysis compared overall survival (OS) and disease-free survival (DFS). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Logistic regression was performed to compare relapse, non-relapse mortality (NRM), acute and chronic graft versus host disease (GVHD), and GVHD-free Relapse-free survival (GRFS). Odds ratios (0R) with 95% CI were calculated. Linear regression was performed to compare platelet and neutrophil engraftment, and the correlation coefficient (R) was calculated. Multivariate analyses were performed for recipient age, gender, ethnicity, Karnofsky's performance status (KPS), and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p<0.05.

Results: A total of 452 patients were included, of which 276 had MUD allo-HCT while 176 had haplo allo-HCT. The median age of the recipients was 57 years (18-77), of which 61% were male (n=277). Ethnicity was Caucasians (n=381, 84%), Hispanics (n=28, 6%), African Americans (n=20, 5%), and others (n=23, 5%). KPS was 60-80% in 67% (n=304) patients and 90% or higher in 33% (n=148) of patients. Fifty-six percent of patients (n=251) had an HCT-CI score of 3 and above. Myeloablative and reduced-intensity conditioning were performed in 169 (37%) and 283 (63%) recipients. The graft source was bone marrow in 224 (49.6%) and 228 (50.4%) had peripheral blood stem cell grafts. The median graft cell dose was 4 million CD34 cells/kg. GVHD prophylaxis included tacrolimus/methotrexate (n=241, 53%) and post-transplant cyclophosphamide-based (n=211, 47%). Hematologic diagnoses included myeloid (n=322, 71%), lymphoid (n=101, 22%), and others (n=29, 7%). In univariate analyses for recipient age, gender, ethnicity, KPS, and HCT-CI, predictors include OS: age (years, HR 1.03, 95% CI 1.01-1.04, p<0.001), HCT-CI (≥3 vs 0-1: HR 1.40, 95% CI 1.03-1.91, p=0.030), and KPS (60-80% vs ≥90%: HR 1.61, 95% CI 1.14-2.26, p=0.006); DFS: age (years, HR 1.02, 95% CI 1.01-1.03, p<0.001) and KPS (60-80% vs ≥90%: HR 1.41, 95% CI 1.04-1.90, p=0.028); GRFS: None; Relapse: None; NRM: age (years, HR 1.02, 95% CI 1.01-1.04, p=0.001); acute GVHD: gender (male vs female, HR 0.59, 95% CI 0.40-0.87, p=0.007); chronic GVHD: KPS (60-80% vs ≥90%: HR 0.64, 95% CI 0.43-0.96, p=0.029); engraftment: None. Multivariate models were adjusted for all significant predictors identified in the univariate analyses. After adjusting for confounders, higher recipient age significantly predicted inferior OS (HR 1.10, 95% CI 1.01-1.04, p=0.0084), inferior DFS (HR 1.02, 95% CI 1.01-1.03, p=0.0012), and higher NRM (OR 1.03, 95% CI 1.01-1.04, p=0.005). Male gender significantly predicted lower risk of acute GVHD ((OR 0.59, 95% CI 0.40-0.86, p=0.007). African American ethnicity compared to Caucasians significantly predicted inferior OS (HR 1.90, 95% CI 1.01-3.58, p=0.046). KPS was a significant predictor of a higher risk of chronic GVHD (HR 0.62, 95% CI 0.40-0.95, p=0.028). HCT-CI did not predict any of the outcomes. No other significant associations were observed between these factors and post-transplant outcomes.

Conclusion: In this single-center study, recipient age significantly affected OS, DFS, and NRM. The recipient's gender had a notable impact on acute GVHD, while ethnicity influenced OS. KPS was associated with chronic GVHD; interestingly, HCT-CI had no impact on post-transplant outcomes. Our findings suggest the need for larger studies to explore and mitigate the sociodemographic determinants of transplant outcomes.

Lutfi:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. McGuirk:CRISPR therapeutics: Consultancy; Caribou bio: Consultancy; Novartis: Consultancy; Kite: Consultancy; Sana technologies: Consultancy; Autolus: Consultancy; NEKTAR therapeutics: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; BMS: Consultancy; Legend biotech: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.