Twelve-year utilization and outcomes of haploidentical hematopoietic stem cell transplantation (HSCT) in the Eastern Mediterranean (EM) region: A multicenter EMBMT registry analysis

Abstract

Haploidentical hematopoietic stem cell transplant (Haplo-HSCT) has emerged as an alternative for patients lacking matched human leukocyte antigen (HLA) donors. The scarcity of stem cell donor registries and cord banks across the Eastern Mediterranean (EM) region has led to increased need of Haplo-HSCT as a mean to overcome this limitation. In this study, we aimed to assess trends in Haplo-HSCT utilization within the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) registry from 2012 to 2024, and describe key clinical and transplant-related factors associated with patient outcomes. We conducted a retrospective, multicenter registry-based analysis of patients who had their first un-manipulated Haplo-HSCT in ten EMBMT centers across six countries, who responded and accepted to participate in the study. Due to the variability in time-to-event reporting across different centers, survival and relapse-related outcomes were analyzed descriptively. Continuous variables were summarized using medians and ranges, and categorical variables were described by counts and percentages. The association between individual baseline variables and patient survival, was conducted using a univariate analysis utilizing the chi-square test. Categorical variables such as patient and transplant characteristics were compared against survival status at last follow-up. All variables were further evaluated in the multivariate analysis. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier survival analysis. Between 2012 and 2024, a total of 673 patients received haplo-HSCT across ten centers, in six EMBMT-registered countries. Median age was 25 years, and the predominant indication for haplo-HSCT was leukemia (64.3%). Transplant was done using stem cells collected from peripheral blood in majority of cases (65.7%), and Total Body Irradiation (TBI) was utilized in 37.6% of all patient. 76.5% had malignant hematological disorders, while 23.5% had non-malignant disorders. Relapse was reported in 232 patients (34.5%) and death in 220 patients (32.7%). Of these, 88 deaths (12.8%) were attributed to disease progression. Haplo-HSCT activity increased steadily over the study period, with a marked increase in the last few years, reflecting broader regional adoption. PFS was 66% and 60% at 1- and 2- years after transplantation. Also, the 1-year and 2-year post-transplant OS was 71% and 65%, respectively. Multivariate analysis identified disease type and chronic GVHD as factors associated with improved outcomes. Despite variability across centers, outcomes were consistent with international benchmarks, underscoring the growing feasibility and therapeutic value of haplo-HSCT in the EMRO region. Haplo-HSCT is increasingly adopted across the EMRO region as the primary alternative donor HSCT modality. Our findings confirm its clinical efficacy, with outcomes comparable to international benchmarks. These results underscore the importance of continued regional collaboration and the development of personalized strategies to address challenges such as graft-versus-host disease (GVHD), disease relapse, and disparities in access to transplantation services.