Haploidentical Hematopoietic Stem Cell Transplantation in Pediatric Transfusion-Dependent Thalassemia: A Systematic Review and Meta-Analysis

Abstract

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) presents a promising therapeutic option for pediatric transfusion-dependent thalassemia, particularly in the scarcity of matched donors. Despite its potential, the comprehensive evaluation of this method through large-scale prospective studies remains lacking. This study aims to systematically summarize the efficacy and safety of haplo-HSCT in thalassemia, thereby providing further evidence-based insights for clinical practice. A comprehensive literature search was conducted across PubMed, Embase, and Web of Science databases through June 2024 to ensure a robust analysis of the available evidence. Data extraction was independently performed by 2 reviewers. The analysis utilized the inverse variance method with a 95% confidence interval (95% CI) to calculate the pooled proportion. To assess the heterogeneity among the studies, Cochran's Q test and Higgins' I-squared statistical methods were utilized. A random-effects model was employed to accommodate the variability between study results. Furthermore, subgroup analyses were explored differences in outcomes based on conditioning regimens and graft versus host disease (GVHD) prophylaxis. Conditioning regimens were categorized into reduced-intensity conditioning and myeloablative conditioning regimens. GVHD prophylaxis was classified into post-transplantation cyclophosphamide and non-post-transplantation cyclophosphamide. In this meta-analysis, we reviewed data from 10 studies encompassing 356 patients with thalassemia who underwent haplo-HSCT. Out of these, 328 patients survived until the follow-up date, resulting in a pooled overall survival rate of 92.4% (95% CI, 86.9-96.7; I² = 54.32%). The thalassemia-free survival was 84.5% (95% CI, 75.3-91.9; I² = 77.64%), and the graft failure rate was 8.1% (95% CI, 2.5-16.4; I² = 81.78%). The transplantation-related mortality stood at 7.4% (95% CI, 3.6-12.5; I² = 55.74%), with infections noted as the primary cause of death. The pooled proportion of acute graft versus host disease (aGVHD), grade 2-4 aGVHD, and grade 3-4 aGVHD were 29.6% (95% CI, 16.7-42.5, I² = 92.48%), 22.3% (95% CI, 10.1-42.1, I² = 80.06%), and 9.1% (95% CI, 2.8-17.7, I² = 67.92%), respectively. Subgroup analyses revealed no significant differences in these outcomes when comparing myeloablative conditioning to reduced-intensity conditioning, or post-transplantation cyclophosphamide to non-post-transplantation cyclophosphamide prophylaxis. However, variations in sample size, patient's age and geographic region among the studies suggest these factors as potential sources of heterogeneity.

Haploidentical hematopoietic stem cell transplantation utilizes donors who are partially HLA-matched, typically family members, making it a viable option for transfusion-dependent thalassemia when fully matched donors are not available.