TCR-αβ/CD 19 Depleted Graft Versus T Replete Graft With Post-Transplant Cyclophosphamide in Children Undergoing Haploidentical Donor Hematopoietic Stem Cell Transplantation for Inborn Errors of Immunity: A Comparative Analysis From India.

Abstract

Background: The study aimed to analyze the outcomes of TCRαβ/CD19-depleted and T-replete graft with post-transplant cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplantation (HSCT) in inborn errors of immunity (IEI).

Patients and methods: We performed a retrospective analysis of children from birth to 18 years of age with IEI who underwent haploidentical HSCT between April 2009 and September 2024, with a minimum follow-up period of 12 months.

Results: A total of 230 children with IEI underwent HSCT in the 15-year period, where 105 (45%) underwent haploidentical HSCT and were included in the analysis with a follow up period of 0.5 to 170 months. TCR-αβ/CD19-depleted HSCT was done in 65 (62%) children, while T-replete graft with PTCY was used in 40 (38%) children. There was no significant difference in engraftment rates, acute and chronic graft versus host disease rates between both the cohorts: T-depleted group-89%, 8.6%, 12% respectively versus T-replete group-85%, 15%, 17.5% respectively. The 5-year overall survival was 62% (95% CI: 48%-73%) in the TCR-αβ/CD 19-depleted cohort in comparison to 54% (95% CI: 48% to 73%) in the PTCY cohort. When the survival was compared in children less than 2 years of age, it was 60% in the TCR-αβ/CD 19 depleted cohort versus 37% in PTCY cohort (p value of 0.001).

Conclusion: Survival was superior in the T depleted cohort as compared to the T replete group, with viral reactivation remaining a persisting challenge. Letermovir prophylaxis and memory cell add-back would be potential strategies to improve survival.