Impact of Early Cyclosporine on Cytokine Release Syndrome and Outcomes in Pediatric Haploidentical Hematopoietic Stem Cell Transplantation.

BACKGROUND

Cytokine release syndrome (CRS) is a frequent early complication of T cell-replete peripheral blood haploidentical hematopoietic stem cell transplantation (PB-haploHSCT), particularly in pediatric recipients. Post-transplant cyclophosphamide (PTCy) is the standard for graft-versus-host disease (GVHD) prophylaxis, but the role of early cyclosporine initiation in this setting remains underexplored.

METHODS

We retrospectively analyzed 50 pediatric patients with hematolymphoid malignancies who underwent PB-haploHSCT with uniform myeloablative conditioning between 2017 and 2024. GVHD prophylaxis included PTCy and cyclosporine initiated on Day -2. CRS was graded according to ASTCT criteria. Survival and relapse outcomes were estimated using Kaplan-Meier and competing risk analyses.

RESULTS

At a median follow-up of 28 months, 68% of patients developed only Grade I CRS, with no cases of Grade ≥ II. The 2-year overall survival (OS), relapse-free survival (RFS), and GVHD-free, relapse-free survival (GRFS) were 72.1%, 65.5%, and 55.4%, respectively. The 2-year transplant-related mortality (TRM) was 6.0%. The cumulative incidence of grade III-IV acute GVHD was 14.1%, while moderate-to-severe chronic GVHD occurred in 6.8%. Although CRS was not associated with inferior survival, it was linked to a lower relapse incidence.

CONCLUSION

Early cyclosporine initiation before PTCy in pediatric PB-haploHSCT appears feasible and may attenuate CRS without increasing GVHD or relapse risk. These findings support further prospective studies to validate early calcineurin inhibitor strategies in pediatric transplant protocols.