DP104 | CYTOKINE RELEASE SYNDROME IN HAPLOIDENTICAL PERIPHERAL BLOOD HEMATOPOIETIC STEM CELL TRANSPLANT PREDICTS A REDUCED INCIDENCE OF RELAPSE.

Background Cytokine release syndrome (CRS) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) reflects early immune activation. While severe CRS may increase transplant-related mortality (TRM), mild to moderate CRS could enhance graft-versus-leukemia (GVL) effects. However, the long-term prognostic significance of CRS after haplo-HSCT remains unclear. Methods We retrospectively analyzed 86 patients undergoing haplo-HSCT at our center between 2008 and 2024. CRS was diagnosed and graded per ASTCT Consensus Grading, in absence of active infection. Patients were stratified according to the presence or absence of CRS within the first four days post-transplant. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), GVHD-relapse-free survival (GRFS), cumulative incidence of relapse (CIR), and TRM. Survival analyses were performed using Kaplan-Meier estimates and competing risk models; multivariate Cox regression identified independent predictors of OS. Results At one and three years, OS rates were 68% and 60% in patients who developed CRS, compared to 65% and 47% in those without CRS (p=0.05). Median OS was not reached in the CRS group, while it was 24 months in patients without CRS. In multivariate analysis, CRS independently predicted improved OS (hazard ratio [HR] 0.38; 95% CI 0.15–0.92; p=0.036), alongside transplantation in first complete remission (CR1: HR 0.36; 95% CI 0.14–0.84; p=0.023). The cumulative incidence of relapse was slightly lower in CRS patients (24% vs 30%; p=NS). Among patients transplanted beyond CR1, CRS conferred a marked advantage: one- and three-year OS rates were 60% and 54% in CRS patients versus 42% and 34% in non-CRS patients (p=0.04), with a significantly reduced CIR (18% vs 61%; p=0.04). No significant differences were observed in the incidence of acute GVHD grade II-IV (22% with CRS vs 26% without CRS) or chronic GVHD (18% vs 22%), nor in TRM rates (12% vs 15%). Conclusions Mild to moderate CRS after haplo-HSCT with PTCY appears to be associated with improved long-term survival, particularly in patients transplanted beyond CR1, without increasing GVHD or TRM risk. These findings suggest that early immune activation may contribute to a potent GVL effect. Prospective studies are warranted to better characterize the biological correlates of CRS and to refine strategies for its management.