CT-169 Cytokine Release Syndrome After Peripheral Blood Haploidentical Stem Cell Transplantation With Post-Transplant Cyclophosphamide: Time of Onset Matters

Abstract

The use of post-transplant cyclophosphamide (PT-Cy) has favored haploidentical hematopoietic stem cell transplantation (haplo-HSCT) when an HLA-matched donor is not available or when an urgent transplant is needed. Although a high percentage of patients receiving PT-Cy haplo-HSCT develop cytokine release syndrome (CRS) after infusion, it only seems to affect prognosis in the reduced proportion of patients that develop severe CRS. Literature regarding the clinical impact of this complication is scarce. The aim of our study is to analyze new CRS characteristics and their prognostic implication on both transplant-related mortality (TRM) and overall survival (OS). From the cohort of 637 patients who underwent allo-HSCT at our center between January 2012 and December 2020, 150 patients who received PT-Cy haplo-TPH were selected for this retrospective analysis. Regarding CRS analysis, 16 patients were excluded due to the impossibility to distinguish between infectious and CRS fever. Median follow-up was 18 months (37 months for alive patients). Most patients (86%) developed CRS. The cohort was divided into two groups: patients who developed early-onset CRS (≤24h after infusion, 50%) and those with late-onset CRS or no CRS. Patients who developed early-onset CRS had a significant increase in first-year TRM (31% vs 15%, log-rank p=0.014) as well as lower first-year OS (60% vs 79%, log-rank p=0.008). Multivariate analysis of first-year TRM identified the following independent prognostic factors: SOS (HR 9.24, p<0.001), aGvHD grade ≥3 (HR 6.89, p<0.001), early-onset CRS (HR 3.09, p=0.007) and patient age at transplantation (HR 1.05 per year increment, p=0.002). Several risk factors were associated with developing early-onset CRS in a multivariate analysis: modified Baltimore haplo-HSCT platform (HR 7.54, p<0.001), active disease at transplantation (HR 2.94, p=0.015) and increased infused CD3+ cells (HR 1.05 per 107/kg increment, p=0.002). Graft-cryopreservation would be a protective factor (HR 0.14, p=0.005). We propose the definition of early-onset CRS as the one that is developed within 24h after haplo-HSCT infusion. Patients who develop early-onset CRS have a higher TRM and lower OS. However, this is a single-center retrospective study and further studies will be required in order to confirm these findings.