Cytokine release syndrome after haploidentical hematopoietic stem cell transplantation with antithymocyte globulin: risk factors analysis and poor impact on outcomes for non-remisssion patients

Abstract

Introduction: Cytokine release syndrome (CRS) is a common complication after T-replete HLA haploidentical hematopoietic cell transplantation (haplo-HCT) with PTCy. We aim to assess the incidence, severity, and impact of CRS on clinical outcomes of patients who received haplo-HCT using Beijing Protocol. Methods: This was a single-enter retrospective analysis of 286 subjects who received haplo-HCT with Antithymocyte Globulin (ATG). Results: We identified 147/268 (54.9%) patients who developed CRS, grade 1 CRS (32.5%) and grade ≥2 CRS (22.4%). Eight patients developed severe CRS. The incidence and severity of CRS did not show significant discrimination among patients who received different doses of ATG. By multivariable analysis, age and the disease status at transplantation were significantly associated with the occurrence of CRS (p =.000 and p =.021). In the univariate analysis for the severity of CRS, compared with CRS grade ≥2, patients with CRS grade 0-1 had higher 1-year overall survival (OS) (p =.009). The cumulative incidence of 100-day grades II-IV acute GVHD was 12.4%. The incidence did not show significant differences between patients with CRS or not. The devolvement of CRS is associated with worse OS, inferior disease-free survival, and higher nonrelapse mortality significantly. But the result appeared to be limited to patients in uncomplete remission status before transplantation. Discussion and Conclusions: CRS is less frequent and milder with a protocol based on ATG. CRS can potentially affect the outcomes after haplo-HCT especially for patients in an uncomplete remission. Prospective clinical trials are needed to provide an appropriate scheme for CRS prophylaxis.