Hematopoietic stem cell boost for persistent neutropenia after CAR-T cell therapy: a GLA/DRST study.

Hematotoxicity after chimeric antigen receptor (CAR)-T cell therapy is associated with infection and death but management remains unclear. We report results of 31 patients receiving hematopoietic stem cell boost (HSCB; 30 autologous, 1 allogeneic) for either sustained severe neutropenia of grade 4 (<0.5 x109/l), sustained moderate neutropenia (less than or equal to 1.5 x109/l) and high risk of infection, or neutrophil count less than or equal to 2.0 x109/l and active infection. Median time from CAR-T cell therapy to HSCB was 43 days and median absolute neutrophil count at time of HSCB was 0.2. Median duration of neutropenia prior to HSCB was 38 days (range, 7-151). Overall neutrophil response rate (recovery or improvement) was observed in 26 patients (84%) within a median of 9 days (95% confidence interval, 7-14). Time to response was significantly associated with the duration of prior neutropenia (p=0.007). All non-responders died within the first year after HSCB. One-year overall survival for all patients was 59% and significantly different for neutropenia ≤38 days (85%) versus neutropenia >38 days prior to HSCB (44%; p=0.029). In conclusion, early or prophylactic HSCB showed quick response and improved outcomes for sustained moderate to severe neutropenia after CAR-T.