Allogeneic CD34+ hematopoietic stem cell boost for prolonged severe cytopenias following CAR T-cell therapy in B-cell acute lymphoblastic leukemia. A retrospective analysis on behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC)

Abstract Hematological toxicity is the most common long-term adverse event after CAR T-cell therapy. Severe cytopenias not resolving over time may result in life-threatening infection or bleeding and the best clinical practice to treat this persisting cytopenias after CAR-T is not well established. Eleven heavily pretreated patients with B-ALL and prolonged cytopenia after CAR-T therapy were successfully treated with an allogeneic CD34+ hematopoietic stem cell (HSC) boost. The median time from CAR T-cell infusion to donor CD34+ HSC boost was 2.8 months and median CD34+ selected dose was 4 x106/kg of recipient weight. The median time to hematological recovery in all three cell lineages was 20 days (range 12–60). One-year event free survival was significantly different for patients relapsing before 6 months post-transplantation (14.3%) vs after 6 months post-transplantation (75%). With a median follow-up after HSC boost of 12 months, overall survival (OS) at 24 months was 31.2% with a median OS of 21 months (95% CI 6.2–35.7). All causes of death were related to disease relapse. In conclusion, we confirm that allogeneic CD34+ HSC boost is an effective and safe therapeutic option that should be considered in patients with primary poor graft function persisting beyond 60–90 days after CAR-T