Safety and feasibility of stem cell boost as a salvage therapy for severe hematotoxicity after CD19 CAR T-cell therapy

CD19 CAR T-cells represent a practice-changing treatment modality for advanced B-cell malignancies. However, refractory cytopenias have emerged as a potentially life-threatening complication that can persist long after lymphodepleting chemotherapy. Whether stem cell rescue is feasible and efficacious after CAR-T has not been addressed. In this retrospective multi-center study, we describe clinical characteristics and outcomes of 13 patients with hyporegenerative bone marrow (BM) failure after CD19 CAR-T, which received a previously collected stem cell graft (10 autologous, 3 allogeneic) to rescue cytopenias. Interestingly, patients already presented with impaired hematopoietic function and high levels of systemic inflammation prior to lymphodepleting chemotherapy, as reflected by high CAR-HEMATOTOX scores (median 4). The median duration of severe neutropenia prior to stem cell boost was 41 days (interquartile range 16-50). The indication for boost was severe pancytopenia (aplasia) in 7 cases and persistent isolated neutropenia/thrombocytopenia in 6 cases. Median day of stem cell boost was day 55 after CAR-T (median 3.1x106/kg CD34+ cells). Engraftment rates were high (neutrophil: 92%, platelet: 70%), with a median time to neutrophil- and platelet engraftment of 15 and 21 days, respectively. Two patients died of invasive fungal infections (day 4 and 17 after stem cell boost). The 1-year progression-free (PFS) and overall survival (OS) rates were 42% and 51%, respectively. These data indicate that the transplantation of available stem cell products for post-CAR-T cytopenias is clinically feasible, safe and efficacious. Further studies are needed to assess, whether a pre-emptive collection of stem cells can be justified in selected high-risk patients.