Abstract:Therapeutic options in B-acute lymphoblastic leukemia (ALL) relapses after anti-CD19 CAR-T cells are still debated. Here, we analysed leukemic cells of a young patient who had several CD19 relapses of B-ALL after hematopoietic stem cells transplant (HSCT) and after anti-CD19 CAR-T cells (tisagenlecleucel). Extensive membrane immunophenotype revealed the appearance of new targets. Lysis sensibility analysis performed by Cr release and long term killing assays revealed the in vitro persistence of sensitivity to cytolytic activity of CAR-T cells. An immunosuppressive monocytic population was identified in the last relapse sample. Mechanisms leading to ALL resistance are analysed and therapeutic options are discussed.