Donor Hematopoietic Stem Cell/Lymphocyte Maintenance Treatment After CAR T-Cell Therapy in Patients With B-Cell Acute Lymphoblastic Leukemia Relapse Following Stem Cell Transplant

Cell Transplant. 2023 Jan-Dec:32:9636897231158155. doi: 10.1177/09636897231158155.

Abstract

Maintaining the efficacy of anti-CD19 chimeric antigen receptor modified (CAR) T-cell therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT) is an urgent problem. In this study, we aimed to compare the efficacy of donor hematopoietic stem cell infusion (DSI) therapy and donor lymphocyte infusion (DLI) therapy as a maintenance therapy after R/R B-ALL patients achieved CR in anti-CD19-CAR T-cell therapy but relapsed after allo-HSCT. In total, 22 B-ALL patients who relapsed after allo-HSCT received anti-CD19-CAR T-cell therapy. Patients who responded to CAR T-cell therapy received DSI or DLI as maintenance therapy. We compared the clinical responses, acute graft versus host disease (aGVHD), expansion of CAR-T-cells, and adverse events between the two groups. In our study, 19 patients received DSI/DLI as maintenance therapy. After DSI/DLI therapy, progression-free survival and overall survival were higher in the DSI group than in the DLI group at 365 days. The grades I and II of aGVHD was observed in four patients (36.4%) in the DSI group. Only one patient developed grade II aGVHD in the DLI group. The peaks of CAR T-cells in the DSI group were higher than those in the DLI group. IL-6 and TNF-α levels increased again in nine of 11 patients after DSI but not in the DLI group. Our findings indicate that for B-ALL patients who relapse after allo-HSCT, DSI is a feasible maintenance therapy if CR is obtained with CAR-T-cell therapy.

Keywords: B-cell acute lymphoblastic leukemia; acute graft versus host disease; donor hematopoietic stem cell infusion; donor lymphocyte infusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Burkitt Lymphoma*
  • Chronic Disease
  • Graft vs Host Disease* / therapy
  • Hematopoietic Stem Cells
  • Humans
  • Immunotherapy, Adoptive
  • Lymphocytes
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Receptors, Chimeric Antigen*
  • Stem Cell Transplantation

Substances

  • Receptors, Chimeric Antigen
  • Adaptor Proteins, Signal Transducing