Donor CD7 Chimeric Antigen Receptor T Cell Bridging to Allogeneic Hematopoietic Stem Cell Transplantation for T Cell Hematologic Malignancy

Transplant Cell Ther. 2023 Mar;29(3):167-173. doi: 10.1016/j.jtct.2022.11.013. Epub 2022 Nov 24.

Abstract

It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution. Here we report on the efficacy and safety of donor CD7 chimeric antigen receptor (CAR) T cell therapy (CAR-T) bridging to allo-HSCT in treating 12 patients with relapsed/refractory (r/r) T-ALL or T-cell lymphoblastic lymphoma (T-LBL). The median time from CAR-T infusion to allo-HSCT was 33.5 days (range, 30 to 55 days). With reduced-intensity conditioning, all patients except 1 successfully engrafted. With a mean follow-up of 301 days (range, 238 to 351 days), the remaining 11 patients were alive and disease-free at their last follow-up. Acute graft-versus-host disease (GVHD) was observed in 3 patients, and chronic GVHD developed in 3 patients, all with a limited pattern. Under the current protocol, infection was the main complication post-transplantation, and all infections were well controlled except in 1 patient, who died of multiple organ failure caused by an infection-induced inflammatory cytokine storm at days 14 post-transplantation. One patient relapsed (CD7+), and 3 patients became minimal residual disease (MRD) positive (CD7+ in 1, CD7- in 1, fusion gene positive only in 1). Subsequently, all 3 of these patients achieved an MRD-negative complete remission with either CD7 CAR-T reinfusion or immunosuppressive agent withdrawal. Our study shows for the first time that a novel strategy of donor CD7 CAR-T bridging to allo-HSCT can be highly effective and feasible in improving disease-free survival for patients with r/r T-ALL or T-LBL.

Keywords: Allogeneic hematopoietic stem cell transplantation; Chimeric antigen receptor T cell therapy; Disease-free survival; Overall survival; T cell acute lymphocytic leukemia; T cell lymphoblastic lymphoma.

MeSH terms

  • Antigens, CD7
  • Graft vs Host Disease* / therapy
  • Hematologic Neoplasms*
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / etiology
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes

Substances

  • Receptors, Chimeric Antigen
  • Antigens, CD7