Safety of allogeneic hematopoietic cell transplant in adults after CD19-targeted CAR T-cell therapy

Blood Adv. 2019 Oct 22;3(20):3062-3069. doi: 10.1182/bloodadvances.2019000593.

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is offered to selected patients after chimeric antigen receptor-modified T-cell (CAR-T) therapy. Lymphodepleting chemotherapy and CAR-T therapy have immunosuppressive and immunomodulatory effects that could alter the safety profile of subsequent allo-HCT. We reviewed our experience with 32 adults (acute lymphoblastic leukemia [ALL], n = 19; B-cell non-Hodgkin lymphoma [NHL]/chronic lymphocytic leukemia [CLL], n = 13) who received an allo-HCT after CAR-T therapy, with a focus on posttransplant toxicities. Myeloablative conditioning (MAC) was used in 74% of ALL patients and 39% of NHL/CLL patients. The median time from CAR-T therapy to allo-HCT was 72 days in ALL patients and 122 days in NHL/CLL patients. Cumulative incidences of grade 3-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 25% and 10%, respectively. All patients had neutrophil recovery (median, 18.5 days) and all but 3 had platelet recovery (median, 12 days). Twenty-two percent had viral or systemic fungal infection within 100 days after allo-HCT. The 100-day and 1-year cumulative incidences of NRM were 16% and 21%, respectively, for ALL patients and 15% and 33%, respectively, for NHL/CLL patients. In ALL patients, later utilization of allo-HCT after CAR-T therapy was associated with higher mortality. In NHL/CLL patients, MAC was associated with higher mortality. Toxicities did not exceed the expected incidences in this high-risk population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / immunology*
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen