Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation

Br J Haematol. 2017 Nov;179(4):598-605. doi: 10.1111/bjh.14923. Epub 2017 Oct 26.

Abstract

Relapse is a common cause of failure in patients with B-cell acute lymphoblastic leukaemia (B-ALL) after haploidentical haematopoietic stem cell transplantation (haplo-HSCT), and non-responders to donor lymphoblastic infusion after HSCT have a very poor prognosis. Although donor-derived CD19-directed chimeric antigen receptor-modified (CAR) T cells can potentially cure leukaemia, their effectiveness and safety have not been confirmed in relapsed B-ALL cases after haplo-HSCT. Between January 2015 and January 2017, two and four patients each received one and two infusions of CAR T cells from haplo-HSCT donors. Five (83·33%) achieved minimal residual disease (MRD)-negative remission; one patient was discharged automatically without evaluation after developing severe thrombotic microangiopathies. Four of five responsive patients relapsed after 2-7 months, and one died of sepsis following MRD-negative remission after a second infusion. None of the other second infusion recipients achieved a second complete remission. Five patients (83·33%) experienced eight courses of grade 1-3 cytokine release syndrome; two were treated with tocilizumab. Two (33·3%) and one patient developed grade 2 and 3 acute graft-versus-host disease (aGVHD), respectively; the former was controlled with glucocorticoids. Donor-derived CAR T-cell infusion seems be effective and safe for relapsed B-ALL after haplo-HSCT, although larger clinical studies are needed.

Keywords: B acute lymphoblastic leukaemia; donor lymphocyte infusions; donor-derived CD19-targeted T-cell infusion; haploidentical haematopoietic stem cell transplantation; relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD19 / immunology*
  • Child
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • Haplotypes
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Male
  • Neoplasm, Residual
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Remission Induction / methods
  • Salvage Therapy / methods
  • T-Lymphocytes / transplantation
  • Treatment Outcome
  • Young Adult

Substances

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