αβ T Cell-Depleted Haploidentical Hematopoietic Stem Cell Transplantation without Antithymocyte Globulin in Children with Chemorefractory Acute Myelogenous Leukemia

Biol Blood Marrow Transplant. 2019 May;25(5):e179-e182. doi: 10.1016/j.bbmt.2019.01.023. Epub 2019 Jan 21.

Abstract

We evaluated the outcome of αβ T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory acute myelogenous leukemia (AML). Twenty-two patients with either primary refractory (n = 10) or relapsed refractory (n = 12) AML in active disease status received a transplant from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent myeloablative conditioning with treosulfan and thiotepa. Antithymocyte globulin was substituted with tocilizumab in all patients and also with abatacept in 10 patients. Grafts were peripheral blood stem cells engineered by αβ T cell and CD19 depletion. Post-transplantation prophylactic therapy included infusion of donor lymphocytes, composed of a CD45RA-depleted fraction with or without a hypomethylating agent. Complete remission was achieved in 21 patients (95%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 18%, and the cumulative incidence of chronic GVHD was 23%. At 2 years, transplantation-related mortality was 9%, relapse rate was 42%, event-free survival was 49%, and overall survival was 53%. Our data suggest that αβ T cell-depleted haploidentical HSCT provides a reasonable chance of long-term survival in a cohort of children with chemorefractory AML and creates a solid basis for further improvement.

Keywords: Abatacept; Chemorefractory acute myelogenous leukemia; Haploidentical; Selective αβ T cell depletion; Tocilizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Lymphocyte Depletion / methods*
  • Lymphocyte Transfusion
  • Receptors, Antigen, T-Cell, alpha-beta*
  • Salvage Therapy / methods*
  • Survival Analysis
  • Transplantation, Haploidentical
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Receptors, Antigen, T-Cell, alpha-beta