Control of graft-versus-host disease with rabbit anti-thymocyte globulin, rituximab, and bortezomib in TCRαβ/CD19-depleted graft transplantation for leukemia in children: a single-center retrospective analysis of two GVHD-prophylaxis regimens

Pediatr Transplant. 2020 Feb;24(1):e13594. doi: 10.1111/petr.13594. Epub 2019 Nov 3.

Abstract

Both acute GVHD and chronic GVHD remain the leading cause of morbidity and death after allogeneic HSCT. We conducted a retrospective analysis comparing two GVHD-prophylaxis regimens: 35 patients received "Regimen 1" (horse ATG, tacrolimus, and methotrexate) and 46 "Regimen 2" (rabbit ATG, rituximab, and peritransplant bortezomib). All 81 patients with a median age of 9 (0.6-23) years with ALL (n = 31) or AML (n = 50) in complete remission received TCRαβ/CD19-depleted transplants between May 2012 and October 2016, from 40 HLA-matched unrelated and 41 haploidentical donors. After a median follow-up of 3.9 years, the CI of acute GVHD II-IV was 15% (95% CI: 7-30) in the "Regimen 2" group and 34% (95% CI: -54) in the "Regimen 1" group, P = .05. "Regimen 2" was also more effective in the prevention of chronic GVHD; the CI at 1 year after HSCT was 7% (95% CI: 2-19) vs 31% (95% CI: 19-51), P = .005. The CI of relapse at 3 years adjusted for the GVHD-prophylaxis regimen groups 31% (95% CI: 19-51) for the "Regimen 1" vs 21% (95% CI: 11-37) for the "Regimen 2", P = .3. The retrospective observation suggests that the use of the rATG, rituximab, and bortezomib was associated with significantly lower rate of GVHD without the loss of anti-leukemic activity.

Keywords: TCRαβ depletion; acute lymphoblastic leukemia; acute myeloblastic leukemia; allogeneic HSCT; anti-thymocyte globulin; bortezomib; pediatric.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adolescent
  • Antigens, CD19
  • Antilymphocyte Serum / therapeutic use*
  • Bortezomib / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Leukemia / immunology
  • Leukemia / therapy*
  • Male
  • Receptors, Antigen, T-Cell, alpha-beta
  • Retrospective Studies
  • Rituximab / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD19
  • Antilymphocyte Serum
  • CD19 molecule, human
  • Immunosuppressive Agents
  • Receptors, Antigen, T-Cell, alpha-beta
  • Rituximab
  • Bortezomib
  • thymoglobulin