Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party

J Hematol Oncol. 2017 Jan 24;10(1):31. doi: 10.1186/s13045-016-0389-4.

Abstract

Background: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored.

Methods: We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.

Results: Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p = 4 × 10-5). Recipient age above 50 years was the only other factor associated with worse survivals.

Conclusions: These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk.

Keywords: Acute myeloid leukemia; Allogeneic stem cell transplantation; GRFS; Graft-versus-host disease; HLA-matched related donor; In vivo T cell depletion; Relapse incidence.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antilymphocyte Serum / therapeutic use
  • Busulfan / therapeutic use
  • Female
  • Graft vs Host Disease / prevention & control
  • HLA Antigens*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Histocompatibility / immunology
  • Humans
  • Leukemia, Myeloid, Acute / therapy*
  • Leukocyte Reduction Procedures
  • Lymphocyte Depletion*
  • Male
  • Middle Aged
  • Myeloablative Agonists / therapeutic use
  • Retrospective Studies
  • T-Lymphocytes
  • Transplantation Conditioning / methods
  • Treatment Outcome
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Antilymphocyte Serum
  • HLA Antigens
  • Myeloablative Agonists
  • Vidarabine
  • Busulfan
  • fludarabine