Impact of Thymoglobulin by Stem Cell Source (Peripheral Blood Stem Cell or Bone Marrow) After Myeloablative Stem Cell Transplantation From HLA 10/10-Matched Unrelated Donors: A Report From the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Transplantation. 2016 Aug;100(8):1732-9. doi: 10.1097/TP.0000000000000976.

Abstract

Background: The impact of antithymocyte globulin (ATG) in the setting of a myeloablative conditioning transplantation remains controversial, especially when using bone marrow (BM) as the stem cell source.

Methods: We therefore conducted a retrospective analysis to investigate the impact of ATG in patients with acute myeloid leukemia or myelodysplastic syndrome receiving myeloablative conditioning followed by a matched 10 of 10 unrelated donor transplant from BM or peripheral blood stem cells (PBSCs). Our study included 356 patients conditioned with cyclophosphamide associated with fractionated total body irradiation or busulfan.

Results: Median follow-up was 17.6 months (range, 0-156). The ATG and PBSCs were the only variables that independently decreased the cumulative incidence (CI) of chronic graft-versus-host disease (GvHD) (hazards ratio [HR], 0.4; 95% CI, 0.21-0.73; P < 0.01; and HR, 0.53; 95% CI, 0.30-0.90; P = 0.02, respectively). The ATG had no impact on overall survival, disease-free survival, relapse, and nonrelapse mortality. In the PBSC group (n = 139), ATG was associated with a lower CI of both grades III to IV acute GvHD (HR, 0.17; 95% CI, 0.03-0.91; P = 0.04), chronic GvHD (HR, 0.31; 95% CI, 0.11-0.87; P = 0.03), and GvHD-free/relapse-free survival (HR, 0.48; 95% CI, 0.29-0.80; P < 0.01), whereas these correlations were not significant in the group of patients (n = 217) receiving BM (HR, 0.36; 95% CI, 0.11-1.93; P = 0.06 for grade III-IV acute GvHD; HR, 0.49; 95% CI, 0.22-1.06; P = 0.08 for chronic GvHD; and HR, 0.69; 95% CI, 0.46-1.01; P = 0.06 for GvHD-free/relapse-free survival).

Conclusions: Although our results confirm the recommendation for ATG to be added after PBSC transplantation, no obvious benefit was identified using this approach in the setting of BM transplantation. Only prospective studies may yield definitive answers to this question.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Antilymphocyte Serum / adverse effects
  • Antilymphocyte Serum / therapeutic use*
  • Bone Marrow Transplantation* / methods
  • Bone Marrow Transplantation* / mortality
  • Busulfan / therapeutic use
  • Chi-Square Distribution
  • Chronic Disease
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • France
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • HLA Antigens / immunology*
  • Histocompatibility
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / surgery*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myeloablative Agonists / therapeutic use
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / surgery*
  • Peripheral Blood Stem Cell Transplantation* / adverse effects
  • Peripheral Blood Stem Cell Transplantation* / methods
  • Peripheral Blood Stem Cell Transplantation* / mortality
  • Proportional Hazards Models
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / mortality
  • Treatment Outcome
  • Unrelated Donors*
  • Whole-Body Irradiation
  • Young Adult

Substances

  • Antilymphocyte Serum
  • HLA Antigens
  • Immunosuppressive Agents
  • Myeloablative Agonists
  • Cyclophosphamide
  • thymoglobulin
  • Busulfan