The Role of Low-dose Anti-thymocyte Globulin as Standard Prophylaxis in Mismatched and Matched Unrelated Hematopoietic Peripheral Stem Cell Transplantation for Hematologic Malignancies

Clin Lymphoma Myeloma Leuk. 2017 Oct;17(10):658-666. doi: 10.1016/j.clml.2017.06.008. Epub 2017 Jun 29.

Abstract

Introduction: Anti-thymocyte globulin (ATG)-based immunosuppressive therapy is often used in allogeneic hematopoietic cell transplantation to reduce incidence and severity of graft-versus-host disease (GVHD).

Patients and methods: In our observational study, ATG (rabbit, Thymoglobulin; Sanofi, 5 mg/kg) was administered as a standardized part of the conditioning in 97 patients with a median age of 34 years (range, 14-58 years), allotransplanted for hematologic malignancies from matched (8/8; n = 52) and allele or antigen mismatched (7/8; n = 43 and 6/8; n = 2) unrelated donors.

Results: Five-year overall survival (OS) was 46.9%, disease-free survival was 46.5%, and treatment-related mortality was 20.6%, with a median follow-up of 29 months (range, 1-145 months). Acute GVHD (grade ≥ II) cumulative incidence was 26.9% in matched versus 50.5% in mismatched patients (P = .060), whereas extensive chronic GVHD was 45.6% versus 50%, respectively (P = .310). Five-year OS was 62.2% for the matched patients and 27.9% for the mismatched patients (P = .003) owing to a higher treatment-related mortality rate in mismatched patients (P = .032). In multivariate analysis including age, gender, time until transplantation, disease phase, mismatched donor, ABO mismatch, number of CD34+ infused, acute and chronic GVHD, the significant unfavorable factors for OS were HLA mismatch and advanced disease phase.

Conclusion: A relatively low-dose ATG is effective in acute GVHD prophylaxis, leading to promising survival rates in matched transplants. Further comparative studies with adjusted ATG dose depending on Human leukocyte antigen disparity or alternative donors are warranted.

Keywords: Anti-thymocyte globulin; Graft-versus-host disease; HLA disparity; Hematologic malignancies; Survival; Unrelated hematopoietic cell transplantation.

MeSH terms

  • Adult
  • Antilymphocyte Serum / administration & dosage*
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Infections / etiology
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Odds Ratio
  • Peripheral Blood Stem Cell Transplantation* / adverse effects
  • Recurrence
  • Retrospective Studies
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors*
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • thymoglobulin