Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors

Blood Adv. 2019 Jan 22;3(2):105-115. doi: 10.1182/bloodadvances.2018025643.

Abstract

Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors' median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; P = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; P = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; P =03) with CB, whereas it improved GRFS (HR, 0.515; P < .01) and decreased grades II to IV aGVHD (HR, 0.576; P < .01), extensive cGVHD (HR, 0.460; P = .02), and NRM (HR, 0.545; P = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Antilymphocyte Serum / therapeutic use*
  • Cause of Death
  • Child
  • Child, Preschool
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute / complications*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Remission Induction
  • Risk Factors
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • thymoglobulin