Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)

Blood. 2012 Apr 5;119(14):3361-9. doi: 10.1182/blood-2011-09-377044. Epub 2012 Jan 10.


Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects
  • Azacitidine / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • Epitopes / immunology
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / therapy
  • Lymphocyte Count
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Transplantation, Homologous


  • Antigens, Neoplasm
  • Antimetabolites, Antineoplastic
  • Cytokines
  • Epitopes
  • Lysosomal-Associated Membrane Protein 1
  • Azacitidine

Associated data

  • ISRCTN/ISRCTN36825171