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

Research output: Contribution to journalArticle

Authors

  • M Dennis
  • NY Jilani
  • J Loke
  • S Siddique
  • Jane Nunnick
  • R Khanum
  • M Cook
  • JA Snowden
  • Michael Griffiths
  • N Russell
  • J Yin
  • C Crawley
  • G Cook
  • P Vyas
  • Charles Craddock

Abstract

Strategies which augment a graft-versus-leukemia (GVL) effect without increasing the risk of graft-versus-host disease (GVHD) are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor antigens on leukemic blasts in vitro and expands immunomodulatory T regulatory cell (Treg) numbers in animal models. Reasoning that AZA might selectively augment a GVL effect we studied the immunological sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplant for Acute Myeloid Leukemia (AML) were treated with monthly courses of AZA and CD8+ T cell responses to candidate tumor antigens and circulating Tregs measured. Post-transplant AZA 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 post transplant compared with a control population (p=0.0127). AZA administration also induced a cytotoxic CD8+ T cell response to a number of tumor antigens including MAGE, BAGE and Wilm's Tumor antigen 1 (WT-1). These data support the further examination of post-transplant AZA as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD. The trial was registered at http://isrctn.org as #ISRCTN36825171.

Details

Original languageEnglish
Pages (from-to)3361-3369
Number of pages9
JournalBlood
Volume119
Issue number14
Publication statusPublished - 10 Jan 2012