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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.

Original publication

DOI

10.1182/blood-2011-09-377044

Type

Journal article

Journal

Blood

Publication Date

05/04/2012

Volume

119

Pages

3361 - 3369

Keywords

Adult, Aged, Antigens, Neoplasm, Antimetabolites, Antineoplastic, Azacitidine, CD8-Positive T-Lymphocytes, Cytokines, Epitopes, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute, Lymphocyte Count, Lysosomal-Associated Membrane Protein 1, Male, Middle Aged, T-Lymphocytes, Regulatory, Transplantation, Homologous