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

作者：Goodyear, Oliver C.; Dennis, Mike; Jilani, Nadira Y.; Loke, Justin; Siddique, Shamyla; Ryan, Gordon; Nunnick, Jane; Khanum, Rahela; Raghavan, Manoj; Cook, Mark; Snowden, John A.; Griffiths, Mike; Russell, Nigel; Yin, John; Crawley, Charles; Cook, Gordon; Vyas, Paresh; Moss, Paul; Malladi, Ram; Craddock, Charles F.^*

来源：Blood, 2012, 119(14): 3361-3369.

DOI：10.1182/blood-2011-09-377044

• VERSUS-HOST-DISEASE
• ACUTE MYELOGENOUS LEUKEMIA
• CANCER-TESTIS ANTIGENS
• LOW-DOSE AZACITIDINE
• BONE-MARROW
• ELDERLY-PATIENTS
• DNA METHYLATION
• EXPRESSION
• FOXP3
• SURVIVAL

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. The trial was registered at http://isrctn.org as #ISRCTN36825171. (Blood. 2012;119(14):3361-3369)

• 出版日期2012-4-5