Journal
BLOOD
Volume 119, Issue 14, Pages 3361-3369Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-09-377044
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Funding
- Cancer Research UK Experimental Cancer Medicine Centre (ECMC) Network
- Central England Haemato-oncology Research Biobank
- Leukaemia and Lymphoma Research
- QE Hospital
- Cure Leukaemia
- National Institute for Health Research (NIHR)
- Celgene
- Medical Research Council [G1000801c] Funding Source: researchfish
- National Institute for Health Research [ACF-2010-09-005] Funding Source: researchfish
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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. The trial was registered at http://isrctn.org as #ISRCTN36825171. (Blood. 2012;119(14):3361-3369)
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