Yazarlar : Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G, Nunnick J, Khanum R, Raghavan M, Cook M, Snowden JA, Griffiths M, Russell N, Yin J, Crawley C, Cook G, Vyas P, Moss P, Malladi R, Craddock CF.

Yayın : Blood

Yayın Yılı : 2012

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22234690

Konu : Lösemi

Literatür İçeriği :  

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 intensityallogeneic 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.

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