Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial

作者：Charles Craddock, Nadira Jilani, Shamyla Siddique, Christina Yap, Josephine Khan, Sandeep Nagra, Janice Ward, Paul Ferguson, Peter Hazlewood, Richard J. Buka, Paresh Vyas, Oliver Goodyear, Eleni Tholouli, Charles Crawley, Nigel H. Russell, Jenny Byrne, Ram Malladi, John A. Snowden, Mike Dennis · 发表于：Transplantation and Cellular Therapy · 年份：2015 · DOI：10.1016/j.bbmt.2015.09.004 · 被引用次数：174 · 研究领域：Acute Myeloid Leukemia Research、Hematopoietic Stem Cell Transplantation、Immune Cell Function and Interaction

Disease relapse is the major causes of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute myeloid leukemia (AML). As well as demonstrating significant clinical activity in AML, azacitidine (AZA) upregulates putative tumor antigens, inducing a CD8(+) T cell response with the potential to augment a graft-versus-leukemia effect. We, therefore, studied the feasibility and clinical sequelae of the administration of AZA during the first year after transplantation in 51 patients with AML undergoing allogeneic SCT. Fourteen patients did not commence AZA either because of transplantation complications or withdrawal of consent. Thirty-seven patients commenced AZA at a median of 54 days (range, 40 to 194 days) after transplantation, which was well tolerated in the majority of patients. Thirty-one patients completed 3 or more cycles of AZA. Sixteen patients relapsed at a median time of 8 months after transplantation. No patient developed extensive chronic graft-versus-host disease. The induction of a post-transplantation CD8(+) T cell response to 1 or more tumor-specific peptides was studied in 28 patients. Induction of a CD8(+) T cell response was associated with a reduced risk of disease relapse (hazard ratio [HR], .30; 95% confidence interval [CI], .10 to .85; P = .02) and improved relapse-free survival (HR, .29; 95% CI, .10 to .83; P = .02) taking into account death as a competing risk. In conclusion, AZA is well tolerated after transplantation ...