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. 2016 Feb;22(2):385-390.
doi: 10.1016/j.bbmt.2015.09.004. Epub 2015 Sep 9.

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

Charles Craddock  1 , Nadira Jilani  2 , Shamyla Siddique  2 , Christina Yap  2 , Josephine Khan  3 , Sandeep Nagra  4 , Janice Ward  4 , Paul Ferguson  5 , Peter Hazlewood  2 , Richard Buka  4 , Paresh Vyas  6 , Oliver Goodyear  7 , Eleni Tholouli  8 , Charles Crawley  9 , Nigel Russell  10 , Jenny Byrne  10 , Ram Malladi  5 , John Snowden  11 , Mike Dennis  12
Affiliations

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

Charles Craddock et al. Biol Blood Marrow Transplant. 2016 Feb.

Abstract

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 and appears to have the capacity to reduce the relapse risk in patients who demonstrate a CD8(+) T cell response to tumor antigens. These observations require confirmation in a prospective clinical trial.

Keywords: Acute myeloid leukemia; Azacitidine; Relapse; Tumor antigens.

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Figures

None
Graphical abstract
Figure 1
Figure 1
RFS of patients according to post-transplantation CD8+ T cell response to tumor antigens.
See this image and copyright information in PMC

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