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dc.contributor.authorCraddock, C
dc.contributor.authorJilani, N
dc.contributor.authorSiddique, S
dc.contributor.authorYap, C
dc.contributor.authorKhan, J
dc.contributor.authorNagra, S
dc.contributor.authorWard, J
dc.contributor.authorFerguson, P
dc.contributor.authorHazlewood, P
dc.contributor.authorBuka, R
dc.contributor.authorVyas, P
dc.contributor.authorGoodyear, O
dc.contributor.authorTholouli, E
dc.contributor.authorCrawley, C
dc.contributor.authorRussell, N
dc.contributor.authorByrne, J
dc.contributor.authorMalladi, R
dc.contributor.authorSnowden, J
dc.contributor.authorDennis, Michael
dc.date.accessioned2015-10-26T10:44:14Zen
dc.date.available2015-10-26T10:44:14Zen
dc.date.issued2015-09-09en
dc.identifier.citationTolerability and clinical activity of post-transplantation Azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA trial. 2015: Biol Blood Marrow Transplanten
dc.identifier.issn1523-6536en
dc.identifier.pmid26363443en
dc.identifier.doi10.1016/j.bbmt.2015.09.004en
dc.identifier.urihttp://hdl.handle.net/10541/581083en
dc.description.abstractDisease 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.
dc.languageENGen
dc.language.isoenen
dc.rightsArchived with thanks to Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantationen
dc.titleTolerability and clinical activity of post-transplantation Azacitidine in patients allografted for acute myeloid leukemia treated on the RICAZA trial.en
dc.typeArticleen
dc.contributor.departmentCentre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UKen
dc.identifier.journalBiology of Blood and Marrow Transplantationen
html.description.abstractDisease 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.


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