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Clonal evolution detected with conventional cytogenetic analysis is a potent prognostic factor in adult patients with relapsed AML
Authors:Hiroaki Shimizu  Akihiko Yokohama  Takuma Ishizaki  Nahoko Hatsumi  Satoru Takada  Takayuki Saitoh  Toru Sakura  Yoshihisa Nojima  Hiroshi Handa
Institution:1. Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan;2. Division of Blood Transfusion Service, Faculty of Medicine, Gunma University Hospital, Maebashi, Gunma, Japan;3. Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan;4. Gunma University School of Health Sciences, Faculty of Medicine, Gunma University, Maebashi, Gunma, Japan
Abstract:We retrospectively investigated 144 patients with relapsed acute myeloid leukemia (AML) to clarify predisposing factors and the prognostic impact of acquisition of additional cytogenetic abnormalities (ACA) at the first relapse. Additional cytogenetic abnormalities are recognized as clonal evolution at the cytogenetic level. Fifty‐nine patients (41%) acquired ACA at the first relapse. The incidences of ACA acquisition varied depending on cytogenetic abnormalities at initial diagnosis. Multivariate analysis identified t(8;21), complex karyotype, and a duration of fewer than 12 months of complete remission as independent predisposing factors for ACA acquisition. Notably, patients with ACA acquisition showed a significantly lower second complete remission rate compared with those without ACA acquisition (20.0% vs 72.5%, respectively, P < .001). Furthermore, the 3‐year overall survival rates after the first relapse were significantly different between patients with and without ACA acquisition (8.5% vs 36.8%, respectively, P < .001). This prognostic significance was confirmed with multivariate analysis. The hazard ratio of ACA acquisition was similar or higher than reported prognostic factors for relapsed AML patients. These findings suggested that clonal evolution detected with conventional cytogenetic analysis at the first relapse induces severe chemo‐refractory characteristics in AML cells and should be considered as a potent prognostic factor when evaluating accurate prognosis in relapsed AML patients.
Keywords:acute myeloid leukemia  clonal evolution  cytogenetic abnormality  relapse  t(8  21)
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