title: Clonal evolution detected with conventional cytogenetic analysis is a potent prognostic factor in adult patients with relapsed AML.
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.
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Hiroaki
authors.identifier: http://orcid.org/0000-0001-7484-7405
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Division of Blood Transfusion Service, Faculty of Medicine, Gunma University Hospital, Maebashi, Gunma, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yokohama
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Ishizaki
authors.affiliation: Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan.
authors.forename: Nahoko
authors.initials: N
authors.lastname: Hatsumi
authors.affiliation: Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takada
authors.affiliation: Gunma University School of Health Sciences, Faculty of Medicine, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Saitoh
authors.affiliation: Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sakura
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060965:Clonal Evolution; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
keywords: acute myeloid leukemia; clonal evolution; cytogenetic abnormality; relapse; t(8;21)