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.

Monitoring of clonal evolution of acute myeloid leukemia identifies the leukemia subtype, clinical outcome and potential new drug targets for post-remission strategies or relapse

“…A previous study in AML provided a contrary prediction, which in an analogous manner defined the clonal evolution as additional cytogenetic abnormalities, and observed a worse prognosis. 37 Our prediction agrees with reported findings in NPM1 - mutated AML, 14 whereby AML patients with clonal evolution ( NPM1 - ) at relapse have a significantly longer remission duration than patients without clonal evolution ( NPM1 + ). The better prognosis associated with patients with new clones (AMA) might be due to the fact that the treatment has been effective in the basal clone.…”

THBS1 Is a Novel Serum Prognostic Factors of Acute Myeloid Leukemia

“…It has been demonstrated that the extensive genetic abnormalities play an important role in the diagnosis, risk assessment, and determination of the prognosis of patients. According to the United States National Comprehensive Cancer Network (NCCN) guideline, the risk classification of AML can be divided into favorable, intermediate, and poor prognosis (5). However, in real clinical practice, many patients with favorable prognosis showed low sensitivity or no response to standard treatment strategy.…”

Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia

“…It is the most common type of adult acute leukemia with an annual incidence of 3-8/10 5 (2). To date, cytogenetic analysis has been one of the most useful prognostic methods to classify AML Original Article patients into different prognostic risk groups (favorable, intermediate, unfavorable) (3). The cytogenetically normal AML (CN-AML), representing 40-50% AML patients, is the largest subset of de-novo AML cases (4,5).…”