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Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch-Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death ('primary refractoriness'). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

Original publication

DOI

10.1038/leu.2014.242

Type

Journal article

Journal

Leukemia

Publication Date

02/2015

Volume

29

Pages

312 - 320

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, Area Under Curve, Clinical Trials as Topic, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Humans, Leukemia, Myeloid, Acute, Male, Middle Aged, Multivariate Analysis, Mutation, Neoplasm, Residual, Prognosis, Regression Analysis, Remission Induction, Treatment Outcome, Young Adult