Fig. 5.

Trisomies 18 and 10 and clonal heterogeneity are robust relapse risk predictors in high‐hyperdiploid B‐cell acute lymphoblastic leukemia (HHD‐B‐ALL) who had achieved minimal residual disease (MRD)‐negativity post‐induction therapy. (A) Contribution of the indicated trisomies at predicting clinical outcome; complete remission (CR) versus relapse (REL). Dots represent individual patient Gini importance values. Boxes represent the quartiles 25–75 and horizontal lines represent the mean value. Error bars represent the SD; n = 10 CR and 12 REL patient samples. (B) Stress tests on the indicated predictors for risk classification at diagnosis (DX) of HHD‐B‐ALL patients (n = 22). Blue bars represent the number of patients properly classified according to disease outcome (CR versus REL) and red bars the number of patients erroneously classified. (C) Classification based on DX samples of HHD‐B‐ALL patients according to risk predictor 3 as either CR (favorable, % trisomies 18 and 10 > 40%) or REL (unfavorable, % trisomies 18 and 10 < 40%) risk groups. Number and percentage of properly classified patients are indicated in the right. (D) Frequency of the indicated chromosome gains in an independent and blind validation cohort of DX samples of favorable (CR, n = 33) and unfavorable (REL, n = 17) HHD‐B‐ALL patients by iFISH analysis of chromosomes 18 and 10. Graphs represent the median values and dots represent the values obtained for individual patients; n = 200 nuclei per sample. (E) Classification of HHD‐B‐ALL patients as CR or REL using the chr18‐chr10 risk predictor (predictor 3) after blind FISH analyses. The DX samples from the validation cohort were initially blind‐grouped as favorable or unfavorable risk based on chr18–chr10 risk predictor results, and then correlated with relapse information (No versus Yes) available from the clinic. 96% (48/50) of patients had achieved MRD negativity after induction therapy. The total number of patients for each group is indicated outside the quadrant. Note that 84% of the 50 HHD‐B‐ALL patients used in this blind and independent validation cohort were properly classified using predictor 3. (F,G) Kaplan–Meier curves for relapse‐free survival (RFS) of HHD‐B‐ALL patients grouped according to the chr18–chr10 risk predictor (F) and clonal heterogeneity defined by the percentage of major clone (PMC) (G) after blind FISH analyses; n = 50 HHD‐B‐ALL samples collected at diagnosis (DX). Analyses for panels (F and G) were performed with the hazard ratios obtained with cox multivariate analyses. [Colour figure can be viewed at wileyonlinelibrary.com]