What is the optimal threshold for aberrant lymphoblasts at diagnosis to predict lymphoid transformation in chronic myeloid leukemia?

We investigated the prognostic value of aberrant lymphoblasts (ALB) detected by flow cytometry (FCM) for predicting lymphoid transformation in patients with newly diagnosed chronic myeloid leukemia (CML). Data from patients with chronic phase CML were retrospectively interrogated to analyze covariates associated with lymphoid transformation-free survival (LTFS) via Cox, Firth-penalized Cox, Inverse Probability of Treatment Weighting-weighted Cox, and Fine-Gray competing risk regression approaches. Among 1081 patients, with a median follow-up of 43 (IQR, 16-70) months, 84 (8%) transformed to lymphoid or myeloid blast phase (LBP, 3%; MBP, 5%). 5-year cumulative incidence of lymphoid transformation and probabilities of LTFS, transformation-free survival and survival were 4% (95% CI, 3%-5%), 96% (95%-97%), 91% (89%-93%), and 95% (93%-96%), respectively. In the 54 patients (5%) with detectable ALB (median 0.3%; IQR, 0.1%-1.1%) at diagnosis, 24 (44%) transformed to LBP, none transformed to MBP. 0.4% ALB was identified as the optimal cutoff for LTFS by X-tile analysis and the maximally selected rank statistics method. All patients were stratified into ALB low- (ALB = 0), intermediate- (0< ALB < 0.4%), and high-risk (ALB ≥0.4%) groups with significant differences in 5-year probabilities of lymphoid transformation (2% [95% CI, 1%-2%] vs. 18% [3%-32%] vs. 91% [70%-100%]; p< 0.001) and LTFS (98% [98%-99%] vs. 82% [69%-98%] vs. 9% [2%-49%]; p< 0.001). Multivariable analyses confirmed that ALB intermediate-/high-risk groups and higher white blood cell count at diagnosis were significantly associated with a higher likelihood of lymphoid transformation. Low-level ALB detected by FCM at diagnosis identifies patients with chronic phase CML at high risk for lymphoid transformation, especially those with ALB ≥0.4%.