What question did this study set out to answer?

The aim is to determine the prognostic value of aberrant lymphoblasts in predicting lymphoid transformation in CML patients.

December 8, 2025

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

Puntos clave

The aim is to determine the prognostic value of aberrant lymphoblasts in predicting lymphoid transformation in CML patients.
Bone marrow aberrant lymphoblasts assessed via flow cytometry (FCM) at diagnosis
Use of X-tile plots to establish optimal cutoff for predicting transformation-free survival
Cox and Fine-Gray regression models utilized for analysis in newly-diagnosed patients
Evaluation of treatment with tyrosine kinase inhibitors (TKIs) including imatinib, nilotinib, and dasatinib.”],
results
7 months (IQR, 3-11 months) on TKI therapy, none transformed to MBP. X-tile analysis identified 0.4% of the ALB as the optimal cutoff value for predicting lymphoid transformation. All 1080 patients were stratified into low- (ALB = 0), intermediate- (0 < ALB <0.4%), and high-risk (ALB ≥0.4%) groups with significant difference in 5-year cumulative incidences of lymphoid transformation (2% [95% CI, 1-2%] vs. 18% [3-32%] vs. 90% [69-100%], p < 0.001) and 5-year probabilities of TFS (98% [98-99%] vs. 82% [69-98%] vs. 10% [2-51%], p < 0.001). Multi-variable analyses by Fine-Gray competing risk, Cox, Firth-penalized Cox, and IPTW-weighted Cox regression models further confirmed that ALB intermediate-/high-risk groups (vs. low-risk) and higher WBC concentrations at diagnosis were significantly-associated with lymphoid transformation.
Among 1,080 CML patients, the median proportion of aberrant lymphoblasts was 0.3%; 53 patients had detectable ALB at diagnosis.
Patients with ALB ≥0.4% showed 90% cumulative incidence of lymphoid transformation at 5 years.
5-year transformation-free survival was 98% in low-risk vs. 10% in high-risk groups, p < 0.001.
98% of patients with detectable ALB achieved complete hematologic response, but 43% transformed to lymphoid blast phase during follow-up.

Resumen

Abstract Abstract Aim: To explore the prognostic proportion of bone marrow aberrant lymphoblasts (ALB) detected by flow cytometry (FCM) for predicting transformation to lymphoid blast phase (LBP) in newly-diagnosed chronic phase patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy. Method: Bone marrow ALB was determined by FCM testing with the detection sensitivity of 0.01% at diagnosis. The X-tile plots were used to determine the optimal cutoff value of continuous co-variates at diagnosis for predicting transformation-free survival (TFS). Cox, Firth-penalized Cox, Inverse Probability of Treatment Weighting (IPTW)-weighted Cox, and Fine-Gray competing risk regression models were used for univariable and multivariable analyses to identify covariates associated with LBP transformation in CML patients on TKI therapy. Results: 1080 chronic phase CML patients with bone marrow blasts 10% and FCM testing were included in this study. 730 (68%), 287 (26%), and 63 (6%) patients were classified in ELTS low-, intermediate-, and high-risk, respectively. Bone marrow ALB was detected in 53 (5%) patients with a median proportion of 0.3% (IQR, 0.1-1.0%; range, 0.01-9.8%). Initial TKIs included imatinib (n = 776, 72%), nilotinib (n = 135, 12%), dasatinib (n = 42, 4%), and flumatinib (n = 127, 12%). With a median follow-up of 42 months (IQR, 16-69 months), 83 (8%) patients transformed to blast phase including LBP (n = 35, 3%) and myeloid blast phase (MBP, n = 48, 5%). 5-year probabilities of TFS and survival were 96% (95% CI, 95-97%) and 97% (95% CI, 96-98%), respectively. Among the 53 patients with detectable ALB, 52 (98%) achieved CHR; 34 (64%), CCyR; 11 (21%), MMR; 23 (43%) transformed to LBP at a median of 7 months (IQR, 3-11 months) on TKI therapy, none transformed to MBP. X-tile analysis identified 0.4% of the ALB as the optimal cutoff value for predicting lymphoid transformation. All 1080 patients were stratified into low- (ALB = 0), intermediate- (0 ALB 0.4%), and high-risk (ALB ≥0.4%) groups with significant difference in 5-year cumulative incidences of lymphoid transformation (2% 95% CI, 1-2% vs. 18% 3-32% vs. 90% 69-100%, p 0.001) and 5-year probabilities of TFS (98% 98-99% vs. 82% 69-98% vs. 10% 2-51%, p 0.001). Multi-variable analyses by Fine-Gray competing risk, Cox, Firth-penalized Cox, and IPTW-weighted Cox regression models further confirmed that ALB intermediate-/high-risk groups (vs. low-risk) and higher WBC concentrations at diagnosis were significantly-associated with lymphoid transformation. Conclusion: Low-level ALB detected by FCM at diagnosis in chronic phase patients with CML predicted high possibility of subsequent lymphoid transformation during TKI therapy, especially in those with ALB ≥0.4%.

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