Latest CML paper summary - What is the optimal threshold for aberrant lymphoblasts at diagnosis to predict lymphoid transformation in chronic myeloid leukemia?
We are pleased to share the latest iCMLf Quarterly CML Paper Summary. The study suggests that routine diagnostic flow cytometry may identify a small subgroup of newly diagnosed chronic phase CML patients at particularly high risk of early lymphoid transformation who could benefit from closer monitoring and potentially more intensive therapeutic strategies.
What is the optimal threshold for aberrant lymphoblasts at diagnosis to predict lymphoid transformation in chronic myeloid leukemia?
Jiang Z et al. Clinical Cytometry, June 2026 (epub ahead of print)
https://doi.org/10.1002/cyto.b.70046
Summary
This retrospective single-centre study from Peking University People's Hospital evaluated whether low levels of aberrant lymphoblasts (ALB), detected by flow cytometry at the time of chronic phase CML diagnosis, can predict subsequent transformation to lymphoid blast phase (LBP). Among 1,081 newly diagnosed patients followed for a median of 43 months, 54 (5%) had detectable ALB at diagnosis and almost half of these patients subsequently developed LBP. Using two independent statistical approaches, the authors identified an ALB threshold of 0.4% as the optimal cut-off for predicting lymphoid transformation.
Patients with ALB ≥0.4% had an exceptionally high risk of LBP, with a 5-year cumulative incidence of 91%, while patients without detectable ALB had a risk of only 2%. Higher presenting white blood cell count (≥306 × 10⁹/L) further increased the risk.
Importantly, ALB predicted lymphoid, but not myeloid, blast transformation.
The study suggests that routine diagnostic flow cytometry may identify a small subgroup of newly diagnosed chronic phase CML patients at particularly high risk of early lymphoid transformation who could benefit from closer monitoring and potentially more intensive therapeutic strategies.
Key points for clinicians
- Routine flow cytometry at diagnosis identified aberrant lymphoblasts (ALB) in approximately 5% of newly diagnosed chronic phase CML patients.
- An ALB threshold of 0.4% was the optimal predictor of future lymphoid blast transformation.
- Patients with ALB ≥0.4% had a 91% 5-year cumulative incidence of lymphoid transformation compared with only 2% in patients without detectable ALB.
- Detectable ALB predicted lymphoid blast phase only; none of the ALB-positive patients developed myeloid blast phase.
- High presenting white blood cell count (≥306 × 10⁹/L) independently increased the likelihood of lymphoid transformation.
- Patients with higher ALB levels achieved molecular responses less frequently and experienced inferior transformation-free and overall survival.
Introduction
Blast phase transformation remains the major cause of treatment failure in CML despite the success of tyrosine kinase inhibitors (TKIs). Although myeloid blast phase is more common, lymphoid blast phase continues to carry a poor prognosis. Current WHO and International Consensus Classification of Myeloid and Lymphoid Neoplasms (ICC) classifications acknowledge that increased lymphoblasts may indicate early lymphoid transformation, but there is no accepted threshold for low-level lymphoblasts detected by flow cytometry.
Previous studies suggested that small populations of immunophenotypically abnormal lymphoblasts may precede lymphoid transformation, but these studies were limited by relatively small sample sizes. This study sought to determine whether ALB detected at diagnosis could identify patients at increased risk and define a clinically meaningful threshold for risk stratification.
Methods
This retrospective analysis included 1,081 patients with newly diagnosed chronic phase CML treated between 2006 and 2025 at a single tertiary referral centre in China.
All patients underwent diagnostic bone marrow flow cytometry before commencing TKI therapy. ALB were identified using standard multiparameter immunophenotyping based on abnormal expression patterns distinguishing them from normal hematogones.
The primary endpoint was lymphoid transformation-free survival[NE1] . Statistical analyses included Kaplan–Meier survival analysis, Cox proportional hazards modelling, Firth-penalised Cox regression, inverse probability weighting, competing-risk analysis, and X-tile methodology to determine the optimal ALB threshold.
Key findings
Patient characteristics
The cohort had a median age of 42 years and median follow-up of 43 months. During follow-up, 84 patients (8%) progressed to blast phase, including 36 (3%) with lymphoid blast phase and 48 (5%) with myeloid blast phase.
Detectable ALB were present in 54 patients (5%), with a median proportion of 0.3%. Among these patients, 44% developed lymphoid blast phase, compared with only 1% of patients without detectable ALB. Transformation also occurred much earlier in ALB-positive patients (median 6 months versus 22 months).
Prognostic value of ALB
An ALB threshold of 0.4% provided the strongest discrimination for lymphoid transformation risk.
Patients were stratified into three groups:
- Low risk: no detectable ALB
- Intermediate risk: ALB <0.4%
- High risk: ALB ≥0.4%
Five-year cumulative incidence of lymphoid transformation was:
- 2% (no ALB)
- 18% (ALB <0.4%)
- 91% (ALB ≥0.4%)
Across multiple multivariable statistical models, ALB remained the strongest independent predictor of lymphoid transformation, with hazard ratios exceeding 130 for the high-risk group in the primary Cox model. Higher presenting WBC count also independently predicted transformation.
Figure: Cumulative incidences of lymphoid transformation and probabilities of lymphoid transformation-free survival by ALB risk groups
Clinical outcomes
Higher ALB burden was associated with poorer molecular responses, inferior transformation-free survival and worse overall survival.
Notably, patients with detectable ALB progressed exclusively to lymphoid blast phase, reinforcing the biological specificity of this marker rather than representing a general marker of disease progression.
Conclusions
This large retrospective study identifies 0.4% aberrant lymphoblasts detected by diagnostic flow cytometry as a clinically meaningful threshold for predicting future lymphoid blast transformation in chronic phase CML. ALB provided strong prognostic information independent of established clinical risk factors and consistently identified patients at markedly increased risk across multiple statistical models.
While the findings require prospective validation and arise from a single institution with considerable flow cytometry expertise, they support consideration of routine diagnostic immunophenotyping in newly diagnosed CML. Incorporating ALB assessment into baseline evaluation could improve early risk stratification and help identify patients who may benefit from closer surveillance or more intensive therapeutic approaches.