Xiao-Shuai Zhang

Blood basophils ≥ 20 percent is reportedly associated with a poor prognosis and used to define accelerated phase of chronic myeloid leukaemia (CML) in some classifications. However, quantification of blood basophils is by percentage is inaccurate. Using a Patient Similarity Network (PSM) approach we identified basophil concentration rather than percentage as the more accurate predictive co-variate. To test this observation we interrogated data for a possible correlation between blood basophils quantified by concentration in a training cohort of 131 subjects with newly-diagnosed chronic phase CML receiving tyrosine kinase-inhibitor (TKI)-therapy. Subjects with a basophil concentration ≥ 12.2 x 10E + 9/L had poorer event-free survival (EFS, Odds Ratio [OR] = 12.3 [95% Confidence Interval [CI]. 4.2, 36.1]; p < 0.0001) and failure-free survival (FFS; OR = 10.4 [3.89, 27.72]; p < 0.0001). TKI switch-free survival and progression-free survival were also correlated with basophil concentration. The negative impact of a high basophil concentration was validated in an independent cohort of 1,870 subjects. We explain why basophil concentration is a more accurate co-variate. Our data indicate blood basophil concentration at diagnosis rather than percentage is a more accurate predictor of outcomes in persons with newly-diagnosed chronic phase CML receiving TKI-therapy.

Whether there is really a distinct accelerated phase (AP) at diagnosis in chronic myeloid leukaemia (CML) in the context of tyrosine kinase-inhibitor (TKI)-therapy is controversial. We studied 2122 consecutive subjects in chronic phase (CP, n = 1837) or AP (n = 285) at diagnosis classified according to the 2020 European LeukemiaNet (ELN) classification. AP subjects with increased basophils only had similar transformation-free survival (TFS) and survival compared with CP subjects classified as ELTS intermediate-risk. Those with increased blasts only had worse TFS but similar survival compared with CP subjects classified as ELTS high-risk. AP subjects with decreased platelets only had similar TFS but worse survival compared with subjects classified as ELTS high-risk. Proportions of CP and AP subjects meeting the 2020 ELN TKI-response milestones were similar. However, worse TFS at 3-month and survival at 6- or 12-month were only in AP subjects failing to meet ELN milestones. Findings were similar using the 2022 International Consensus Classification (ICC) criteria for AP replacing decreased platelets with additional cytogenetic abnormalities. Our data support the 2022 WHO classification of CML eliminating AP. We suggest adding a very high-risk cohort to the ELTS score including people with increased blasts or decreased platelets and dividing CML into 2 phases at diagnosis: CP and acute or blast phases.

Whether there is really a distinct accelerated phase (AP) at diagnosis in chronic myeloid leukemia (CML) in the context of tyrosine kinase-inhibitor (TKI)-therapy and whether co-variates identified as characterizing AP are simply adverse co-variates for outcomes, we studied 2,122 consecutive subjects in chronic phase (CP, n = 1,837) or AP (n = 285) according to the European LeukemiaNet (ELN) classification. AP subjects with increased basophils only had similar transformation-free survival (TFS) and survival compared with CP subjects in ELTS intermediate-risk. AP subjects with increased blasts only had worse TFS but similar survival compared with CP subjects in the ELTS high-risk; AP subjects with decreased platelets only, similar TFS but worse survival. Proportions of CP and AP subjects meeting the 2020 ELN TKI-response milestones were similar. However, worse outcomes were only seen in AP subjects failing to meet ELN milestones. Findings were similar using the 2022 International Consensus Classification (ICC) criteria replacing decreased platelets with additional cytogenetic abnormalities. Our data support the 2022 WHO classification of CML eliminating AP. We suggest adding a very high-risk cohort to the ELTS score including people with increased blasts or decreased platelets and dividing CML into 2 phases: CP and acute phase.

It is vital for physicians and persons with chronic myeloid leukemia (CML) to accurately predict the likelihood of achieving a major molecular response (MMR) and a deep molecular response (DMR; at least MR⁴) at the start of imatinib-therapy, which could help in decision making of treatment goals and strategies. To answer this question, we interrogated data from 1369 consecutive subjects with chronic phase CML receiving initial imatinib-therapy to identify predictive co-variates. Subjects were randomly-assigned to training (n = 913) and validation (n = 456) datasets. Male sex, higher WBC concentration, lower haemoglobin concentration, higher percentage blood blasts and larger spleen size were significantly-associated with lower cumulative incidences of MMR and MR⁴ in training dataset. Using Fine-Gray model, we developed the predictive scoring systems for MMR and MR⁴ which classified subjects into the low-, intermediate- and high-risk cohorts with significantly-different cumulative incidences of MMR and MR⁴ with good predictive discrimination and accuracy in training and validation cohorts with high area under the receiver-operator characteristic curve (AUROC) values. These data may help physicians decide appropriateness of initial imatinib therapy.