Clinical Impact of Basophilia during Cytoreduction in Patients with Chronic Myeloid Leukaemia

Background:

Despite the elevated basophils at diagnosis may have a prognostic value in chronic myeloid leukemia (CML), there is limited information about the clinical relevance of the changes in relative and absolute peripheral blood basophils counts during the initial cytoreduction treatment in newly diagnosed CML.

Methods:

This study included a real-world cohort of newly diagnosed 136 BCR-ABL1+ CML patients (56 females/80 males, median age of 58 years, range: 24-92 years) indicated for the first-line tyrosine kinase inhibitor (TKI) treatment. Blood counts and laboratory parameters were assessed at the diagnosis and during first month of cytoreduction treatment with hydroxyurea and/or first line TKI (imatinib or nilotinib in 11 cases). The median follow-up of the patients was 6.3 years (range: 3.5 months - 15.7 years). Kaplan-Mayer curves, odds ratio including 95% confidence intervals (CI) and receiver operation curves (ROC) were calculated using R software.

Results:

At diagnosis, there was high interindividual heterogeneity in basophil percentage (median 4%, range 0-45%) and basophil absolute counts (median 4.6, range 0-67.6x 10⁹/L). During the first months of cytoreduction treatment, 65 (47.8%) patients had a decrease or stable values in basophil percentage and 71 (52.2%) had increased basophil percentages comparing to the diagnosis. Elevated absolute basophil counts after cytoreduction was evident in 26 (19%) patients, predominantly in young males, with high risk Sokal score, splenomegaly, high leukocyte counts and increased lactate dehydrogenase levels at the diagnosis. The higher percentage (>15%) of basophils at diagnosis was associated with a later cytogenetic response (p=0.011), however we did not prove the prognostic impact for achieving treatment response of relative basophils counts after cytoreduction on overall, even at levels >20%. However, patients with lower absolute counts of basophils at diagnosis had a lower risk for introduction of the second or higher lines of TKI treatment (odds ratio 0.109, 95%CI 0.044-0.270), using absolute basophil count of 12.2x10⁹/L as a threshold revealed from ROC (AUC 0.733). Similar results were observed for absolute counts (0.463, 0.217-0.984) and relative counts (>15%, 0.371, 0.143-0.963) of basophils after cytoreduction. Our pilot data suggest that the increase in relative basophilia in CML patients during cytoreduction may be linked to a slower clearance of basophils from peripheral blood comparing to the neutrophils.

Conclusion:

Our study on real-world cohort CML patients showed that progression of relative basophilia is a common phenomenon during the cytoreduction and it has no independent prognostic value for achievement of treatment response and survival of patients. However, our data suggested that a high absolute basophil counts at the diagnosis of CML and after the cytoreduction treatment are associated with the risk for a subsequent change in the TKI treatment. Future studies focused on absolute basophil counts in larger cohorts of CML patients are warranted to confirm our results.

Supported by MH CZ - DRO (FNOl, 00098892), IGA_LF_2022_001.

Papajik:Abbvie: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Minarik:Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BSM: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; EUSA Pharma: Consultancy, Honoraria; GSK: Consultancy, Honoraria; JANSSEN: Consultancy, Honoraria; SANOFI: Consultancy, Honoraria; TAKEDA: Consultancy, Honoraria.