Vitamin D Deficiency Negatively Affects Responses in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors
Authors: Chuengviroj Vitida , Niprapan Piangrawee , Punnachet Teerachat , Hantrakun Nonthakorn , Hantrakool Sasinee , Rattanathammethee Thanawat , Chai-Adisaksopha Chatree , Rattarittamrong Ekarat , Tantiworawit Adisak , Norasetthada Lalita , Piriyakhuntorn Pokpong 
Published: December 2024

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm harboring the hallmark BCR::ABL1 fusion gene, which is targeted by tyrosine kinase inhibitors (TKIs). In addition to its role in calcium homeostasis, vitamin D has immune-modulating effects. Several small studies have found lower vitamin D levels in CML patients with inadequate responses to TKIs. However, the prevalence of vitamin D deficiency and its impact on CML patients remain underexplored.
Objective: To evaluate the impact of vitamin D status on treatment outcomes in CML patients.
Methods: We conducted a cross-sectional study from September 2023 to July 2024 at the Outpatient Hematology Clinic, Faculty of Medicine, Chiang Mai University. Patients with chronic phase CML who had been receiving any TKIs for at least 1 year post-diagnosis were eligible. The key exclusion criterion was a history of receiving vitamin D supplements. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured at the time of enrollment. Demographic data and response rates of CML were retrospectively collected. Outcomes measured included the prevalence of vitamin D deficiency in CML patients and the major molecular response (MMR) rate at any time between the normal and deficient vitamin D groups. Vitamin D deficiency was defined as serum 25(OH)D below 20 ng/ml. TKI failure was determined according to the European LeukemiaNet 2013 response criteria. Multivariable logistic regression analysis was performed using factors with p-values less than 0.10 from univariable analyses to assess the effect of vitamin D deficiency on the MMR rate.
Results: A total of 124 chronic phase CML patients were enrolled. The prevalence of vitamin D deficiency among CML patients was 16.1%. Age, sex, comorbidities, and the EUTOS long-term survival (ELTS) score were not significantly different between the vitamin D-deficient and non-deficient groups. The TKI failure rate was comparable between groups (25.0% vs 22.1%, p=0.778). The distribution of TKIs used was 74.4% imatinib, 19.0% nilotinib, and 6.6% dasatinib. The duration of TKI treatment was similar between the deficient and non-deficient groups (mean±SD, 11.1±6.4 vs 11.3±5.5 years, p=0.904). CML patients with vitamin D deficiency had a lower rate of MMR at any time compared to patients in the non-deficient group (75.0% vs 93.2%, p=0.018). Univariable analyses showed that lower age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93-1.01; p=0.080), history of TKI failure or intolerance (OR, 0.20; 95% CI, 0.05-0.70; p=0.012), and vitamin D deficiency (OR, 0.21; 95% CI, 0.06-0.77; p=0.018) were associated with a lower rate of MMR. Further multivariable analysis revealed that vitamin D deficiency and a history of TKI failure or intolerance were significantly associated with a lower MMR rate (adjusted OR, 0.23; 95% CI, 0.06-0.95; p=0.042 and AOR, 0.18; 95% CI, 0.05-0.68; p=0.012, respectively).
Conclusion: The prevalence of vitamin D deficiency in CML patients was 16.1%. Notably, vitamin D deficiency was significantly associated with a lower MMR rate in CML patients treated with TKIs. Our findings suggest that deficient vitamin D levels could negatively affect molecular responses in chronic phase CML patients.