Background Tyrosine kinase inhibitors like imatinib have become the cornerstone of therapy in chronic phase-chronic myeloid leukemia (CML-CP). However, the role of hydroxyurea (HU), a deoxyribonucleic acid synthesis inhibitor, has been less explored in the disease. Hence, the present study was conducted to compare the efficacy of structured dose of HU based on baseline total leukocyte count (TLC) with imatinib in CML patients.

Method An open-label randomized controlled trial was conducted in 90 newly diagnosed CML-CP patients, aged ≥ 18 years. Patients were randomized to receive either baseline leucocyte count-based structured dose of HU with imatinib or imatinib monotherapy for 3 months. Quantitative real-time polymerase chain reaction for BCR-ABL1 to assess early molecular response (EMR) and safety evaluation according to the Common Terminology Criteria for Adverse Events version 5 was done.

Results Median age of patients was 36.5 years (36 [interquartile range [IQR]: 30–45] in I-HU, 38 [IQR: 31–47] in imatinib monotherapy) with male predominance. Fatigue was the most common symptom at diagnosis. Splenomegaly was seen in 89% (median spleen size: 10 [IQR: 6–15] cm). At 3 months, complete hematological response was seen in 74 patients (36 in I-HU, 38 in imatinib monotherapy). Overall, 68 patients achieved EMR (34 in I-HU, 34 in imatinib monotherapy, p = 0.53). The most common hematological toxicity, anemia, was seen in 80 patients (41 in I-HU, 39 in imatinib monotherapy). In 37 patients, nonhematological toxicities seen were nausea and vomiting (20 in I-HU, 17 in imatinib monotherapy). No dose limiting toxicities were reported.

Conclusion Addition of upfront TLC-based dosing of HU to imatinib was not found to significantly improve the hematological response and EMR at 3 months. However, long-term studies with a larger sample size with structured dose of HU can be undertaken as it forms a preferred adjunctive therapy for initial, rapid cytoreduction in hyperviscosity or leukostasis-related symptoms in patients of CML.

All participants were informed about the purpose of the trial, consented, and the trial was conducted in accordance with the Declaration of Helsinki. Authors confirm that necessary IRB and/or ethics committee approvals have been obtained. The study was approved by the Institute Ethics Committee (AIIMS/IEC/18/571). Trail has been registered under Clinical Trail Registry India (CTRI/ 2019/08/020879).

A written informed consent was obtained from the patients for publication.

The raw data and materials are available upon request.

The authors have declared no competing interest.

R.C., U.K.N., P.D., N.S., and M.N.: Protocol design, methodology, and statistical considerations; R.C., U.K.N., A.B., D.C., S.V., A.R., A.Bak., and A.M.: Acquisition of data and patient management; A.B., S.P., R.C., V.D., and U.K.N.: Analysis and interpretation of data; A.B., S.P., R.C., V.D., and U.K.N.: Took part in drafting the article or revising it critically for important intellectual content; All authors agreed to submit to the current journal; All authors gave final approval of the version to be published; All authors agree to be accountable for all aspects of the work.

Received: 02 March 2024

Accepted: 26 July 2024

Article published online:
18 September 2024

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