Hydroxyurea Bridging Before Frontline TKI Therapy in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: A Critical Appraisal

Hydroxyurea-based cytoreduction before tyrosine kinase inhibitor (TKI) initiation remains common in newly diagnosed chronic-phase chronic myeloid leukemia (CML), yet its contemporary value is uncertain. This critical narrative review examines the historical rationale, biologic basis, clinical evidence, and guideline positions relevant to hydroxyurea use before or immediately around frontline TKI therapy. Hydroxyurea can lower leukocyte and platelet counts rapidly and may provide short-term symptomatic relief while diagnostic confirmation is pending or when definitive treatment access is briefly delayed. However, contemporary evidence does not support routine pretreatment in clinically stable chronic-phase CML. Observational studies have shown no improvement in European LeukemiaNet response milestones, no acceleration of molecular response kinetics, and possible disadvantages including delayed TKI initiation, greater hematologic toxicity, and more treatment interruptions. Randomized studies evaluating early hydroxyurea together with imatinib likewise have not demonstrated meaningful molecular or hematologic benefit over TKI therapy alone. Current guidelines consistently position hydroxyurea as a selective, time-limited bridging option rather than a standard pretreatment strategy. In modern practice, the priority should be rapid initiation of definitive BCR::ABL1-directed therapy once the diagnosis is confirmed and access is secured. Hydroxyurea retains a limited role in selected situations such as symptomatic proliferative burden, suspected leukostasis, clinically important thrombocytosis, or short unavoidable logistical delay to TKI initiation.