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Updated: Jun 23, 2025

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Successful maintenance of a sustained molecular response in CML patients receiving low-dose tyrosine kinase
Yan Li1, Pu Kuang1, Huanling Zhu1
1Department of Hematology, Institute of Hematology, West China Hospital of Sichuan University, Chengdu, P.R. China.
Background:
The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission.
Objectives:
This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML.
Design:
This was a retrospective study.
Methods:
Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction.
Results:
This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8-98.7) and 90.5% (95% CI: 81.3-95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction (p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients.
Conclusion:
Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.
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