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Updated: Jul 19, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Front-Line Tyrosine Kinase Inhibitors in Pediatric Chronic Myeloid Leukemia: A Study on Efficacy and Safety
Jae Won Yoo1, Suejung Jo1, Moon Bae Ahn1
1Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Insights
Dasatinib showed faster and deeper molecular responses than imatinib in children with chronic myeloid leukemia (CML). Both tyrosine kinase inhibitors (TKIs) were well-tolerated, though dasatinib was associated with greater height decline.
Area of Science:
- Pediatric Hematology
- Oncology
- Pharmacology
Background:
- Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm.
- Tyrosine kinase inhibitors (TKIs) are standard first-line therapy for pediatric CML.
- Limited data exist on front-line TKI efficacy and safety in children.
Purpose of the Study:
- To compare the efficacy and safety of imatinib (IMA) versus dasatinib (DSA) as front-line TKIs in pediatric CML patients.
- To evaluate molecular and cytogenetic response rates and adverse events.
Main Methods:
- Retrospective study of 51 pediatric patients with newly diagnosed CML (chronic or accelerated phase).
- Patients received either imatinib (N=33) or dasatinib (N=18) as front-line therapy.
- Assessed complete cytogenetic response (CCyR), early molecular response (EMR), major molecular response (MMR), and deep molecular response (DMR) at various time points.
Main Results:
- CCyR rates at 12 months were similar (IMA: 92.3%, DSA: 100%, p=0.305).
- EMR rates were higher with dasatinib (100%) versus imatinib (80%, p=0.043).
- Dasatinib showed faster and higher cumulative rates of MMR (p=0.002) and DMR (p=0.004) by 12 and 24 months.
- Both TKIs were well-tolerated, but dasatinib was associated with a greater height decline between 1-2 years.
Conclusions:
- Dasatinib achieved faster and higher molecular responses compared to imatinib in pediatric CML.
- Both TKIs demonstrated an acceptable safety profile, with notable differences in growth impact.
- Long-term outcomes and growth effects require further investigation.
Abstract:
We conducted a retrospective study on 51 pediatric patients with newly diagnosed chronic myeloid leukemia chronic phase or accelerated phase. The patients were classified into the IMA group (N = 33), treated with imatinib, and the DSA group (N = 18), treated with dasatinib, as front-line tyrosine kinase inhibitors (TKIs). At 12 months, the rates of complete cytogenetic response were similar between the IMA group (92.3%) and DSA group (100%) (p = 0.305). However, the rate of early molecular response was higher in the DSA group than in the IMA group (100.0% vs. 80.0%, p = 0.043). By 12 and 24 months, the DSA group showed faster and higher cumulative rates of both major (DSA group: 72.2% and 100%, respectively; IMA group: 41.2% and 68.7%, respectively; p = 0.002) and deep molecular responses (DSA group: 26.0% and 43.6%, respectively; IMA group: 13.8% and 17.5%, respectively; p = 0.004). Both TKIs were well tolerated. Although the height standard deviation scores decreased in both groups, the height decline was greater in the DSA group between one and two years from the start of TKI therapy. In this study, dasatinib achieved faster and higher molecular responses with an acceptable safety profile. Further follow-up is necessary to assess the long-term outcomes of TKI treatment in children.
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