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Effect of imatinib on growth in children with chronic myeloid leukemia
Deepthi Boddu1, Priyakumari Thankamony1, C S Guruprasad1
1a Department of Pediatric Oncology, Regional Cancer Centre , Thiruvananthapuram , Kerala, India.
Insights
Long-term imatinib treatment for pediatric Chronic Myeloid Leukemia (CML) can impact growth, particularly in prepubertal children. However, final adult height remains within normal limits, suggesting catch-up growth potential.
Area of Science:
- Pediatric Oncology
- Endocrinology
- Hematology
Background:
- Imatinib is a crucial treatment for pediatric Chronic Myeloid Leukemia (CML).
- Long-term imatinib use may lead to off-target effects, including impaired longitudinal growth.
- Regional socioeconomic factors might influence growth outcomes in children with CML.
Purpose of the Study:
- To assess the long-term impact of imatinib on the growth of children with CML in Kerala.
- To investigate if growth impairment differs between prepubertal and pubertal children.
- To compare growth outcomes with sibling height and mid-parental height.
Main Methods:
- Longitudinal growth (height Z-scores) was evaluated in 36 children (≤14 years) with CML receiving imatinib for ≥1 year.
- Height Z-scores were analyzed using WHO AnthroPlus, comparing prepubertal and pubertal groups.
- Paired t-tests and comparisons with sibling/mid-parental heights were performed.
Main Results:
- A decrease in height Z-scores was observed in both prepubertal and pubertal children.
- The reduction in height Z-scores was more pronounced when imatinib therapy began during the prepubertal stage (p=0.0018).
- Despite initial stunting, final adult heights were within WHO normal limits, and no participants were stunted by age 19.
Conclusions:
- Imatinib therapy initiated in prepubertal children with CML is associated with significant initial stunting.
- Long-term imatinib use does not necessarily lead to permanent growth impairment, as catch-up growth occurs.
- Final adult height in children with CML treated with imatinib can reach normal reference values.
Abstract:
Imatinib is a preferred drug for pediatric Chronic Myeloid Leukemia (CML). Long-term use has inhibitory effects on other tyrosine kinase pathways causing off-target complications such as growth impairment. Our aim was to evaluate impact of long-term use on longitudinal growth in children with CML in Kerala. We hypothesized that the impact would be lesser compared to Northern India as Kerala has the lowest rates of underweight and stunting, with a high literacy rate and per capita income. Children ≤14 years of age, diagnosed with CML and received imatinib for at least 1 year were included. Girls >9 years of age and boys >11 years were considered pubertal. Height Z scores were derived using WHO AnthroPlus. Paired t test compared difference of Z scores in prepubertal and postpubertal age groups. Height Z scores were compared with mid-parental height and sibling height Z scores. Thirty-six children were included (M = 21; F = 15). Median duration of imatinib exposure was 84 months. Decrease in longitudinal growth affected children in both prepubertal and postpubertal age groups. Decrease in height Z scores was more in prepubertal age group when imatinib therapy was initiated (p = .0018). Of 10 patients currently above 19 years (of whom 8 were in pubertal age and 2 in prepubertal age at start of imatinib) none are stunted. Patient's height Z scores was lesser compared to sibling height Z scores (p = .027). Children on continuous imatinib showed a significant stunting when treatment was initiated during prepubertal age. There is a catch-up of growth as the final height reached is within normal limits of WHO reference values.
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