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Volume 30, Issue 33
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Background

Chronic Myeloid Leukemia (CML) is a rare myeloproliferative disease in childhood. Treatment in CML includes Tyrosine Kinase Inhibitors (TKIs), which inhibit the cytoplasmic kinase BCR/ABL. Tyrosine kinases play a key role in the secretion of growth hormone and insulin-like growth factor 1 (IGF-1).

Objective

The aim of this systematic review was to study the effect of TKIs on the growth of children and adolescents with CML.

Methods

English-language publications were searched in the PubMed/Cochrane library/Google Scholar databases (2002-2023), and retrieved studies were assessed according to PRISMA-Statement and Newcastle-Ottawa-scale.

Results

The search strategy yielded 1066 articles. After applying the inclusion/exclusion criteria, 941 were excluded based on title screening and 111 on abstract review. The systematic review included 14 articles (11 retrospective observational studies/3 clinical trials). Twelve studies reported data on the prevalence of growth disorders after the administration of 1st generation TKIs (imatinib). Two studies reported a negative effect of 2nd generation TKIs (dasatinib/nilotinib) on physical growth. Four studies recorded a decrease in height z-score after treatment compared to baseline. Two 1st-generation TKIs studies reported data on children's final height; one reported restoration of final height to normal after the onset of puberty, despite initial slowing, and the final height was lower than mid-parental target height. Serum IGF-1 levels were reported in 2 studies to be within normal range, while in 3 studies, a significant decrease was documented. Considerable study heterogeneity was observed related to dosage/duration of treatment/disease phase/stage of puberty/ethnicity.

Conclusion

A negative effect of TKIs on the growth and final height of children was noted.

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/content/journals/cpd/10.2174/0113816128309071240626114308
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Impact of Tyrosine Kinase Inhibitors (TKIs) on Growth in Children and Adolescents with Chronic Myeloid Leukemia: A Systematic Review
Curr. Pharm. Des. 30, 2631 (2024); https://doi.org/10.2174/0113816128309071240626114308
/content/journals/cpd/10.2174/0113816128309071240626114308
/content/journals/cpd/10.2174/0113816128309071240626114308
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  • Article Type:     Review Article
Keyword(s): adolescents; Chronic myeloid leukemia; dasatinib; growth failure; imatinib; nilotinib; tyrosine kinase inhibitors

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