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Systematic Review Article

Impact of Tyrosine Kinase Inhibitors (TKIs) on Growth in Children and Adolescents with Chronic Myeloid Leukemia: A Systematic Review

In Press, (this is not the final "Version of Record"). Available online 12 July, 2024
Author(s): Dimitra Katsarou, Eleni P. Kotanidou, Vasiliki Rengina Tsinopoulou, Athanasios Tragiannidis, Emmanouil Hatzipantelis and Assimina Galli-Tsinopoulou*
Published on: 12 July, 2024

DOI: 10.2174/0113816128309071240626114308

Price: $95

Abstract

Background: Chronic Myeloid Leukemia (CML) is a rare myeloproliferative disease in childhood. Treatment in CML includes Tyrosine Kinase Inhibitors (TKI's), which inhibit the cytoplasmic kinase BCR/ABL. Tyrosine kinases play a key role in the secretion of growth hormone and insulin-like growth factor1 (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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