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


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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.

About the authors

Dimitra Katsarou

Program of Postgraduate Studies "Adolescent Medicine and Adolescent Health Care", School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki

Email: info@benthamscience.net

Eleni Kotanidou

Program of Postgraduate Studies "Adolescent Medicine and Adolescent Health Care", School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki

Email: info@benthamscience.net

Vasiliki Tsinopoulou

2nd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, AHEPA University General Hospital,, Aristotle University of Thessaloniki

Email: info@benthamscience.net

Athanasios Tragiannidis

2nd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, AHEPA University General Hospital,, Aristotle University of Thessaloniki

Email: info@benthamscience.net

Emmanouil Hatzipantelis

Program of Postgraduate Studies "Adolescent Medicine and Adolescent Health Care", School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki

Email: info@benthamscience.net

Assimina Galli-Tsinopoulou

Program of Postgraduate Studies "Adolescent Medicine and Adolescent Health Care", School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki

Author for correspondence.
Email: info@benthamscience.net

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