Program of Postgraduate Studies "Adolescent Medicine and Adolescent Health Care", School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
2nd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital, Thessaloniki, 54636, Greece.
Curr Pharm Des. 2024;30(33):2631-2642. doi: 10.2174/0113816128309071240626114308.
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).
The aim of this systematic review was to study the effect of TKIs on the growth of children and adolescents with CML.
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.
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.
A negative effect of TKIs on the growth and final height of children was noted.
慢性髓性白血病（CML）是儿童期罕见的骨髓增生性疾病。CML 的治疗包括酪氨酸激酶抑制剂（TKI），它抑制细胞质激酶 BCR/ABL。酪氨酸激酶在生长激素和胰岛素样生长因子 1（IGF-1）的分泌中起关键作用。
本系统评价的目的是研究 TKI 对 CML 儿童和青少年生长的影响。
在 PubMed/Cochrane 图书馆/Google Scholar 数据库中搜索英文出版物（2002-2023 年），并根据 PRISMA 声明和纽卡斯尔-渥太华量表评估检索到的研究。
搜索策略产生了 1066 篇文章。在应用纳入/排除标准后，根据标题筛选排除了 941 篇，根据摘要审查排除了 111 篇。系统评价包括 14 篇文章（11 篇回顾性观察研究/3 项临床试验）。12 项研究报告了第一代 TKI（伊马替尼）给药后生长障碍发生率的数据。两项研究报告了第二代 TKI（达沙替尼/尼洛替尼）对身体生长的负面影响。四项研究记录了治疗后身高 z 分数与基线相比的下降。两项第一代 TKI 研究报告了儿童最终身高的数据；其中一项报告了青春期发病后最终身高恢复正常，尽管最初生长缓慢，最终身高低于中父母靶身高。两项研究报告了 IGF-1 血清水平在正常范围内，而在三项研究中记录了显著下降。观察到与治疗剂量/持续时间/疾病阶段/青春期阶段/种族有关的相当大的研究异质性。
TKI 对儿童的生长和最终身高有负面影响。
