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.
CONCLUSIONS: A negative effect of TKIs on the growth and final height of children was noted.
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.
CONCLUSIONS: A negative effect of TKIs on the growth and final height of children was noted.
摘要：
背景：慢性髓系白血病（CML）是一种罕见的儿童骨髓增殖性疾病。CML的治疗包括酪氨酸激酶抑制剂（TKI），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。
目的：本系统评价的目的是研究TKIs对儿童和青少年CML生长的影响。
方法：在PubMed/Cochrane图书馆/GoogleScholar数据库（2002-2023）中搜索了英文出版物，根据PRISMA-Statement和Newcast-Ottawa量表对检索到的研究进行评估。
结果：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名，根据摘要审查排除了111名。系统评价包括14篇文章(11项回顾性观察性研究/3项临床试验)。12项研究报告了第1代TKIs（伊马替尼）给药后生长障碍患病率的数据。两项研究报告了第二代TKIs（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与基线相比身高z评分降低。两项第一代TKIs研究报告了儿童最终身高的数据；一项报告了青春期开始后最终身高恢复正常，尽管最初放缓，最终身高低于父母中间的目标身高。2项研究报告血清IGF-1水平在正常范围内，在3项研究中，记录了显着下降。观察到相当大的研究异质性与剂量/治疗持续时间/疾病阶段/青春期阶段/种族有关。
结论：注意到TKIs对儿童的生长和最终身高有负面影响。
目的：本系统评价的目的是研究TKIs对儿童和青少年CML生长的影响。
方法：在PubMed/Cochrane图书馆/GoogleScholar数据库（2002-2023）中搜索了英文出版物，根据PRISMA-Statement和Newcast-Ottawa量表对检索到的研究进行评估。
结果：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名，根据摘要审查排除了111名。系统评价包括14篇文章(11项回顾性观察性研究/3项临床试验)。12项研究报告了第1代TKIs（伊马替尼）给药后生长障碍患病率的数据。两项研究报告了第二代TKIs（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与基线相比身高z评分降低。两项第一代TKIs研究报告了儿童最终身高的数据；一项报告了青春期开始后最终身高恢复正常，尽管最初放缓，最终身高低于父母中间的目标身高。2项研究报告血清IGF-1水平在正常范围内，在3项研究中，记录了显着下降。观察到相当大的研究异质性与剂量/治疗持续时间/疾病阶段/青春期阶段/种族有关。
结论：注意到TKIs对儿童的生长和最终身高有负面影响。
