【摘要】 目的 酪氨酸激酶抑制剂（TKI）治疗使慢性髓系白血病（CML）长期缓解，但同时影响患儿身高、心理健康和生活质量。成人研究表明，掌握指征的TKI停药有机会获长时间无治疗缓解（TFR）,但在儿童特别是停药身高获益的研究罕有。方法 用泛华南儿童CML协作组SCCCG（PLUS）-CML的中期数据，观察伊马替尼、达沙替尼、尼洛替尼对CML儿童身高的影响、停药的安全性及身高增长。结果 伊马替尼、达沙替尼、尼洛替尼均影响身高增长，身高缓慢发生率分别75.8%、68.8%、70.6%;青春期开始治疗者仍有较快身高增长期，但最终仍身材矮。达国际共识停药标准的TKI停药10例，自行停药4例。前者确诊CML和TKI停药的中位年龄分别为7和12岁；TKI治疗达深度缓解(DMR,BCR::ABL1≤10^-4)中位需时12.5个月，TKI累计中位治疗62.5个月，持续DMR中位时间52.5个月；5例随访3（n=2）、6、12和24个月仍TFR,另5例3个月内BCR::ABL1>10^-3,重启TKI治疗中位4个月再获DMR;可获身高数据的7例中，青春期中期之前停药的5例身高追赶，青春末期停药2例身高无增长。未达标准自行停药的4例，重启TKI治疗中位7个月仍未达DMR。结论 三种TKI均抑制CML患儿身高增长，青春期中期前TKI停药可实现TFR并有身高追赶；把握指征的前提下停药，复发再用TKI可较快重获DMR,初步显示其安全性和可行性。更多还原

【Abstract】 Objective Tyrosine kinase inhibitors（TKIs） have transformed the management of chronic myeloid leukemia（CML） by enabling long-term remission. However, their use in children raises concerns regarding growth impairment, psychological well-being, and overall quality of life. While adult studies have shown that TKI discontinuation under strict criteria can achieve long-term treatment-free remission（TFR）, data on pediatric patients, particularly regarding growth recovery after TKI cessation, remain limited. Methods We analyzed interim data from the SCCCG（PLUS）-CML Collaborative Group to assess the impact of imatinib, dasatinib, and nilotinib on linear growth, as well as the safety and growth outcomes following TKI discontinuation. Results All three TKIs were associated with growth deceleration, with incidences of 75.8%, 68.8%, and 70.6% for imatinib, dasatinib, and nilotinib, respectively. Patients who initiated TKI therapy during puberty experienced a transient growth spurt but remained shorter at final height. Among 14 patients who discontinued TKIs, 10 met international eligibility criteria for TKI discontinuation, whereas 4 discontinued therapy on their own. In the eligible group, the median age at CML diagnosis and TKI discontinuation was 7 and 12 years, respectively. The median time to achieve deep molecular remission(DMR; BCR::ABL1 ≤10^-4) was 12.5 months, with a median cumulative TKI exposure of 62.5 months and a median duration of sustained DMR of 52.5 months. During follow-up, 5 patients remained in TFR at 3（n=2）, 6, 12, and 24 months, whereas 5 relapsed within 3 months(BCR::ABL1 >10^-4) and regained DMR within a median of 4 months after TKI reinitiation. Among the 7 patients with available height data, 5 who discontinued TKIs before mid-puberty demonstrated catch-up growth, while 2 who stopped treatment in late puberty showed no further height gain. By contrast, 4 patients who discontinued TKIs without meeting TFR criteria failed to regain DMR after a median of 7 months of retreatment. Conclusions All three TKIs negatively affect height growth in children with CML. Discontinuation before mid-puberty may allow both TFR and catch-up growth. When performed under appropriate clinical criteria, TKI withdrawal appears feasible and safe, as reinitiation effectively restores DMR upon relapse.更多还原