儿童慢性髓系白血病停酪氨酸激酶抑制剂后无治疗缓解结局的临床分析  

Clinical analysis of treatment free remission outcomes after discontinuation of tyrosine kinase inhibitors in childhood chronic myeloid leukemia

作　　者：赵慧芳 梁立新[2] 祖璎玲 张春蕾 王娟 王献伟 宋永平 魏旭东 张䶮莉 Zhao Huifang;Liang Lixin;Zu Yingling;Zhang Chunlei;Wang Juan;Wang Xianwei;Song Yongping;Wei Xudong;Zhang Yanli(Department of Hematology,the Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450008,China;Department of Hematology,Sanmenxia Central Hospital,Sanmenxia 472000,China)

机构地区：[1]郑州大学附属肿瘤医院,河南省肿瘤医院血液科,郑州450008 [2]三门峡市中心医院血液科,三门峡472000

出　　处：《中华儿科杂志》2025年第3期272-277,共6页Chinese Journal of Pediatrics

摘　　要：目的分析慢性髓系白血病(CML)患儿停酪氨酸激酶抑制剂(TKI)后的无治疗缓解(TFR)结局。方法回顾性队列研究。收集河南省肿瘤医院2016年9月30日至2022年1月30日经TKI规范治疗后达到稳定深层分子学反应(DMR)≥2年且有强烈停TKI意愿的14例年龄<18岁的CML慢性期患儿的临床资料。按停TKI后TFR结局不同分为失去主要分子学反应(MMR)组和未失去MMR组,采用Mann-Whitney U检验和Fisher确切概率法比较两组患儿临床特征。结果14例停TKI患儿,男7例、女7例;确诊时年龄14.0(4.8,17.0)岁,停TKI时年龄22.0(12.5,27.0)岁。8例患儿停TKI前应用伊马替尼治疗,6例患儿停TKI前二线更换二代TKI尼洛替尼或达沙替尼治疗。14例患儿随访时间37.0(27.8,47.5)个月,7例在停TKI后3.0(2.0,11.0)个月失去MMR。停TKI治疗6个月时,8例患儿获得TFR;12和24个月时,7例患儿获得TFR。6例停TKI前应用过二代TKI治疗的患儿中,2例分别在停二代TKI后3和11个月失去MMR,4例患儿获得TFR;8例应用伊马替尼治疗的停药患儿中,5例在停伊马替尼3.0(2.0,9.0)个月失去MMR,3例获得TFR。未失去MMR组7例患儿和失去MMR组7例患儿的确诊和停TKI时年龄、TKI治疗至获得DMR的时间、停TKI前TKI治疗时间、停TKI前DMR持续时间、应用二代TKI治疗等方面差异均无统计学意义(均P>0.05)。7例失去MMR的患儿均立即重启TKI治疗,治疗2.0(2.0,11.0)个月全部重获DMR。无患儿疾病进展。停TKI后仅1例患儿出现轻度骨痛,口服解热镇痛药物可缓解。结论部分TKI治疗获得持续稳定DMR≥2年的CML患儿可以停TKI获得TFR。停TKI前更长的TKI治疗时间和DMR持续时间以及应用二代TKI治疗均可能让更多CML患儿有机会获得TFR。Objective To analyze the treatment-free remission(TFR)outcomes after discontinuation of tyrosine kinase inhibitor(TKI)in children with chronic myeloid leukemia(CML).Methods In this retrospective cohort study,clinical data of 14 chronic phase CML children aged<18 years who had achieved stable deep molecular response(DMR)for≥2 years after standardized treatment with TKI and had a strong desire to discontinue TKI at Henan Cancer Hospital from September 30,2016 to January 30,2022 were collected retrospectively.According to the different TFR outcomes after discontinuation of TKI,patients were divided into loss of major molecular response(MMR)group and without loss of MMR group,differences in clinical characteristics between the two groups of children were analyzed using Mann-Whitney U test and Fisher exact test.Results Out of 14 children with TKI discontinuation,7 were male and 7 were female.The age at diagnosis was 14.0(4.8,17.0)years,and the age at TKI discontinuation was 22.0(12.5,27.0)years.Among them,8 children were treated with imatinib prior to TKI discontinuation and 6 children were treated with second-line substitution of the second-generation TKI nilotinib or dasatinib prior to TKI discontinuation.The follow-up time was 37.0(27.8,47.5)months,and 7 cases lost MMR at the time of discontinuation of 3.0(2.0,11.0)months.Eight children gained TFR at 6 months,7 children gained TFR at 12 and 24 months.Amongst the 6 children who received second-generation TKI prior to TKI discontinuation,2 children lost MMR at 3 and 11 months and 4 children gained TFR,among the 8 children who discontinued imatinib,5 children lost MMR at the time 3.0(2.0,9.0)months and 3 children gained TFR.The age at diagnosis and TKI discontinuation,the time from TKI treatment to the acquisition of DMR,the duration of TKI treatment before TKI discontinuation,the duration of DMR before TKI discontinuation,and the number of children treated with second-generation TKI were not statistically different between the 7 children in the group that did not l

关 键 词：白血病 髓样 慢性期 儿童 蛋白酪氨酸激酶类 

分 类 号：R733.72[医药卫生—肿瘤]