Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML.
Discontinuation of Imatinib in Children with Chronic Myeloid Leukemia: A Study from the International Registry of Childhood CML.
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DOI：
10.3390/cancers13164102
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发表时间：
2021-08-15
期刊：
影响因子：
5.2
通讯作者：
Borisevich M
中科院分区：
文献类型：
--
作者：
Millot F;Suttorp M;Ragot S;Leverger G;Dalle JH;Thomas C;Cheikh N;Nelken B;Poirée M;Plat G;Versluys B;Lausen B;Borisevich M
约50%对酪氨酸激酶抑制剂（TKI）有持续深度分子反应（DMR）的慢性粒细胞白血病（CML）成人患者可以永久停止治疗而不会发生分子复发。关于停药的建议仅适用于成人，因为儿童CML是一种非常罕见的疾病，代表一个单独的实体。本回顾性研究的目的是在国际儿童CML登记研究中评估在DMR定义为BCR-ABL 1/ABL 1 < 0.01%（MR 4）的背景下，伊马替尼停药后至少2年仍保持分子学缓解的儿童比例。确定了18例在诊断CML时年龄小于18岁的患者，这些患者在伊马替尼停药后表现出持续的DMR。停药后，6、12和36个月的无分子缓解率分别为61%、56%和56%。我们的研究结果代表了儿科CML领域医生关于停药建议的基础。在儿童慢性粒细胞白血病（CML）国际登记研究中，我们确定了18例诊断为CML时年龄小于18岁的慢性期患者，这些患者对伊马替尼表现出持续的深度分子学缓解（DMR），定义为BCR-ABL 1/ABL 1 < 0.01%（MR 4）至少两年，随后停用伊马替尼。停药前，伊马替尼的中位持续时间为73.2个月（范围：32-109），MR 4的中位持续时间为46.2个月（范围：23.9-98.6）。7例患者在停药后4.1个月（范围1.9-6.4）发生主要分子学缓解（MMR）丧失，因此重新开始伊马替尼治疗。9例无分子复发的患者停药后的中位分子随访时间为51个月（范围，6-100）。6、12和36个月时的无分子缓解率分别为61%（95% CI，38-83%）、56%（95% CI，33 -79%）和56%（95% CI，33-79%）。在停药后经历分子复发的7名儿童中，有6名在重新开始伊马替尼治疗后重新获得DMR（中位数，4.7个月;范围，2.5-18）。未观察到戒断综合征。在单变量分析中，年龄、性别、索卡尔和ELTS评分、伊马替尼治疗和停药前DMR持续时间对无治疗缓解无影响。这些数据表明，伊马替尼可以安全地在持续MR 4至少两年的儿童中停用。
About 50% of adults with chronic myeloid leukemia (CML) in sustained deep molecular response (DMR) to tyrosine kinase inhibitors (TKI) could discontinue the treatment permanently without molecular relapse. Recommendations regarding discontinuation apply only for adults because childhood CML is a very rare disease and represents a separate entity. The aim of our retrospective study was to assess within the International Registry of Childhood CML, the rate of children remaining in molecular response after discontinuation of imatinib in a context of DMR defined as BCR-ABL1/ABL1 < 0.01% (MR4) for at least two years. Eighteen patients less than 18 years old at diagnosis of CML exhibiting a sustained DMR followed by imatinib discontinuation were identified. After discontinuation, the molecular free remission rate was 61%, 56% and 56% at 6, 12 and 36 months, respectively. Our findings represent the basis of recommendation regarding discontinuation for physicians involved in the pediatric CML field. Within the International Registry of Childhood Chronic Myeloid Leukemia (CML), we identified 18 patients less than 18 years old at diagnosis of CML who were in the chronic phase and exhibiting a sustained deep molecular response (DMR) to imatinib defined as BCR-ABL1/ABL1 < 0.01% (MR4) for at least two years followed by discontinuation of imatinib. Before discontinuation, the median duration of imatinib was 73.2 months (range, 32–109) and the median duration of MR4 was 46.2 months (range, 23.9–98.6). Seven patients experienced loss of major molecular response (MMR) 4.1 months (range, 1.9–6.4) after stopping and so restarted imatinib. The median molecular follow-up after discontinuation was 51 months (range, 6–100) for the nine patients without molecular relapse. The molecular free remission rate was 61% (95% CI, 38–83%), 56% (95% CI, 33–79%) and 56% (95% CI, 33–79%) at 6, 12 and 36 months, respectively. Six of the seven children who experienced molecular relapse after discontinuation regained DMR (median, 4.7 months; range, 2.5–18) after restarting imatinib. No withdrawal syndrome was observed. In univariate analysis, age, sex, Sokal and ELTS scores, imatinib treatment and DMR durations before discontinuation had no influence on treatment free remission. These data suggest that imatinib can be safely discontinued in children with sustained MR4 for at least two years.
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