Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
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DOI：
10.1200/jco.2008.21.2514
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发表时间：
2009-11-01
影响因子：
45.3
通讯作者：
Camitta, Bruce
中科院分区：
文献类型：
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作者：
Schultz, Kirk R.;Bowman, W. Paul;Camitta, Bruce
目的甲磺酸伊马替尼是一种靶向药物，可用于治疗Ph+急性淋巴细胞白血病(ALL)，Ph+急性淋巴细胞白血病(ALL)是儿童ALL的高危人群之一。患者和方法我们评估了伊马替尼(340 mg/m(2)/d)联合强化化疗方案是否改善了1~21岁Ph+ALL(N=92)儿童的预后，并与接受相同化疗而不使用伊马替尼的Ph-ALL患者(N=65)进行了毒性比较。在接受伊马替尼治疗的5个患者队列中，伊马替尼的暴露逐渐增加，从维持治疗前的42天(队列1；n=7)到连续280天(队列5；n=50)。人类白细胞抗原相合的同胞捐献者接受了血液和骨髓移植，并在骨髓移植后给予伊马替尼6个月。结果连续应用伊马替尼改善了5名队列患者的预后，3年无事件生存率(EFS)为80%+/-11%(95%CI，%至90%)，是历史对照组(35%+/-4%；P<；.0001)的两倍多。接受化疗加伊马替尼的第5组患者的3年EFS相似(88%+/-11%；95%CI，66%至96%)或兄弟姐妹供者骨髓移植(57%+/-22%；95%CI，30.4%至76.1%)。在强化化疗中加入伊马替尼没有明显的毒性反应。第5组中伊马替尼剂量越大，诱导后残留病负担越高的儿童的生存率越高。结论伊马替尼联合强化化疗可改善Ph+ALL儿童和青少年的3年EFS，且毒性无明显增加。骨髓移植加伊马替尼并不比单用骨髓移植有任何优势。需要额外的随访来确定这种治疗对长期EFS的影响，并确定化疗加伊马替尼是否可以取代骨髓移植。
PurposeImatinib mesylate is a targeted agent that may be used against Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups.Patients and MethodsWe evaluated whether imatinib (340 mg/m(2)/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT.ResultsContinuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% +/- 11% (95% CI, 64% to 90%), more than twice historical controls (35% +/- 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% +/- 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% +/- 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction.ConclusionImatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.