Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group
Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group
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DOI：
10.1200/jco.2015.64.6364
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发表时间：
2016-08-01
影响因子：
45.3
通讯作者：
Van Dongen, Jacques
中科院分区：
文献类型：
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作者：
Pieters, Rob;de Groot-Kruseman, Hester;Van Dongen, Jacques
目的通过加强化疗，儿童急性淋巴细胞白血病(ALL)的疗效明显改善。第一个月的微小残留病(MRD)水平可以预测预后，并可能选择接受减少或强化治疗的患者。方法根据第一和第二疗程化疗后的MRD水平对1~18岁的ALL患者进行分层。此后，对无法检测到的MRD(标准风险)的患者的治疗大大减少，而对中(中风险)和高(高风险)MRD水平的患者加强治疗。连续778名患者入选。分析方法为意向处理。结果基于MRD的标准风险患者的5年无事件生存率(EFS)为93%(SE 2%)，5年生存率为99%(SE 1%)，5年累积复发率为6%(SE 2%)。基于MRD的中危患者在强化治疗(包括30周的天冬酰胺酶暴露和地塞米松/长春新碱冲击)后的5年EFS率(88%，SE 2%)显著高于历史对照组(76%，SE 6%)。在以MRD为基础的高危患者中，强化化疗和干细胞移植导致了显著更好的5年EFS率(对照组为78%，SE 8%v16%，SE 8%)。与之前的荷兰儿童肿瘤学小组方案相比，总体结果显著改善(5年EFS率87%，5年存活率92%，5年累积复发率8%)。结论在根据不可检测的MRD水平选择的ALL儿童中，四分之一的儿童化疗显著安全地减少，而不会危及生存率。中度和高度MRD患者的预后随着治疗的加强而改善。(C)2016年度美国临床肿瘤学会
PurposeOutcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification.MethodsPatients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to-treat. Outcome was compared with historical controls.ResultsIn MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe.MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5-year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols.ConclusionChemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification. (C) 2016 by American Society of Clinical Oncology