Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: Results of the European Organization for Research and Treatment of Cancer 58881 Randomized Phase III Trial
Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: Results of the European Organization for Research and Treatment of Cancer 58881 Randomized Phase III Trial
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DOI：
10.1200/jco.2001.19.7.1935
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发表时间：
2001-04-01
影响因子：
45.3
通讯作者：
Otten, J
中科院分区：
文献类型：
--
作者：
Millot, F;Suciu, S;Otten, J
目的：欧洲癌症研究和治疗组织58881研究旨在通过一项前瞻性多中心随机试验，测试大剂量阿糖胞苷(Ara-C)静脉注射加甲氨蝶呤(MTX)治疗高危急性淋巴细胞白血病(ALL)或接受柏林-法兰克福-明斯特(BFM)方案治疗的III和IV期淋巴母细胞淋巴瘤的儿童，在减少中枢神经系统和系统性复发方面的价值。0.8或T细胞系)ALL或III、IV期淋巴母细胞淋巴瘤被随机分成两组，分别接受4个疗程的甲氨蝶呤(5 g/m(2)，每2周24小时)和4次鞘内甲氨蝶呤(A组)或相同的治疗方案(A组)或在每次甲氨蝶呤滴注后12小时和24小时内追加I-ID IV Ara-C(1 g/m(2))(B组)。653例ALL(593例)或淋巴母细胞淋巴瘤(60例)患者被随机分成两组：323例被分配到A组(不使用Ara-C)，330例被分配到B组(使用Ara-C)。总共报告了190个事件(177个复发和13个无复发的死亡)，中位随访时间为6.5年(范围为2-10年)。无论是单独使用(5.6%和3.3%)还是合并使用(5.3%和4.6%)，两组患者的中枢神经系统复发发生率相似。两组估计的6年无病生存率相似(对数等级P=0.67)：A组70.4%(SE=2.6%)，B组71.0%(SE=2.5%)。ALL和LL患者6年无病生存率相似：70.2%(SE=1.9%)和76.3%(SE=5.6%)。鞘内注射MTX治疗高危ALL或III和IV期淋巴母细胞淋巴瘤，采用我们的基于BFM的治疗方案，其中省略了头部照射。令人失望的是，根据该方案中使用的剂量方案，HD Ara-C添加到HD MTX中，尽管耐受性良好，但未能进一步降低中枢神经系统复发的发生率或改善总体DFS。(C)2001年，由美国临床肿瘤学会主办。
Purpose: The European Organization for Research and Treatment of Cancer 58881 study was designed to test in a prospective multicentric randomized trial the value of high-dose (HD) intravenous (IV) cytarabine (Ara-C) added to HD IV methotrexate (MTX) to reduce the incidence of CNS and systemic relapses in children with increased-risk acute lymphoblastic leukemia (ALL) or stage III and IV lymphoblastic lymphoma treated with a Berlin-Frankfurt-Munster (BFM)-based regimen.Patients and Methods: After completion of induction-consolidation phase, children with increased-risk (risk factor > 0.8 or T-lineage) ALL or stage III and IV lymphoblastic lymphoma were randomized to receive four courses of I-ID MTX (5 g/m(2) over 24 hours every 2 weeks) and four intrathecal administrations of MTX (Arm A) or the same treatment schedule with additional I-ID IV Ara-C (1 g/m(2) in bolus injection 12 and 24 hours after the start of: each MTX infusion) (Arm B).Results: Between January 1990 and January 1996, 653 patients with ALL (593 patients) or lymphoblastic lymphoma (60 patients) were randomized: 323 were assigned to Arm A (without Ara-C) and 330 to Arm B (with Ara-C). A total of 190 events (177 relapses and 13 deaths without relapse) were reported, and the median follow up was 6.5 years (range, 2 to 10 years). The incidence rates of CNS relapse were similar in both arms whether isolated (5.6% and 3.3%, respectively) or combined (5.3% and 4.6%, respectively). The estimated 6-year disease-free survival (DFS) rate was similar (log-rank P = .67) in the two treatment groups: 70.4% (SE = 2.6%) in Arm A and 71.0% (SE = 2.5%) in Arm B. The 6-year DFS rate was similar for ALL and LL patients: 70.2% (SE = 1.9%) versus 76.3% (SE = 5.6%).Conclusion: Prevention of CNS relapse was satisfactorily achieved with HD IV MTX and intrathecal injections of MTX in children with increased-risk ALL or stage III and IV lymphoblastic lymphoma treated with our BFM-based treatment protocol in which cranial irradiation was omitted. Disappointingly, with the dose schedule used in this protocol, HD Ara-C added to HD MTX, although well tolerated, failed to further decrease the incidence of CNS relapse or to improve the overall DFS. (C) 2001 by American Society of Clinical Oncology.