Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group.
Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group.
复制标题
拥有六年经验，采用综合方法治疗复发性儿童急性淋巴细胞白血病 (ALL-REZ BFM 85)。
DOI：
10.1182/blood.v78.5.1166.bloodjournal7851166
复制
发表时间：
1991
期刊：
影响因子：
20.3
通讯作者：
H. Riehm
中科院分区：
文献类型：
--
作者：
G. Henze;R. Fengler;R. Hartmann;B. Kornhuber;G. Janka;D. Niethammer;H. Riehm
在1985年4月至1987年3月期间，130名年龄不超过18岁的急性淋巴细胞白血病（ALL）首次复发的儿童和青少年在分层和随机多中心试验ALL-REZ BFM 85中登记，该试验设计用于接受强化一线治疗的患者。分层标准为复发的时间和部位：一线治疗停止后6个月或6个月内骨髓（BM）复发（A组），治疗后6个月以上BM复发（B组），以及任何时间的孤立性髓外复发（C组）。治疗包括交替的综合化疗，包括随机给予高剂量或中剂量甲氨蝶呤（HDMTX：12 g/m2，4小时输注; IDMTX：1 g/m2，36小时输注）。在维持治疗期间，患者接受每日口服硫鸟嘌呤和每两周静脉注射（IV）MTX。总体第二次完全缓解（CR）率为92%（A、B和C组：88%、92%和100%），6年无事件生存率（EFS）概率为0.31 ± 0.04（A、B和C组：0.18 ± 0.05、0.30 ± 0.07和0.72 ± 0.11）。HDMTX未证明上级于IDMTX，这导致提前停止随机化。风险因素分析显示早期复发，特别是18个月内BM复发，T细胞表型是预后不良的独立预测因素。BM复发后中枢神经系统（CNS）复发的发生率为19%，表明IV/鞘内（IT）MTX对CNS的再预防不足。对于17名在第二次CR中接受HLA相容同胞骨髓移植的儿童，5年时的EFS为0.53 +/- 0.12。其结局不受上述危险因素的影响。使用所提出的治疗方案，即使在密集的一线治疗之后，也可以在约三分之一的患者中实现持久的第二次缓解。
Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL-REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front-line treatment.