Long-Term Outcome in Children With Relapsed Acute Lymphoblastic Leukemia After Time-Point and Site-of-Relapse Stratification and Intensified Short-Course Multidrug Chemotherapy: Results of Trial ALL-REZ BFM 90
Long-Term Outcome in Children With Relapsed Acute Lymphoblastic Leukemia After Time-Point and Site-of-Relapse Stratification and Intensified Short-Course Multidrug Chemotherapy: Results of Trial ALL-REZ BFM 90
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DOI：
10.1200/jco.2009.25.1983
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发表时间：
2010-05-10
影响因子：
45.3
通讯作者：
von Stackelberg, Arend
中科院分区：
文献类型：
--
作者：
Tallen, Gesche;Ratei, Richard;von Stackelberg, Arend
目的多中心试验ALL-REZ BFM（即，急性淋巴细胞白血病复发柏林-法兰克福-明斯特）90旨在通过复发时间和复发部位适应性分层以及通过引入新的化疗元素来改善复发急性淋巴细胞白血病（ALL）儿童的预后，并在一个大型，患者和方法525例患者分为风险组A（早期骨髓[BM]复发），B（晚期BM复发），和C（孤立的髓外复发）接受交替短程强化综合化疗（在区块R1、R2或R3中）和颅/颅脊髓照射，随后维持治疗。与历史对照组相比，R3组（高剂量阿糖胞苷和依托泊苷）被引入以改善结局。早期BM或T-ALL复发患者（预后不良组[PPG]）有资格接受实验方案。117例患者接受了干细胞移植（SCT）。结果10年无事件生存率（pEFS）和总生存率（pOS）的概率（和标准差）分别为0.30 +/- .02和0.36 +/- .02。策略组之间存在显著差异（pEFS（A）= .17 +/- .03; pEFS（B）= .43 +/- .04; pEFS（C）= .54 +/- .06; pEFS（PPG）= .15 +/- .03;对数秩P < .001）。高危组A加PPG的患者接受SCT的效果优于接受化疗的患者（pEFS = 0.33 +/- .05 v0.20 +/- .05; P = .005）。pEFS与试验ALL-REZ BFM 85/87相似（0.36 +/-0.03。v 0.37 +/- .03; P = .419;排除PPG）。时间点，复发部位，免疫表型，SCT是显着的预测pEFS在多变量analysis.ConclusionMore三分之一以上的患者在这个大的，以人群为基础的试验治愈。无论是R3还是化疗强度的适应都不能改善pEFS或克服预后因素。在高危患者中，缓解诱导方案必须改进，在达到第二次完全缓解的患者中应推荐异基因SCT。
PurposeThe multicenter trial ALL-REZ BFM (ie, Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Munster) 90 was designed to improve prognosis for children with relapsed acute lymphoblastic leukemia (ALL) by time-to-relapse-and site-of-relapse-adapted stratification and by introduction of novel chemotherapy elements and to evaluate new prognostic parameters in a large, population-based cohort.Patients and MethodsFive hundred twenty-five patients stratified into risk groups A (early bone marrow [BM] relapses), B (late BM relapses), and C (isolated extramedullary relapses) received alternating short-course intensive polychemotherapy (in blocks R1, R2, or R3) and cranial/craniospinal irradiation followed by maintenance therapy. Block R3 (high-dose cytarabine and etoposide) was introduced to improve the outcome compared with historical controls. Patients with early BM or T-ALL relapse (poor prognosis group [PPG]) were eligible for experimental regimens. One hundred seventeen patients received stem-cell transplantation (SCT).ResultsThe probabilities (and standard deviations) of event-free survival (pEFS) and overall survival (pOS) at 10 years were 0.30 +/- .02 and 0.36 +/- .02, respectively. Significant differences existed between strategic groups (pEFS(A) = .17 +/- .03; pEFS(B) = .43 +/- .04; pEFS(C) = .54 +/- .06; pEFS(PPG) = .15 +/- .03; log-rank P < .001). Patients of high-risk groups A plus PPG did better with SCT than with chemotherapy (pEFS = .33 +/- .05 v 0.20 +/- .05; P = .005). The pEFS was similar to trials ALL-REZ BFM 85/87 (.36 +/- .03. v 0.37 +/- .03; P = .419; PPG excluded). Time point, site of relapse, immunophenotype, and SCT were significant predictors of pEFS in multivariate analyses.ConclusionMore than one third of patients in this large, population-based trial were cured. Neither R3 nor adaptation of chemotherapy intensity was capable of improving pEFS or of overcoming prognostic factors. In high-risk patients, remission induction regimens must be improved, and allogeneic SCT should be recommended in patients achieving second complete remission.