Schrappe M, Reiter A, Ludwig W D, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H
Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Federal Republic of Germany (FRG).
Blood. 2000 Jun 1;95(11):3310-22.
Trial ALL-BFM 90 was designed to improve outcome in patients with childhood acute lymphoblastic leukemia (ALL) by using a reduced treatment regimen. Patients were stratified into a standard-risk group (SRG), a medium-risk group (MRG), both defined by adequate early treatment response; and a high-risk group (HRG), defined by inadequate response to the cytoreductive prednisone prephase, induction failure, or Philadelphia-chromosome-positive ALL. Four treatment modifications were evaluated: dose intensification in induction by a more rapid drug sequence; administration of L-asparaginase during consolidation therapy in the MRG (randomized); enforced consolidation by rotational elements in the HRG; and reduction in the dose of anthracyclines and use of only 12-Gy preventive cranial radiotherapy in the MRG and HRG, with the aim of avoiding toxicity. Among all 2178 patients (</= 18 years of age), the 6-year event-free survival (EFS) rate (+/- SE) was 78% +/- 1%, with a median observation time of 4.8 years. EFS was 85% +/- 2% in the SRG (n = 636) and 82% +/- 1% in the MRG (n = 1299). L-asparaginase did not improve outcome in the MRG: the event-free interval was 83% +/- 2% with L-asparaginase (n = 528) and 81% +/- 2% without it (n = 557). Because there were more systemic relapses in the HRG (n = 243), EFS was 34% +/- 3%, an outcome inferior to that in the HRG in a previous trial, ALL-BFM 86, in which EFS was 47% +/- 5% (P =.04). The rates of isolated central nervous system relapse in the MRG and HRG were 0.8% and 1.6%, respectively; thus, the 12-Gy preventive cranial radiotherapy regimen apparently provided sufficient central nervous system prophylaxis. The overall improvement over the results in ALL-BFM 86 (6-year EFS, 72%; P =. 001) was based on fewer recurrences among patients in the MRG with B-cell-precursor ALL, indicating an advantage of more condensed induction therapy. In multivariate analysis, inadequate in vivo response emerged as the strongest adverse prognostic variable.
ALL-BFM 90试验旨在通过采用简化治疗方案来改善儿童急性淋巴细胞白血病（ALL）患者的治疗结果。患者被分为标准风险组（SRG）、中风险组（MRG），这两组均由早期治疗反应充分来定义；以及高风险组（HRG），由对细胞减灭性泼尼松前期治疗反应不足、诱导失败或费城染色体阳性ALL来定义。评估了四项治疗调整措施：诱导期通过更快速的药物给药顺序强化剂量；中风险组在巩固治疗期间给予L-天冬酰胺酶（随机分组）；高风险组通过轮换方案强制进行巩固治疗；以及中风险组和高风险组减少蒽环类药物剂量并仅使用12 Gy预防性颅脑放疗，目的是避免毒性。在所有2178例（≤18岁）患者中，6年无事件生存率（EFS）（±SE）为78%±1%，中位观察时间为4.8年。标准风险组（n = 636）的EFS为85%±2%，中风险组（n = 1299）为82%±1%。L-天冬酰胺酶并未改善中风险组的治疗结果：使用L-天冬酰胺酶组（n = 528）的无事件间期为83%±2%，未使用者（n = 557）为81%±2%。由于高风险组（n = 243）的全身复发更多，EFS为34%±3%，这一结果低于之前ALL-BFM 86试验中高风险组的结果，后者的EFS为47%±5%（P = 0.04）。中风险组和高风险组孤立性中枢神经系统复发率分别为0.8%和1.6%；因此，12 Gy预防性颅脑放疗方案显然提供了足够的中枢神经系统预防。与ALL-BFM 86试验结果（6年EFS，72%；P = 0.001）相比，总体改善基于中风险组B细胞前体ALL患者中复发减少，表明更密集诱导治疗的优势。在多变量分析中，体内反应不足成为最强的不良预后变量。
