Conter V, Aricò M, Valsecchi M G, Rizzari C, Testi A M, Messina C, Mori P G, Miniero R, Colella R, Basso G
Department of Pediatrics, University of Milano, Italy.
J Clin Oncol. 1995 Oct;13(10):2497-502. doi: 10.1200/JCO.1995.13.10.2497.
To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy.
Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], < 0.8); intermediate risk (IR) were patients with an RI > or = 0.8 but less than 1.2; and high risk (HR) were those with an RI > or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients.
Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group.
Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.
评估强化治疗以及在以柏林-法兰克福-明斯特（BFM）方案为基础的强化化疗的中危急性淋巴细胞白血病（ALL）儿童中，延长鞘内注射甲氨蝶呤替代颅脑照射的效果。
396例非B-ALL儿童被纳入意大利儿科血液学和肿瘤学会（AIEOP）ALL 88研究。标准风险（SR）包括肿瘤负荷低的患者（BFM风险指数[RI]，<0.8）；中危（IR）是RI≥0.8但小于1.2的患者；高危（HR）是诊断时RI≥1.2或有中枢神经系统受累的患者。治疗方案是ALL-BFM 86研究的改良版。针对中枢神经系统的治疗包括大剂量甲氨蝶呤（HD-MTX；5 g/m²，共四个疗程）加鞘内注射甲氨蝶呤（IT-MTX；九剂）；IR患者在继续治疗期间额外接受延长的IT-MTX（九剂）；仅对HR患者进行颅脑照射。
在375例（94.7%）达到缓解的儿童中，1.3%发生了除复发外的不良事件。6年时的无事件生存率（EFS）总体为66.6%（标准误2.4）；SR患者为80.7%（4.5），IR患者为77.5%（3.9），HR患者为54.5%（3.7）。107例儿童（27.0%）复发。孤立性中枢神经系统复发发生在20例儿童（5.0%）中：SR组5例（6.3%），IR组1例（0.8%），HR组14例（7.1%）。估计6年无中枢神经系统白血病生存率总体为94.6%（1.2）：SR组为93.5%（2.8），IR组为99.1%（0.9），HR组为92.3%（2.0）。
在接受基于BFM方案的强化化疗且给予延长鞘内化疗的IR ALL患者中，可以安全地省略颅脑照射。由于SR组中枢神经系统疾病控制不够完全，这些数据对HD-MTX预防中枢神经系统疾病的有效性提出了质疑，并支持延长鞘内化疗的保护作用。
