Bührer C, Henze G, Hofmann J, Reiter A, Schellong G, Riehm H
Departments of Pediatric, Hannover Medical School, FRG.
Haematol Blood Transfus. 1990;33:500-3. doi: 10.1007/978-3-642-74643-7_90.
In treatment of childhood ALL, prevention of CNS relapse by cranial irradiation is followed by considerable long-term sequelae. In the three ALL-BFM (Berlin-Frankfurt-Münster) trials 70, 76, and 79, employing radiotherapy (8.5 Gy craniospinal, 18 or 24 Gy cranial irradiation) in all arms, the incidence of CNS relapses (isolated and combined) in standard-risk patients (SR, 60% of all children) was consistently less than 6%. A risk factor (RF) calculated from absolute blast number, liver, and spleen size at diagnosis was used to stratify patients in the subsequent trials ALL-BFM 81 and 83. In ALL-BFM 81, SR patients (RF less than 1.2) were randomized to receive 18 Gy cranial irradiation or intermediate-dose i.v. methotrexate (ID-MTX) (4 x 0.5 g/m2). In ALL-BFM 83, the SR group was further subdivided into group SR low (SR-L, RF less than 0.8) and group SR high (SR-H, RF 0.8 - less than 1.2). SR-L patients received no irradiation, and were tested by randomization for the effectiveness of an intensive reinduction regimen (protocol III). SR-H patients were randomized for 12 or 18 Gy. The results were as follows: In patients of both trials with RF less than 0.8, radiotherapy could be replaced by ID-MTX plus protocol III. Without protocol III, relapses increased from 15.7% to 31.7%. Concomitantly, the fraction of relapses with CNS involvement increased from 26.7% to 36.4%. However, SR patients with RF between 0.8 and 1.2 could not be protected by reinduction alone (isolated/overall CNS relapse rate with irradiation, 4%/5%; without irradiation, 11%/22%). Dosages of 12 and 18 Gy were found to be equally protective.
在儿童急性淋巴细胞白血病（ALL）的治疗中，通过颅脑照射预防中枢神经系统（CNS）复发会带来相当多的长期后遗症。在ALL-BFM（柏林-法兰克福-明斯特）的三项试验70、76和79中，所有治疗组均采用放射治疗（全脑脊髓照射8.5 Gy，颅脑照射18或24 Gy），标准风险患者（SR，占所有儿童的60%）的CNS复发（孤立性和合并性）发生率始终低于6%。根据诊断时的原始细胞绝对计数、肝脏和脾脏大小计算出的风险因素（RF）用于在随后的ALL-BFM 81和83试验中对患者进行分层。在ALL-BFM 81中，SR患者（RF小于1.2）被随机分为接受18 Gy颅脑照射或中等剂量静脉注射甲氨蝶呤（ID-MTX）（4×0.5 g/m²）。在ALL-BFM 83中，SR组进一步细分为SR低危组（SR-L，RF小于0.8）和SR高危组（SR-H，RF 0.8至小于1.2）。SR-L患者不接受照射，并通过随机分组测试强化再诱导方案（方案III）的有效性。SR-H患者被随机分为接受12或18 Gy照射。结果如下：在两项试验中RF小于0.8的患者中，放射治疗可被ID-MTX加方案III替代。没有方案III时，复发率从15.7%增至31.7%。同时，CNS受累的复发比例从26.7%增至36.4%。然而，RF在0.8至1.2之间的SR患者不能仅通过再诱导得到保护（接受照射时孤立性/总体CNS复发率为4%/5%；未接受照射时为11%/22%）。发现12 Gy和18 Gy的剂量具有同等的保护作用。
