Koizumi S, Fujimoto T
Department of Pediatrics, Kanazawa University School of Medicine, Japan.
Int J Hematol. 1994 Feb;59(2):99-112.
The Children's Cancer and Leukemia Study Group (CCLSG) has conducted, since 1981, a series of protocols for treatment of acute lymphoblastic leukemia (ALL) in childhood. In a randomized control study of the 811 protocol (1981-1983) for standard-risk ALL, an intermittent cyclic regimen of an intermediate-dose of methotrexate (MTX) plus 6-mercaptopurine (6MP) showed significant superiority for maintenance chemotherapy as compared with conventional continuous administration of a low dose of the two drugs. The event-free survival (EFS) rate at 10 years was 65.4% for the intermittent cyclic regimen, while the EFS rate of continuous regimen was 36.1% (P < 0.01). The intermittent cyclic regimen may also be effective in preventing extramedullary relapses. In the 841 protocol (1984-1987), the three-drug induction therapy consisting of vincristine (VCR), prednisone (PDN) and L-asparaginase (L-ASP) improved the EFS rate (94.1% at 8 years) as compared with the two-drug therapy consisting of VCR and PDN (64.1%, P < 0.05). In the 874 protocol (1987-1990) two regimens with or without cranial irradiation for standard-risk patients were compared with respect to their ability to prevent central nervous system (CNS) leukemia and to improve overall outcome of ALL. The regimen with cranial irradiation showed a 79.9% EFS rate at 5 years, whereas the regimen without cranial irradiation demonstrated a 69.1% EFS rate (not significantly). Life-table analysis of serial CCLSG protocols for ALL in which the cyclic administration of intermediate-dose MTX plus 6MP has been standardized as maintenance therapy revealed that the outcome of allover ALL has gradually improved with increase of the EFS rate; 41.4% for the 811 protocol, 51.4% for the 841 protocol to 54.4% for the more recent 874 protocol.
自1981年以来，儿童癌症与白血病研究组（CCLSG）开展了一系列针对儿童急性淋巴细胞白血病（ALL）的治疗方案。在一项针对标准风险ALL的811方案（1981 - 1983年）的随机对照研究中，与常规持续低剂量给予甲氨蝶呤（MTX）和6 - 巯基嘌呤（6MP）相比，中等剂量MTX加6MP的间歇循环方案在维持化疗方面显示出显著优势。间歇循环方案的10年无事件生存率（EFS）为65.4%，而持续方案的EFS率为36.1%（P < 0.01）。间歇循环方案在预防髓外复发方面可能也有效。在841方案（1984 - 1987年）中，与由长春新碱（VCR）和泼尼松（PDN）组成的两药疗法相比，由VCR、泼尼松（PDN）和L - 天冬酰胺酶（L - ASP）组成的三药诱导疗法提高了EFS率（8年时为94.1%）（两药疗法的EFS率为64.1%，P < 0.05）。在874方案（1987 - 1990年）中，比较了标准风险患者接受或不接受颅脑照射的两种方案预防中枢神经系统（CNS）白血病和改善ALL总体结局的能力。接受颅脑照射的方案5年EFS率为79.9%，而未接受颅脑照射的方案EFS率为69.1%（无显著差异）。对CCLSG针对ALL的系列方案进行生命表分析，其中中等剂量MTX加6MP的循环给药已标准化作为维持治疗，结果显示随着EFS率的提高，ALL的总体结局逐渐改善；811方案为41.4%，841方案为51.4%，到最近的874方案为54.4%。
