Shimizu H, Kikuchi M, Takaue Y, Utsumi J, Takeda T, Fujimoto T
Department of Pediatrics, Aichi Medical University, Japan.
Int J Hematol. 1995 Feb;61(2):85-96. doi: 10.1016/0925-5710(94)00349-j.
From 1985 to 1989, 69 patients with non-Hodgkin's lymphoma (NHL) were treated by members of the Children's Cancer and Leukemia Study Group of Japan with a protocol consisting of vincristine, prednisolone, cyclophosphamide, doxorubicin, high-dose methotrexate (HD-MTX), mercaptopurine and cytarabine; central nervous system (CNS) prophylaxis with intrathecal MTX and hydrocortisone (NHL855). The 4-year event-free survival (EFS) was 78% (S.E., 10%) for patients with localized disease (n = 18) and 38% (S.E., 7%) for those with advanced disease (n = 51). Among the patients with advanced disease, those with non-lymphoblastic lymphoma tended to have a better 4-year EFS than those with lymphoblastic lymphoma (52% vs. 25%). Based on these findings, we initiated a new protocol NHL890 in which patients were assigned to two different chemotherapies according to the histology. Non-lymphoblastic subtype was treated almost identically to NHL855 while asparaginase and VP-16 were newly added in the consolidation-maintenance phase in advanced-stage lymphoblastic lymphoma. Sixty-seven patients with advanced disease were assessable. The overall 4-year EFS for advanced disease improved to 69% (S.E., 6%). A significant improvement was gained in the lymphoblastic lymphoma with a 4-year EFS of 56% (S.E., 11%) as compared with 25% (S.E., 9%) in the preceding study (P < 0.05). These findings suggest the importance of histology in the treatment of advanced-stage non-Hodgkin's lymphoma in childhood.
1985年至1989年期间，日本儿童癌症与白血病研究组的成员采用包含长春新碱、泼尼松龙、环磷酰胺、阿霉素、大剂量甲氨蝶呤（HD-MTX）、巯嘌呤和阿糖胞苷的方案，对69例非霍奇金淋巴瘤（NHL）患者进行了治疗；采用鞘内注射甲氨蝶呤和氢化可的松进行中枢神经系统（CNS）预防（NHL855）。局限性疾病患者（n = 18）的4年无事件生存率（EFS）为78%（标准误，10%），晚期疾病患者（n = 51）的4年无事件生存率为38%（标准误，7%）。在晚期疾病患者中，非淋巴细胞性淋巴瘤患者的4年EFS往往优于淋巴细胞性淋巴瘤患者（52%对25%）。基于这些发现，我们启动了一项新方案NHL890，根据组织学将患者分为两种不同的化疗方案。非淋巴细胞性亚型的治疗与NHL855几乎相同，而在晚期淋巴细胞性淋巴瘤的巩固维持阶段新添加了天冬酰胺酶和依托泊苷。67例晚期疾病患者可进行评估。晚期疾病的总体4年EFS提高到了69%（标准误，6%）。淋巴细胞性淋巴瘤有显著改善，4年EFS为56%（标准误，11%），而在前一项研究中为25%（标准误，9%）（P < 0.05）。这些发现表明组织学在儿童晚期非霍奇金淋巴瘤治疗中的重要性。
