Randomized study of individualized induction therapy with or without VCR, and of maintenance of 4 or 12 courses in adult AML: JALSG-AML87. Japan Adult Leukemia Study Group (JALSG).
Randomized study of individualized induction therapy with or without VCR, and of maintenance of 4 or 12 courses in adult AML: JALSG-AML87. Japan Adult Leukemia Study Group (JALSG).
复制标题
有或没有 VCR 的个体化诱导治疗以及成人 AML 4 或 12 个疗程维持的随机研究：JALSG-AML87。
作者：
R. Ohno;T. Kobayashi;Y. Morishima;A. Hiraoka;K. Imai;N. Asoh;K. Tsubaki;M. Tomonaga;I. Takahashi;K. Kodera
我们在这项研究中提出了 2 个问题。首先是VCR在诱导治疗中的附加作用，其次是维持治疗的持续时间。成人 AML 接受个体化反应导向诱导治疗，每日使用山嵛酰 Ara-C 200 mg/m2 + 每日 6MP 70 mg/m2 + 第 1-4 天使用泼尼松龙 40 mg/m2 + 第 1-3 天使用 DNA 40 mg/m2，另外在第 7、8、11、12 天使用（对于 M3，每日 DNR 50 mg/m2） (BHAC-DMP) 直到骨髓严重发育不良，原始细胞少于 5%。第 1-4 天，患者被随机分配至 BHAC-DMP 或 BHAC-DMP + VCR 0.35 mg/m2 组。获得CR后，联合I.T进行3个疗程的强化巩固治疗。 MTX+Ara-C+PSL。维持强化治疗随机分为每 2 个月进行 4 或 12 个疗程。年龄大于或等于 60 岁的患者接受了约 2/3 的减少剂量。从1987年6月到1989年9月，19个机构连续登记了265例成人AML，其中258例可评估。年龄范围从 15 岁到 79 岁（中年 48 岁）。在 258 名患者中，有 200 名 (77.5%) 达到 CR（209 名 60 岁以下患者中，80% 获得 CR，49 名 60 岁以上患者中，65% 获得 CR）。出乎意料的是，添加 VCR 显着降低了 BHAC-DMP 的高 CR 率（84% 至 70%，p = 0.007）。中位随访时间为 37 个月，总生存率为 37%，无事件生存 (EVS) 为 27%。 200例CR病例的生存率、持续CR率和无病生存率（DFS）分别为45%、40%和35%。接受 12 个疗程维持治疗的患者显示出更好的 DFS（P = 0.0555）。 VCR 组的 EFS 明显较差。通过多变量分析，实现 CR 的显着预后因素是年龄小于 60 岁、PS 0-2 以及不添加 VCR。较长 DFS 的重要因素是一个疗程诱导 CR、FAB M3 或 M5 以及年龄小于 50 岁。目前的多机构研究证实了日本多个中心报告的以反应为导向的个体化治疗的高 CR 率，但未能支持一个中心报告的 VCR 的额外效果。
We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.