Ohno R, Kobayashi T, Morishima Y, Hiraoka A, Imai K, Asoh N, Tsubaki K, Tomonaga M, Takahashi I, Kodera K
Dept. of Medicine, Nagoya Univ. School of Med., Branch Hospital, Japan.
Leukemia. 1992;6 Suppl 2:92-5.
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.
在本研究中，我们提出了两个问题。第一个是长春新碱（VCR）在诱导治疗中的附加作用，第二个是维持治疗的持续时间。成年急性髓系白血病（AML）患者接受以个体化反应为导向的诱导治疗，具体方案为：在第1 - 4天给予山嵛酸阿糖胞苷200 mg/m²每日 + 6 - 巯基嘌呤70 mg/m²每日 + 泼尼松龙40 mg/m²，在第1 - 3天以及第7、8、11、12天给予柔红霉素40 mg/m²（M3型患者在第1 - 4天给予柔红霉素50 mg/m²每日）（BHAC - DMP），直至骨髓严重增生低下，原始细胞少于5%。患者被随机分为接受BHAC - DMP方案组或BHAC - DMP + VCR 0.35 mg/m²（第1 - 4天）方案组。获得完全缓解（CR）后，给予3个疗程的强化巩固治疗并联合鞘内注射甲氨蝶呤 + 阿糖胞苷 + 泼尼松龙。维持强化治疗被随机分为每2个月进行4个疗程或12个疗程。年龄大于或等于60岁的患者接受约2/3减量剂量。从1987年6月至1989年9月，19个机构连续登记了265例成年AML患者，其中258例可评估。年龄范围为15至79岁（中位数为48岁）。在258例患者中，200例（77.5%）获得CR（年龄小于60岁的209例中80%获得CR，年龄大于或等于60岁的49例中65%获得CR）。出乎意料的是，添加VCR显著降低了BHAC - DMP的高CR率（从84%降至70%，p = 0.007）。在中位随访37个月时，总生存率为37%，无事件生存率（EVS）为27%。200例CR患者的生存率、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DFS更好（P = 0.0555）。VCR组的EFS明显更差。通过多因素分析，实现CR的显著预后因素为年龄小于60岁、体能状态（PS）0 - 2且未添加VCR。DFS更长的显著因素为一个疗程诱导CR、FAB M3或M5型以及年龄小于50岁。本多机构研究证实了日本多个中心报道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道的VCR的附加作用。
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