INTENSIVE POSTREMISSION CHEMOTHERAPY IN ADULTS WITH ACUTE MYELOID-LEUKEMIA
INTENSIVE POSTREMISSION CHEMOTHERAPY IN ADULTS WITH ACUTE MYELOID-LEUKEMIA
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DOI：
10.1056/nejm199410063311402
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发表时间：
1994-10-06
影响因子：
158.5
通讯作者：
FREI, E
中科院分区：
文献类型：
--
作者：
MAYER, RJ;DAVIS, RB;FREI, E
背景资料。在以前未经治疗的成人原发急性髓系白血病(AML)中，约65%的人在接受阿糖胞苷和蒽环类药物治疗时进入完全缓解状态。然而，当传统的缓解后治疗时，这种反应很少是持久的。非对照试验表明，缓解后强化治疗可能延长这些完全缓解时间。我们用柔红霉素3天和阿糖胞苷7天治疗1088例新诊断的AML患者，并随机分配完全缓解的患者接受三种剂量之一的四个疗程的阿糖胞苷：持续输注每平方米每天100毫克，连续输注五天，或每平方米3g，在第1、3和5天每12小时(每天两次)输注一次。然后所有患者接受每月四个疗程的维持治疗。在693名完全缓解的患者中，596名患者被随机分配接受缓解后阿糖胞苷治疗。中位随访52个月后，三组患者的无瘤生存率差异有统计学意义(P=0.003)。相对于100毫克组，3毫克组的风险比为0.67(95%可信区间为0.53至0.86)，400毫克组为0.75(95%可信区间为0.60至0.94)。对于60岁或以下的患者，四年后持续完全缓解的概率在100毫克组为24%，400毫克组为29%，3毫克组为44%(P=0.002)。相比之下，对于60岁以上的患者，在三个缓解后阿糖胞苷组中，四年后保持无病的概率均为16%或更低。这些数据支持阿糖胞苷在60岁或更年轻的急性髓细胞白血病患者中存在剂量-反应效应的概念。这一年龄组的大剂量方案的结果与在首次缓解期间接受异基因骨髓移植的类似患者的报告类似。
Background. About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions.Methods. We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment.Results. Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). in contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups.Conclusions. These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.