Zittoun R, Jehn U, Fière D, Haanen C, Löwenberg B, Willemze R, Abels J, Bury J, Peetermans M, Hayat M
Service d'Hématologie, Hôtel-Dieu, Paris, France.
Blood. 1989 Mar;73(4):896-906.
The value of a postremission treatment in acute myelogenous leukemia (AML), with alternating combinations of non-cross-resistant drugs, has been prospectively assessed. Of 515 evaluable patients, 347 (67.4%) entered into complete remission (CR), following induction treatment with daunorubicin (DNR), vincristine (VCR), and cytosine arabinoside (ara-C). After one consolidation course, 248 patients were randomized for six courses of intensive maintenance: either repeated treatment with DNR-VCR-ara-C, or alternating treatment where amsacrine (AMSA) was combined with high dose ara-C on cycle 1,3, and 5 and with 5-azacytidine on cycle 2, 4, and 6. Ninety-nine patients were not randomized: 57 were introduced in a bone marrow transplantation (BMT) program, and 42 went off study, mainly for treatment toxicity or refusal. The main prognostic factors for achievement of CR were performance status, cytogenetics, and age, and for the disease-free survival (DFS): age and number of courses to CR. The rate of second remission was fairly high (64%) for patients relapsing off therapy. The DFS appeared identical (median, 53 weeks), in the two randomized arms, the alternating treatment not showing superiority to the repeated one, in spite of an increased toxicity. The median overall survival for patients achieving a CR was 90 weeks. The reason for the failure of alternating maintenance treatment to improve the DFS is probably related to an insufficient dose intensity: five patients who relapsed during maintenance arm B achieved a second CR with a more intensive combination of high-dose ara-C and AMSA. In addition, 60 patients underwent a BMT (43 allogeneic and 17 autologous). The DFS of patients treated with allogeneic BMT tended to be superior to the one obtained with the chemotherapy program. However the overall survival, as well as the event-free survival, seemed equivalent, including patients who relapsed before the planned BMT. Comparisons between allogeneic BMT, autologous BMT, and intensive consolidation during first CR deserve further prospective studies in AML.
对急性髓性白血病（AML）采用非交叉耐药药物交替联合进行缓解后治疗的价值已得到前瞻性评估。在515例可评估患者中，347例（67.4%）在接受柔红霉素（DNR）、长春新碱（VCR）和阿糖胞苷（ara-C）诱导治疗后进入完全缓解（CR）。经过一个巩固疗程后，248例患者被随机分为六个强化维持疗程组：一组为重复使用DNR-VCR-ara-C治疗，另一组为交替治疗组，在第1、3和5周期将安吖啶（AMSA）与大剂量ara-C联合使用，在第2、4和6周期与5-氮杂胞苷联合使用。99例患者未被随机分组：57例进入骨髓移植（BMT）项目，42例退出研究，主要原因是治疗毒性或拒绝治疗。实现CR的主要预后因素为体能状态、细胞遗传学和年龄，无病生存（DFS）的主要预后因素为年龄和达到CR所需的疗程数。治疗后复发患者的第二次缓解率相当高（64%）。在两个随机分组的治疗组中，DFS似乎相同（中位数为53周），交替治疗组尽管毒性增加，但并未显示出优于重复治疗组。达到CR的患者的总生存中位数为90周。交替维持治疗未能改善DFS的原因可能与剂量强度不足有关：在维持治疗组B中复发的5例患者通过大剂量ara-C和AMSA更强化的联合治疗实现了第二次CR。此外，60例患者接受了BMT（43例为异基因移植，17例为自体移植）。接受异基因BMT治疗的患者的DFS往往优于化疗方案组。然而，总生存以及无事件生存似乎相当，包括在计划进行BMT之前复发的患者。在AML中，异基因BMT、自体BMT和首次CR期间的强化巩固治疗之间的比较值得进一步进行前瞻性研究。
