Rees J K, Gray R G, Swirsky D, Hayhoe F G
Lancet. 1986 Nov 29;2(8518):1236-41. doi: 10.1016/s0140-6736(86)92674-7.
Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6-thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse-free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure-related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0.003) survival.
1978年至1983年间，1127例初发急性髓系白血病（AML）患者参与了医学研究委员会（MRC）的第8次AML试验。所有患者均接受了相同的诱导治疗，包括柔红霉素、阿糖胞苷和6-硫鸟嘌呤——即DAT（1 + 5）方案。进入完全缓解的67%的患者被随机分配接受两疗程或六疗程的DAT巩固治疗。55岁以下的成年人被随机分配接受鞘内注射阿糖胞苷和甲氨蝶呤进行中枢神经系统（CNS）预防。最后，在接受阿糖胞苷和6-硫鸟嘌呤（AT）维持治疗1年后仍处于缓解期的患者被随机分配接受环磷酰胺、长春新碱、阿糖胞苷和泼尼松龙（COAP）的晚期强化治疗或继续接受AT治疗。整个组的中位生存期为12个月；首次缓解的中位持续时间为15个月，5年无复发生存率估计为18%。与生存不良最密切相关的因素是体能状态和就诊时的年龄，但即使在60岁以上的患者中，也有一半进入了缓解期。六疗程的DAT巩固治疗在减少晚期复发数量方面比两疗程有微小优势，但在生存方面无显著优势。晚期强化治疗比继续AT维持治疗显示出略微显著的优势。CNS复发的发生率较低，且不受预防措施的影响。第二次缓解率从首次缓解期短于6个月时的10%到持续超过2年时的61%不等。40例患者在首次缓解期接受了组织相容性同种异体骨髓移植。与手术相关的死亡率很高，尤其是在30岁以上的患者中。因此，至少在最初，移植组的生存期比一组接受化疗的可比患者短。在整个试验过程中治疗规范保持不变，但在试验后半期入组的患者生存期更好（p = 0.003）。
