Matthews J P, Bishop J F, Young G A, Juneja S K, Lowenthal R M, Garson O M, Cobcroft R G, Dodds A J, Enno A, Gillett E A, Hermann R P, Joshua D E, Ma D D, Szer J, Taylor K M, Wolf M, Bradstock K F
Peter MacCallum Cancer Institute, Melbourne, Australia.
Br J Haematol. 2001 Jun;113(3):727-36. doi: 10.1046/j.1365-2141.2001.02756.x.
Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.
澳大利亚白血病研究组（ALSG）在1984年至1991年间进行了两项连续的强化诱导治疗随机试验，研究失败模式以确定剂量强化的影响。患者接受标准剂量阿糖胞苷和柔红霉素（7 - 3）、7 - 3加依托泊苷（7 - 3 - 7）或7 - 3加高剂量阿糖胞苷（大剂量阿糖胞苷 - 3 - 7）化疗。FAB M3形态的患者被排除。失败时间（TTF）定义为从随机分组到诱导死亡或因无反应者退出研究的时间，或完全缓解（CR）患者复发或死亡的时间。在470例急性髓系白血病初治患者中，估计86%在随机分组后10年内失败，原因是17%的随机分组患者在诱导期死亡，另有17%未达到CR，44%复发，8%的患者在CR期死亡。估计66%的患者在该期间因难治性疾病或复发而失败（疾病相关失败）。多因素分析确定年龄和外周血原始细胞计数是与总体TTF最显著相关的预处理因素。这些因素与细胞遗传学一起，与疾病相关失败显著相关。诱导期使用大剂量阿糖胞苷显著降低了疾病相关失败率，首次CR时进行异基因移植也是如此。大剂量阿糖胞苷的影响不依赖于细胞遗传学风险组。
