Kenneth F. Bradstock and Warwick Benson, Westmead Hospital, University of Sydney; Arno Enno, Sandra Deveridge, and Philip Rowlings, Calvary Mater Newcastle Hospital, Newcastle; Luke Coyle, Royal North Shore Hospital, St Leonards; Campbell Tiley, Central Coast Health, Gosford; John Moore, St Vincent's Hospital; Mark Hertzberg, Prince of Wales Hospital, Sydney; Kimberly Cartwright, Wollongong Hospital, Wollongong; Ilona Cunningham, Concord Repatriation General Hospital, Concord; John Taper, Nepean Hospital, Penrith, New South Wales; Emma Link, Juliana Di Iulio, and John F. Seymour, Peter MacCallum Cancer Centre; Jeff Szer, Andrew Grigg, Andrew W. Roberts, and John F. Seymour, University of Melbourne; Andrew H. Wei, Monash University; Anthony Schwarer, Box Hill Hospital; Lynda Campbell, Victorian Cancer Cytogenetics Service, Melbourne; Jeff Szer, Andrew Grigg, and Andrew W. Roberts, Royal Melbourne Hospital, Parkville; Phillip Campbell, Deakin University School of Medicine, Geelong, Victoria; Paula Marlton, Anthony K. Mills, and Devinder Gill, University of Queensland, Brisbane, Queensland; Ray M. Lowenthal, University of Tasmania, Hobart, Tasmania; Ian D. Lewis and Peter Bardy, Royal Adelaide Hospital; Uwe Hahn, Queen Elizabeth Hospital, Adelaide, South Australia; James D'Rozario, The Canberra Hospital, Garran, Canberra, Australia Capital Territory; Gavin Cull, Sir Charles Gairdner Hospital; Michael F. Leahy, University of Western Australia; and Paul Cannell, Royal Perth Hospital, Perth, Western Australia, Australia.
J Clin Oncol. 2017 May 20;35(15):1678-1685. doi: 10.1200/JCO.2016.70.6374. Epub 2017 Apr 3.
Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m daily for 5 days, etoposide 75 mg/m daily for 5 days, and idarubicin 9 mg/m daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3-internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation ( P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm ( P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3-internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity.
在急性髓系白血病（AML）的诱导治疗中，较高剂量的蒽环类药物柔红霉素已被证明可以提高缓解率和生存率。我们假设，通过在巩固治疗期间增加蒽环类药物剂量，可以进一步改善成人 AML 的治疗结果。
在诱导治疗后完全缓解的 AML 患者被随机分配接受两个周期的巩固治疗，方案为阿糖胞苷 100 mg/m2，每天一次，连用 5 天；依托泊苷 75 mg/m2，每天一次，连用 5 天；柔红霉素 9 mg/m2，每天一次，连用 2 天或 3 天（标准组和强化组）。主要终点为无白血病生存（LFS）。
293 名年龄在 16 岁至 60 岁之间的患者（排除伴有核心结合因子 AML 和急性早幼粒细胞白血病的患者）被随机分配至治疗组（标准组 146 例，强化组 147 例）。两组在年龄、细胞遗传学风险、FLT3 内串联重复和 NPM1 基因突变方面均具有可比性。标准组 120 例（82%）和强化组 95 例（65%）患者完成了计划的巩固治疗（P<0.001）。强化组的严重中性粒细胞减少症和血小板减少症持续时间延长，但严重非血液学毒性无差异。中位随访时间为 5.3 年（范围，0.6 至 9.9 年），强化组的 LFS 明显优于标准组（3 年 LFS，47%[95%CI，40%至 56%]比 35%[95%CI，28%至 44%]；P=0.045）。5 年时，强化组的总生存率为 57%，标准组为 47%（P=0.092）。在细胞遗传学亚组或 FLT3 内串联重复和 NPM1 基因突变亚组中，强化巩固治疗并没有表现出选择性获益的证据。
在成人 AML 的巩固治疗中增加柔红霉素的累积剂量可提高 LFS，而不会增加非血液学毒性。
