60mg·m^-2·d^-1柔红霉素联合标准剂量阿糖胞苷诱导治疗≤65岁初治急性髓系白血病患者的疗效和安全性分析

Analysis of the safety and efficacy of 60 mg·m^-2·d^-1 daunorubicin combined with standard dose of cytarabine as induction therapy in acute myeloid leukemia patients under 65 years old

目的观察60 mg·m^-2·dv-1柔红霉素（DNR）联合标准剂量阿糖胞苷（DA）方案诱导治疗≤ 65岁初治急性髓系白血病（AML）的长期疗效和安全性。方法回顾性分析116例2012年7月至2016年2月接受基于DNR 60 mg·m^-2·d^-1的DA诱导方案治疗且≤65岁初治非急性早幼粒细胞白血病的AML患者的临床资料，包括治疗后完全缓解（CR）率、总生存（OS）时间、无病生存（DFS）时间以及近期和远期的不良反应。结果116例患者中，DA方案诱导治疗1个疗程后CR 78例（67.2%），≤2个疗程CR共94例（81.0%）。第1疗程诱导治疗中仅3例（2.6%）发生早期死亡。有1例患者在诱导化疗后6个月时发现无症状性心脏射血分数减低。89例患者接受了1-4个疗程巩固治疗。在中位随访24（1-46）个月后，中位DFS时间为25个月，中位OS时间未到达。Cox多因素分析显示，遗传学危险分层是影响DFS的独立预后因素（HR=0.258, 95% CI 0.100-0.664，P=0.005），遗传学危险分层（HR=0.309, 95% CI 0.126-0.756，P=0.010）以及是否接受大于1个疗程大剂量阿糖胞苷巩固治疗（HR=0.370, 95% CI 0.179- 0.765，P=0.007）是影响OS的独立预后因素。结论含DNR 60 mg·m^-2·d^-1的DA方案诱导治疗≤65岁初治AML患者可获得较高CR率，且不良反应无明显增加。

ObjectiveTo evaluate the long-term safety and efficacy of high-dose daunorubicin（DNR）（60 mg·m^-2·d^-1）combined with standard dose of cytarabine（DA）as induction therapy in patients under 65 years old with newly diagnosed acute myeloid leukemia（AML）.MethodsThe complete remission（CR）rate, disease free survival（DFS）, overall survival（OS）and side effects of therapy were retrospectively assayed in 116 patients with newly diagnosed AML who were younger than 65 years old and received daunorubicin（60 mg · m^-2·d^-1）combined with cytarabine（Ara-C 200 mg ·m^-2·d^-1）as induction therapy at Peking Union Medical College Hospital during July 2012 to February 2016.ResultsOf 116 patients, 78 cases（67.2%）achieved CR after first course of induction treatment, 94（81.0%）achieved CR after two courses of induction, and early death occurred in only 3 patients（2.6%）during the first course of induction treatment. Only 1 patient had asymptomatic decreased ejection fraction after 6 months of induction treatment. Eighty nine patients received 1 to 4 courses of consolidation. With a median follow-up of 24（1-46）months, the median DFS was 25 months and median OS was not achieved yet. Cox regression multifactor analysis showed genetics risk groups was the only risk factor for DFS（HR=0.258, 95% CI 0.100-0.664, P=0.005）, while genetics risk groups（HR=0.309, 95% CI 0.126-0.756, P=0.010）and whether patients received more than one cycle of high dose of Ara-C as consolidation therapy（HR= 0.370, 95% CI 0.179-0.765, P=0.007）were independent factors associated with OS.ConclusionsIn young adults with AML, intensifying induction therapy with a high daily dose of daunorubicin（60 mg/m^2）could improve the rate of complete remission without obvious side effects.