Objective: To compare the efficacy and toxicities of combining homoharringtonine (HHT)±daunorubicin (DNR) with all-trans-retinoic acid (ATRA) based therapy and DNR plus ATRA based therapy in newly diagnosed low/intermediate risk acute promyelocytic leukemia (APL).
Methods: A total of 96 newly diagnosed patients with APL were randomized to HHT group, DNR group and HHT+ DNR group prospectively. The complete remission (CR) rate, the overall survival (OS) and event-free survival (EFS) of three groups were analyzed.
Results: There were 31 patients in HHT group, 33 patients in DNR group and 32 patients in HHT+ DNR group. The baseline characteristics of three groups were similar. No patient died during induction therapy. The morphologic CR rate was 100.0%. The median time to peak WBC counts in HHT+DNR group (4 days, range: 1-23 days) was significantly shorter than that in HHT group (9 days, range: 1-27 days) (P=0.008) and DNR group (7 days, range: 1-27 days) (P=0.240). There was no difference among three groups about the incidence of differentiation syndrome, the median interval to achieve CR, peak WBC counts and transfusions (P >0.05). All patients achieved complete molecular remission (CMR) during consolidation therapy. The interval to achieve CMR was no significantly difference among three groups (P >0.05). The 3-year OS rates for HHT group, DNR group and HHT+DNR group were 95.0%, 100.0% and 91.0%, respectively (P=0.595). The 3-year EFS rates for three groups were 93.0%, 90.0% and 85.0% (P=0.382). No difference was found in the incidence of adverse events among three groups (P >0.05).
Conclusions: Similar to DNR plus ATRA based therapy, HHT plus ATRA based induction and consolidation therapy should be one of highly-efficient treatment options for newly diagnosed APL. Clinical trial registration Chinese Clinical Trial Registry, ChiCTR-TRC-12002628.
目的: 比较高三尖杉酯碱（HHT）±柔红霉素（DNR）联合全反式维甲酸（ATRA）和以DNR为基础的方案治疗初诊中低危急性早幼粒细胞白血病（APL）患者的疗效及耐受性。
方法: 采用前瞻性随机对照研究方法，将96例初诊中低危APL患者随机分配至HHT组、DNR组和HHT+DNR组，比较三组患者的完全缓解（CR）率、总生存（OS）及无事件生存（EFS）情况。
结果: HHT组31例，DNR组33例，HHT+DNR组32例，三组患者一般资料具有可比性。三组治疗方案诱导治疗CR率均为100%，无早期死亡患者。三组诱导治疗期间WBC达峰值的中位时间分别为9(1~27）、7(1~27）和4(1~23）d，HHT+DNR组短于HHT组（P=0.008）和DNR组（P=0.240）。三组治疗方案在维甲酸综合征的发生率，达CR的中位时间，WBC峰值及血小板、红细胞、血浆输注量方面的差异均无统计学意义（P值均>0.05）。所有患者均在巩固治疗阶段达分子生物学完全缓解（CMR），三组患者达CMR的时间差异无统计学意义（P>0.05）。HHT组、DNR组及HHT+DNR组的3年OS率分别为95.0%、100.0%、91.0%；3年EFS率分别为93.0%、90.0%、85.0%，差异均无统计学意义（P值分别为0.595和0.382）。三组患者不良事件发生率比较差异无统计学意义（P>0.05）。
结论: 以HHT联合ATRA为基础的诱导、巩固治疗方案可以有效治疗初诊APL，疗效与以蒽环类药物为基础的方案类似，可以作为APL的治疗选择之一。