三氧化二砷联合小剂量全反式维甲酸诱导急性早幼粒细胞白血病缓解的疗效分析

Therapeutic effects of combination of arsenic trioxide with low-dose all-trans retinoic acid on induction of remission acute promyeloeytic leukemia

目的 观察三氧化二砷(As2O3)联合小剂量全反式维甲酸(ATRA)诱导初发和复发的急性早幼粒细胞白血病(APL)患者缓解的疗效和不良反应。方法 对联合应用As2O3和小剂量ATRA治疗的108例APL患者(80例为初治患者,28例为复发患者)的完全缓解率、达完全缓解所需时间、早期病死率和不良反应进行观察,并与单独应用ATRA组(40例为初治患者,25例为复发患者)或As2O3组(36例为初治患者,15例为复发患者)进行比较。联合用药组治疗方法为As2O3(1mg/ml)10ml加入5%葡萄糖溶液500ml每天1次,静脉点滴,ATRA10mg,每天3次,口服。结果 在初发患者组,联合用药与单独应用ATRA、As2O3组相比,完全缓解率无统计学意义(分别为92 .5%、83. 8%和90 .0%,P>0 .05),在复发患者组,联合用药组的完全缓解率(71 .4%)高于单用ATRA组(20. 0%,P<0. 05)。在初发组和复发组,联合用药组获得完全缓解所需的时间皆短于单用As2O3组(P<0. 05),早期死亡率低于ATRA组(P<0 .05),与单用药组相比,联合用药组的毒副作用并未增加。结论 联合用药诱导APL缓解的疗效优于单用药组,不良反应少,是一种值得推广应用的方案。

Objective To observe the therapeutic efficacy and side effects of arsenic trioxide (As_2O_3)combined with low-dose all-trans retinoic acid (ATRA) on remission induction in newly-diagnosed and relapsed patients with acute promyeloeytic leukemia (APL). Methods 224 patients of APL, 156 newly diagnosed patients, aged 34 (13~62), with a male/female ratio 0f 1.56, and 28 relapsed patients, aged, aged 34 (12~63), with a male/female ratio of 1.89, underwent As_2O_3+ATRA therapy. The therapeutic effects was compared with that of As_2O_3 alone treatment on 40 newly diagnosed patients and 25 relapsed patients and that of ATRA alone treatment on 36newly diagnosed patients and 15 relapsed patients. The treatment protocol for the combination group was as following: As_2O_3 was administered intravenously at a dose of 10 mg/day and ATRA was given orally three times per day at a dose of 10 mg. The complete remission (CR) rate, period to CR, incidence of early death and side effects were observed in the three groups. Results In the newly-diagnosed patients, there was no significant difference in CR rate among the three groups(92.5% for the As_2O_3/LD-ATRA group, 83.8% for the ATRA group, and 90% for the As_2O_3 group respectively)In comparison with As_2O_3 alone, administration of LD-ATRA to the patients in the As_2O_3/LD-ATRA group significantly shortened the period to CR (the medium time to CR was 28 days for the As_2O_3/LD-ATRA group and 39 days for the As_2O_3 group respectively). As compared to ATRA alone, treatment with As_2O_3 with low-dose ATRA showed a significantly lower incidence of early death (2.5% for the As_2O_3/LD-ATRA group and 13.9% for the ATRA group respectively). In the relapsed patients, the CR rate was significantly higher in the group treated with As_2O_3/LD-ATRA (71.4% for the As_2O_3/LD-ATRA group, 32.0% for the ATRA group, and 43.0% for the As_2O_3 group respectively). The combined use of LD-ATRA with As_2O_3 did not further enhance toxic side effects as compared to As_2O_3 alone or ATRA alone. Conclusion As_2O_3/LD-ATRA regimen is superior to either regimen given alone to patients with APL. It is an efficient therapeutic approach to APL patients using a combination of As_2O_3 with low-dose ATRA.