全反式维甲酸联合三氧化二砷治疗急性早幼粒细胞白血病的疗效观察

Effects of Combination Therapy with All-Trans Retinoic Acid and Arsenic Trioxide on Acute Promyelocytic Leukemia

背景与目的:三氧化二砷(arsenictrioxide,As2O3)治疗急性早幼粒细胞白血病作用机制与全反式维甲酸(all-transretinonicacid,ATRA)有所不同,前者主要是加速细胞的凋亡,后者是诱导细胞的分化。但两者均能抑制急性早幼粒细胞白血病组织因子(tissuefactor,TF)mRNA的转录,降低TF水平和促凝活性,从而改善患者的出凝血异常。本研究旨在探讨两药联合应用能否提高疗效及是否加重不良反应。方法:采用历史对照分组。2000年1月～2001年10月的22例急性早幼粒细胞白血病作为ATRA组,其中初治17例,复发5例;单用ATRA治疗,剂量为25mg/(m2·d),分两次口服,一个疗程最长不超过50天。2001年11月～2003年6月的急性早幼粒细胞白血病19例为联合治疗组,其中初治15例,复发4例,采用As2O3与ATRA联合治疗。治疗剂量为0.1%As2O3溶液10ml,加入5%葡萄糖溶液中静脉滴注,每天1次,持续4～6h,28天为一疗程,ATRA的剂量用法同前组。结果:ATRA治疗组22例中19例(初治16例,复发3例)获完全缓解,完全缓解率为86.4%。联合治疗组19例中17例(初治15例,复发2例)获完全缓解,缓解率为89.5%。病死率ATRA组为18.6%,共3例(1例初治,2例复发);联合治疗组为10.5%,共2例(均为复发者)。完全缓解率和病死率两组比较无统计学差异(P>0.05)。达到完全缓解的中位时间。

BACKGROUND & OBJECTIVE: The mechanism of effect of arsenic t ri oxide on promyelocytic leukemia is different from that of all- trans retinoic a cid. Arsenic trioxide exerts its action by accelerating cell apoptosis, while al l- trans retinoic acid by inducing cell differentiation. However, both drugs ca n inhibit the transcription of tissue factor (TF) mRNA in acute promyelocytic le ukemia, and decrease TF level and coagulative activity to normalize coagulopathy . The objective of the study was to observe whether combination of the two drugs could improve efficacy or in contrary accentuate adverse reactions. METHODS: Tw o groups of patients with acute promyelocytic leukemia were included. Twenty- t wo patients (17 untreated cases and 5 relapsed cases) from January 2000 to Octob er 2001 in group Ⅰ were treated only with oral retinoic acid [25 mg/(m2· d) i n two divided doses] for less than 50 days. Ninteen cases (15 untreated cases an d 4 relapsed cases) from November 2001 to June 2003) in Group Ⅱ were treated w ith combination of arsenic trioxide and all- trans retinoic acid. 0.1% AS2O3 10 ml in 500 ml 5% glucose solution was given intravenously for 4 to 6 hours p er day for 28 days. The dosage of retinoic acid in group Ⅱ was the same as tha t in group Ⅰ . RESULTS: Nineteen of 22 cases in retinoic acid- treated group ( group Ⅰ )(16 untreated cases and 3 relapsed cases) achieved complete remission (CR). The CR rate was 86.4% . Seventeen of 19 cases in combination therapy grou p (group Ⅱ )(15 untreated cases and 2 relapsed cases) achieved CR. The CR rate was 89.5% . The death rates were 13.6% (3/22, 1 untreated case, 2 relapsed ca ses) in group Ⅰ and 10.5% (2/19, 2 relapsed cases) in group Ⅱ , respectivel y. The median time to CR was 23 days in group Ⅰ and 26 days in group Ⅱ , and the median time to normalization of coagulopathy was 7 days in group Ⅰ and 4 d ays in group Ⅱ . Significant differences were found between the two groups. No significant adverse reaction was observed in both groups. CONCLSUION: The CR rat e and death rate were not different between the two groups. The combination ther apy with AS2O3 and all- trans retinoic acid can shorten the time to CR and norm alization of coagulopathy.