全反式维甲酸联合亚砷酸致急性早幼粒细胞白血病患者肝功能损害临床观察

摘要/Abstract

摘要： 目的观察全反式维甲酸(ATRA)联合亚砷酸(ATO)对急性早幼粒细胞白血病(APL)患者肝功能损害情况。方法回顾2012年1月至2021年4月河南科技大学第一附属医院收治初诊APL患者92例(男50例、女42例),年龄40(12, 77)岁,其中ATRA、ATO单独诱导38例(单独诱导组),联合诱导54例(联合诱导组)。计量资料采用Mann-Whitney U检验,计数资料采用卡方检验;以Kaplan-Meier法进行生存分析,差异比较采用log-rank检验。结果联合诱导组和单独诱导组CR时间分别为27(20, 38)d和35(25, 50)d,差异具有统计学意义(P<0.05);联合诱导组和单独诱导组肝功能损害为36例(66.7%)和14例(36.8%),差异具有统计学意义(P<0.05);联合诱导组和单独诱导组Ⅲ/Ⅳ度肝功能损害为23例(42.6%)和5例(13.1%),差异具有统计学意义(P<0.05)。87例获得血液学CR患者继续完成巩固治疗(>2周期),其中23例接受超1周期ATRA联合ATO巩固化疗,3例(13.0%)发生肝功能损害。ATRA联合ATO巩固治疗肝功能损害发生率显著低于联合诱导治疗(P<0.05)。52例完成巩固治疗患者继续接受ATRA、ATO序贯维持治疗,其中12例(23.1%)发生肝功能损害,ATRA、ATO序贯维持治疗肝功能损害发生率显著低于联合诱导治疗(P<0.05)。随访截止2021年4月。诱导、巩固及维持治疗接受ATO化疗70例,其中Ⅲ/Ⅳ度肝功能损害28例,Ⅲ/Ⅳ度肝功能损害和非Ⅲ/Ⅳ度肝功能损害患者OS率为92.8%(26/28)和95.2%(40/42),差异无统计学意义(P>0.05);EFS率为85.7%(24/28)和90.5%(38/42),差异无统计学意义(P>0.05)。结论 ATRA与ATO联合诱导方案可有效缩短APL患者达CR时间,同时也增加了肝功能损害风险,不过多数患者为一过性肝功能损害,接受ATRA联合ATO的巩固、维持治疗方案患者较联合诱导期肝功能损害比例显著下降。此外,ATO造成的肝损害并不影响患者预后。

关键词: 急性早幼粒细胞白血病, 全反式维甲酸, 亚砷酸, 肝功能损害

Abstract: Objective To observe the effect of all-trans retinoic acid (ATRA) combined with arsenious acid (ATO) on liver function damage in patients with acute promyelocytic leukemia (APL).Methods From January 2012 to April 2021, 92 newly diagnosed APL patients (50 males and 42 females), aged 40 (12, 77) years, were reviewed. Among them, 38 cases were induced by ATRA or ATO alone, and 54 cases were induced by the combination treatment. Mann-Whitney U-test was used for measurement data and chi-square test was used for counting data. Kaplan-Meier method was used for survival analysis, and log-rank test was used for difference comparison.Results The complete remission (CR) time of combined induction group and single induction group was 27 (20, 38) days and 35 (25, 50) days, and the difference was statistically significant (P<0.05). There were 36 cases (66.7%) and 14 cases (36.8%) of liver function damage in combined induction group and single induction group respectively, and the difference was statistically significant (P<0.05). There were 23 cases (42.6%) and 5 cases (13.1%) of grade Ⅲ/Ⅳ liver damage in combined induction group and single induction group, and the difference was statistically significant (P<0.05). 87 patients with hematological CR continued to complete consolidation therapy (> 2 cycles), among which 23 patients received ATRA combined with ATO consolidation chemotherapy over 1 cycle, and 3 patients (13.0%) had liver function damage. The incidence of liver damage in ATRA combined with ATO consolidation therapy was significantly lower than that in combined induction therapy (P<0.05). 52 patients who completed consolidation therapy continued to receive ATRA and ATO sequential maintenance therapy, of which 12 patients (23.1%) had liver function damage. The incidence of liver function damage in ATRA and ATO sequential maintenance therapy was significantly lower than that in combined induction therapy (P<0.05). Patients were followed up until April 2021. 70 patients received ATO chemotherapy after induction, consolidation and maintenance treatment, including 28 patients with grade Ⅲ/Ⅳ liver damage. The overall survival (OS) rates of patients with grade Ⅲ/Ⅳ liver damage and non-grade Ⅲ/Ⅳ liver damage were 92.8% (26/28) and 95.2% (40/42), with no significant difference (P>0.05). Event free survival (EFS) rates were 85.7% (24/28) and 90.5% (38/42), with no significant difference (P>0.05).Conclusion ATRA combined with ATO can effectively shorten the time of reaching CR in APL patients, while increases the risk of liver function damage. However, the liver damage of most patients is transient and reversible. Compared with induction period of ATRA combined with ATO, the proportion of liver damage was significantly lower in patients receiving consolidation and maintenance therapy. In addition, liver damage caused by ATO does not affect the prognosis of patients.

Key words: Acute promyelocytic leukemia, All-trans retinoic acid, Arsenious acid, Liver function damage

王艳秋, 薛娟, 陈梦露. 全反式维甲酸联合亚砷酸致急性早幼粒细胞白血病患者肝功能损害临床观察[J]. 肝脏, 2022, 27(7): 810-813.

WANG Yan-qiu, XUE Juan, CHEN Meng-lu. Clinical observation of liver function damage in patients with acute promyelocytic leukemia induced by all-trans retinoic acid combined with arsenious acid[J]. Chinese Hepatolgy, 2022, 27(7): 810-813.

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