Clinical Investigation Of Hepatotoxicity With Newly Diagnosed Acute Promyelocytic Leukemia Treated With Arsenic Trioxide

Background:Arsenic trioxide(ATO)has dual roles in inducing apoptosis and cell differentiation in acute promyelocytic leukemia(APL).On the basis of all-trans retinoic acid(ATRA),the combined ATO induced treatment of APL has the advantages of high cure rate and low recurrence rate,but there are few special clinical studies on the treatment related liver toxicity.Objective:To observe the clinical efficacy of ATRA combined with ATO in the treatment of primary APL,and the Hepatotoxicity from ATO for APL patients during induction,consolidation and maintenance treatment;and to analyze the risk factors affecting the liver toxicity of APL patients.Methods:A retrospective analysis of 131 newly diagnosed APL patients since January 2003 to December 2017,including 82 cases with ATRA plus ATO,31 cases with ATRA alone and 18cases with ATO alone,was performed to investigate the clinical efficacy and the liver toxicity.To observed the liver enzymes during the induction,consolidation and maintenance of the treatment,and analyzed the risk factors of liver toxicity.and the moderate and severe liver function injury.The effect of moderate and severe liver damage on the prognosis.Results:1.Efficacy comparison:The rates of complete remission(CR)in ATRA+ATO group,ATRA group and ATO group were 97.6%,93.5%and 94.4%,respectively.There was no significant difference in complete remission rate between ATRA+ATO double drug group and ATRA or ATO monotherapy group(96.3%vs 91.8%,P=0.267).However,the time of APL patients in the double drug group was shorter than that of APL patients in the single drug group[(20~41)vs 35(25~51),P<0.001],the overall survival(OS)rate of the double drug group and the single drug group was 96.8%and 91.4%respectively(P=0.380),the relapse rates were 2.6%and5.7%respectively(P=0.410).The estimated 5 year OS rates were 96.0%and 91.0%,respectively,while the estimated 5 year relapse-free survival(RFS)was 95.2%and 90.6%,respectively.The difference has statistical significance.(P=0.385).2.comparison of Hepatotoxicity:the incidence of hepatotoxicity in the double drug group was 75.6%,which was significantly higher than that of the single drug group(P<0.001),and the incidence of grade 3/4 hepatotoxicity in the double drug group was 47.6%,as that of the single drug group was 14.3%(P<0.001);the ratio of the abnormalities of alanine aminotransferase(ALT),aspartate aminotransferas(AST)and?-glutamyl transpeptidas(GGT)in the double drug groups and the peak value of ALT and the peak AST were higher than those of the single drug group.The difference was statistically significant(P<0.05),and the incidence of liver function injury during the consolidation and maintenance treatment was significantly lower than that during the induction therapy(P<0.001).3.The characteristics of liver enzymes during induction therapy:ALT,AST,GGT levels were dynamic changes during the ATO induction therapy;ALT,AST,GGT began to rise at first weeks and reached the peak in second weeks.The difference was statistically significant(P<0.05)compared with the pre treatment level.4.The high risk factors of liver toxicity:double drug induction,WBC?50×10~9/L and differentiation syndrome were independent risk factors for liver function injury(P=0.012,0.021,0.044),and the short-term accumulation of ATO was not associated with liver toxicity.Conclusion:ATRA combined with ATO double drug induction regimen shortened the time of APL patients to CR and aggravates the liver toxicity,most liver function damage is transient and reversible.Double drug induction,first diagnosis of WBC?50×10~9/L and differentiation syndrome are independent risk factors for liver function damage.