三氧化二砷致小儿急性早幼粒细胞白血病器官功能损害的临床研究

目的 探讨治疗剂量三氧化二砷（As2O3）对急性早幼粒细胞白血病（APL）患儿肝脏、肾脏、心脏的毒副作用.方法 对65例初诊初治APL患儿应用As2O3静脉滴注诱导缓解治疗同时动态监测患儿肝脏、肾脏及心脏功能的毒性反应.结果 （1）65例患儿应用As2O3治疗后发生肝脏损害19例（29.2％）,轻度15例（23.1％）,中度4例（6.2％）,治疗前丙氨酸氨基转移酶为（19.9±9.5） U/L,治疗第1、2周分别为（24.3±11.8）、（25.0±14.4） U/L,显著高于治疗前（P均＜0.05）,治疗第3周基本恢复正常;治疗前天冬氨酸氨基转移酶为（28.5±8.8） U/L,治疗第1、2、3周分别为（38.3±16.5）、（39.1±15.5）、（35.3±20.6） U/L,显著高于治疗前（P＜0.05或0.01）,第4周后基本恢复正常.（2）治疗前尿胱氨酸蛋白酶抑制剂C为（1.98±0.68） mg/L,治疗第2、3、4周分别为（2.51±1.45）、（3.05±1.13）、（2.46±1.21） mg/L,显著高于治疗前（P＜0.05或0.01）;治疗前尿β2微球蛋白为（0.51±0.23） mg/L,治疗第2、3、4周分别为（1.08±0.45）、（0.69±0.55）、（0.71±0.48） mg/L,显著高于治疗前（P＜0.05或0.01）;于治疗第5周降至正常.（3）9例患儿在诱导缓解期出现心悸、心前区不适及心率增快表现,均为轻度,在治疗3周后症状消失;肌酸激酶在治疗后第2周[（90.2 ±32.5） U/L]高于治疗前[（78.5±22.3）U/L],肌酸激酶同工酶在治疗第2、3周[（8.3±4.8）、（8.5±5.6） U/L]显著高于治疗前[（6.3±3.5） U/L],血清肌酸激酶同工酶质量在第4周时[（3.9±2.0）g/L]仍明显高于治疗前[（2.8±1.9）g/L],其后逐渐恢复正常.结论 常规剂量As2O3治疗小儿APL的肝脏、肾脏、心脏毒性较小,且为一过性、可逆性,多发生于As2O3治疗的第1～～3周.血丙氨酸氨基转移酶、天冬氨酸氨基转移酶和尿胱氨酸蛋白酶抑制剂、β2微球蛋白及血肌酸激酶同工酶质量为指示器官功能损害的敏感指标.

Adverse effect of arsenic trioxide treatment on vital organs in the process of treating childhood acute promyelocytic leukemia

Objective To explore the adverse effect of arsenic trioxide （As2O3） on liver,kidney and heart function during treating children patients with acute promyelocytic leukemia （APL） at therapeutic dose.Methods Sixty-five APL cases received As2O3 by intravenous drip and organic toxicity were selected as our subjects.The indices of liver,heart and kidney were measured.Results Of all subjects,19 cases（29.2％） occurred liver damage,including 15 cases（23.1％） mild and 4 cases（6.2％） moderate toxicity.The levels of alanine aminotransferase of patients before treatment was （19.9 ±9.5） U/L,and （24.3 ± 11.8） U/L,（25.0 ± 14.4） U/L at 1 st and 2nd weeks after treatment,higher than those before the treatment （P ＜ 0.05）.However,level of alanine aminotransferase was back to normal at 3th weeks after treatment.Meanwhile the levels of aspartate aminotransferase at 1st,2nd and 3th weeks after treatment were （38.3 ± 16.5）,（39.1 ± 15.5）,（35.3 ± 20.6） U/L respectively,higher than that before treatment（（28.5 ± 8.8） U/L,P ＜ 0.05 or 0.01）,and it was back to normal at 4th weeks.（2） The levels of urinary cystatin C were （2.51 ± 1.45） mg/L,（3.05 ± 1.13） mg/L,（2.46 ± 1.21） mg/L at 2nd,3th,4th weeks after treatment,significantly higher than that before treatment （（1.98 ±0.68） mg/L,P ＜0.05 or 0.01）.And the levels of urinary β2 microglobulin at 2nd,3th,4th weeks after treatment were significantly higher than that before treatment （P ＜0.05 or 0.01） and back to normal at 5 weeks after treatment.（3） Nine cases at remission stage showed the symptoms of palpitation,precordial discomfort and increased heart rate,and all those symptoms were mild.And the symptoms disappear at the 3th week after the treatment.Creatine kinase at the 2nd weeks after treatment was （90.2 ± 32.5） U/L,higher than that before treatment （（78.5 ± 22.3） U/L）.The levels of creatine kinase isoenzyme at 2nd,3th weeks after treatment were （8.3 ± 4.8） U/L,（8.5 ± 5.6） U/L,higher than that before treatment （（6.3 ± 3.5） U/L）.The serum creatine kinase mass at 4th weeks（（3.9 ±2.0） g/L） was significantly higher than that before treatment （（2.8 ± 1.9） g/L）,and then gradually be back to normal.Conclusion The routine dose As2O3 in treatment of APL children show less toxicity in liver,kidney,and heart Those adverse effects are transient,reversible and they occurred at 1-3 week after As2O3 treatment.Serum alanine aminotransferase,aspartate aminotransferase and urinary cystine protease inhibitors,β2 micro ring protein and serum creatine kinase MB mass might be served as sensitive indicators of organ damage.