急性白血病化疗对肝功能的影响
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摘要
1.背景与目的
急性白血病是血液系统恶性肿瘤,目前,联合化疗是治疗急性白血病的主要有效方法,但由于化疗药物多有肝脏毒性,由此带来的相关肝损伤在一定程度上影响了化疗的应用及治疗效果。本研究通过回顾分析514例急性白血病患者资料,并采用SPSS 16.0软件进行统计,研究急性白血病化疗后肝功能损伤的发病率,并对其相关因素进行分析,同时研究护肝治疗对于化疗后肝功能损伤的意义,为临床上减少肝功能损伤的发生、提高化疗疗效提供理论依据。
2.材料和方法
研究浙江大学医学院第一附属医院于2009年1月至2011年3月收治的急性白血病患者,应用Danan的药物性肝损害相关评价标准对是否存在药物性肝损进行评价。根据谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)及总胆红素(T-Bil)升高程度分为肝功能异常、轻、中、中度肝功能损害。统计包括性别、年龄、疾病类型、化疗方案、乙肝病毒感染、化疗阶段、肝损伤发生时间、肝功能开始恢复时间、肝功能完全恢复时间、是否进行护肝治疗、护肝疗效等因素,采用SPSS16.0软件进行统计分析,计数资料组间差异采用X2检验,计量资料组间差异采用两个独立样本的t检验。
3.研究结果
化疗后相关肝损伤发生与年龄、疾病类型、化疗方案、化疗阶段有关,与性别无关,急性髓细胞白血病与急性淋巴细胞白血病在肝功能损伤发生时间、肝功能开始恢复时间、肝功能完全恢复时间、护肝治疗及疗效方面均有差异。
4.结论
1.急性淋巴细胞白血病和急性髓细胞白血病的肝损程度以肝功能异常及轻度肝功能损害为主。
2.男、女性别在急性淋巴细胞白血病和急性髓细胞白血病中的化疗相关肝损伤发病率及肝损伤程度上无显著性差异。
3.急性淋巴细胞白血病患者比急性髓细胞白血病患者更易发生化疗后肝损伤,但不会明显加重肝损程度。临床中应该更加重视监测急性淋巴细胞白血病病人的肝功能情况。
4.在急性淋巴细胞白血病患者中,各种程度肝损在年龄上为均匀分布。但在急性髓细胞白血病患者中,年长病人的化疗后肝损程度比年轻病人轻,提示应更加关注。
5.在乙肝患者中预防使用抗病毒药物有助于减少化疗后肝损的发生,保证化疗过程顺利进行。
6.在两种类型急性白血病中,诱导缓解期比巩固强化期更易发生化疗后肝损,且急性淋巴细胞白血病患者在诱导缓解期比急性髓细胞白血病患者更易发生肝损。
7.急性淋巴细胞白血病化疗后引起的肝损比急性髓细胞白血病化疗后引起的更难以恢复。在急性淋巴细胞白血病中,应更提倡积极治疗化疗后肝损,可使肝功能提前开始恢复,可能对缩短肝功能恢复时间亦有益处。但在急性髓细胞白血病中的作用尚需进一步研究。
1.Back ground and Objective
Acute leukemia is a kind of hematological tumors. At present, combined chemotherapy is the mainly effective treatment of it. However, chemotherapy-induced liver injury has limited the selection of chemotherapy regimens as well as the effects. This study is to investigate the incidence and related factors of chemotherapy-induced liver injury and to provide evidence for both reducing the occurrence of chemotherapy-induced liver injury and treating acute leukemia patients more effectively.
2. Material and Method
Investigating 514 acute leukemia patients who received treatment in the first Affiliated Hospital of Zhejiang University School of Medicine from January,2009 to March,2011. Liver injury was divided into four grades according to the levels of ALT, AST, ALP and Total Bilirubin. Using SPSS 16.0 software to analyze data of relative factors, such as gender, age, disease type and so on.
3.Results
The incidence of chemotherapy-induced liver injury was significant correlated with age, disease type, chemotherapy regiments and the period of treatment. Acute lymphocyte leukemia (ALL) and acute myelogenous leukemia (ALL) also have significant difference in the time of liver injury and recovery. However, gender and HBV infection would not increase the incidence rate.
4.Conclusions
1.The types of chemotherapy-induced liver injury in acute leukemia are mainly liver dysfunction and mild.
2.Gender is not relative factors to increase the incidence rate of chemotherapy-induced liver injury
3.ALL patients are easier to have chemotherapy-induced liver injury than AML patients.
4.1n AML, young patients have less serious live injury than old patients.
5.Different period of treatment has significant correlated relation with the incidence of chemotherapy-induced liver injury
6.Lamivudie prophylaxis is good to reduce the incidence rate of chemotherapy-induced liver injury.
7.1t is recommended to protect live in ALL by drugs. However, its role in AML is not clear.
急性白血病是血液系统恶性肿瘤,目前,联合化疗是治疗急性白血病的主要有效方法,但由于化疗药物多有肝脏毒性,由此带来的相关肝损伤在一定程度上影响了化疗的应用及治疗效果。本研究通过回顾分析514例急性白血病患者资料,并采用SPSS 16.0软件进行统计,研究急性白血病化疗后肝功能损伤的发病率,并对其相关因素进行分析,同时研究护肝治疗对于化疗后肝功能损伤的意义,为临床上减少肝功能损伤的发生、提高化疗疗效提供理论依据。
2.材料和方法
研究浙江大学医学院第一附属医院于2009年1月至2011年3月收治的急性白血病患者,应用Danan的药物性肝损害相关评价标准对是否存在药物性肝损进行评价。根据谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)及总胆红素(T-Bil)升高程度分为肝功能异常、轻、中、中度肝功能损害。统计包括性别、年龄、疾病类型、化疗方案、乙肝病毒感染、化疗阶段、肝损伤发生时间、肝功能开始恢复时间、肝功能完全恢复时间、是否进行护肝治疗、护肝疗效等因素,采用SPSS16.0软件进行统计分析,计数资料组间差异采用X2检验,计量资料组间差异采用两个独立样本的t检验。
3.研究结果
化疗后相关肝损伤发生与年龄、疾病类型、化疗方案、化疗阶段有关,与性别无关,急性髓细胞白血病与急性淋巴细胞白血病在肝功能损伤发生时间、肝功能开始恢复时间、肝功能完全恢复时间、护肝治疗及疗效方面均有差异。
4.结论
1.急性淋巴细胞白血病和急性髓细胞白血病的肝损程度以肝功能异常及轻度肝功能损害为主。
2.男、女性别在急性淋巴细胞白血病和急性髓细胞白血病中的化疗相关肝损伤发病率及肝损伤程度上无显著性差异。
3.急性淋巴细胞白血病患者比急性髓细胞白血病患者更易发生化疗后肝损伤,但不会明显加重肝损程度。临床中应该更加重视监测急性淋巴细胞白血病病人的肝功能情况。
4.在急性淋巴细胞白血病患者中,各种程度肝损在年龄上为均匀分布。但在急性髓细胞白血病患者中,年长病人的化疗后肝损程度比年轻病人轻,提示应更加关注。
5.在乙肝患者中预防使用抗病毒药物有助于减少化疗后肝损的发生,保证化疗过程顺利进行。
6.在两种类型急性白血病中,诱导缓解期比巩固强化期更易发生化疗后肝损,且急性淋巴细胞白血病患者在诱导缓解期比急性髓细胞白血病患者更易发生肝损。
7.急性淋巴细胞白血病化疗后引起的肝损比急性髓细胞白血病化疗后引起的更难以恢复。在急性淋巴细胞白血病中,应更提倡积极治疗化疗后肝损,可使肝功能提前开始恢复,可能对缩短肝功能恢复时间亦有益处。但在急性髓细胞白血病中的作用尚需进一步研究。
1.Back ground and Objective
Acute leukemia is a kind of hematological tumors. At present, combined chemotherapy is the mainly effective treatment of it. However, chemotherapy-induced liver injury has limited the selection of chemotherapy regimens as well as the effects. This study is to investigate the incidence and related factors of chemotherapy-induced liver injury and to provide evidence for both reducing the occurrence of chemotherapy-induced liver injury and treating acute leukemia patients more effectively.
2. Material and Method
Investigating 514 acute leukemia patients who received treatment in the first Affiliated Hospital of Zhejiang University School of Medicine from January,2009 to March,2011. Liver injury was divided into four grades according to the levels of ALT, AST, ALP and Total Bilirubin. Using SPSS 16.0 software to analyze data of relative factors, such as gender, age, disease type and so on.
3.Results
The incidence of chemotherapy-induced liver injury was significant correlated with age, disease type, chemotherapy regiments and the period of treatment. Acute lymphocyte leukemia (ALL) and acute myelogenous leukemia (ALL) also have significant difference in the time of liver injury and recovery. However, gender and HBV infection would not increase the incidence rate.
4.Conclusions
1.The types of chemotherapy-induced liver injury in acute leukemia are mainly liver dysfunction and mild.
2.Gender is not relative factors to increase the incidence rate of chemotherapy-induced liver injury
3.ALL patients are easier to have chemotherapy-induced liver injury than AML patients.
4.1n AML, young patients have less serious live injury than old patients.
5.Different period of treatment has significant correlated relation with the incidence of chemotherapy-induced liver injury
6.Lamivudie prophylaxis is good to reduce the incidence rate of chemotherapy-induced liver injury.
7.1t is recommended to protect live in ALL by drugs. However, its role in AML is not clear.
引文
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[3].朱兴虎,夏学鸣.100例初发急性白血病患者肝功能变化的分析.苏州大学学报(医学版)2002；22(1)：87-89
[4].曹家月,王永兴,郭梅,孙珍.化疗药物性肝损害及胃肠道反应的防治.陕西医学杂志,2010年10月第39卷第10期：1405-1406
[5].白平昌,药物性肝损害的发生机制和预防.中西医结合肝病杂志,2009年第19卷第3期：184-186
[6].原小利,全反式维甲酸治疗急性早幼粒细胞白血病副作用的观察及护理,中国误诊学杂志,2006.6(6)：166
[7].黄宁,药物性肝病发生机制研究现状.实用肝脏病杂志,2006,9(2)：117-119
[8].Danall G, Bellichou C. Causality assessment of adverse reactions to drugs. A novel method based on the conclusions of international consensus meetings:application to drug—induced liver injuries. J Clin Epidemiol,1993,46:1323-1330.
[9]. Maria VA, Vctorino RM. Development and validation of a clinicalscale for the diagnosis of drugs-induced hepatitis. Hepatology,1997,26:664v669.
[10]. Yang BH, Zhang YT, zhang CY. Drug-induced liver injury. Linchuang He Shiyan Yixue Zazhi,2003,2:62-64.
[11].许彪,何卫平,两种国际诊断标准对230例药物性肝损害诊断的分析比较,Chin J Hepatol, DECEMber 2007, Vol 15, No.12:926-929
[12]. Bellichou C. Criteria of drug—induced liver disorders. Report of an international consensus meeting. J Hepatol,1990, U:272—276
[13].厉有名.药物性肝损害的临床类型及诊断策略Chin J Hepatol, July 2004, Vol 12. No.7 445-446
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[16]. Markus S Schaich, Thomas Illmer,et al, Intensified double induction therapy with high dose mitoxantrone, etoposide, m-amsacrine and high dose ara-C for patients aged 61-65 years with acute myeloid leukemia. Haematologica 2002; 87:808-815
[17]. Hoofnagle JH, Dusheiko GM, Schafer DF et al. Reactivationof chronic hepatitis B virus infection by cancer chemotherapy.Ann Intern Med 1982; 96:447-449.
[18]. Scullard GH, Smith CI, Merigan TC, Robinson WS, Gregory PB. Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. Gastroenterology 1981; 81:987-991.
[19]. Steinberg JL, Yeo W, Zhong S et al. Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumors:precore/core mutations may play an important role. J Med Virol 2000; 60:249-255.
[20]. Yih-Lin Chung, Tzung-Yuan Tsai. Promyelocytic Leukemia Nuclear Bodies Link the DNA Damage Repair Pathway with Hepatitis B Virus Replication: Implications for Hepatitis B Virus Exacerbation during Chemotherapy and Radiotherapy. Mol Cancer Res 2009;7:1672-1685.
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[23].张伟华,任秀红.急性白血病患者在化疗中的肝功能损害.实用医学杂志1094年第10卷2期82-83
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[7].黄宁.药物性肝病发生机制研究现状.实用肝脏病杂志,2006,9(2)：117-119
[8].DanaIl G, Bellichou C. Causality assessment of adverse reactions to drugs. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol,1993,46: 1323-1330.
[9].Maria VA, Vctorino RM. Development and validation of a clinical scale for the diagnosis of drugs-induced hepatitis. Hepatology,1997,26:664—669.
[10]. Yang BH, Zhang YT, zhang CY. Drug-induced liver injury. Linchuang He Shiyan Yixue Zazhi,2003,2:62-64.
[11].许彪,何卫平.两种国际诊断标准对230例药物性肝损害诊断的分析比较.Chin J Hepatol, DECEMber 2007, Vol 15, No.12:926-929
[12]. Benichou C. Criteria of drug- induced disorders. Report of an international consensus meeting. J Hepatol,1990,11(2):272-6
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[2].Takai S, Tsurumi H, Ando K,et al.Prevalence of hepatitis B and C virus infection in haematological malignancies and liver injury following chemotherapy. Eur J Haematol,2005,74(2):158-165
[3].朱兴虎,夏学鸣.100例初发急性白血病患者肝功能变化的分析.苏州大学学报(医学版)2002；22(1)：87-89
[4].曹家月,王永兴,郭梅,孙珍.化疗药物性肝损害及胃肠道反应的防治.陕西医学杂志,2010年10月第39卷第10期：1405-1406
[5].白平昌,药物性肝损害的发生机制和预防.中西医结合肝病杂志,2009年第19卷第3期：184-186
[6].原小利,全反式维甲酸治疗急性早幼粒细胞白血病副作用的观察及护理,中国误诊学杂志,2006.6(6)：166
[7].黄宁,药物性肝病发生机制研究现状.实用肝脏病杂志,2006,9(2)：117-119
[8].Danall G, Bellichou C. Causality assessment of adverse reactions to drugs. A novel method based on the conclusions of international consensus meetings:application to drug—induced liver injuries. J Clin Epidemiol,1993,46:1323-1330.
[9]. Maria VA, Vctorino RM. Development and validation of a clinicalscale for the diagnosis of drugs-induced hepatitis. Hepatology,1997,26:664v669.
[10]. Yang BH, Zhang YT, zhang CY. Drug-induced liver injury. Linchuang He Shiyan Yixue Zazhi,2003,2:62-64.
[11].许彪,何卫平,两种国际诊断标准对230例药物性肝损害诊断的分析比较,Chin J Hepatol, DECEMber 2007, Vol 15, No.12:926-929
[12]. Bellichou C. Criteria of drug—induced liver disorders. Report of an international consensus meeting. J Hepatol,1990, U:272—276
[13].厉有名.药物性肝损害的临床类型及诊断策略Chin J Hepatol, July 2004, Vol 12. No.7 445-446
[14]. John S. Penta, Daniel D Von Hoff, et al. Hepatotoxicity of Combination Chemotherapy for Acute Myelocytic Leukemia. Annals of Internal Medicine, 1977,Volume 37,Number2 247-248
[15]. De beer E L, Bottone A E, Voest E E. Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment. Eur J Pharmacol,2001, 415(1):1134-1136
[16]. Markus S Schaich, Thomas Illmer,et al, Intensified double induction therapy with high dose mitoxantrone, etoposide, m-amsacrine and high dose ara-C for patients aged 61-65 years with acute myeloid leukemia. Haematologica 2002; 87:808-815
[17]. Hoofnagle JH, Dusheiko GM, Schafer DF et al. Reactivationof chronic hepatitis B virus infection by cancer chemotherapy.Ann Intern Med 1982; 96:447-449.
[18]. Scullard GH, Smith CI, Merigan TC, Robinson WS, Gregory PB. Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. Gastroenterology 1981; 81:987-991.
[19]. Steinberg JL, Yeo W, Zhong S et al. Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumors:precore/core mutations may play an important role. J Med Virol 2000; 60:249-255.
[20]. Yih-Lin Chung, Tzung-Yuan Tsai. Promyelocytic Leukemia Nuclear Bodies Link the DNA Damage Repair Pathway with Hepatitis B Virus Replication: Implications for Hepatitis B Virus Exacerbation during Chemotherapy and Radiotherapy. Mol Cancer Res 2009;7:1672-1685.
[21]. R. Idilman, M. Arat,et al. Lamivudine prophylaxis in HBV carriers with malignancies. Journal of Viral Hepatitis.2004,11,141-147
[22]. Giuseppe Rossi, Annamaria Pelizzari, et al. Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. British Journal of Haematology,2001,115,58-62
[23].张伟华,任秀红.急性白血病患者在化疗中的肝功能损害.实用医学杂志1094年第10卷2期82-83
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