大剂量甲氨蝶呤治疗血液肿瘤的临床现状分析
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摘要
目的:了解某三级甲等医院(以下简称"该院")血液内科大剂量甲氨蝶呤治疗血液肿瘤的情况。方法:收集2015年4月至2017年4月该院血液内科使用注射用大剂量甲氨蝶呤患者的电子病历,设计临床数据统计观察表(纸质版)并录入患者的临床数据,利用Epidata 3.1软件建立电子数据库并进行数据转录,最后使用Excel软件统计数据。对患者基本情况、治疗信息、用药前评估、碱化情况、水化情况、亚叶酸钙解救及漱口水治疗、治疗药物监测与不良事件等各临床指标进行统计分析。结果:共纳入19例患者(31例次),所有患者都进行了碱化、亚叶酸钙解救及治疗药物监测;化疗期间水化覆盖率为87.1%(27例次);93.5%(29例次)的患者使用了漱口水进行口腔黏膜炎的预防和治疗;2例患者发生严重肾损伤,1例患者发生严重肝损伤;恶心、非预期呕吐、口腔黏膜炎和4级骨髓抑制的发生率分别为22.6%(7例次)、12.9%(4例次)、25.8%(8例次)和48.4%(15例次)。结论:血液内科大剂量甲氨蝶呤的使用总体较规范,相关治疗环节需进一步完善。药师可使用多种方法优化大剂量甲氨蝶呤的使用。
OBJECTIVE: To investigate the current status of high-dose methotrexate in the treatment of hematological malignancies in a grade Ⅲ level A hospital(hereinafter referred to as "the hospital"). METHODS: Electronic medical records of patients with high-dose methotrexate for injection in the department of hematology of the hospital from Apr. 2015 to Apr. 2017 were collected. The clinical data observation table(paper version) was designed and the clinical data were recorded. Epidata 3.1 was used to establish the electronic database and transcribe the data. Patients' basic information, treatment information, pre-medication evaluation, alkalization, hydration, calcium folic acid rescue and mouthwash treatment, therapeutic drug monitoring and adverse events were statistically analyzed. RESULTS: A total of 19 patients(31 case-times) were enrolled, and all patients underwent alkalization, calcium folic acid rescue and therapeutic drug monitoring. During chemotherapy, the hydration coverage rate was 87.1%(27 case-times). And 93.5%(29 case-times) used mouthwash for the prevention and treatment of oral mucositis. There were 2 patients developed severe kidney injury and 1 patient developed severe liver injury. The incidences of nausea, undesired vomiting, oral mucositis, and grade Ⅳ myelosuppression were 22.6%(7 case-times), 12.9%(4 case-times), 25.8%(8 case-times), and 48.4%(15 case-times). CONCLUSIONS: The use of high-dose methotrexate in the department of hematology is generally standardized, and relevant treatment links need to be further improved. Pharmacists can use a variety of methods to optimize the use of high-dose methotrexate.
OBJECTIVE: To investigate the current status of high-dose methotrexate in the treatment of hematological malignancies in a grade Ⅲ level A hospital(hereinafter referred to as "the hospital"). METHODS: Electronic medical records of patients with high-dose methotrexate for injection in the department of hematology of the hospital from Apr. 2015 to Apr. 2017 were collected. The clinical data observation table(paper version) was designed and the clinical data were recorded. Epidata 3.1 was used to establish the electronic database and transcribe the data. Patients' basic information, treatment information, pre-medication evaluation, alkalization, hydration, calcium folic acid rescue and mouthwash treatment, therapeutic drug monitoring and adverse events were statistically analyzed. RESULTS: A total of 19 patients(31 case-times) were enrolled, and all patients underwent alkalization, calcium folic acid rescue and therapeutic drug monitoring. During chemotherapy, the hydration coverage rate was 87.1%(27 case-times). And 93.5%(29 case-times) used mouthwash for the prevention and treatment of oral mucositis. There were 2 patients developed severe kidney injury and 1 patient developed severe liver injury. The incidences of nausea, undesired vomiting, oral mucositis, and grade Ⅳ myelosuppression were 22.6%(7 case-times), 12.9%(4 case-times), 25.8%(8 case-times), and 48.4%(15 case-times). CONCLUSIONS: The use of high-dose methotrexate in the department of hematology is generally standardized, and relevant treatment links need to be further improved. Pharmacists can use a variety of methods to optimize the use of high-dose methotrexate.
引文
[1] LaCasce AS.Therapeutic use and toxicity of high-dose methotrexate[DB/OL].Wolters Kluwer.2018.[2018-01-31](2019-02-14).https://www.uptodate.com/contents/therapeutic-use-and-toxicity-of-high-dose-methotrexate?search=Therapeutic%20use%20and%20toxicity%20of%20high-dose%20methotrexate&source=Out%20of%20date%20-%20zh-Hans&selectedTitle=1～68.
[2] 魏盈盈,焦溦溦,程思,等.大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病的血药浓度与不良反应的相关性[J].中国医院药学杂志,2014,34(22):1915-1918.
[3] 贾锐.大剂量甲氨蝶呤治疗儿童白血病血药浓度与疗效的关系[J].当代医学,2018,24(31):161-162.
[4] Hegyi M,Arany A,Semsei AF,et al.Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma[J].Oncotarget,2017,8(6):9388-9398.
[5] Wang CP.Monitoring and Treatment of Acute Kidney Injury in Chil-dren with Acute Lymphoblastic Leukemia After High Dose Metho-trexate Chemotherapy[J].Iran J Pharm Res,2016,15(4):957-961.
[6] 张峻,杨龙,唐薇,等.大剂量甲氨蝶呤在急性淋巴细胞白血病患儿中的群体药动学[J].中国医院药学杂志,2007,27(8):1061-1065.
[7] 汪洋,张华年,李思婵,等.应用人工神经网络评估大剂量甲氨蝶呤化疗后的骨髓抑制[J].中国现代应用药学,2017,34(6):881-887.
[8] Mei S,Li X,Jiang X,et al.Population Pharmacokinetics of High-Dose Methotrexate in Patients With Primary Central Nervous System Lymphoma[J].J Pharm Sci,2018,107(5):1454-1460.
[9] Ettinger LJ,Chervinsky DS,Freeman AI,et al.Pharmacokinetics of methotrexate following intravenous and intraventricular administra-tion in acute lymphocytic leukemia and non-Hodgkin's lymph-oma[J].Cancer,1982,50(9):1676-1682.
[10] Hande KR,Balow JE,Drake JC,et al.Methotrexate and hemodialysis[J].Ann Intern Med,1977,87(4):495-496.
[11] Suzuki K,Doki K,Homma M,et al.Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy[J].Br J Clin Pharmacol,2009,67(1):44-49.
[12] 曲艳凝,江滨,王宇航,等.大剂量阿糖胞苷、甲氨蝶呤静脉滴注后药物浓度检测及相互作用研究[J].中华血液学杂志,2012,33(12):1049-1051.
[13] Thomas MH,Gutterman LA.Methotrexate toxicity in a patient rec-eiving trimethoprim-sulfamethoxazole[J].J Rheumatol,1986,13(2):440-441.
[2] 魏盈盈,焦溦溦,程思,等.大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病的血药浓度与不良反应的相关性[J].中国医院药学杂志,2014,34(22):1915-1918.
[3] 贾锐.大剂量甲氨蝶呤治疗儿童白血病血药浓度与疗效的关系[J].当代医学,2018,24(31):161-162.
[4] Hegyi M,Arany A,Semsei AF,et al.Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma[J].Oncotarget,2017,8(6):9388-9398.
[5] Wang CP.Monitoring and Treatment of Acute Kidney Injury in Chil-dren with Acute Lymphoblastic Leukemia After High Dose Metho-trexate Chemotherapy[J].Iran J Pharm Res,2016,15(4):957-961.
[6] 张峻,杨龙,唐薇,等.大剂量甲氨蝶呤在急性淋巴细胞白血病患儿中的群体药动学[J].中国医院药学杂志,2007,27(8):1061-1065.
[7] 汪洋,张华年,李思婵,等.应用人工神经网络评估大剂量甲氨蝶呤化疗后的骨髓抑制[J].中国现代应用药学,2017,34(6):881-887.
[8] Mei S,Li X,Jiang X,et al.Population Pharmacokinetics of High-Dose Methotrexate in Patients With Primary Central Nervous System Lymphoma[J].J Pharm Sci,2018,107(5):1454-1460.
[9] Ettinger LJ,Chervinsky DS,Freeman AI,et al.Pharmacokinetics of methotrexate following intravenous and intraventricular administra-tion in acute lymphocytic leukemia and non-Hodgkin's lymph-oma[J].Cancer,1982,50(9):1676-1682.
[10] Hande KR,Balow JE,Drake JC,et al.Methotrexate and hemodialysis[J].Ann Intern Med,1977,87(4):495-496.
[11] Suzuki K,Doki K,Homma M,et al.Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy[J].Br J Clin Pharmacol,2009,67(1):44-49.
[12] 曲艳凝,江滨,王宇航,等.大剂量阿糖胞苷、甲氨蝶呤静脉滴注后药物浓度检测及相互作用研究[J].中华血液学杂志,2012,33(12):1049-1051.
[13] Thomas MH,Gutterman LA.Methotrexate toxicity in a patient rec-eiving trimethoprim-sulfamethoxazole[J].J Rheumatol,1986,13(2):440-441.