Analysis of factors influencing major adverse events in patients with hematologic neoplasms and treated with high-dose methotrexate regimens
10.3760/cma.j.issn.1008-5734.2019.03.003
- VernacularTitle:含大剂量甲氨蝶呤方案治疗血液肿瘤主要不良事件影响因素的分析
- Author:
Yuzhen ZOU
1
;
Dan MEI
;
Qiang FU
;
Minghui DUAN
;
Chen YANG
Author Information
1. 中国医学科学院北京协和医学院北京协和医院药剂科 100730
- Publication Type:Journal Article
- Keywords:
Methotrexate;
Hematologic neoplasms;
Drug monitoring;
Drug toxicity;
Blood drug concentration
- From:
Adverse Drug Reactions Journal
2019;21(3):166-175
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the factors influencing major adverse events in patients with hematologic neoplasms and treated with high-dose methotrexate (HDMTX) chemotherapy regimens.Methods Medical records of all inpatients with hematologic neoplasms treated with HDMTX chemotherapy regimens in Peking Union Medical College Hospital from January 2014 to February 2016 were collected by Hospital Information System and retrospectively analyzed in combination with the adverse events surveillance files within 48 hours after HDMTX treatment,established by clinical pharmacists of hematology department.The effects of age,body mass index (BMI),methotrexate (MTX) dosage,time of intravenous infusion,liver and kidney function before administration,blood drug concentration of 20 hours after completion of one treatment cycle,and chemotherapy regimens on adverse events of ≥ grade Ⅱ were analyzed by single factor and multiple factor analysis.Results A total of 324 inpatients were entered in the study,including 179 males and 145 females with a median age of 43 (14-77) years.There were 72 inpatients with acute lymphoblastic leukemia,208 with non-Hodgkin lymphoma,and 44 with Langerhans cell histiocytosis.A total of 1 050 cycles of HDMTX were administered to the 324 patients.Within 48 hours after the HDMTX treatment,159 patients had 289 times of adverse events of ≥ grade Ⅱ.The incidence of adverse events of ≥grade Ⅱ was 49.07％ and the adverse events accounted for 27.52％ of the treatment cycles.Elevated serum alanine aminotransferase (ALT) was the most common adverse event [the incidence was 25.62％ (83/324)and the constituent ratio was 10.38％ (109/1 050)],followed by nausea and vomiting [the incidence was 11.73％ (38/324) and the constituent ratio was 5.43％ (57/1 050)] and elevated serum creatinine (Scr)level [the incidence was 8.64％ (28/324) and the constituent ratio was 2.76％ (29/1 050)].Multiple factor analysis showed that MTX dosage,time of intravenous infusion,and ALT level before administration were significant factors affecting ALT elevation after administration;BMI,blood drug concentration of 20 hours after completion of one treatment cycle,serum total bilirubin (TBil) and before administration were significant factors affecting Scr elevation after administration;serum TBil level before administration was the only significant factor affecting TBil elevation after administration;blood drug concentration of 20 hours after completion of one treatment cycle was the only significant factor in oral mucositis;MTX dosage,four-hour intravenous infusion regimen,and GDP/ML regimen (gemcitabine + dexamethasone + cisplatin + HDMTX +pegaspargase) were significant factors influencing adverse neuro-logical events.Conclusions After HDMTX regimen chemotherapy,patients with baseline dysfunction of liver and kidney and a 24-hour intravenous infusion regimen may increase the risk of liver and kidney injury;overweight patients may have an increased risk of kidney injury;GDP/ML regimen,4-hour intravenous infusion regimen,and higher MTX dosages may increase the risk of neurological adverse events;high blood concentration of 20 hours after completion of one treatment cycle may be a risk factor of kidney injury and oral mucositis.
