大剂量甲氨喋呤治疗180例儿童急性淋巴细胞白血病的疗效、副作用和血药浓度监测意义  

Efficacy,Side Effects and Blood Concentration Monitoring of High-dose Methotrexate in Treatment of 180 Children with Acute Lymphoblastic Leukemia

作　　者：王弘[1] 迟昨非[1] 李爽[1] 王秀丽[1] 郝良纯[1] 

机构地区：[1]中国医科大学附属盛京医院儿科,辽宁沈阳110004

出　　处：《中国实验血液学杂志》2011年第4期949-952,共4页Journal of Experimental Hematology

摘　　要：本研究采用回顾性方法分析大剂量甲氨喋呤(HD-MTX)为主的HD-MTX-CF+VDT方案在儿童急性淋巴细胞性白血病(ALL)髓外防治中的作用及意义,并分析HD-MTX的毒副作用及动态MTX血药浓度监测在该方案中的重要作用,以避免或减轻HD-MTX的毒副作用,及时调整亚叶酸钙(CF)的解救剂量或必要时与以血浆置换,保证化疗的安全性及降低患儿骨髓外复发的几率。对180例ALL患儿先后进行380次HD-MTX-CF+VDT方案的髓外防治,其中诱导缓解期患儿122例,维持期患儿58例;低危组68例、中危组80例、高危组32例。结果表明:HD-MTX的毒副作用包括皮肤黏膜损害、胃肠道反应、肝功能及肾功能受累、发热、骨髓抑制、感染、过敏反应、极少数心肌损害等,占36.3%,均为可逆性损害。本组患儿出现MTX排泄延迟者110例,24小时MTX浓度>10μm o l/L者3例、44小时>1.0μm o l/L者50例、68小时>0.1μm o l/L者57例,以合理调整CF解救剂量及对症治疗保护脏器功能均使MTX血药浓度降到0.1μm o l/L以下的无毒浓度,1例发生肾功能不全并治愈。结论:以HD-MTX为主的髓外防治方案对提高ALL患儿长期缓解及无事件生存率至关重要,但其相关副作用及风险性也随着MTX的剂量增大而增加,且MTX在体内代谢程度存在较大个体差异,因而在治疗过程中动态监测MTX的血药浓度,指导适时适量的CF解救是HD-MTX方案能够安全有效实施的前提和保障。This study was purposed to investigate the effects of high-dose methotrexate （HD-MTX）-CF ＋ VDT protocol on pediatric acute lymphoblastic leukemia （ALL） by means of retrospective analysis. MTX plasma concentration was dynamically detected and evaluated so as to avoid or reduce the side effects of HD-MTX, and adjust the time and dosage of calcium folinate （CF） or carry out the plasma exchange as occasion requires. Totally 180 cases of ALL were enrolled in this study, and received 380 administration of HD-MTX-CF ＋ VDT protocol, including 122 patients with induction therapy as well as 58 cases during maintenance therapy, among which 68 cases were defined as low risk, 80 cases as middle risk and 32 cases as high risk. 2.0 g/m2 MTX , 3.0 g/m2 MTX, and 5.0 g/m2 MTX were individually used according to low risk, middle risk or T immunohistochemical expression. The results indicated that 36. 3% cases showed the side-effects of HD-MTX including mucocutaneous lesions, gastrointestinal reaction, hepatic dysfunction, renal damage, fever, myelosuppression, cardiotoxicity, infection and allergic response. All of these side effects were reversible through treatment. The elimination delay of MTX occurred in 110 cases, out of which 3 cases got MTX concentration 〉 10 μmol/L at 24 hours, 50 cases 〉 1.0 μmol/L at 44 hours, the remaining 57 cases 〉 0. 1 μmol/L at 68 hours. CF dosage was adjusted according to the concentration of MTX until it was less than 0.1 μmol/L. 1 case had renal interstitial inflammation and acute renal failure, but finally he was cured. No patients received plasma exchange or died. It is concluded that the extramedullary leukemia control protocol, in which MTX is main drug, is effective therapy for obtaining long-term remission and event-free survival rate in ALL patients, but the side effects and risks increase along with the increase of MTX dose. The metabolic level of HD-MTX has found to be obvious individual, so the dynamic monitoring of MTX concentration in plasma and administration

关 键 词：甲氨喋呤 血药浓度 急性淋巴细胞性白血病 儿童 髓外防治 

分 类 号：R733.1[医药卫生—肿瘤]