不同剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病的血药浓度监测及不良反应临床研究

发布时间：2018-06-12 10:00

本文选题：儿童急性淋巴细胞白血病 + 甲氨蝶呤　；参考：《广西医科大学》2012年硕士论文

【摘要】：目的：观察不同剂量的大剂量甲氨蝶呤（high-dose methotrexate，HD-MTX）连续24小时（hour，h）静脉滴注在儿童急性淋巴细胞白血病（acutelymphoblastic leukemia，ALL）髓外白血病防治中的血药浓度和不良反应，为制定个体化用药方案提供参考依据。方法：回顾性分析64例ALL患儿238例次HD-MTX方案化疗的临床资料。根据MTX给药剂量分为A、B两组：A组5g/m2，共161例次， B组3g/m2，共77例次。首剂MTX开始滴入后36h予甲酰四氢叶酸钙（calciumfolinate，CF）解救，检测MTX48h、72h血药浓度，并据此调整CF的剂量和次数，，直至安全浓度。比较A、B组48h和72h MTX血药浓度分布情况、不良反应的发生率及严重程度，以及不良反应的发生率及严重程度与MTX血药浓度的关系。结果：两种剂量HD-MTX48h、72h血药浓度分布差异无统计学意义（P＞0.05），48hMTX血药浓度均超过安全浓度，其中29.1%48hMTX血药浓度＞1.0μmol/L，62.6%72hMTX血药浓度＞0.1μmol/L。HD-MTX化疗后常见的不良反应包括消化道反应、黏膜损害、骨髓抑制、肝功能损害及继发感染，皮肤过敏、药物热少见，未见泌尿系统、神经系统和心功能等损害表现。A组各种不良反应的发生率均高于B组，但差异无统计学意义（P＞0.05）。消化道反应、黏膜损害的发生率和严重程度与48hMTX血药浓度有关（P＜0.05）。骨髓抑制的发生率与48hMTX血药浓度无统计学相关性（P＞0.05），但其严重程度与48hMTX血药浓度有统计学相关性（P＜0.05）。皮肤过敏反应、肝功能损害、继发感染的发生率和严重程度与48hMTX血药浓度无统计学相关性（P＞0.05）。72hMTX血药浓度＜0.1μmol/L者，不良反应的发生率低，程度轻；＞0.1μmol/L者，继续解救至＜0.1μmol/L，除黏膜损害外，其他不良反应如消化道反应、皮肤过敏反应、肝功能损害、骨髓抑制及继发感染等的发生率及严重程度增加无统计学意义（P＞0.05）。结论：48h以后MTX血药浓度与初始给药剂量无关。不良反应的发生率和严重程度与给药剂量无关，但与48hMTX血药浓度有关。72hMTX血药浓度＞0.1μmol/L者，继续解救至安全浓度以下，不良反应的发生率及严重程度无显著增加。在监测MTX血药浓度下，实行个体化治疗，可防止严重不良反应的发生。
[Abstract]:Objective: to observe the blood drug concentration and adverse reactions of high dose methotrexate high-dose HD-MTX intravenous drip in the prevention and treatment of acute lymphoblastic leukemia (ALL) in children with acute lymphoblastic leukemia (ALL) for 24 hours. Methods: the clinical data of 238 cases of HD-MTX regimen chemotherapy in 64 children with all were analyzed retrospectively. According to the dosage of MTX, they were divided into two groups: group A, group A: 5 g / m ~ 2, total 161 times, group B, 3 g / m ~ 2, 77 cases. The first dose of MTX was treated with calcium folate CFF at 36h after the first dose was dripped. The plasma concentration of MTX was measured at 48h and 72h, and the dosage and times of CF were adjusted to the safe concentration. To compare the distribution of MTX concentration at 48h and 72h in group A and B, the incidence and severity of adverse reactions. Results: there was no significant difference in plasma concentration of MTX between two doses of HD-MTX 48 h and 72 h (P > 0.05). Among them, 29.1 HhMTX blood drug concentration > 1.0 渭 mol / L, 62.6 rhMTX blood concentration > 0.1 渭 mol / L HD-MTX blood drug concentration > 0.1 渭 mol / L HD-MTX chemotherapy common adverse reactions including gastrointestinal reactions, mucosal damage, bone marrow suppression, liver function damage and secondary infection, skin allergies, drug fever rare, no urinary system, The incidence of adverse reactions in group A was higher than that in group B, but there was no significant difference (P > 0.05). The incidence and severity of digestive tract reaction and mucosal damage were related to the serum concentration of MTX at 48 h (P < 0.05). There was no significant correlation between the incidence of bone marrow suppression and the serum concentration of MTX at 48 h (P > 0.05), but the severity was significantly correlated with the serum concentration of MTX at 48 h (P < 0.05). There was no significant correlation between the incidence and severity of skin allergic reaction, liver function damage, secondary infection and 48 h MTX blood concentration (P > 0.05 渭 mol / L, P > 0.05 .72 h MTX < 0.1 渭 mol / L, P > 0.1 渭 mol / L, except mucosal damage). There was no significant difference in the incidence and severity of other adverse reactions such as digestive tract reaction, skin allergic reaction, liver function damage, bone marrow depression and secondary infection (P > 0.05). Conclusion there is no correlation between MTX concentration and initial dose of MTX after 48 hours. The incidence and severity of adverse reactions were not related to the dosage of the drug, but the incidence and severity of adverse reactions were not significantly increased when the blood concentration of MTX was higher than 0.1 渭 mol / L at 48h, but the incidence and severity of adverse reactions were not significantly increased. Under the monitoring of MTX concentration, individualized treatment can prevent the occurrence of serious adverse reactions.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R733.71

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