本文選題：兒童急性淋巴細(xì)胞白血病 + 甲氨蝶呤　； 參考：《廣西醫(yī)科大學(xué)》2012年碩士論文

【摘要】：目的：觀察不同劑量的大劑量甲氨蝶呤（high-dose methotrexate，HD-MTX）連續(xù)24小時(shí)（hour，h）靜脈滴注在兒童急性淋巴細(xì)胞白血�。╝cutelymphoblastic leukemia，ALL）髓外白血病防治中的血藥濃度和不良反應(yīng)，為制定個(gè)體化用藥方案提供參考依據(jù)。 方法：回顧性分析64例ALL患兒238例次HD-MTX方案化療的臨床資料。根據(jù)MTX給藥劑量分為A、B兩組：A組5g/m2，共161例次， B組3g/m2，共77例次。首劑MTX開始滴入后36h予甲酰四氫葉酸鈣（calciumfolinate，CF）解救，檢測MTX48h、72h血藥濃度，并據(jù)此調(diào)整CF的劑量和次數(shù)，，直至安全濃度。比較A、B組48h和72h MTX血藥濃度分布情況、不良反應(yīng)的發(fā)生率及嚴(yán)重程度，以及不良反應(yīng)的發(fā)生率及嚴(yán)重程度與MTX血藥濃度的關(guān)系。 結(jié)果：兩種劑量HD-MTX48h、72h血藥濃度分布差異無統(tǒng)計(jì)學(xué)意義（P＞0.05），48hMTX血藥濃度均超過安全濃度，其中29.1%48hMTX血藥濃度＞1.0μmol/L，62.6%72hMTX血藥濃度＞0.1μmol/L。HD-MTX化療后常見的不良反應(yīng)包括消化道反應(yīng)、黏膜損害、骨髓抑制、肝功能損害及繼發(fā)感染，皮膚過敏、藥物熱少見，未見泌尿系統(tǒng)、神經(jīng)系統(tǒng)和心功能等損害表現(xiàn)。A組各種不良反應(yīng)的發(fā)生率均高于B組，但差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）。消化道反應(yīng)、黏膜損害的發(fā)生率和嚴(yán)重程度與48hMTX血藥濃度有關(guān)（P＜0.05）。骨髓抑制的發(fā)生率與48hMTX血藥濃度無統(tǒng)計(jì)學(xué)相關(guān)性（P＞0.05），但其嚴(yán)重程度與48hMTX血藥濃度有統(tǒng)計(jì)學(xué)相關(guān)性（P＜0.05）。皮膚過敏反應(yīng)、肝功能損害、繼發(fā)感染的發(fā)生率和嚴(yán)重程度與48hMTX血藥濃度無統(tǒng)計(jì)學(xué)相關(guān)性（P＞0.05）。72hMTX血藥濃度＜0.1μmol/L者，不良反應(yīng)的發(fā)生率低，程度輕；＞0.1μmol/L者，繼續(xù)解救至＜0.1μmol/L，除黏膜損害外，其他不良反應(yīng)如消化道反應(yīng)、皮膚過敏反應(yīng)、肝功能損害、骨髓抑制及繼發(fā)感染等的發(fā)生率及嚴(yán)重程度增加無統(tǒng)計(jì)學(xué)意義（P＞0.05）。 結(jié)論：48h以后MTX血藥濃度與初始給藥劑量無關(guān)。不良反應(yīng)的發(fā)生率和嚴(yán)重程度與給藥劑量無關(guān)，但與48hMTX血藥濃度有關(guān)。72hMTX血藥濃度＞0.1μmol/L者，繼續(xù)解救至安全濃度以下，不良反應(yīng)的發(fā)生率及嚴(yán)重程度無顯著增加。在監(jiān)測MTX血藥濃度下，實(shí)行個(gè)體化治療，可防止嚴(yán)重不良反應(yīng)的發(fā)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.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R733.71

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