【摘要】：目的：大劑量甲氨蝶呤（high-dose methotrexate，HD-MTX）治療是兒童急性淋巴細(xì)胞白血�。╝cute lymphoblastic leukemia，ALL）髓外預(yù)防（也稱作庇護(hù)所治療）及強(qiáng)化治療的重要方案，但HD-MTX的毒性反應(yīng)需要亞葉酸鈣（calciumfolinate，CF）解救，而CF在解救甲氨蝶呤的毒性作用同時(shí)也對其抗白血病作用有影響，目前在兒童ALL治療領(lǐng)域并無CF解救時(shí)間及劑量的“金標(biāo)準(zhǔn)”。我們發(fā)現(xiàn)st.Jude兒童研究醫(yī)院的XV方案與國內(nèi)的方案不同，它試圖減少HD-MTX治療中CF解救次數(shù)及解救劑量以確保HD-MTX更佳的抗白血病細(xì)胞的作用。本文對比分析不同的HD-MTX解救時(shí)間，旨在尋求兒童ALL治療中更加有效而又安全的HD-MTX治療方案。 方法：2006年9月至2013年4月，27例于大連兒童醫(yī)院接受HD-MTX治療的急性淋巴細(xì)胞白血病患兒，發(fā)病年齡2.9歲至16歲，男性19例，女性8例，，共86例次HD-MTX（5g/m2）治療，全部HD-MTX治療在治療開始前1天及化療開始后水化堿化至甲氨蝶呤血漿藥物濃度≤0.1μmol/L，全部甲氨蝶呤藥量24小時(shí)靜脈輸注，并分別監(jiān)測甲氨蝶呤血漿藥物濃度，A組甲氨蝶呤治療開始后第36小時(shí)亞葉酸鈣解救，56例次，B組甲氨蝶呤治療開始后第42小時(shí)亞葉酸鈣解救，30例次，兩組均每6小時(shí)使用1次亞葉酸鈣，直至甲氨蝶呤血漿藥物濃度≤0.1μmol/L停止解救。觀察○123小時(shí)，42小時(shí)，66小時(shí)等不同時(shí)間點(diǎn)甲氨蝶呤血漿藥物濃度、○2CF解救次數(shù)、○3CF總用量及○4化療開始后1至7天發(fā)生的骨髓抑制、肝功能異常、口腔肛門黏膜損害、胃腸粘膜反應(yīng)、皮疹及繼發(fā)感染等甲氨蝶呤毒副反應(yīng)，不良反應(yīng)根據(jù)北京協(xié)和醫(yī)院抗癌藥物毒性反應(yīng)分度表分為Ⅰ度至Ⅳ度。所有數(shù)據(jù)分析由SPSS13.0完成。 結(jié)果： 1.兩種方案的甲氨蝶呤42小時(shí)及時(shí)66小時(shí)血漿藥物濃度無統(tǒng)計(jì)學(xué)差異（P值＞0.05）。 2.兩種方案CF補(bǔ)充解救次數(shù)及（CF總劑量/甲氨蝶呤總劑量）比值無統(tǒng)計(jì)學(xué)差異。 3.甲氨蝶呤毒副反應(yīng)以骨髓抑制（83.72%）、肝功能異常（48.84%）、胃腸道反應(yīng)（20.93%）、口腔肛門黏膜損害（17.44%）最為常見。 4.36小時(shí)CF解救與42小時(shí)解救的毒副作用對比無明顯差異，所比較的骨髓抑制（P值0.062）、口腔肛門黏膜損害（P值0.372）、胃腸道反應(yīng)（P值0.442）、肝功能異常（P值0.386）、皮疹（P值0.540）、感染（P值0.236）6個方面P值均＞0.05，無統(tǒng)計(jì)學(xué)差異。 結(jié)論 1. HD-MTX（5g/m2）治療42小時(shí)開始CF解救與36小時(shí)開始CF解救的安全性相同。 2.從42小時(shí)開始CF解救甲氨蝶呤可減少CF使用次數(shù)。 3.延遲6小時(shí)開始CF解救HD-MTX時(shí)間，從理論上可以增加HD-MTX抗白血病作用，可以安全地應(yīng)用于臨床。
[Abstract]:Objective: high dose methotrexate (high-dose methotrexate,HD-MTX) is an important regimen for the prevention of extramedullary prevention (also known as shelter therapy) and intensive treatment in children with acute lymphoblastic leukemia (acute lymphoblastic leukemia,ALL). However, the toxic reaction of HD-MTX needs to be rescued by calcium folinate (calciumfolinate,CF), while the toxicity of methotrexate (MTX) is also affected by CF. There is no gold standard for CF rescue time and dose in the field of ALL treatment in children. We found that the XV regimen in st.Jude Children's Research Hospital is different from that in China. It tries to reduce the number and dosage of CF rescue in HD-MTX treatment to ensure the better anti-leukemia cells of HD-MTX. The aim of this paper is to find a more effective and safe HD-MTX regimen in the treatment of ALL in children by comparing and analyzing the different time of HD-MTX rescue. Methods: from September 2006 to April 2013, 27 children with acute lymphoblastic leukemia treated with HD-MTX in Dalian Children's Hospital, aged 2.9 to 16 years, 19 males and 8 females. A total of 86 HD-MTX (5g/m2) treatments were performed. All patients were treated with HD-MTX at 1 day before treatment and 1 day after chemotherapy. The plasma concentration of methotrexate was less than 0.1 渭 mol/L,. The total methotrexate was injected intravenously at 24 hours after treatment, and the plasma concentration of methotrexate was less than 0.1 渭 mol/L,. The plasma concentration of methotrexate was monitored respectively. In group A, calcium folate was rescued 36 hours after the start of methotrexate therapy, 56 times, and in group B, calcium folate was rescued at 42 hours after the beginning of methotrexate therapy, 30 times. Both groups were treated with calcium folate once every 6 hours until the plasma concentration of methotrexate 鈮

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