儿童白血病大剂量甲氨蝶呤不同时间解救安全性分析

发布时间：2019-01-01 16:55

【摘要】：目的：大剂量甲氨蝶呤（high-dose methotrexate，HD-MTX）治疗是儿童急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）髓外预防（也称作庇护所治疗）及强化治疗的重要方案，但HD-MTX的毒性反应需要亚叶酸钙（calciumfolinate，CF）解救，而CF在解救甲氨蝶呤的毒性作用同时也对其抗白血病作用有影响，目前在儿童ALL治疗领域并无CF解救时间及剂量的“金标准”。我们发现st.Jude儿童研究医院的XV方案与国内的方案不同，它试图减少HD-MTX治疗中CF解救次数及解救剂量以确保HD-MTX更佳的抗白血病细胞的作用。本文对比分析不同的HD-MTX解救时间，旨在寻求儿童ALL治疗中更加有效而又安全的HD-MTX治疗方案。 方法：2006年9月至2013年4月，27例于大连儿童医院接受HD-MTX治疗的急性淋巴细胞白血病患儿，发病年龄2.9岁至16岁，男性19例，女性8例，，共86例次HD-MTX（5g/m2）治疗，全部HD-MTX治疗在治疗开始前1天及化疗开始后水化碱化至甲氨蝶呤血浆药物浓度≤0.1μmol/L，全部甲氨蝶呤药量24小时静脉输注，并分别监测甲氨蝶呤血浆药物浓度，A组甲氨蝶呤治疗开始后第36小时亚叶酸钙解救，56例次，B组甲氨蝶呤治疗开始后第42小时亚叶酸钙解救，30例次，两组均每6小时使用1次亚叶酸钙，直至甲氨蝶呤血浆药物浓度≤0.1μmol/L停止解救。观察○123小时，42小时，66小时等不同时间点甲氨蝶呤血浆药物浓度、○2CF解救次数、○3CF总用量及○4化疗开始后1至7天发生的骨髓抑制、肝功能异常、口腔肛门黏膜损害、胃肠粘膜反应、皮疹及继发感染等甲氨蝶呤毒副反应，不良反应根据北京协和医院抗癌药物毒性反应分度表分为Ⅰ度至Ⅳ度。所有数据分析由SPSS13.0完成。 结果： 1.两种方案的甲氨蝶呤42小时及时66小时血浆药物浓度无统计学差异（P值＞0.05）。 2.两种方案CF补充解救次数及（CF总剂量/甲氨蝶呤总剂量）比值无统计学差异。 3.甲氨蝶呤毒副反应以骨髓抑制（83.72%）、肝功能异常（48.84%）、胃肠道反应（20.93%）、口腔肛门黏膜损害（17.44%）最为常见。 4.36小时CF解救与42小时解救的毒副作用对比无明显差异，所比较的骨髓抑制（P值0.062）、口腔肛门黏膜损害（P值0.372）、胃肠道反应（P值0.442）、肝功能异常（P值0.386）、皮疹（P值0.540）、感染（P值0.236）6个方面P值均＞0.05，无统计学差异。 结论 1. HD-MTX（5g/m2）治疗42小时开始CF解救与36小时开始CF解救的安全性相同。 2.从42小时开始CF解救甲氨蝶呤可减少CF使用次数。 3.延迟6小时开始CF解救HD-MTX时间，从理论上可以增加HD-MTX抗白血病作用，可以安全地应用于临床。
[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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