大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病血药浓度监测的临床意义

目的：探讨大剂量甲氨蝶呤（high-dose methorexate,HDMTX）在儿童急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）髓外白血病预防治疗中血药浓度监测的临床意义,同时观察不良反应的发生及严重程度并进行安全性的评估。方法：将30例ALL患者按临床分型分为A、B两组。A组为低危型,B组为中危、高危型。两组分别给予甲氨蝶呤22（MTX）3g/m^2、4g/m^2静脉注射。结果：A组56例次在第6次四氢叶酸钙（calcium folinate,Cf）解救后100%血药浓度≤0.1mol/L,而B组80例次仍有28.75%未达到安全水平,需要增加CF解救剂量。不良反应中肝损害、黏膜损害、皮肤损害、骨髓抑制为最常见,组间比较有显著差异性,B组发生率高于A组,损害程度Ⅰ～Ⅲ度,Ⅳ度损害未发生。结论：22HDMTX预防儿童ALL髓外白血病时,MTX≤3g/m^2的治疗剂量,CF的常规解救次数应减少;当MTX剂量〉3g/m时,需要监测血药浓度,根据血药浓度的结果,决定是否给予增加CF解救剂量。在建立血药浓度监测机制、充分水化碱化的2基础上,加强护理,应用HDMTX3～4g/m^2预防髓外白血病是安全可行的。

Clinical Significance on Monitoring the Serum Concentration of High Dose of Methotrexate in Treatment of Children with Acute Lymphoblastic Leukemia

Objective To explore the clinical significance of the serum concentration monitoring in HDMTX treatment for children with acute lymphoblastic leukemia and observe the adverse reaction.Methods Thirty children with ALL were divided into two groups.Agroup were the children with ALL with standard risk,and B 2 2 group were the children with middle and high risk.The two groups were given MTX 3g/m^2,4g/m^2 respectively.Results After six rescues of CF,the serum concentration of MTX in 100%A group were decreased to non-toxic concentration,but the concentration of MTX in 28.75%B group were not decreased to safe standard,so more rescues were needed in B group.In the common adverse effects the groups of hepatic damage,mucosal damage, shin lesions and bone marrow suppression were significiant difference,and B group were higher than in the A group.The mild to moderate damages were common.The rate of the adversed effects in B group was higher than in A group.Conclusion To prevent extramedullary leukemia in the children with ALL,monitoring the serum concentration of MTX is needed.We adjusted the dose of CF according to the serum concentration of 2 MTX.The dose of HDMTX 3～4g/m^2 is safe and faesible when adequate hydration and alkalization are used.