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目的分析10例急性淋巴细胞白血病完全缓解期儿童应用大剂量甲氨蝶呤(HD-MTX),出现口腔黏膜损害继发感染的临床表现,探讨合理的预防措施及治疗方案。方法10例急性淋巴细胞白血病患儿处于完全缓解期,根据临床分型,分别给予MTX 3.0 g/m2(标危)~5.0g/m2(高危),加三联鞘注一次,MTX静滴36小时开始四氢叶酸钙解救,15 mg/m2/次,首剂加倍,常规采取四氢叶酸钙漱口,并监测MTX 24及68小时血药浓度。结果10例患儿于用药72小时后出现口腔黏膜损害,占同期HD-MTX化疗病人的3.7%(3度6例,4度4例),10例患儿均伴有发热;8例伴有粒细胞减低;5例伴有肝肾功能损害;5例伴有皮肤潮红。口腔黏膜分泌物培养:表皮葡萄球菌2例,溶血葡萄球菌及阴沟肠杆菌1例,肺炎克雷伯氏菌、产酸克雷伯氏菌、缓症链球菌、人葡萄球菌、铜绿假单胞菌各1例,草绿色链球菌及卡他布兰汉氏菌2例。根据口腔分泌物药敏结果分别给予抗感染及抗真菌治疗,辅以静脉丙种球蛋白、成份输血、集落细胞刺激因子等支持治疗,同时加强口腔护理,10例患儿均于治疗后10~12天体温正常,4周痊愈。结论(1)MTX血药浓度监测及合理的四氢叶酸钙解救方案可减少HD-MTX化疗毒副反应。(2)合理使用抗菌药物,尤其是根据口腔黏膜分泌物培养及药敏结果及时调整治疗方案可使绝大多数患儿的感染得到有效的控制。(3)强有力的支持治疗和细致的口腔护理可加快溃疡的愈合。
Objective To analyze the clinical manifestations of high-dose methotrexate (HD-MTX) in 10 children with complete remission of acute lymphoblastic leukemia and secondary oral mucosal lesions, and to explore reasonable preventive measures and treatment options. Methods Ten patients with acute lymphoblastic leukemia were in complete remission. MTX 3.0 g / m 2 (standard risk) to 5.0 g / m 2 (high risk) were given according to the clinical classification. Start calcium leucovorin rescue, 15 mg / m2 / time, the first dose doubled, routine take calcium folinate gargle, and monitoring of MTX 24 and 68 hours plasma concentration. Results In 10 cases, oral mucosal damage occurred 72 hours after treatment, accounting for 3.7% (3 cases in 6 cases and 4 cases in 4 cases) of HD-MTX chemotherapy in the same period. All 10 cases were accompanied by fever. In 8 cases, Granulocytopenia; 5 cases with liver and kidney dysfunction; 5 cases accompanied by skin flushing. Oral mucosal secretions culture: Staphylococcus epidermidis in 2 cases, Staphylococcus aureus and Enterobacter cloacae in 1 case, Klebsiella pneumoniae, Klebsiella oxytoca, Streptococcus sobrinus, Staphylococcus aureus, Pseudomonas aeruginosa 1 case of bacteria, Streptococcus viridans and 2 cases of Catebacterium trachomatis. According to oral drug susceptibility results were given anti-infective and anti-fungal treatment, combined with intravenous gamma globulin, blood transfusion, colony stimulating factor and other supportive treatment, while strengthening oral care, 10 cases of children after treatment 10 ~ 12 Heaven body temperature normal, 4 weeks heal. Conclusion (1) MTX blood concentration monitoring and reasonable rescue program of calcium folinate can reduce HD-MTX chemotherapy side effects. (2) The rational use of antibacterial drugs, especially according to the oral mucosal secretions culture and drug sensitivity results timely adjustment of treatment programs can make the vast majority of children infected effectively controlled. (3) strong supportive care and meticulous oral care can speed up the healing of ulcers.