Janka G E, Mack R, Helmig M, Haas R J, Bidlingmaier F
Oncology. 1984;41(4):225-32. doi: 10.1159/000225828.
In 86 children with acute lymphocytic leukemia (ALL) and in 6 children with medulloblastoma 253 24-hour methotrexate (MTX) infusions with 150, 500, and 700 mg/m2 were performed. MTX concentrations in plasma and cerebrospinal fluid (CSF) were measured with a specific radioimmunoassay. In 131 infusions with 500 mg/m2 given to patients with ALL in remission, the MTX plasma concentration 24 h after the end of infusion did not exceed 7 X 10(-7) mol/1. Mild hematologic toxicity occurred in 22% of the treatment cycles. In contrast 8/45 infusions given to patients with ALL in relapse were associated with delayed MTX elimination followed by severe toxicity. The CSF: plasma ratio of MTX measured during 58 infusions did not exceed 11% in patients with ALL in remission, but was above this value in 13/34 infusions in patients with leukemia of the central nervous system (CNS). 24-hour MTX infusions with 500 mg/m2 were as hepatotoxic as 4- to 6-hour infusions with 3-8.5 g/m2. With MTX as single agent no remissions were achieved in 8 patients with ALL in relapse. The addition of asparaginase in 10 patients resulted in 3 complete and 2 partial remissions. In patients with ALL in first remission clinical results confirmed the value of intensive MTX therapy for disease-free survival.
对86例急性淋巴细胞白血病（ALL）患儿和6例髓母细胞瘤患儿进行了253次甲氨蝶呤（MTX）24小时输注，剂量分别为150、500和700mg/m²。采用特异性放射免疫分析法测定血浆和脑脊液（CSF）中的MTX浓度。在缓解期的ALL患者中进行的131次500mg/m²输注，输注结束后24小时的MTX血浆浓度未超过7×10⁻⁷mol/L。22%的治疗周期出现轻度血液学毒性。相比之下，复发期ALL患者的45次输注中有8次与MTX清除延迟及严重毒性相关。缓解期ALL患者的58次输注中测得的CSF:血浆MTX比值不超过11%，但中枢神经系统（CNS）白血病患者的34次输注中有13次高于该值。500mg/m²的MTX 24小时输注与3 - 8.5g/m²的4 - 6小时输注肝毒性相当。作为单一药物，8例复发期ALL患者未实现缓解。10例患者加用天冬酰胺酶后，3例完全缓解，2例部分缓解。初治缓解期ALL患者的临床结果证实了强化MTX治疗对无病生存的价值。
