大剂量甲氨蝶呤预防儿童中枢神经系统白血病的作用

THE EFFECTS OF HIGH DOSE METHOTREXATE ON CHILDHOOD CENTRAL NERVOUS SYSTEM LEUKEMIA PROPHYLAXIS

目的探讨大剂量甲氨喋呤（NDMTX）对急性淋巴细胞白血病（ALL）儿童中的中枢神经系统白血病（CNSL）的预防作用。方法12例病儿接受了56次HDMTX（每次3．0g／m2）治疗。应用荧光偏振免疫法测定MTX的血清和脑脊液浓度。结果血清MTX的最高浓度为（0．87～1．23）×10-4mol／L，用药24h后有效浓度仍在（1．0～70） ×10-7mol／L范围内。脑脊液的MTX浓度在（2.0～8．8）×-7mol／L，足以杀灭中枢神经系统内的白血病细胞，除一例出现严重中毒外，其余病例不良反应均较轻。9例坚持治疗18个月（6～66个月）者，除一例复发外，8例连续完成缓解。结论NDMTX治疗有利于减少ALL儿童CNSL的复发，有提高长期无病生存率的作用。

Objectives To investigate the effects of high-dose methotrexate (HDMTX) on central nervous system leukemia (CNSL) prophylaxis in childhood acute lymphoblastic leukemia(ALL). Methods 12 children with ALL received HDMTX treatment (3. 0g/m2,every times) MTX serum and cerebrospinal fluid(CSF) concentrations were determined by fluorescence polarization immunoassay- Results The highest concentration of MTX in serum reaches at (0. 87-1. 23) ×10-4mol/L and still remained the effective level of (1. 0-7. 0 × 10-4mol/L) at the 24th hour. At the completion of HDMTX,the MTX concentration in CSF was (2. 0-8- 8) × 10-7mol/L which was the required satisfactory concentration for killing leukemic cells. There were no severe toxic side effects except for one patient. At median follow-up of 18 months (range 6-66),one case has a CNS relapse with concurrent bone marrow relapse. 8 cases have got continuous complete remission. Conclusions A24 hours infusion of HDMTX 3.0g/m2 in conjunction with an intrathecal MTX therapy is effective in proventing CNSL and in increasing the long-term disease-free survival.