| Objective: High-dose methotrexate (HD-MTX) plays an important role in both shelter treatment and systemic intensive treatment for the children with acute lymphoblastic leukemia (ALL). HD-MTX also makes significant contribution to the improved event-free survival (EFS) for the children with ALL. However, with the increased dosage of MTX applied, the safty of HD-MTX were widely evaluated clinically. The efficacy and safety of HD-MTX treatment, as well as plasma concentration of methotrexate have been evaluated in this study in order to assess the HD-MTX regimen applied in 04 protocol for the pediatric patients with ALL.Methods: 72 cases of children with ALL received a total of 309 cases of HD-MTX (3g/m2) treatment. The plasma concentration of methotrexate was monitored starting from he fourty second hour, and a reasonable times for folate rescue was adjusted according to the plasma methotrexate concentration. Adverse effects were recorded after HD-MTX chemotherapy, and the follow-up visit was taken to the end of December 2009. The data analysis was completed by SPSS13.0.Results:1. The plasma MTX concentration in the fourty second hour was 0.45±0.77(0～6.85)umol/L, and 0.32±0.53 (0.02～3.87)umol/L in the fourty eighted hour. The plasma MTX concentration at 42h was significantly related to that of 48h. The regression equation was as follows: C48h= -0.04+0.59×C42h. It is probable that the plasma MTX concentration at 48h was below 0.25 umol/L when the 42h plasma MTX concentration was below 0.49 umol/L, and if the 42h plasma MTX concentration was greater than 1.76 umol/L, the 48h plasma MTX concentration was likely to be greater than 1umol/L.The pediatric patients with the plasma MTX concentration below 0.25 umol/L in the fourty eighted hour accounted for 82.7%, 91.3% below 0.5 umol/L and 4.3% was greater than 1 umol/L. 75% of the pediatric patients carried out no more than three times of CF rescue, and 83.8% of the pediatric patients didn't need CF rescue for six times, wheras 11.9% of the pediatric patients needed six to eight times, and 1.5% of the children needed CF rescue for more than eight times.2. Bone marrow suppression, gastrointestinal symptoms and infections were common adverse effects. Serious and fatal adverse effects were not found in HD-MTX chemotherapy in this study. There were significant difference in incidence and degree of bone marrow suppression between group A and B. The same result was obtained in other adverse effects exclude erythra.3. The overall recurrence rate of HD-MTX treatment in 04 protocol for children with ALL was 13.89%. The incidence of central nervous system leukemia was 4.17%, and the five-year event-free survival was 62.6%.Conclusion:1. The plasma MTX concentration in the fourty second hour was safe in 82.7% of the pediatric patients applying the HD-MTX treatment, while 4.3% of the pediatric patients may experience toxic concentration. The plasma MTX concentration at 42h was significantly related to that of 48h. The regression equation was as follows: C48h= -0.04+0.59×C42h. It is probable that the plasma MTX concentration at 48h was below 0.25 umol/L when the 42h plasma MTX concentration was below 0.49 umol/L, and if the 42h plasma MTX concentration was greater than 1.76 umol/L, the 48h plasma MTX concentration was likely to be greater than 1umol/L. 83.8% of the pediatric patients didn't need CF rescue for six times, while 1.5% of the pediatric patients needed CF rescue for more than eight times. The individual CF rescue was implemented under the monitoring of plasma methotrexate concentrations in order to achieve effective anti-tumor effect and avoid the serious adverse effect.2. Bone marrow suppression, gastrointestinal symptoms and infections were common adverse effects. Serious and fatal adverse effects were not found in HD-MTX chemotherapy in this study. Adverse effects were associated with the delayed excretion of MTX. The higher the plasma MTX concentration was, the more adverse effects occured, and the more severe adverse effects occured. Serious and fatal adverse effects could be prevented and controled by clinically measure and plasma methotrexate concentration monitoring.3. The incidence of central nervous system leukemia was 4.17%, and the five-year event-free survival was 62.6% in 04 protocol with HD-MTX treatment for children with ALL.
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