Medium and High-Dose Methotrexate-Induced Toxicity in Children with Acute Lymphoblastic Leukemia

Background: Methotrexate has an important role in treatment of acute leukemia. We measured methotrexate level in CSF and blood of children with acute lymphoblastic leukemia to determine complications and outcomes. Materials and Methods: One hundred and twenty patients (73 male, 47 female), with mean age at diagnosis of 6.1 years (11mo_15years) entered the study. Patients were divided into two groups receiving consolidation therapy of medium-dose MTX 2g/m2/24hrs, or high- dose MTX 5g/m2/24hrs respectively. Clinical features, concentration and pharmacokinetic parameters of MTX, as well as serum creatinine were assessed. Results: The mean serum MTX levels (24 hours after therapy) was 8.9_ 9.8 µmol/L after 4 courses. The mean serum MTX level 48 hours after therapy was 0.3-0.42 µmol/L after 4 courses. The mean CSF MTX levels after therapy was 0.22 µmol/L. The mean serum creatinine before and after MTX therapy were not different between two groups. Mucositis was observed as grade 0 in 65.8%, grade 1 in 15%, grade 2in 15%, grade 3 in 3.3% and grade 4 in 0.8% of patients. CNS relapse was observed in 20.8% patients. The mean MTX level after 24 hours in patients with CNS relapse were lower than the mean MTX level in patients with no CNS relapse. Mortality in patients with severe mucositis was higher than patients with mild mucositis (P value <.001). Mortality in patients with CNS relapse was greater than patients without CNS relapse. Conclusion: Routine assessment of the serum MTX levels for medium dose MTX is not necessary, however, careful clinical monitoring of these patient is mandatory. Monitoring the plasma concentration of MTX is necessary in high dose MTX therapy. Keywords: Leukemia, treatment, side effect, methotrexate