Evidence for CSF accumulation of 5-methyltetrahydrofolate during repeated courses of methotrexate plus folinic acid rescue
1989

Study on 5-Methyltetrahydrofolate Accumulation in Cerebrospinal Fluid

Sample size: 36 publication Evidence: moderate

Author Information

Author(s): A. Thyss, G. Milano, M.C. Etienne, P. Paquis, J.L. Roche, P. Grelier, M. Schneider

Primary Institution: Centre Antoine Lacassagne, Hôpital Pasteur, Nice, France

Hypothesis

Does repeated administration of folinic acid combined with methotrexate lead to accumulation of 5-methyltetrahydrofolate in cerebrospinal fluid?

Conclusion

The study found that 5-methyltetrahydrofolate accumulates in cerebrospinal fluid during repeated treatments, which may affect the efficacy of methotrexate.

Supporting Evidence

  • 5-MTHF was the only detectable product in cerebrospinal fluid.
  • 5-MTHF was cleared very slowly from cerebrospinal fluid with a half-life of 85 hours.
  • Five out of eight children showed progressive accumulation of 5-MTHF in cerebrospinal fluid.

Takeaway

When kids get treated for leukemia with certain medicines, a substance called 5-MTHF can build up in their spinal fluid, which might make the treatment less effective.

Methodology

The study involved two groups: normal volunteers receiving folinic acid and children with leukemia treated with methotrexate and folinic acid, with samples taken from both plasma and cerebrospinal fluid.

Limitations

The study was limited to a small number of children and did not include patients with meningeal disease.

Participant Demographics

28 normal volunteers (17 males, 11 females) aged 23-77 years and 8 children (6 males, 2 females) aged 2-9 years.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.01

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