Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy--an MR analysis

Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):913-8. doi: 10.1016/0360-3016(95)00565-g.


Purpose: The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone.

Methods and materials: Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients' age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature review.

Results: Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy.

Conclusion: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient's age and CRT dose.

MeSH terms

  • Adolescent
  • Brain / drug effects*
  • Brain / radiation effects*
  • Brain Damage, Chronic / chemically induced
  • Brain Damage, Chronic / etiology*
  • Brain Damage, Chronic / pathology
  • Child
  • Child, Preschool
  • Cranial Irradiation / adverse effects*
  • Female
  • Humans
  • Infant
  • Lymphoma, Non-Hodgkin / therapy*
  • Magnetic Resonance Imaging
  • Male
  • Methotrexate / adverse effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Regression Analysis


  • Methotrexate