Nuclear magnetic resonance abnormalities of the cerebral white matter in children with acute lymphoblastic leukemia and malignant lymphoma during and after central nervous system prophylactic treatment with intrathecal methotrexate

Cancer. 1992 Oct 1;70(7):1997-2004. doi: 10.1002/1097-0142(19921001)70:7<1997::aid-cncr2820700732>;2-g.


Background: A prospective study was conducted to test the feasibility of nuclear magnetic resonance (NMR) imaging in the early diagnosis of treatment-induced leukoencephalopathy.

Methods: The study group included 16 patients with acute lymphoblastic leukemia and 4 patients with malignant lymphoma. All were given intravenous and intrathecal (IT) methotrexate (MTX) for central nervous system prophylaxis. Serial NMR studies were performed before and/or during induction-consolidation cycles.

Results: NMR imaging disclosed leukoencephalopathy in 8 of the 20 patients (40%) in the early stages of treatment. In six of the eight, the leukoencephalopathy was resolved after temporary or permanent interruption of IT MTX, and chemotherapy was completed successfully. The other two patients are being treated. Transient neurologic abnormalities developed in two of the eight patients.

Conclusions: The possible causal relationship between leukoencephalopathy and the antimetabolic effects of MTX is discussed. This study clearly shows that NMR imaging is valuable in the early diagnosis and management of treatment-induced leukoencephalopathy.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Diseases / chemically induced*
  • Brain Diseases / diagnosis*
  • Central Nervous System Neoplasms / prevention & control
  • Cerebral Cortex / pathology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Injections, Intravenous
  • Injections, Spinal
  • Lymphoma / drug therapy*
  • Lymphoma / metabolism
  • Magnetic Resonance Imaging*
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Prospective Studies


  • Methotrexate