Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis

Int J Radiat Oncol Biol Phys. 2001 Jul 1;50(3):759-63. doi: 10.1016/s0360-3016(01)01513-9.


Purpose: To evaluate the long-term brain metabolite changes on (1)H-MRS in acute lymphoblastic leukemia (ALL) patients who had intrathecal methotrexate (ITMTX) and cranial irradiation (CRT) for central nervous system (CNS) prophylaxis against CNS relapse.

Methods and materials: Thirty-seven ALL patients (12 females, 25 males) with history of ITMTX and CRT for CNS prophylaxis were studied. Age ranges at the time of diagnosis and at magnetic resonance examination were 0.8-13 years and 12-27 years, respectively. The interval since diagnosis was 5.6-19 years. T2-weighted and gradient-recalled echo (GRE) magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H-MRS) were performed to assess brain injury.

Results: On MRI, 3 leukoencephalopathy (LEP) and 1 infarct were detected. Twenty-two patients had evidence of hemosiderin. On (1)H-MRS no statistically significant difference in choline (Cho)/creatine (Cr) and N-acetylaspartate (NAA)/Cr was associated with LEP. A lower Cho/Cr (p = 0.006) and NAA/Cr (p = 0.078) was observed in brains with hemosiderin. Linear-regression analysis showed no statistically significant relationship between NAA/Cr or Cho/Cr with age at diagnosis, but there was a statistically significant decreasing trend of NAA/Cr and Cho/Cr with the interval since diagnosis.

Conclusion: Long-term brain injury in ALL survivors after CNS prophylaxis with ITMTX and CRT was reflected by decreasing NAA/Cr and Cho/Cr with the interval since diagnosis. The lower Cho/Cr associated with hemosiderin but not LEP suggested a different pathophysiology for these brain lesions.

MeSH terms

  • Adolescent
  • Adult
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / radiation effects
  • Brain Infarction / chemically induced
  • Brain Infarction / etiology
  • Brain Infarction / metabolism
  • Cerebrovascular Disorders / chemically induced
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / metabolism
  • Child
  • Choline / metabolism
  • Cranial Irradiation / adverse effects*
  • Creatine / metabolism
  • Female
  • Humans
  • Injections, Spinal
  • Magnetic Resonance Spectroscopy
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / radiotherapy
  • Radiation Injuries / etiology
  • Radiation Injuries / metabolism
  • Time Factors


  • Antimetabolites, Antineoplastic
  • Aspartic Acid
  • N-acetylaspartate
  • Creatine
  • Choline
  • Methotrexate