title: 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.
abstract: OBJECTIVE
  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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong, China. yl190chan@cuhk.edu.hk
authors.forename: Y L
authors.initials: YL
authors.lastname: Chan
authors.forename: D J
authors.initials: DJ
authors.lastname: Roebuck
authors.forename: M P
authors.initials: MP
authors.lastname: Yuen
authors.forename: K W
authors.initials: KW
authors.lastname: Yeung
authors.forename: K Y
authors.initials: KY
authors.lastname: Lau
authors.forename: C K
authors.initials: CK
authors.lastname: Li
authors.forename: K W
authors.initials: KW
authors.lastname: Chik
mesh_terms: D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D020520:Brain Infarction / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism; D002648:Child; D002794:Choline / Q000378:metabolism; D016371:Cranial Irradiation / Q000009:adverse effects*; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; D008727:Methotrexate