White matter disease induced by high-dose chemotherapy: longitudinal study with MR imaging and proton spectroscopy.
OBJECTIVE
The purpose of this study was to determine the time course for development of white matter changes induced by high-dose chemotherapy.


METHODS
Eight patients with advanced breast cancer were entered into a prospective, longitudinal trial that included examination by MR imaging and proton MR spectroscopy before chemotherapy and through 12 months after treatment with carmustine, cyclophosphamide, and cisplatin, combined with autologous hematopoietic progenitor cell support (AHPCS).


RESULTS
Six patients completed induction chemotherapy, at which time all MR imaging studies appeared normal. At 3 months after the conclusion of high-dose chemotherapy and beyond, three of the four patients remaining in the study showed an increasing volume of white matter changes, which appeared to stabilize during the period from 6 months to 1 year. Maximal volumes of abnormal white matter ranged from 73 to 166 cm3. MR spectroscopy showed little or no change in metabolic ratios through the period of observation, although there was a suggestion of small transient treatment-related decreases in the ratio of N-acetyl aspartate (NAA) to creatine.


CONCLUSIONS
White matter changes are common sequelae of treatment with high-dose chemotherapy combined with AHPCS, occurring early in the period following high-dose chemotherapy, with a rapid and progressive accumulation to about 6 months, but not accompanied by persistent neurologic symptoms. The MR spectroscopic analyses suggest a minimal disturbance of the neuronal marker NAA, a finding that may in part explain the good neurologic outcome.
Brown
M S
MS
Department of Radiology, University of Colorado Health Sciences Center, Denver 80262, USA.
Stemmer
S M
SM
Simon
J H
JH
Stears
J C
JC
Jones
R B
RB
Cagnoni
P J
PJ
Sheeder
J L
JL
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001927:Brain Diseases / Q000139:chemically induced* / Q000175:diagnosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003401:Creatine / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies
D001224:Aspartic Acid; D003520:Cyclophosphamide; C000179:N-acetylaspartate; D003401:Creatine; D002945:Cisplatin; D002330:Carmustine