WHITE-MATTER DISEASE INDUCED BY HIGH-DOSE CHEMOTHERAPY - LONGITUDINAL-STUDY WITH MR-IMAGING AND PROTON SPECTROSCOPY

PURPOSE: The purpose of this study was to determine the time course fo r development of white matter changes induced by high-dose chemotherap y. METHODS: Eight patients with advanced breast cancer were entered in to a prospective, longitudinal trial that included examination by MR i maging and proton MR spectroscopy before chemotherapy and through 12 m onths after treatment with carmustine, cyclophosphamide, and cisplatin , combined with autologous hematopoietic progenitor cell support (AHPC S). RESULTS: Six patients completed induction chemotherapy, at which t ime all MR imaging studies appeared normal, At 3 months after the conc lusion of high-dose chemotherapy and beyond, three of the four patient s remaining in the study showed an increasing volume of white matter c hanges, which appeared to stabilize during the period from 6 months to 1 year, Maximal volumes of abnormal white matter ranged from 73 to 16 6 cm(3), MR spectroscopy showed little or no change in metabolic ratio s through the period of observation, although there was a suggestion o f small transient treatment-related decreases in the ratio of N-acetyl aspartate (NAA) to creatine, CONCLUSION: White matter changes are com mon sequelae of treatment with high-dose chemotherapy combined with AH PCS, occurring early in the period following high-dose chemotherapy, w ith a rapid and progressive accumulation to about 6 months, but not ac companied by persistent neurologic symptoms, The MR spectroscopic anal yses suggest a minimal disturbance of the neuronal marker NAA, a findi ng that may in part explain the good neurologic outcome.