Cognitive performance and magnetic resonance imaging findings after high-dose systemic and intraventricular chemotherapy for primary central nervous system lymphoma.
BACKGROUND
Long-term neurotoxicity is a frequent complication of combined radiotherapy and chemotherapy in patients with primary central nervous system lymphoma. Treatment protocols without radiotherapy have been implemented to avoid this; however, little detailed neuropsychologic and neuroradiologic data exist to assess the frequency of long-term treatment sequelae in this patient group.


OBJECTIVE
To determine whether a polychemotherapy regimen based on high-dose methotrexate results in cognitive impairment and/or changes detectable by magnetic resonance imaging of the brain during long-term follow-up.


METHODS
Twenty patients with histologically proven primary central nervous system lymphoma were treated with a novel chemotherapy protocol that included systemic and intraventricular administration of methotrexate and cytarabine (ara-C). Standardized neuropsychologic testing and magnetic resonance imaging investigations were performed prior to therapy and prospectively during a median follow-up period of 36 months (range, 21-69 months).


RESULTS
Ten patients achieved durable remissions without relapse for more than 1 year after completion of chemotherapy. There was no gross cognitive decline in any of these patients during the follow-up period. In contrast, magnetic resonance imaging revealed therapy-induced white matter changes in 5 of these patients.


CONCLUSIONS
We conclude that chemotherapy alone is associated with a low risk of long-term neurotoxicity in primary central nervous system lymphoma. Methotrexate-induced white matter lesions detectable on magnetic resonance imaging are not inevitably associated with significant cognitive decline.
Fliessbach
Klaus
K
Department of Neurology, University of Bonn, Bonn, Germany.
Urbach
Horst
H
Helmstaedter
Christoph
C
Pels
Hendrik
H
Glasmacher
Axel
A
Kraus
Jürgen A
JA
Klockgether
Thomas
T
Schmidt-Wolf
Ingo
I
Schlegel
Uwe
U
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000523:psychology; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009483:Neuropsychological Tests
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate