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Evidence for acute neurotoxicity after chemotherapy
Author(s) -
Petzold Axel,
Mondria Tjeerd,
Kuhle Jens,
Rocca Maria A.,
Cornelissen Jan,
te Boekhorst Peter,
Lowenberg Bob,
Giovani Gavin,
Filippi Massimo,
Kappos Ludwig,
Hintzen Rogier
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22169
Subject(s) - medicine , neurotoxicity , chemotherapy , atrophy , biomarker , oncology , expanded disability status scale , neurodegeneration , gastroenterology , multiple sclerosis , toxicity , immunology , disease , biochemistry , chemistry
Abstract Objective Chronic neurotoxicity is a recognized long‐term complication following chemotherapy in a range of diseases. Neurotoxicity adversely affects patients' quality of life. The objective of this study is to examine whether there is evidence of acute neurotoxicity. Methods This prospective study included patients with secondary progressive multiple sclerosis (SPMS‐BMT, n = 14) and hematological malignancies (HM‐BMT, n = 17) receiving chemotherapy as preconditioning for bone marrow transplant. The control groups included SPMS patients matched for demographic and clinical data (SPMS‐PL, n = 14) and healthy controls (n = 14). Neurodegeneration was assessed at baseline and longitudinally (months 1, 2, 3, 6, 9, 12, 24, and 36), combining a clinical scale for disability (Expanded Disability Status Scale [EDSS]), a serum protein biomarker for neurodegeneration (neurofilaments, NfH‐SMI35), and brain atrophy measures (magnetic resonance imaging). Results Disability progression was significantly more acute and severe following chemotherapy compared to placebo. Immediately after starting chemotherapy, serum NfH‐SMI35 levels increased in 79% ( p < 0.0001) of SPMS‐BMT patients and 41% ( p < 0.01) of HM‐BMT patients compared to 0% of SPMS‐PL patients or healthy controls. In SPMS‐BMT serum NfH‐SMI35 levels were > 100‐fold higher 1 month after chemotherapy (29.73ng/ml) compared to baseline (0.28ng/ml, p < 0.0001). High serum NfH‐SMI35 levels persisting for at least 3 months were associated with sustained disability progression on the EDSS ( p < 0.05). Brain atrophy rates increased acutely in SPMS‐BMT (−2.09) compared to SPMS‐PL (−1.18, p < 0.05). Interpretation Neurotoxicity is an unwanted acute side effect of aggressive chemotherapy. ANN NEUROL 2010