Evidence for acute neurotoxicity after chemotherapy
Corresponding Author
Axel Petzold MD, PhD
Department of Neuroimmunology, UCL Institute of Neurology, Queen Square, London, United Kingdom
VU Medical Center, Dept. of Neurology, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsSearch for more papers by this authorTjeerd Mondria
Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands
Search for more papers by this authorJens Kuhle MD
Departments of Neurology and Clinical Neuroimmunology University Hospital, University of Basel, Basel, Switzerland
Search for more papers by this authorMaria A. Rocca MD
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy
Search for more papers by this authorJan Cornelissen MD
Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorPeter te Boekhorst MD, PhD
Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorBob Lowenberg MD, PhD
Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorGavin Giovannoni MBBCh, PhD
Blizard Institute of Cell and Molecular Science, Queen Mary University of London, Department of Neurology, Barts, and the London NHS Trust, the Royal London Hospital, Whitechapel, London, United Kingdom
Search for more papers by this authorMassimo Filippi MD
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy
Search for more papers by this authorLudwig Kappos MD
Departments of Neurology and Clinical Neuroimmunology University Hospital, University of Basel, Basel, Switzerland
Search for more papers by this authorRogier Hintzen MD, PhD
Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands
Search for more papers by this authorCorresponding Author
Axel Petzold MD, PhD
Department of Neuroimmunology, UCL Institute of Neurology, Queen Square, London, United Kingdom
VU Medical Center, Dept. of Neurology, De Boelelaan 1117, 1081 HV Amsterdam, The NetherlandsSearch for more papers by this authorTjeerd Mondria
Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands
Search for more papers by this authorJens Kuhle MD
Departments of Neurology and Clinical Neuroimmunology University Hospital, University of Basel, Basel, Switzerland
Search for more papers by this authorMaria A. Rocca MD
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy
Search for more papers by this authorJan Cornelissen MD
Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorPeter te Boekhorst MD, PhD
Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorBob Lowenberg MD, PhD
Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
Search for more papers by this authorGavin Giovannoni MBBCh, PhD
Blizard Institute of Cell and Molecular Science, Queen Mary University of London, Department of Neurology, Barts, and the London NHS Trust, the Royal London Hospital, Whitechapel, London, United Kingdom
Search for more papers by this authorMassimo Filippi MD
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy
Search for more papers by this authorLudwig Kappos MD
Departments of Neurology and Clinical Neuroimmunology University Hospital, University of Basel, Basel, Switzerland
Search for more papers by this authorRogier Hintzen MD, PhD
Department of Neurology, MS Center ErasMS, Erasmus MC, Rotterdam, the Netherlands
Search for more papers by this authorAbstract
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
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