Evidence for acute neurotoxicity after chemotherapy.

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.

• Authors: Axel Petzold, Tjeerd Mondria, Jens Kuhle, Maria A Rocca, Jan Cornelissen, Peter te Boekhorst, Bob Lowenberg, Gavin Giovannoni, Massimo Filippi, Ludwig Kappos, Rogier Hintzen
• Journal: Annals of neurology (Ann Neurol) Vol. 68 Issue 6 Pg. 806-15 (Dec 2010) ISSN: 1531-8249 [Electronic] United States
• PMID: 21194151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Neurofilament Proteins
• neurofilament protein H
• Trimethoprim, Sulfamethoxazole Drug Combination
• Prednisolone

Topics

• Acute Disease
• Adult
• Anti-Infective Agents (adverse effects)
• Bone Marrow Transplantation (adverse effects)
• Brain (pathology)
• Case-Control Studies
• Disability Evaluation
• Drug-Related Side Effects and Adverse Reactions
• Female
• Hematologic Neoplasms (drug therapy, surgery)
• Humans
• Longitudinal Studies
• Magnetic Resonance Imaging (methods)
• Male
• Middle Aged
• Multiple Sclerosis, Chronic Progressive (drug therapy, surgery)
• Neurofilament Proteins (blood)
• Neurotoxicity Syndromes (blood, diagnosis, etiology)
• Prednisolone (adverse effects)
• Single-Blind Method
• Statistics, Nonparametric
• Time Factors
• Trimethoprim, Sulfamethoxazole Drug Combination (adverse effects)