J Clin Neurol.  2019 Oct;15(4):511-516. 10.3988/jcn.2019.15.4.511.

Prediction of Chemotherapy-Induced Peripheral Neuropathy in Patients with Lymphoma and Myeloma: the Roles of Brain-Derived Neurotropic Factor Protein Levels and A Gene Polymorphism

Affiliations
  • 1Hematology Unit and Laboratories, Galilee Medical Center, Naharia, Israel. davidA@GMC.gov.il
  • 2Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
  • 3Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
  • 4The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.

Abstract

BACKGROUND AND PURPOSE
Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that plays an essential role in the maintenance of the nervous system. We have evaluated the peripheral blood protein levels of BDNF and the valine-to-methionine substitution at codon 66 (Val66Met) single-nucleotide polymorphism (SNP) as potential biomarkers for the early recognition of chemotherapy-induced peripheral neuropathy (CIPN) in non-Hodgkin lymphoma and multiple myeloma patients.
METHODS
CIPN was assessed in 45 patients at the diagnosis and during vincristine or bortezomib-based therapy using objective [reduced version of the Total Neuropathy Score (TNSr)] and subjective (FACT-GOG-NTx) tools. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) questionnaire. BDNF protein levels and the Val66Met SNP were determined using ELISA and Sanger sequencing.
RESULTS
The pretreatment BDNF protein level was inversely correlated with the maximum TNSr, FACT-GOG-NTx, and PHQ-9 scores in both genotypes. BDNF patients with the Val/Val genotype demonstrated significantly higher maximum FACT-GOG-NTx and PHQ-9 scores than those with the Val/Met and Met/Met genotypes (Met-BNDF carriers). Correlations between PHQ-9 and TNSr score were found only in Met-BDNF carriers, suggesting that peripheral neuropathy and depression coincide in Met-BDNF carriers.
CONCLUSIONS
Determining the BDNF protein levels before initiating chemotherapy might be a useful tool for CIPN risk assessment and preemptive dose modification. The present data should be validated in larger studies that include other neurotoxic agents.

Keyword

BDNF; chemotherapy-induced peripheral neuropathy; Val66Met single-nucleotide polymorphism; non-Hodgkin lymphoma; multiple myeloma

MeSH Terms

Biomarkers
Brain-Derived Neurotrophic Factor
Codon
Depression
Diagnosis
Drug Therapy
Enzyme-Linked Immunosorbent Assay
Genes, vif*
Genotype
Humans
Lymphoma*
Lymphoma, Non-Hodgkin
Multiple Myeloma
Nervous System
Neurons
Peripheral Nervous System Diseases*
Risk Assessment
Vincristine
Biomarkers
Brain-Derived Neurotrophic Factor
Codon
Vincristine
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