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
10.3988/jcn.2019.15.4.511
- Author:
David AZOULAY
1
;
Sami GIRYES
;
Roni NASSER
;
Rivka SHARON
;
Netanel A HOROWITZ
Author Information
1. Hematology Unit and Laboratories, Galilee Medical Center, Naharia, Israel. davidA@GMC.gov.il
- Publication Type:Original Article
- Keywords:
BDNF;
chemotherapy-induced peripheral neuropathy;
Val66Met single-nucleotide polymorphism;
non-Hodgkin lymphoma;
multiple myeloma
- MeSH:
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
- From:Journal of Clinical Neurology
2019;15(4):511-516
- CountryRepublic of Korea
- Language:English
-
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.
