23 results match your criteria pathogenesis vipn

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Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment.

Int J Mol Sci 2021 Apr 16;22(8). Epub 2021 Apr 16.

Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.

Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Read More

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Effect of pyridoxine plus pyridostigmine treatment on vincristine-induced peripheral neuropathy in pediatric patients with acute lymphoblastic leukemia: a single-center experience.

Neurol Sci 2021 Sep 13;42(9):3681-3686. Epub 2021 Jan 13.

Department of Pediatric Hematology and Oncology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.

Background: Vincristine (VCR), which is a key component of chemotherapy, is important for survival. VCR is associated with a well-known side effect, including neurotoxicity.

Aims: The aim of this study was to evaluate the features of vincristine-induced peripheral neuropathy (VIPN) and the effectiveness of pyridoxine plus pyridostigmine therapy in children with acute lymphoblastic leukemia. Read More

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September 2021

Genetic factors influencing the development of vincristine-induced neurotoxicity.

Expert Opin Drug Metab Toxicol 2021 Feb 6;17(2):215-226. Epub 2020 Dec 6.

Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca , Monza, Italy.

: One of the most common side effects during vincristine (VCR) use is the establishment of VCR-induced peripheral neuropathy (VIPN). Among several risk factors that can influence the development of VIPN, such as cumulative dose and patient's age, sex, ethnicity, and genetic variants, this review is focused on the genetic variability. : A literature research was performed firstly using the following PubMed search string but also other relevant papers cited by the selected articles were included. Read More

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February 2021

Vincristine-induced peripheral neuropathy: A mini-review.

Neurotoxicology 2020 12 11;81:161-171. Epub 2020 Oct 11.

Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Vincristine (VCR), an alkaloid extracted from vinca, is often used in combination with other chemotherapeutic drugs to treat a variety of cancers, such as acute lymphoblastic leukaemia (ALL), malignant lymphoma, and neuroblastoma. However, VCR possesses dose-dependent neurotoxicity, which is the main factor restricting its application. Vincristine-induced peripheral neuropathy (VIPN) not only limits the dose of VCR and leads to the discontinuation of treatment but also triggers serious damage to the physical and mental health of patients. Read More

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December 2020

Association of CEP72 rs924607 TT Genotype with Vincristine-induced Peripheral Neuropathy Measured by Motor Nerve Conduction Studies.

Klin Padiatr 2020 Nov 2;232(6):331-333. Epub 2020 Sep 2.

Unit for Special Laboratory Diagnostics, University Medical Centre Ljubljana, Division of Paediatrics, Ljubljana, Slovenia.

Vincristine is at the core of many treatment protocols for childhood malignancies. The major dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN) which may cause morbidity and disrupt curative treatment. Several studies have tried to identify pharmacogenetic biomarkers for susceptibility to vincristine-induced toxicity (Egbelakin A et al. Read More

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November 2020

Fluoroquinolone prophylaxis does not increase risk of neuropathy in children with acute lymphoblastic leukemia.

Cancer Med 2020 09 25;9(18):6550-6555. Epub 2020 Jul 25.

Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.

Background: Fluoroquinolone antibiotics are frequently utilized in pediatric oncology patients as prophylaxis or step-down therapy following broad spectrum beta-lactam therapy for febrile neutropenia. Concerns regarding neurotoxicity limit the use of these agents. No studies have evaluated the association between fluoroquinolone use and neurotoxicity in pediatric oncology patients receiving other neurotoxic agents such as vincristine. Read More

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September 2020

Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy.

Korean J Anesthesiol 2020 10 12;73(5):434-444. Epub 2020 Feb 12.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Studies investigating the correlation between spinal adenosine A1 receptors and vincristine-induced peripheral neuropathy (VIPN) are limited. This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in the rat model of VIPN.

Methods: Vincristine (100 μg/kg) was intraperitoneally administered for 10 days (two 5-day cycles with a 2-day pause) and VIPN was induced in rats. Read More

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October 2020

Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy.

Int J Hematol 2020 May 28;111(5):686-691. Epub 2020 Jan 28.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common and life-long toxicity in lymphoma patients receiving current standard chemotherapy. The association between VIPN and genetic polymorphisms is largely unknown in adult lymphoma patients. To examine the possible relationship between known genetic polymorphisms in patients with pediatric acute lymphoblastic leukemia and incidence of VIPN in adult patients with B cell lymphoma, we examined CEP72 rs924607, ETAA1 rs17032980, MTNR1B rs12786200, CYP3A5 rs776746, rs7963521, and rs1045644 genetic polymorphisms in samples from 56 adult patients with B-cell lymphoma who received rituximab, cyclophosphamide, doxorubicin, VCR, and prednisone (R-CHOP) chemotherapy. Read More

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Measuring vincristine-induced peripheral neuropathy in children with cancer: validation of the Dutch pediatric-modified Total Neuropathy Score.

Support Care Cancer 2020 Jun 16;28(6):2867-2873. Epub 2019 Nov 16.

Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology Amsterdam, Amsterdam, The Netherlands.

Purpose: The aims were to evaluate the construct validity and reliability of the Dutch version of the pediatric-modified Total Neuropathy Score (ped-mTNS) for assessing vincristine-induced peripheral neuropathy (VIPN) in Dutch pediatric oncology patients aged 5-18 years.

Methods: Construct validity (primary aim) of the ped-mTNS was determined by testing hypotheses about expected correlation between scores of the ped-mTNS (range: 0-32) and the Common Terminology Criteria for Adverse Events (CTCAE) (range: 0-18) for patients and healthy controls and by comparing patients and controls regarding their total ped-mTNS scores and the proportion of children identified with VIPN. Inter-rater and intra-rater reliability and measurement error (secondary aims) were assessed in a subgroup of study participants. Read More

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Vincristine-induced peripheral neurotoxicity: A prospective cohort.

Pediatr Hematol Oncol 2020 Feb 4;37(1):15-28. Epub 2019 Nov 4.

Department of Pediatrics, BC Children's Hospital, Vancouver, BC, Canada.

Vincristine-induced peripheral neuropathy (VIPN) is a serious and pervasive problem, affecting 12-78% of pediatric patients, based on retrospective studies. The study objective was to prospectively collect a cohort of well-phenotyped patients receiving vincristine in order to accurately classify and grade their neurotoxicity. All children in British Columbia with leukemia or lymphoma requiring vincristine between 2013 and 2016 were approached for consent. Read More

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February 2020

Obesity as a Potential Risk Factor for Vincristine-induced Peripheral Neuropathy.

J Pediatr Hematol Oncol 2020 10;42(7):e637-e640

Indiana University School of Medicine, Indianapolis, IN.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Vincristine is a core chemotherapeutic agent for patients with ALL; unfortunately, ∼78% will develop vincristine-induced peripheral neuropathy (VIPN). VIPN can result in vincristine dose reductions that decrease therapeutic efficacy: making it important to understand which children are at highest risk for VIPN. Read More

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October 2020

Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia.

Clin Pharmacol Ther 2019 06 21;105(6):1421-1428. Epub 2019 Jan 21.

Indiana University School of Medicine, Indianapolis, Indiana, USA.

Vincristine is one of the core chemotherapy agents used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, one of the major toxicities resulting from vincristine exposure is vincristine-induced peripheral neuropathy (VIPN). When VIPN results in significant morbidity, the vincristine dose may need to be reduced, thus potentially decreasing the effectiveness of treatment. Read More

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Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients identified using whole-exome sequencing.

Pharmacogenomics 2018 10 7;19(15):1181-1193. Epub 2018 Sep 7.

Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, QC, H3T1C5, Canada.

Aim: To identify genetic markers associated with vincristine-induced peripheral neuropathy (VIPN) in childhood acute lymphoblastic leukemia.

Patients & Methods: Whole-exome sequencing data were combined with exome-wide association study to identify predicted-functional germline variants associated with high-grade VIPN. Genotyping was then performed for top-ranked signals (n = 237), followed by validation in independent replication group (n = 405). Read More

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October 2018

Pharmacogenomics of Vincristine-Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes.

Clin Pharmacol Ther 2019 02 17;105(2):402-410. Epub 2018 Aug 17.

BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.

Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia (ALL). Unfortunately, clinical utility is restricted by dose-limiting vincristine-induced peripheral neuropathies (VIPN). We sought to determine the association of VIPN with a recently identified risk variant, CEP72 rs924607, and drug absorption, distribution, metabolism, and excretion (ADME) gene variants in pediatric ALL. Read More

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February 2019

Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth.

Neurobiol Dis 2018 03 29;111:59-69. Epub 2017 Nov 29.

KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium. Electronic address:

As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Read More

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CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer.

Pediatr Blood Cancer 2018 03 8;65(3). Epub 2017 Nov 8.

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.

Background: Vincristine (VCR) is a critical part of treatment in pediatric malignancies and is associated with dose-dependent peripheral neuropathy (vincristine-induced peripheral neuropathy [VIPN]). Our previous findings show VCR metabolism is regulated by the CYP3A5 gene. Individuals who are low CYP3A5 expressers metabolize VCR slower and experience more severe VIPN as compared to high expressers. Read More

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Vincristine-induced peripheral neuropathy in children with cancer: A systematic review.

Crit Rev Oncol Hematol 2017 Jun 6;114:114-130. Epub 2017 Apr 6.

Department of Pediatric Hematology/Oncology, VU University Medical Center Amsterdam, Postbus 7057, 1007, MB, Amsterdam, The Netherlands.

Vincristine-induced peripheral neuropathy (VIPN) is a dose-limiting side effect of vincristine (VCR) treatment in children, leading to diminished quality of life. Much remains unknown about the underlying mechanisms of VIPN. This review systematically summarizes the available literature concerning contributing factors of VIPN development in children. Read More

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Vincristine-induced peripheral neuropathy in survivors of childhood acute lymphoblastic leukaemia.

Pediatr Blood Cancer 2017 Aug 31;64(8). Epub 2017 Jan 31.

Division of Paediatric Neurology, Department of Paediatrics, University of Malaya, Kuala Lampur, Malaysia.

Background: Vincristine, an essential component of childhood acute lymphoblastic leukaemia (ALL) therapeutic protocols, is associated with dose-dependent neurotoxicity, but its long-term morbidity in treated children has not been clearly elucidated. The aim of this study is to determine the prevalence of vincristine-induced peripheral neuropathy (VIPN) among Malaysian childhood ALL survivors and its impact on motor function and quality of life.

Procedure: Survivors of childhood ALL aged 4-18 years who had completed chemotherapy for 2 years or more were evaluated for VIPN using both the clinical Total Neuropathy Score (cTNS) and nerve conduction studies. Read More

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Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer.

Support Care Cancer 2017 03 9;25(3):701-708. Epub 2016 Nov 9.

Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY, 10032, USA.

Background: Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented.

Methods: Fifty-six patients between the ages of 5-21 with newly diagnosed leukemia, lymphoma, extracranial solid tumor or medulloblastoma and expected to receive a minimum cumulative dose of 6 mg/m of vincristine over a 30-week period were eligible. Read More

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Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia.

J Peripher Nerv Syst 2015 Mar;20(1):37-46

School of Medicine, Indiana University, Indianapolis, IN, USA.

Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1-18 years who received vincristine at one of four academic children's hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©-Five (PNPS©-5). Read More

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Measuring vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia.

Cancer Nurs 2013 Sep-Oct;36(5):E49-60

School of Nursing, University of Michigan, Ann Arbor, MI, USA.

Background: Vincristine-induced peripheral neuropathy (VIPN) is difficult to quantify in children.

Objective: The study objective was to examine the reliability, validity, and clinical feasibility of several VIPN measures for use in children with acute lymphoblastic leukemia.

Interventions/methods: Children (n = 65) aged 1 to 18 years receiving vincristine at 4 academic centers participated in the study. Read More

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Increased risk of vincristine neurotoxicity associated with low CYP3A5 expression genotype in children with acute lymphoblastic leukemia.

Pediatr Blood Cancer 2011 Mar 11;56(3):361-7. Epub 2010 Nov 11.

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

Background: This study evaluates the relationship between cytochrome P450 (CYP) 3A5 genotype and vincristine-induced peripheral neuropathy (VIPN) in children with precursor B cell acute lymphoblastic leukemia (preB ALL). We have shown in vitro that vincristine is metabolized significantly more efficiently by CYP3A5 than by CYP3A4. We also found that vincristine neurotoxicity is less common in African-Americans (70% express CYP3A5) than in Caucasians. Read More

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