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Severe Vincristine-Induced Neuropathic Pain: A Case Report with Pharmacogenetic Analysis and Literature Review.

ABSTRACT: Vincristine-induced peripheral neuropathy (VIPN) is a common adverse effect of vincristine (VCR) for which there is no preventative or curative treatment. Here, we report a case of a patient suffering from severe VCR-related neurotoxicity. To explore the possible causes of severe VIPN in this patient, a set of genes involved in VCR metabolism, transport or are related to the cytoskeleton, microtubules, and inherited neurological diseases gene polymorphisms were examined via pharmacogenetic analyses. The genotyping results revealed the presence of a complex pattern of polymorphisms in CYP3A5, ABCC2, SYNE2, BAHD1, NPSR1, MTNR1B, CEP72, miR-4481 and miR-3117. A comprehensive understanding of all the pharmacogenetic risk factors for VIPN may explain the occurrence of severe neurotoxicity in our patient. This case brings to light the potential importance of pharmacogenetic testing in clinical practice. It also exemplifies the importance of developing early-detection strategies to optimize treatment regimens through prior risk stratification while reducing adverse drug reactions and personalizing therapy.

SUBMITTER: Hu YH

PROVIDER: S-EPMC9809358 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Severe Vincristine-Induced Neuropathic Pain: A Case Report with Pharmacogenetic Analysis and Literature Review.

Hu Ya-Hui YH Li Gui-Zhou GZ Long Jia-Yi JY Yang Qing-Yan QY Zhang Yong Y Chen Feng F Wang Yong-Ren YR

Pharmacogenomics and personalized medicine 20221230

Vincristine-induced peripheral neuropathy (VIPN) is a common adverse effect of vincristine (VCR) for which there is no preventative or curative treatment. Here, we report a case of a patient suffering from severe VCR-related neurotoxicity. To explore the possible causes of severe VIPN in this patient, a set of genes involved in VCR metabolism, transport or are related to the cytoskeleton, microtubules, and inherited neurological diseases gene polymorphisms were examined via pharmacogenetic analy ...[more]

PMID: 36605068

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Project description:Background: One of the most serious complications of cranial radiotherapy is the development of radiation-induced glioma, which is estimated to occur in 1 to 4% of patients who have received cranial irradiation and has a worse prognosis than sporadic glioblastoma. To date, owing to its rarity, no standard of care has been established for radiation-induced glioma. Although comprehensive genetic analysis has recently uncovered the molecular characteristics of radiation-induced glioma, the full picture remains unclear, and the molecular features associated with treatment response and prognosis are poorly understood. Case presentation: A 45-year-old man presented with generalized seizures caused by multiple brain tumors involving the right frontal lobe, thalamus, and brainstem. The patient had a history of whole-brain radiotherapy for the recurrence of Burkitt's lymphoma at the age of 12. He underwent craniotomy, and the histological diagnosis was a high-grade glioma with isocitrate dehydrogenase-wildtype, which was presumed to be a radiation-induced glioma that developed 33 years after whole-brain irradiation. The Heidelberg DNA-methylation brain classifier most closely matched diffuse pediatric-type high-grade glioma, receptor tyrosine kinase-1 subtype, which is a typical methylation class of radiation-induced glioma. Methylation-specific polymerase chain reaction showed that the O6-methylguanine-DNA methyltransferase gene promoter was unmethylated. Next-generation sequencing identified CDKN2A/B deletion as well as co-amplification of several receptor tyrosine kinase-encoding genes including PDGFRA, KIT, and KDR, which are all located on chromosome 4q12. Amplification of this region is present broadly across cancers and is associated with a poor prognosis in sporadic glioblastoma. Nevertheless, the patient received conventional chemoradiotherapy with temozolomide. Subsequent multimodal imaging with magnetic resonance imaging and 11C-methionine positron emission tomography revealed complete remission of all lesions. Two years later, the patient is currently alive with a favorable performance status. Conclusions: Despite radiation-induced glioma with molecular features suggestive of an aggressive phenotype, our patient unexpectedly responded well to conventional chemoradiotherapy, resulting in complete remission that is exceptional in sporadic glioblastoma. Our case indicates that some of the radiation-induced gliomas may have distinct molecular characteristics involved in the therapeutic response that differ from those of sporadic glioblastomas.

Dataset Information

Severe Vincristine-Induced Neuropathic Pain: A Case Report with Pharmacogenetic Analysis and Literature Review.

Publications

Severe Vincristine-Induced Neuropathic Pain: A Case Report with Pharmacogenetic Analysis and Literature Review.

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