• Clin. Pharmacol. Ther. · Mar 2017

    An Inherited Genetic Variant in CEP72 Promoter Predisposes to Vincristine-Induced Peripheral Neuropathy in Adults With Acute Lymphoblastic Leukemia.

    • W Stock, B Diouf, K R Crews, D Pei, C Cheng, K Laumann, S J Mandrekar, S Luger, A Advani, R M Stone, R A Larson, and W E Evans.
    • Section of Hematology Oncology, University of Chicago Medicine and Comprehensive Cancer Center, Chicago, Illinois, USA.
    • Clin. Pharmacol. Ther. 2017 Mar 1; 101 (3): 391-395.

    AbstractPeripheral neuropathy is a major toxicity of vincristine, yet no strategies exist for identifying adult patients at high-risk. We used a case-control design of 48 adults receiving protocol therapy for acute lymphoblastic leukemia (ALL) who developed vincristine-induced neuropathy (NCI grade 2-4) during treatment, and 48 matched controls who did not develop grade 2-4 neuropathy. Peripheral neuropathy was prospectively graded by National Cancer Institute (NCI) criteria. CEP72 promoter genotype (rs924607) was determined using polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) genotyping. Frequency of the CEP72 T/T genotype was higher in cases (31% vs. 10%, P = 0.0221) and the incidence of vincristine-induced neuropathy (grades 2-4) was significantly higher in patients homozygous for the CEP72 T/T genotype. 75% of the 20 patients homozygous for the CEP72 T allele developed grade 2-4 neuropathy, compared to 44% of patients with CEP72 CC or CT genotype (P = 0.0221). The CEP72 polymorphism can identify adults at increased risk of vincristine-induced peripheral neuropathy.© 2016 American Society for Clinical Pharmacology and Therapeutics.

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