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

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Abstract

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. Mutation analysis was performed by direct sequencing. The median age was 65 years (range 30–79). The median cumulative dose of VCR was 12 mg (range 2–16). VIPN was documented in 42 patients (75%), and 9 (16%) had grade 2–4 VIPN. Age, impaired glucose tolerance, number of cycles of R-CHOP, and VCR cumulative dose were not associated with incidence of VIPN. There was no association between the incidence of grade 2–4 or any grade VIPN and these six genetic polymorphisms. These results indicate that CEP72, MTNR1B, ETAA1, CYP3A5, rs7963521, and rs1045644 genetic polymorphisms are not associated with VIPN in patients with B-cell lymphoma who received R-CHOP.

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Acknowledgements

We thank the following institutions for providing patient data and specimens: Suzuka General Hospital, Suzuka Kaisei General Hospital, Mie University Hospital, Takeuchi Hospital, Tohyama Hospital, Matsusaka City Hospital, Matsusaka General Hospital, Saiseikai Matsusaka General Hospital, Ise Red Cross Hospital, and Ise Municipal General Hospital (all in Mie Prefecture, Japan). We also thank Life Science Research Center, Center for Molecular Biology and Genetics, Mie University. This study was presented in part at the 2019 American Society of Hematology Annual Meeting, December 7–10, 2019, Orlando, FL.

Funding

This study was supported in part by the National Cancer Center Research and Development Fund (26-A-4, 29-A-3, M.Y.) and the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (JP18ck0106439, M.Y.).

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Authors and Affiliations

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

    Akihiko Sawaki, Kana Miyazaki, Motoko Yamaguchi, Toshifumi Takeuchi, Kyoko Kobayashi, Isao Tawara & Naoyuki Katayama

  2. Pathology Division, Mie University Hospital, Tsu, Japan

    Hiroshi Imai

  3. Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Japan

    Ryoichi Ono & Tetsuya Nosaka

Authors
  1. Akihiko Sawaki
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  2. Kana Miyazaki
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  3. Motoko Yamaguchi
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  4. Toshifumi Takeuchi
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  5. Kyoko Kobayashi
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  6. Hiroshi Imai
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  10. Naoyuki Katayama
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Correspondence to Motoko Yamaguchi.

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Conflict of interest

AS, KM, MY, and IT report grants from Astellas Pharma, Kyowa Kirin, Ono Pharmaceutical, and Takeda Pharmaceutical, outside the submitted work. NK reports honoraria from Chugai Pharmaceutical and Celgene, and grants from Astellas Pharma, Kyowa Kirin, Ono Pharmaceutical, and Takeda Pharmaceutical, outside the submitted work. The other authors declare that they have no conflict of interest.

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Sawaki, A., Miyazaki, K., Yamaguchi, M. et al. Genetic polymorphisms and vincristine-induced peripheral neuropathy in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Int J Hematol 111, 686–691 (2020). https://doi.org/10.1007/s12185-020-02832-x

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  • DOI: https://doi.org/10.1007/s12185-020-02832-x

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