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

概要

Background
Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common and life-long toxicity in lymphoma patients who received current standard chemotherapy. Several genetic polymorphisms are associated with the incidence of VIPN in children and adults with acute lymphoblastic leukemia (ALL). This study aimed to elucidate a possible relationship between VIPN in adult patients with B-cell lymphoma who received rituximab, cyclophosphamide, doxorubicin, VCR, and prednisone (R-CHOP) and known genetic polymorphisms in patients with pediatric ALL.

Methods
CEP72, ETAA1, MTNRlB, CYP3A5, rs7963521 and rslO45644 genetic polymorphisms were examined in samples from 56 adult patients with B-cell lymphoma treated with R-CHOP. Mutation analysis was performed by direct sequencing.

Results
The median age of patients was 65 years (range, 30-79). The median cumulative dose of VCR was 12 mg/m2 (range, 2-16). VIPN was documented in 42 patients (78%): 33 had grade 1,and 9 had grade 2 to 4. Eight (66%) of 12 patients with the ΟΕΡ72ΎΎ genotype and 34 (74%) of 46 patients with the CEP72 CT/CC genotype experienced any grade VIPN (P= 0.7). Age, impaired glucose tolerance, the number of cycles of R- CHOP, and the VCR cumulative dose were not associated with the incidence of VIPN. There was no association between VIPN and these six genetic polymorphisms.

Conclusions
These results indicated that CEP72, MTNR1B,ETAAl, CYP3A5, rs7963521,and rslO45644 genetic polymorphisms are not associated with VIPN in patients with B- cell lymphoma who received R-CHOP.