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Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy. Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed. Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.415.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found. Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy.
Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy. Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed. Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.415.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found. Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy.
Н ейробластома (НБ) -это злокачественное новообразование (ЗНО), развивающееся из клеток-предшественников симпатиче-ской нервной системы, на долю которого приходится 7-8% всех ЗНО у детей в возрасте 0-14 лет [1-3].
Background. Malignancies of thoracic and abdominal localization are the second in pediatric oncopathology, after hemoblastoses. A progress in treatment of this heterogeneous tumors had been achieved by surgery approaches, chemotherapy, supportive care and irradiation role definition in multimodal therapy. Inspite of high survival rate, health condition of pediatric thoracic and abdominal cancer survivours in 5 years and more time in our country are unknown. Aim. To analyze health condition of pediatric thoracic and abdominal cancer survivours and kids, who were born in survivours families. Materials and methods. 324 patients, survived from thoracic and abdominal malignancies were enrolled the study from 1979 to 2015. Patients were subdided into 2 groups: 1st - 126 (38.9%) patients, treated from 1979 to 1996 and 2nd - 198 (61.1%) patients - from 1997 to 2015. Such approach aligned with historical treatment modification - upward 1996 modern anticancer treatment protocols are using and indications for irradiation are limited. Results. By improving therapy of nephroblastoma, decreased number of skeletal disorders from 11.5% in 1st group to 3.9% in 2nd, but increased concomitant renal complications from 5.3% to 21.5% and endocrinopathy from 2.4% to 6.7% in 1st and 2nd groups respectively. In hepar tumours survivours, chronic gastroduodenitis and pancreatoduodenopathy were registrated in 25% and 16% in 1st and 2nd groups respectively. In neuroblastoma survivours, locomotor system pathology (including osteoporosis) was found in 12.1%. Second malignant tumours in period from 8 months to 25 years after end of treatment were in 0,9%, benign - 1,6% of pediatric thoracic and abdominal cancer survivours. Kids, who were born in survivours families, had health condition as their equals in age without oncological family anamnesis. Conclusions. Catamnesis of pediatric thoracic and abdominal cancer survivours can predict possible complications, develop individual rehabilitation and personalized follow up programs. Besides, afterhistory data can help in development of complex treatment approaches for this heterogenous tumours.
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