Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population

Pinarli, Faruk Guclu/0000-0002-3241-2478; Albayrak, Meryem/0000-0003-2711-5150WOS: 000406231400018PubMed: 28697165Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.Gazi University Scientific Research Projects UnitGazi University [SBE-01/2011-72]Supported by Gazi University Scientific Research Projects Unit with a project number of SBE-01/2011-72

Analysis of geographical variations in the epidemiology and management of non-valvular atrial fibrillation: results from the RAMSES registry.

Objective: This study aimed to determine the differences in terms of demographic characteristics and preferred stroke prevention strategies for patients with non-valvular atrial fibrillation living in seven geographical regions of Turkey.Methods: In total, 6273 patients were enrolled to this prospective, observational RAMSES study. The patients were divided into seven groups based on the geographical region of residence.Results: In terms of the geographical distribution of the overall Turkish population, the highest number of patients were enrolled from Marmara (1677, 26.7%). All demographic characteristics were significantly different among regions. Preferred oral anticoagulants (OACs) also differed between geographical regions; non-vitamin K OACs were preceded by warfarin in East Anatolia, Aegean, Southeast Anatolia, and Black Sea. Nearly one-third of the patients (28%) did not receive any OAC therapy. However, the number of patients not receiving any OAC therapy was higher in Southeast Anatolia (51.1%) and East Anatolia (46.8%) compared with other geographical regions of Turkey. Inappropriate use of OACs was also more common in East and Southeast Anatolia.Conclusion: This study was the first to show that the demographic differences among the geographical regions may result in different prefer-ences of stroke prevention strategies in Turkey. OACs are still under- or inappropriately utilized, particularly in the eastern provinces of Turkey