Polimorfismos de los genes ABCB1 y CYP2C8 en pacientes sometidos a TASPE. Análisis farmacogenético del Paclitaxel en la toxicidad y movilización de progenitores hemopoyéticos
Thesis
Fundations. The efficacy of paclitaxel plus rhG-CSF on of hematopoietic progenitors mobilization, has been tested in hematological patients. Farmacogenetics of paclitaxel has high inter-individual variability. CYP2C8 and ABCB1 genes involved in metabolism and transport that could affect inter-individual variability. Objective. Evaluated in a retrospective cohort of patients undergoing PBSCT, the effect of some single nucleotide polymorphisms (in CYP2C8 and ABCB1 genes) on the effective mobilization and hematologic toxicity induced by paclitaxel. Materials and Methods. A group of 107 patients received paclitaxel and rhG-CSF as mobilizing scheme. Polymorphisms were genotyped for ABCB1 gene rs1045642 A> G, rs2032582 ABCB1 C> A, ABCB1 rs2032582 C> T, rs10509681 CYP2C8 C> T and CYP2C8 rs11572080 A> G. Results. The use of paclitaxel has succeeded in mobilizing more than 80% of patients with lymphoma or myeloma (p = 0.0021), but it was not in acute leukemia. In patients with myeloma, the variable G> ABCB1 rs1045642 was associated with poor mobilization (p = 0.018) and greater hematologic toxicity (p = 0.034). The allele C> rs10509681 CYP2C8 was associated with increased toxicity in patients with lymphoma (p = 0.045) and multiple myeloma (p = 0.042), and homozygous TT allele had a higher hematologic toxicity compared with CT or CC carriers (p = 0.027). Conclusion. This study suggests that allelic SNPs of the variables analyzed in the genes CYP2C8 and ABCB1 in some patient groups affect the ability to mobilize and affect the degree of hematologic toxicity.
