Assuntos
Sulfatos de Condroitina/administração & dosagem , Dermatan Sulfato/administração & dosagem , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Heparitina Sulfato/administração & dosagem , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/prevenção & controle , Adolescente , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Microangiopatias Trombóticas/etiologiaRESUMO
Calcineurin inhibitors are necessary as immunosuppressants during hematopoietic SCT (HSCT) to prevent alloreactivity, but have unfortunate toxicities. So, we investigated the association of gene polymorphisms with the initial calcineurin inhibitor concentration and the subsequent drug dose from day 1 to day 28 among patients who underwent HSCT at a single institution. We analyzed 58 serial cases of Japanese patients receiving GVHD prophylaxis with CsA (21 cases) or tacrolimus (37 cases). We investigated eight single-nucleotide polymorphisms: rs4244285 (CYP2C19), rs15524, rs4646450, rs3800959, rs776746 (CYP3A5), rs1128503, rs2032582 and rs1045642 (MDR1). The CsA concentration was significantly higher when the genotype of CYP3A5 rs15524 was T/T (P=0.044) or rs776746 was G/G (P=0.027). The CYP3A5 rs776746 and rs4646450 genotypes were also associated with tacrolimus concentration (P=0.013 and P=0.0058, respectively). The dosage of tacrolimus was remarkably reduced from day -1 to day 28 when the patient had the CYP3A5 rs4646450 C/C and/or rs776746 G/G genotype (P=0.0010 and P=0.0021, respectively). In this study, we show that genetic variation has a predictable effect on the pharmacological responses to calcineurin inhibitors in HSCT patients.
Assuntos
Inibidores de Calcineurina , Ciclosporina/sangue , Sistema Enzimático do Citocromo P-450/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Tacrolimo/sangue , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Ciclosporina/administração & dosagem , Ciclosporina/farmacocinética , Sistema Enzimático do Citocromo P-450/metabolismo , Inibidores Enzimáticos/sangue , Inibidores Enzimáticos/farmacocinética , Feminino , Genótipo , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinéticaRESUMO
UFT, antitumor agent containing uracil and futraful (FT-207), was given orally to 14 patients with recurrent or advanced carcinomas (6 gastric, 5 colorectal and 3 other carcinomas) and the clinical effects were evaluated. One PR (partial response) 1 NC (no change) and 9 PD(progressive disease) were obtained among 11 evaluable patients. Response rate was 9.1% (1/11), and overall response rate was 14.3% (2/14). According to Karnofsky's criteria, 2 responders (better than I-A) were obtained and response rate was 15.4% (2/13).