RESUMEN
Drug-related toxicities represent an important clinical concern in chemotherapy, genetic variants could help tailoring treatment to patient. A pharmacogenetic multicentric study was performed on 508 pediatric acute lymphoblastic leukemia patients treated with AIEOP-BFM 2000 protocol: 28 variants were genotyped by VeraCode and Taqman technologies, deletions of GST-M1 and GST-T1 by multiplex PCR. Toxicities were derived from a central database: 251 patients (49.4%) experienced at least one gastrointestinal (GI) or hepatic (HEP) or neurological (NEU) grade III/IV episode during the remission induction phase: GI occurred in 63 patients (12.4%); HEP in 204 (40.2%) and NEU in 44 (8.7%). Logistic regression model adjusted for sex, risk and treatment phase revealed that ITPA rs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1 rs246240 and ADORA2A rs2236624 homozygous mutated genotypes were associated to NEU and HEP, respectively. These three variants could be putative predictive markers for chemotherapy-related toxicities in AIEOP-BFM protocols.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedades Gastrointestinales/genética , Enfermedades del Sistema Nervioso/genética , Farmacogenética/métodos , Variantes Farmacogenómicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Niño , Preescolar , Ensayos Clínicos como Asunto , Quimioterapia de Consolidación/efectos adversos , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Eliminación de Gen , Predisposición Genética a la Enfermedad , Glutatión Transferasa/genética , Humanos , Quimioterapia de Inducción/efectos adversos , Lactante , Modelos Logísticos , Masculino , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Enfermedades del Sistema Nervioso/inducido químicamente , Pruebas de Farmacogenómica/métodos , Fenotipo , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Valor Predictivo de las Pruebas , Pirofosfatasas/genética , Receptor de Adenosina A2A/genética , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Canales de Potasio Éter-A-Go-Go/genética , Recurrencia Local de Neoplasia/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/genética , Pediatría , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
In a case group of 341 perimenopausal women the following signs of reduced trophism of external genitalia have been studied: mons pubis hair rarefaction, pale mucosae, labia minora edge thinning, and labia minora involution, as well as their correlation with age, time lapse after the menopause, and plasma FSH, LH, progesterone and 17-beta-estradiol. Signs of reduced trophism appear to be present even in the younger considered ages, but a positive trend with age is shown. The passage from less than one year inveral from the menopause to one to three years interval shows the most marked increase in the appearance of involutional aspects, but at six years from the menopause one fourth of the women still show normal trophism of the external genitalia. An inverse relation with 17-beta-estradiol levels is shown for pale mucosae and labia minora edge thinning while the trend of mons pubis hair rarefaction shows no relation with the hormone level. An inverse relation is shown for progesterone levels and the trend of mons pubis hair rarefaction, while for the other signs of reduced trophism the same kind of relation as for 17-beta-estradiol was shown. FSH and LH levels show an inverse relation with "normal" trophism, a direct relation with pale mucosae and labia minora involution, and no relation with mons pubis hair rarefaction and labia minora edge thinning.
Asunto(s)
Estradiol/sangre , Hormona Folículo Estimulante/sangre , Genitales Femeninos/anatomía & histología , Hormona Luteinizante/sangre , Menopausia , Progesterona/sangre , Adulto , Factores de Edad , Femenino , Humanos , Persona de Mediana EdadRESUMEN
During the last decade the development of a great amount of knowledge about the menopause has allowed to establish almost standardized hormonal treatments in order to prevent its symptoms and its late sequelae. Nevertheless, up to now the relationship between typical climacteric symptoms and the actual risk of late sequelae has not been assessed. The climacteric symptoms have hence been related to the involutional aspects of the external genitalia and to the levels of the sex steroids and gonadotropin hormones. An inverse relation between neuropsychical manifestations (insomnia, anxiety, depression, reduced memory, reduced libido) and 17-beta-oestradiol and progesterone levels has been shown. On the contrary, FSH and LH levels showed a direct relationship with neurovegetative symptoms. The relationship between the involutional aspects of the external genitalia and the atrophy related and the neuropsychical symptoms shows the need to evaluate these classes of symptoms, which appear to be most related to oestrogen and progesterone deprivation, in decision making toward hormonal replacement therapy.