Asunto(s)
Perforación Intestinal/inducido químicamente , Mieloma Múltiple/tratamiento farmacológico , Talidomida/efectos adversos , Anciano , Anciano de 80 o más Años , Diverticulitis/diagnóstico por imagen , Diverticulitis/cirugía , Femenino , Humanos , Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/etiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Estudios Retrospectivos , Talidomida/administración & dosificación , Tomografía Computarizada por Rayos XAsunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Mutación Missense , Mutación Puntual , Policitemia/congénito , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/química , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Secuencia Conservada , Eritropoyetina/fisiología , Exones/genética , Femenino , Heterocigoto , Humanos , Prolina Dioxigenasas del Factor Inducible por Hipoxia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Policitemia/genética , Procolágeno-Prolina Dioxigenasa/metabolismo , Mapeo de Interacción de Proteínas , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Transducción de Señal/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismoRESUMEN
Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as <0·01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial.