RESUMEN
The presence of p53 mutation or deletion predicts for poor response to conventional therapy in chronic lymphocytic leukemia (CLL). We sought to determine whether the humanized anti-CD52 antibody alemtuzumab was effective in this patient group. Thirty-six patients with fludarabine-refractory CLL were treated with alemtuzumab, 15 (42%) of whom had p53 mutations or deletions. Clinical responses in patients with p53 mutations, deletions, or both were noted in 6 (40%) of 15 versus 4 (19%) of 21 of patients without. The median response duration for this subset of patients was 8 months (range, 3-17 months). These data suggest that alemtuzumab may be an effective therapy for patients with CLL with p53 mutations or deletions.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Genes p53 , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Vidarabina/análogos & derivados , Anciano , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Evaluación de Medicamentos , Resistencia a Medicamentos , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Estudios Retrospectivos , Eliminación de Secuencia , Resultado del Tratamiento , Vidarabina/uso terapéuticoRESUMEN
Select cytogenetic abnormalities such as del(17)(p13.1) and del(11)(q22-q23)predict rapid disease progression and inferior survival in chronic lymphocytic leukemia (CLL). We sought to determine the impact of the four most common interphase cytogenetic abnormalities in 28 CLL patients relative to response to three-times-a-week rituximab therapy. Abnormalities were noted in 25 of the 28 patients to include del(13)(q14.3) [n = 16 (57%)], del(11)(q22.3) [n = 10 (36%)], +12 [n = 6 (21%)], del(17)(p13.1) [n = 5 (18%)], and normal [n = 3 (11%)]. Only a minority of each of these occurred as sole abnormalities. To categorize patients into one specific group, we used the hierarchical order del(17)(p13.1) > del(11)(q22.3) > trisomy 12 > del(13)(q14.3) to prioritize. Response to rituximab was noted to vary by cytogenetic group: del(17)(p13.1), 0% [n = 5]; del(11)(q22.3), 66% [n = 9]; del(13)(q14.3), 86% [n = 7]; +12, 25% [n = 4], and normal, 0% [n = 3]. Response was significantly lower (P = 0.05) in patients with del(17)(p13.1) as compared with those with other abnormalities. These data suggest that interphase cytogenetics in CLL may be predictive of a response to rituximab therapy and provide support for additional studies validating risk-adapted therapy in this disease.