RESUMEN
Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline-based chemoimmunotherapy regimens designed to treat de novo diffuse large B-cell lymphoma achieve modest clinical benefit. R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B-cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first-line R-EPOCH at our institution between 1 January 2006 and 31 May 2014. The median progression-free survival (PFS) was 3·5 months [95% confidence interval (CI): 2·0-7·6] and median overall survival (OS) was 5·9 months (95% CI: 3·2-10·3). Toxicity was high and 30% of patients died without progression or response. Patients with a complex CLL karyotype had significantly shorter PFS and OS (P = 0·005 and P = 0·002, respectively). Multivariable analysis identified complex CLL karyotype as the most significant predictor of decreased survival [Hazard ratio (HR) 2·72, 95% CI: 1·14-6·52, P = 0·025], adjusting for number of prior CLL treatments (P = 0·036). Richter Syndrome patients with complex CLL karyotype experience poor survival with R-EPOCH treatment and novel approaches are needed for these patients. In contrast, survival of patients without a complex CLL karyotype was similar to patients with de novo diffuse large B-cell lymphoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Progresión de la Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Etopósido/efectos adversos , Etopósido/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Cariotipo , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/efectos adversos , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Rituximab/administración & dosificación , Resultado del Tratamiento , Vincristina/efectos adversos , Vincristina/uso terapéuticoAsunto(s)
Encefalopatías/etiología , Síndrome Hemolítico-Urémico/complicaciones , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico , Encefalopatías/diagnóstico , Encefalopatías/tratamiento farmacológico , Encefalopatías/patología , Femenino , Síndrome Hemolítico-Urémico/tratamiento farmacológico , Humanos , Convulsiones/diagnóstico , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Índice de Severidad de la EnfermedadRESUMEN
The appropriate dose of antithymocyte globulin (ATG) to be utilized in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplant (alloHSCT) is as yet unknown. We retrospectively compared patients who received 7.5 mg/kg (R-ATG, 39 patients) and 6 mg/kg (r-ATG, 97 patients). The cumulative incidences of acute graft-versus-host disease (aGVHD) grade II-IV at 180 days were 46% and 41% and of aGVHD grade III-IV were 11% and 18% in r-ATG and R-ATG, respectively (p > 0.30). The respective estimated cumulative incidences at 24 months of cGVHD were 42% and 44% (p > 0.30). There was no significant difference in non-relapse mortality (p = 0.22), cumulative incidence of relapse (p = 0.53), progression-free survival (p = 0.69) or overall survival (p = 0.95). In conclusion, a decreased ATG dose of 6 mg/kg was associated with a similar proportion of GVHD to 7.5 mg/kg ATG. Given the increasing number of RIC HSCTs performed worldwide, the correct dose and preparation of ATG should be defined by prospective randomized trials.