RESUMEN
This study was conducted to evaluate the expression of fibrinogen receptors on platelets of Philadelphia-negative chronic myeloproliferative neoplasm (MPN) patients. We collected blood samples from 40 consecutive MPN patients and healthy volunteers. We performed flow cytometry analysis of P-selectin expression and integrin beta-3, activation of glycoprotein (GP) IIb/IIIa and fibrinogen receptor exposure (PAC-1 binding). Surprisingly, we found a very low PAC-1 binding capacity in MPN patients; however, the expression of PAC-1 was almost completely recovered with aspirin intake. We hypothesize that the hypercoagulable states observed in MPN patients could depend on a primarily plasma-driven impairment of fibrin turnover and thrombin generation.
Asunto(s)
Aspirina/uso terapéutico , Fibrinógeno/uso terapéutico , Trastornos Mieloproliferativos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/farmacología , Plaquetas , Enfermedad Crónica , Fibrinógeno/farmacología , Humanos , Persona de Mediana EdadRESUMEN
To retrospectively assess the efficacy of bendamustine alone and with rituximab (R-B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39-85). Forty-three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1-8). Twenty-two patients received bendamustine alone and 87 patients received R-B (median B dosage: 100 mg/m(2) per day, range 90-130 mg/m(2) per day). The overall response rate was 69·6% (complete response 28·6%; partial response 41%), and was significantly higher in patients treated with R-B (P = 0·014) and in those responsive to the previous treatment (P=0·04). After a median follow-up of 7·9 months (range 1-148), the median progression-free survival was 16 months and the median duration of response was 13 months. Median overall survival (OS) was 16·8 months for the whole cohort; patients not responding to the treatment had a significantly worse outcome than those who attained a response (P = 0·0001). In multivariate analysis, only resistant disease status at start of bendamustine treatment (HR 3·2, 95% CI 1·4-7·3, P = 0·006) had an independent prognostic value for OS. Toxicity was manageable and mostly haematological. In conclusion, in our experience R-B was an effective and well-tolerated treatment for relapsed/refractory CLL patients, producing a remarkable high CR rate and mild toxicity.