JAK2 ALLELE BURDEN IN PATIENTS WITH PHILADELPHIA NEGATIVE MYELOPROLIFERATIVE NEOPLASMS

Background The JAK2V617F allele burden (JAK-AB) plays a central role in chronic myeloproliferative neoplasms (cMPNs); its presence has also been advocated in the differential diagnosis of cMPNs and as independent risk factor for venous thromboembolic complications. New treatment with Ruxolitinib may decrease JAK-AB but at the present, it is not clear the clinical advantage of such reduction Aims Primary aim of the current study was to evaluate at diagnosis the JAK-AB in patients with Philadelphia negative cMPNs, in order to evaluate any association with standard demographic, clinical and laboratory parameters with particular reference to thrombotic risk. Methods Peripheral blood samples from patients with Ph-negative cMPNs were collected, DNA from leucocytes was analysed for Jak-2 (V617F) gene mutation with amplification-refractory mutation system (ARMS) PCR, subsequently a real-time quantitative polymerase chain reaction (qRT-PCR) for JAK2V617F allele burden measurement was applied. A multivariate analysis was than performed to evaluate any association of AB with demographic and clinical data. Results One hundred and twelve patients with Philadelphia negative cMPNs were investigated: 52 females with a median age at diagnosis of 69 years (age range: 18-95 years), 60 males with a median age of 68 years (age range: 18-82 years). Thirty-four patients had Essential Thrombocythemia (ET), fifty-two had Polycythaemia Vera (PV) and twenty-six had primary myelofibrosis (PMF). JAK2-AB of patients with an age of 69 years, was respectively evaluated. Patients older than 69 years showed a significantly higher JAK2-AB . JAK-AB was significantly reduced in ET, when compared to PV and PMF. No correlation was found between median values of allele burden and IPSS and DIPSS scores. In patients with PV (n=52), a significant correlation was observed between allele burden and WHO2008 scoring system. No significant correlation was found between allele burden and thrombotic risk according to IPSET-t and IPSET-ET for PV and ET, respectively. Patients with a previous history of thrombosis had the highest JAK2-AB. In PMF, a positive correlation between JAK-AB and grading of fibrosis was found only for the highest grades (PMFIII and IV). JAK-AB had a positive correlation with splenomegaly in PMF. Conclusion Our report cannot confirm any correlation between allele burden and thrombotic risk, according to currently adopted scoring systems. A previous history of thrombosis is however associated with the highest AB in all cases

Bendamustine in combination with rituximab for elderly patients with previously untreated B-cell chronic lymphocytic leukemia: A retrospective analysis of real-life practice in Italian hematology departments

he front-line therapy for CLL young and fit patients is chemo-immunotherapy with fludarabine-cyclophosphamide-rituximab (FCR). FCR regimen results in a significant myelosuppression and high rates of early and late infections especially in elderly patients. German CLL study group compared FCR vs. bendamustine-rituximab (BR) in fit untreated patients. The response rates with BR or FCR were comparable, BR could be an alternative 1st-line treatment for elderly patients. Here we report retrospective data of 70 elderly (≥65 years) CLL patients from 12 Italian centers treated with BR as front-line therapy. The primary end points were overall response rate (complete remission/partial remission) and safety. Forty-seven males and 23 females, with a median age of 72 years, were included in the study. Eight patients were unfit for CIRS. The OR rate was 88.6% (31.4% CR and 57.2% PR). Progression free survival, treatment free survival and overall survival rates at 2-years were 79%, 90.3% and 89.6%, respectively. Only del17 was independent unfavorable parameter on the response rate and PFS. Our results indicate that BR front-line at standard dose provides a high response rate with a good safety profile, even if more than 50% of patients experienced a bendamustine dose reduction until 70mg/m(2)