Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

Rituximab maintenance in follicular lymphoma patients

Rituximab maintenance(RM)therapy following successful induction has recently emerged as a highly effective treatment for follicular lymphoma(FL).Randomized trials analyzing the impact of RM compared to observation alone have demonstrated a significantly better outcome in terms of progression-free survival(but not overall survival)in patients(pts)who received as first-line treatment single-agent rituximab,standard chemotherapy(CVP)and recently also immunochemotherapy(R-CHOP,R-CVP or R-FND),as shown by preliminary results of the PRIMA trial.Also in the setting of relapsed disease,RM has shown significant benefit either after chemotherapy or immunochemotherapy.RM has been generally well tolerated,and treated pts developed only mild toxicity,mainly a small increased rate of neutropenia,hypogammaglobulinaemia and self-limiting upper-respiratory tract infections.Moreover,no cumulative or unexpected toxicities were observed and quality of life was not affected.These data have established RM therapy as an important part of multi-modal therapeutic strategies in patients affected by FL.

Myelofibrosis: Prognostication and cytoreductive treatment

Myeloproliferative neoplasms include three diseases: polycythemia vera, essential thrombocythemia and primary myelofibrosis(PMF), currently diagnosed according to the 2008 World Health Organization criteria. Patients with PMF may encounter many complications, and, among these, disease progression is the most severe. Concerning prognostication of Myelofibrosis(MF), the International Prognostic scoring system(IPSS)(International Prognostic Scoring System) model at diagnosis and the Dynamic IPSS(DIPSS) anytime during the course of the disease may be useful to define survival of MF patients. The IPSS and the DIPSS are based on age greater than 65 years, presence of constitutional symptoms, hemoglobin level less than 10 g/d L, leukocyte count greater than 25 × 109/L, and circulating blast cells 1% or greater. Cytogenetic profile and mutational analysis seem to be the next step to implement MF prognostication. Concerning treatments, hydroxyurea has been considered until now the drug of choice when an anti-myeloproliferative effect is needed, but recent data on JAK inhibitors demonstrated a significant effect of these drugs on splenomegaly and symptoms.