Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi.

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.

Clinical characteristics and factors predicting evolution of asymptomatic IgM monoclonal gammopathies and IgM-related disorders.

We evaluated the prognostic features of 384 asymptomatic IgM-monoclonal gammopathies (aIgM-MGs) and 74 IgM-related disorders (IgM-RDs), two clinically distinct groups as proposed by the Second International Workshop on Waldenström's Macroglobulinemia (WM). The cumulative probability of evolution to lymphoid malignancy at 5 and 10 years was 8% (95% CI, 5-13%) and 29% (95% CI, 21-38%), respectively, in aIgM-MGs; it was 9% (95% CI, 4-20%) and 16% (95% CI, 7-31%), respectively, in IgM-RDs (P=0.26). At a median follow-up of 45 months (12-233), 45 aIgM-MGs (11.7%) evolved to symptomatic WM (n=41), non-Hodgkin's lymphoma (NHL) (n=2), IgM multiple myeloma (n=1), and primary amyloidosis (n=1). At a median follow-up of 60 months (13-195), seven IgM-RDs (9.5%) evolved to symptomatic WM (n=6), and B-chronic lymphocytic leukaemia (n=1). At univariate analysis, in aIgM-MGs bone marrow lymphoplasmacytic infiltration, high erythrocyte sedimentation rate (ESR), haemoglobin level, IgM size, and lymphocytosis significantly correlated with evolution probability. At multivariate analysis, the latter two parameters strongly correlated with prognosis, haemoglobin being associated with a trend for a higher progression risk. In IgM-RDs IgM size, neutropenia, lymphocytosis, detectable Bence Jones proteinuria, and high ESR were associated with evolution probability. In conclusion, asymptomatic IgM-MGs and IgM-RDs are distinct clinical entities with similar probability of transformation to lymphoid malignancy.

Treatment of patients with high-grade non-Hodgkin's lymphoma aged over 70 years with an all-oral regimen combining idarubicin, etoposide and alkylators.

In elderly patients age-specific comorbidity often reduces the possibility of administering intensive chemotherapy and of obtaining response to treatment. Therefore, chemotherapy must differ from that for non-elderly patients, while maintaining the primary goal of a complete clinical response. We treated 19 patients over the age of 70 years (median age 75 years, range 70-86) with stage II-IV high-grade non-Hodgkin's lymphoma (NHL) with a combination regimen including idarubicin plus etoposide and prednimustine (or chlorambucil+prednisone), all administered orally on an outpatient basis. The therapeutic schedule included six 5-day courses of idarubicin 20 mg/sqm on day 1 (or 10 mg/sqm on days 1 and 3 in the nine patients last treated), etoposide 60 mg/sqm/12 h days 2-5, prednimustine 60 mg/sqm days 2-5, G-CSF 300 microg/day from day+7 until PMN>1000/microl. In ten patients prednimustine was replaced by chlorambucil 10 mg/sqm, days 2-5, and prednisone 50 mg days 2-5, because of non-availability of the drug. Of the 19 patients submitted to this regimen 15 (79%) obtained a clinical response: eight reached a complete response (CR), and seven a partial response (PR). Hematologic toxicity was generally mild. Only three patients had to be hospitalised for infection. Except alopecia, non-hematologic toxicities were negligible. At a median follow-up of 16 months, five of eight patients who obtained CR relapsed (median CR duration 7 months). The actuarial median survival is 34 months (range 6-46). This study demonstrates the feasibility and efficacy of an all-oral regimen including idarubicin, plus etoposide and prednimustine (or chlorambucil+prednisone) in NHL patients aged over 70 years.