Non-Hodgkin's Lymphomas Associated With Positive Hepatitis-C Virus Infection: A Prospective Multicentric Observational Study On Behalf Of The “Rete Ematologica Lombarda/Hematology Network Of Lombardia Region”

The association between hepatitis-C virus (HCV) infection and non-Hodgkin’s lymphomas (NHL) has been demonstrated in epidemiological studies. In Lombardia, a densely populated region of northern Italy with around 10 millions of inhabitants, the prevalence of infected people is around 5%. In 2008, the “Rete Ematologica Lombarda” (Hematology Network of Lombardia region) started a prospective multicentric observational study, with the aim to collect data on virological and hematological features, on treatment and outcome of HCV-related NHL. Herein, we present the final results of this study.

Between January 2008 and December 2012, 241 consecutive adult patients (pts) with first diagnosis of NHL associated with HCV-positivity were enrolled in this prospective observational study (“Registro Lombardo dei Linfomi HCV-positivi”), approved by the Regional Administration and by IRBs of 10 Hematology Centres of Lombardia region. All pts signed a written informed consent. HIV-positive pts were excluded.

Median age at lymphoma diagnosis was 69 years (yrs) (range 32-90); females were 60%. Histotypes were classified as follows: diffuse large B-cell lymphoma (DLBCL) (44%), marginal zone lymphoma (MZL) (28%), follicular lymphoma (10%), low-grade B-cell lymphoma NOS (10%), small lymphocytic lymphoma (SLL) (3%), lymphoplasmacytic lymphoma (3%), mantle cell lymphoma (1%), peripheral T-cell lymphoma NOS (1%). Ann Arbor stage was III-IV in 79% of pts, with bone marrow involvement in 47%. ECOG score was ≥ 2 in 16% of pts; 63% of pts showed at least one extranodal localization (spleen in 22%, skin in 11%, liver in 10%, Waldeyer’s ring in 5%, ocular adnexa in 3%). Virological features and treatment details are summarized in Table 1. HCV-positivity was detected before the diagnosis of NHL in 166 pts (69%) and median time between HCV detection and NHL diagnosis was 11 yrs. Serum monoclonal component (p=0.003), autoimmunity manifestations (p<0.001) and cryoglobulinemia (p=0.002) resulted more frequent in indolent NHL respect to aggressive subtypes. A shorter overall survival (OS) was observed in pts with ECOG ≥ 2 (p<0.001), hemoglobin < 12 g/dl (p=0.008), albumin < 3.5 g/dl (p=0.005), platelets < 100 x 10⁹/L (p<0.001) and lactate dehydrogenase ≥ UNL (p=0.031). Data on first line treatment for NHL were available in 231 pts: 178 pts (77%) received chemotherapy (CHT) [plus Rituximab (R) in 122]; anthracycline contain-regimens (+/- R) were used in 121 pts (52%). Forty pts (17%) developed liver toxicity of any grade (grade III-IV in 19 pts) and 22 pts (10%) interrupted early the treatment. Fifty-three pts were treated with antiviral therapy (AT) for active HCV infection and among them 12 pts (8 MZL, 3 low-grade B-cell lymphoma NOS, 1 SLL) were treated with AT as first anti-lymphoma therapy; 8 pts obtained a virological response and a complete lymphoma response, 2 pts had a partial response (HCV-RNA negative in 1), 1 pt had neither hematological nor virological response and 1 pt is still on therapy. After a median follow-up of 32 months, 47 pts (20%) died (24 with aggressive NHL, 23 with indolent NHL): 23 due to lymphoma, 10 due to cirrhosis/hepatocarcinoma, 7 due to other solid neoplasms, 7 due to other causes.

In this prospective study conducted in Lombardia, a northern region of Italy, the most common histologies of HCV-associated NHL are DLBCL and MZL. In nearly 70% of pts, first detection of HCV positivity preceded the lymphoma diagnosis. A proportion of pts developed meaningful liver toxicity and/or were not able to complete the therapeutic program. In the indolent lymphomas treated with AT as first anti-lymphoma approach, virological and hematological responses are achieved in about two thirds of pts.

No relevant conflicts of interest to declare.