Hematological and virological features of non-Hodgkin's lymphomas associated with hepatitis C virus infection : a prospective observational study on behalf of the rete ematologica lombarda (REL)

Introduction: The association between hepatitis C virus (HCV) infection and non- Hodgkin’s lymphomas (NHL) has been demonstrated in epidemiological studies. HCV infection is still a public health problem; in Lombardia, a densely populated region of northern Italy with around 10 millions of inhabitants, the prevalence of infected people is around 5%. In order to study the features of HCV-related NHL, we pursue a prospective multicentric observational study in Lombardia. We present here the characteristics and evolution of the patients (pts) included in this study. Methods: Since January 2008 we collected histological, clinical and therapeutic data of 218 consecutive pts with NHL and HCV infection, diagnosed in Hematology Centres of the ‘‘Rete Ematologica Lombarda’’ (Lombardy Hematology Network). This prospective observational study (Registro Lombardo dei Linfomi HCV-positivi) was approved by the Regional Administration and by IRBs of participating institutions. All pts signed a written informed consent. Results: Males/females ratio was 87/131; median age at diagnosis was 68 yrs (range 36-84). Histotypes were: 99 DLBCL, 57 MZL (19 splenic, 13 nodal, 25 extranodal of MALT), 22 follicular lymphoma, 6 small lymphocytic lymphoma, 6 lymphoplasmocytic lymphoma, 2 mantle cell lymphoma, 26 low-grade B-cell lymphoma NOS. Ann Arbor stage was III-IV in 171, with bone marrow involvement in 96; ECOG score was ‡ 2 in 34. 133 pts showed at least one extranodal localization (spleen in 42, skin in 25, Waldeyer’s ring in 10, ocular adnexa in 8). Virological data are summarized in Table 1. Presence of serum MC (p=0.003), autoimmunity (p<0.001), cryoglobulinemia (p=0.005) were statistically associated with indolent NHL. 144 pts had a known HCV-positivity before the diagnosis of NHL and 40 pts (28%) were treated with antiviral therapy. Data on treatment were available in 201 pts. 151 pts received chemotherapy (in 97 with Rituximab). A grade 3-4 WHO liver toxicity developed in 12 pts and 5 pts interrupted the treatment. Pts with liver toxicity and/or drug reduction of dosage and/or early interruption of therapy showed a worse OS (p=0.01) and PFS (p=0.03). Conclusions: In this prospective collection of data within a regional hematology network most frequently reported histologies are DLBCL and MZL. In a significant proportion of indolent and aggressive lymphoma pts, first detection of HCV infection is concurrent to lymphoma diagnosis. HCV infection seems to hamper, in a significant subset of cases, full dose administration of (immuno)-chemotherapy.