HCV Infection in Nongastric Marginal Zone B-Cell Lymphoma of MALT.
Authors: Arcaini Luca , Burcheri Sara , Rossi Andrea , Passamonti Francesco , Colombo Nora , Paulli Marco , Boveri Emanuela , Brusamolino Ercole , Molteni Alfredo , Pulsoni Alessandro , Cox Maria Christina , Orsucci Lorella , Fabbri Alberto , Frezzato Maurizio , Voso Maria Teresa , Zaja Francesco , Pascutto Cristiana , Morra Enrica , Cortelazzo Sergio , Lazzarino Mario 
Published: April 2020

Abstract
The aim of this study is to define the HCV infection in nongastric marginal zone B-cell lymphoma of MALT. We studied 208 patients (pts) diagnosed and treated in Hematology Units joined in a cooperative Italian survey on marginal zone neoplasms. Median age was 64.4 years (126 F, 82 M). In 90% of pts a single mucosal site was involved (skin or subcutaneous tissue 27%, salivary glands 18%, orbit 14%, Waldeyer’s ring 13%, lung 9%, bowel 4%, other sites 6%). The ratio between stage I - II and stage III – IV was 1.2. 48% of pts showed nodal involvement. Among the 84 pts with stage IV disease, 60% were stage IV because of BM involvement, 10% had &gt;1 MALT site or a diffuse involvement and 30% had both features. 17% had a small MC (24 IgM, 9 IgG and 3 IgA). An autoimmune background was present in 15 pts. HCV infection was documented in 60 of 172 pts (35%). Most HCV+ pts (97%) showed a single MALT site. The distribution of sites between HCV+ and HCV− cases was statistically significant (p=0.03) with HCV+ pts showing a more frequent involvement of skin or subcutaneous tissue (35%), salivary glands (25%), orbit (15%). BM+ was present in 37%. 42% of pts had nodal disease and 43% showed signs of chronic active hepatitis. HCV-RNA was detected in 22/24 pts (92%). Characteristics associated with to HCV+ were female sex (p=0.004), age &gt;60 yrs (p=0.007), no leukemic disease (0.01). NHL localizations leading to Ann Arbor stage IV in HCV+ and HCV− pts were statistically different (p=0.03): 71% of HCV+ pts had a single MALT site with BM+. After first line therapy 73% achieved CR and 17% PR for an ORR of 90%. The ORR was 65% in pts receiving CHT, 76% in pts treated with RT, 90% in those treated with surgery. 30% experienced relapse (46) or progression (16) after a median of 18 mo from response. In 30 cases the relapse/progression occurred at the original disease sites. The median duration of F-U was 2.7 years. The estimated 5-years OS and EFS for all pts were 83 % (95% CI, 76%–90%) and 37% (95% CI, 28%–46%) respectively. At the time of last F-U, 29 pts were dead (9 from NHL). In univariate analysis, poorer OS with: multiple MALT sites (p=0.0003), B symptoms (p=0.003), ECOG ≥2 (p=0.00005), leukemic disease (p=0.006), bulky disease (p=0.0003), abnormal LDH (p=0.0007), stage III–IV (p=0.001), nodal involvement (p=0.0004), no CR/PR (p=0.0009). Orbit and skin localizations were significantly associated with a better OS (p=0.0005). Among pts with stage IV disease, those with no BM involvement had a longer OS (p=0.04). In multivariate analysis, features significantly associated with poorer OS were: BM+ (p=0.004), ECOG≥2 (p=0.007), Hb ≤11 g/dl (p=0.04), presence of a MC (p=0.04). In conclusion, this study demonstrates that nongastric marginal zone lymphoma are characterized by a high prevalence of HCV infection. Pts with involvement of a single MALT site, especially orbit, skin, and salivary glands, are those with the highest prevalence of HCV. Among HCV+ pts, almost half show signs of active chronic hepatitis. HCV-related nongastric lymphomas of MALT seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.