Incidence and characteristics of non-hodgkin lymphomas in a multicenter case file of patients with hepatitis C virus-related symptomatic mixed cryoglobulinemias

Background: Some patients with cryoglobulinemic syndrome(CS) develop frank non-Hodgkin lymphoma(NHL), but the incidence and timing of this event are stillpoorly defined.Methods: A retrospective multicenter study was performedof hepatitis C virus–positive patients with CS observedin 11 Italian centers belonging to the Italian Groupfor the Study of Cryoglobulinemia.Results: The inclusion criteria were satisfied by 1255patients. During a cumulative follow-up of 8928 patientyears,59 cases of NHL were diagnosed, for an estimatedrate of 660.8 new cases per 100000 patient-years with224.1 new cases of aggressive NHL subtypes per 100000patient-years. More than 90% of the patients developingNHLs had type II cryoglobulins. The NHLs were classifiedas nonaggressive in 31 cases (53%), aggressive in 20(34%), and mucosa-associated lymphoid tissue lymphomasin 6 (10%); 2 cases were unclassifiable. The mediantime from the diagnosis of CS to the clinical onset of NHLwas 6.26 years (range, 0.81-24 years). The clinical courseand response to chemotherapy in the patients with CSwho had NHL were similar to those usually described inpatients with NHL without CS; the course of the CS onlymarginally benefited from chemotherapy.Conclusions: The overall risk of NHL in patients withCS is about 35 times higher than in the general population(12 times higher if nonaggressive lymphomas are excluded).The presence of CS did not significantly affectthe treatment of newly diagnosed lymphomas.