Background: Some patients with cryoglobulinemic syndrome (CS) develop frank non-Hodgkin lymphoma (NHL), but the incidence and timing of this event are still poorly defined.
Methods: A retrospective multicenter study was performed of hepatitis C virus-positive patients with CS observed in 11 Italian centers belonging to the Italian Group for the Study of Cryoglobulinemia.
Results: The inclusion criteria were satisfied by 1,255 patients. During a cumulative follow-up of 8,928 patient-years, 59 cases of NHL were diagnosed, for an estimated rate of 660.8 new cases per 100,000 patient-years with 224.1 new cases of aggressive NHL subtypes per 100,000 patient-years. More than 90% of the patients developing NHLs had type II cryoglobulins. The NHLs were classified as nonaggressive in 31 cases (53%), aggressive in 20 (34%), and mucosa-associated lymphoid tissue lymphomas in 6 (10%); 2 cases were unclassifiable. The median time from the diagnosis of CS to the clinical onset of NHL was 6.26 years (range, 0.81-24 years). The clinical course and response to chemotherapy in the patients with CS who had NHL were similar to those usually described in patients with NHL without CS; the course of the CS only marginally benefited from chemotherapy.
Conclusions: The overall risk of NHL in patients with CS 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 affect the treatment of newly diagnosed lymphomas.