Long-Term Follow-Up of Monoclonal Gammopathies in Gaucher Disease Patients on Enzyme Replacement Therapy.

Abstract

Gaucher Disease is a lysosomal storage disease in which glucocerebroside accumulates in macrophages because of a deficiency of the lysosomal enzyme, β-glucocerebrosidase. Polyclonal and monoclonal gammopathies (MG) have been frequently associated with long-standing Gaucher Disease, and there have been reports suggesting an increased incidence of multiple myeloma (MM) in these patients. Chronic stimulation of the immune system secondary to progressive glucocerebroside storage and increased expression of cytokines such as Interleukin 6 have all been postulated to be the mechanism underlying this association. The purpose of this study was to ascertain the incidence and natural history of MG in Type 1 Gaucher Disease patients on enzyme replacement therapy (ERT) followed for up to 15 years. Twenty-eight patients with Type I Gaucher Disease on ERT seen at a single medical center were selected for the analysis. Of the twenty-eight patients, 17 (60.7%) were male; 11 (39.3%) were female; and the median age at the initiation of therapy was 42 years (range 25–85 years). Serum protein electrophresis (SPEP), immunofixation, and immunoglobulin quantitation were performed in all of these patients before initiating ERT and at intervals during follow-up. The patients were categorized into three groups based on their initial SPEP results: Group 1: those with normal SPEP pattern; Group 2: those with polyclonal gammopathy; and Group 3: those with MG. At the time of initiation of ERT, Group 1 contained 12 patients (42.8%) while Groups 2 and 3 each had 8 patients (28.6%). During follow up for a median of 8.5 years (range 1–15 years), 2 patients from the Group 1 (16.7%) and 4 patients from Group 2 (50%) developed MG. Of the patients in Group 3, 3 patients (21.4%) reverted to a normal SPEP pattern. Overall, 14 patients (50%) in all three groups had a MG identified at the time of initiation of therapy or during follow-up: 3 (all in Group 3) reverted to a normal SPEP pattern while the other 11 patients showed no change in M-spike levels after a median of 8.5 years of follow up. All 14 patients with MG had a monoclonal IgG immunoglobulin, and 3 of them also had a monoclonal IgM immunoglobulin. There was no association between the occurance or type of MG with any particular Gaucher Disease genotype, patient age, or other clinical variable. Only one of the patients developed a malignancy: an elderly man with MG developed Hodgkin's Disease. None of our patients developed MM. In conclusion, these data confirm the high rate of MG in patients with Gaucher Disease but a low rate of progression to any other plasmacytic or lymphocytic disorder.