Clinical Disparities between Primary Versus Secondary MGUS in Veteran Patients.

Background: Monoclonal gammopathy of unknown significance (MGUS) is characterized by low levels of a monoclonal protein (M protein) in the serum or urine that is produced by a single clone of plasma cells. Though published evidence indicates that the incidence of MGUS increases with age, the clinical differences between young versus older MGUS patients are not completely understood. We investigated the age-dependent clinical characteristics of veteran patients with MGUS.

Objective: To identify age-dependent disparities in the clinical characteristics of veteran patients with primary versus secondary MGUS.

Methods: A retrospective chart review of 327 MGUS patients seen at the Kansas City Veteran Affairs Medical Center over the last 20 years was performed. “Primary” MGUS was defined as presence of monoclonal immunoglobulin protein (M-spike) in the absence of multiple myeloma (MM), primary amyloidosis, or leukemia/lymphoma. In this report, we use the term “Secondary” MGUS when an M-spike is associated with HIV, or non-HIV-infections, and/or autoimmune diseases. In the final analysis, we broadly subdivided patient with MGUS into age-group ≤ 55 years and ≥ 55 years.

Results: Of the total 327 patients, 14% (44/327) belonged to the age group ≤ 55 years. In our analysis, “Secondary” MGUS was more prevalent in patients ≤ 55 years (30/44; 68%) as compared to that in the ≥ 55 years age group (25/283; 8.5%; p-value <0.0001). In the veteran population, the majority of patients ≤ 55 years age had hepatitis C-associated “Secondary” MGUS (45%). HIV-associated MGUS was also more prevalent in the younger age group (4/44; 9%) as compared to age ≥ 55 years (0/283). Secondary MGUS co-existing with autoimmune disorders was comparatively more common in the younger age group than the older patients (13.6% versus 4.5%; p-value <0.05). IgA subtype was surprisingly not seen in MGUS patients with age ≤ 55 years. Most importantly, MGUS transformation into MM was not seen even after a prolonged follow-up of 20 years in the younger age group of patients.

Conclusion: MGUS in young patients (age ≤ 55 years) is often found in conditions associated with chronic antigenic stimulation or immunosuppression, such as chronic hepatitis B or C, HIV infections, and autoimmune diseases. We thus recommend that young patients (age ≤ 55 years) with MGUS undergo testing for hepatitis B/C, HIV infection if there is a possible history of exposure to these viruses. Our analysis also suggests that these so-called “secondary” MGUS are benign disorders.

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