Comparative Study of Immune Status to Infectious Agents in Elderly Patients with Multiple Myeloma, Waldenstrom's Macroglobulinemia, and Monoclonal Gammopathy of Undetermined Significance

Abstract

Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n ‫؍‬ 25), WM (n ‫؍‬ 16), and MGUS (n ‫؍‬ 18) and in age-matched controls (n ‫؍‬ 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls. In contrast, levels of antibodies specific for staphylococcal teichoic acid, Moraxella catarrhalis, candida, aspergillus, and measles virus were similarly decreased in MM and MGUS patients. Comparable titers in all study groups were seen against Haemophilus influenzae type b (Hib), borrelia, toxoplasma, and members of the herpesvirus family. Finally, a uniform lack of antibodies was noted against Streptococcus pyogenes, salmonella, yersinia, brucella, francisella, and herpes simplex virus type 2. To conclude, although MM patients displayed the most depressed humoral immunity, significantly decreased antibody levels were also evident in patients with WM and MGUS, particularly against Staphylococcus aureus, pneumococci, and varicella. Conversely, immunity was retained for Hib and certain herpesviruses in all study groups.Patients with malignancies and dysfunctions of the B-cell lineage have impaired immunity and an increased risk of contracting severe infections. This is well documented in the case of multiple myeloma (MM), while Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS) have been less studied in this respect. Despite the use of prophylactic antimicrobial agents, infections remain a leading cause of morbidity and mortality in MM patients (7,32). Bacterial infections predominate, in particular those caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli (7,23,29). However, the introduction of autologous stem cell transplantation and novel therapeutic agents, e.g., thalidomide, bortezomib, and lenalidomide, has led to a shift in the spectrum of infections in MM patients such that viral and fungal infections are increasingly diagnosed (1, 29). The highest risk of infection occurs within the first months after diagnosis of MM (32), especially in patients with renal failure (7, 29). Augustson et al. showed that 45% of early deaths in MM (within 60 days of diagnosis) were due to infections, mainly pneumonia and sepsis (5).Information regarding which types of infections that tend to afflict patients with WM or MGUS is sparse. In a study of 217 WM patients, the second most frequent cause of death next to disease progression was infectious diseases (19% of deaths); again, sepsis and pneumonia predominated (15). An increased risk of bacteremia has prev...

Risk of Invasive Haemophilus influenzae Type b (Hib) Disease in Adults with Secondary Immunodeficiency in the Post-Hib Vaccine Era

“…However, an earlier study found that among 46 patients with multiple myeloma, prevaccination anti-PRP levels were comparable to that of the healthy United Kingdom adult population (36). A recent paper reported that 80% of multiple myeloma patients had anti-Hib IgG levels of Ͼ0.15 g/ml (17). In contrast, in our study, only 45% of myeloma patients had antibody levels above this cutoff.…”

Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy

“…Low baseline levels of specific exposure antibodies against various bacterial, viral, fungal, and protozoan pathogens have been described in these disorders (44). B-cell antimicrobial dysfunction increases progressively from monoclonal gammopathy of undetermined significance (MGUS) to Waldenstrom macroglobulinemia to MM (31, 44).…”

Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients

“…9,10 It has also been shown that multiple myeloma patients display a low immune response to infections and vaccines, and that it also predicted a higher risk of infection. 11,12 In addition to the inherent immunodeficiency, some small studies have described a changing spectrum of infections in MM, possibly related to the more intensive treatment approach of recent years, suggesting that the novel agents may increase the risk of infections in MM patients. [13][14][15][16] Several studies have indicated that elderly MM patients in particular are highly susceptible to infections.…”