Infections in Patients with Multiple Myeloma in the Era of High-Dose Therapy and Novel Agents

University Hospital, Universidade Federal do Rio de Janeiro, Brazil.
Clinical Infectious Diseases (Impact Factor: 8.89). 10/2009; 49(8):1211-25. DOI: 10.1086/605664
Source: PubMed


The introduction of stem cell transplantation and the novel anti-myeloma agents, bortezomib, thalidomide, and lenalidomide, have improved the outcome of patients with multiple myeloma. These advances have transformed myeloma into a chronic condition, with multiple relapses and salvage therapies, all of which result in cumulative immunosuppression and higher risk of infection. In addition to the immunodeficiency related to myeloma and its complications, the type of anti-myeloma therapy used also plays a role in the development of infection. Therapy with bortezomib increases the risk for reactivation of herpes simplex and herpes zoster viruses, whereas the application of stem cell transplantation has broadened the spectrum of infection to include those caused by Clostridium difficile, cytomegalovirus, and opportunistic moulds. Key to the management of infection is the understanding of the specific risk factors and periods during which patients are at risk; this allows the anticipation of the likely pathogen(s) and the application of risk-adjusted prophylactic and treatment strategies.

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    • "Ten rodzaj terapii wiąże się również z uszkodzeniem ochronnej bariery, jaką stanowią błony śluzowe przewodu pokarmowego . Do zwiększonej predyspozycji do infekcji przyczyniają się również takie czynniki ryzyka, jak podeszły wiek, unieruchomienie (związane najczęściej z zaawansowanymi zmianami kostnymi) oraz ostra lub przewlekła niewydolność nerek [8] [27]. Do najczęstszych rodzajów infekcji w SzP należą zakażenia dróg oddechowych wywoływane przez Streptococcus pneumoniae, Staphylococcus sp. "
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    ABSTRACT: Infections play an important role in the mortality of patients with chronic lymphocytic leukemia (CLL) and plasma cell myeloma (PMC). Susceptibility to infections in CLL and MM results from complex defects of humoral and cell-mediated immunity including hypogammaglobulinemia. Potential methods of prevention of bacterial infections in CLL and PCM include vaccination against Streptococcus pneumoniae and Haemophilus influenzae, prophylactic use of antibiotics and intravenous or subcutaneous polyclonal immunoglobulin (IG) replacement. Majority of clinical trials evaluating IG substitution strategy in CLL and MM that were mainly performed in 1980’ and 1990’, have shown significant reduction in number of bacterial infections. However, IG replacement has not been associated with prolonged patients’ survival while it carries important costs to healthcare systems. Based on these findings, prophylactic IG replacement therapy is mainly indicated in selected patients with high risk of infectious complications, especially those with hypogammaglobulinemia and history of severe or recurrent bacterial infections. In this paper we propose practical rules of IG replacement therapy in CLL and PMC.
    Acta haematologica Polonica 04/2015; 46(3). DOI:10.1016/j.achaem.2015.04.002
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    • "Although well- and better-tolerated, the use of novel therapies results in an increased risk of opportunistic infections as well as the shift in the spectrum of infections in MM. Novel therapeutic agents increase the risk of viral infections; bortezomib therapy for instance, increases the risks of herpes zoster reactivation in the first few months of treatment due to the immunosuppressive effects on T cells (34, 35). Dexamethasone use is associated with a greater risk of infections, and associates with depressed cell-mediated immunity against cytomegalovirus and varicella-zoster virus (36, 37). "
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    ABSTRACT: The plasma cell proliferative disorders monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) are characterized by an accumulation of transformed clonal plasma cells in the bone marrow and production of monoclonal immunoglobulin. They typically affect an older population, with median age of diagnosis of approximately 70 years. In both disorders, there is an increased risk of infection due to the immunosuppressive effects of disease and conjointly of therapy in MM, and response to vaccination to counter infection is compromised. The underlying factors in a weakened immune response in MGUS and MM are as yet not fully understood. A confounding factor is the onset of normal aging, which quantitatively and qualitatively hampers humoral immunity to affect response to infection and vaccination. In this review, we examine the status of immune alterations in MGUS and MM and set these against normal aging immune responses. We focus primarily on quantitative and functional aspects of B-cell immunity. Furthermore, we review the current knowledge relating to susceptibility to infectious disease in MGUS and MM, and how efficacy of conventional vaccination is affected by proliferative disease-related and therapy-related factors.
    Frontiers in Immunology 06/2014; 5:257. DOI:10.3389/fimmu.2014.00257
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    • "In addition, early infections frequently lead to substantial delays and dose reduction in subsequent chemotherapy with increased risk of treatment failure [2]. There were well-known various factors that contribute to the increasing risk of infection including immunoparesis, the placement of vascular catheters, type of therapy applied, extent of prior therapy, and presence of comorbidities and organ dysfunction [1]. The use of steroid also affects the development of infection. "
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    ABSTRACT: The association between hyperglycemia and infections during induction chemotherapy has been reported in a number of hematologic disorders. This retrospective study evaluated the incidence of hyperglycemia during induction therapy in 155 patients with newly diagnosed multiple myeloma (MM) and its effect on serious infections during the first 60 days of induction. A total of 20 (12.9%) patients developed overt hyperglycemia (≥200 mg/dL) during induction therapy. Serious infections occurred in 28 (18.1%) of 155 patients and infection-related mortality within 2 months after treatment was 0.6% (1 patient). In a univariate analysis, overt hyperglycemia, poor performance status (≥2), International Staging System III, lymphopenia (<500/ μ L), and elevated serum creatinine (≥2 mg/dL) were found to be associated with serious infections. In multivariate analysis, only overt hyperglycemia (HR 7.846, 95% CI 2.512-24.503, P < 0.001) and poor performance status (HR 5.801, 95% CI 1.974-17.050, P = 0.001) remained significant. In conclusion, this study demonstrated an association between hyperglycemia and serious infections during induction therapy in patients with MM.
    04/2014; 2014:413149. DOI:10.1155/2014/413149
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