Immune Dysfunction

The susceptibility to bacterial infections in patients with myeloma has long been recognized.89 Infection may be the presenting feature in 10% of patients. Patients at the initiation of treatment and at relapse are at higher risk for infection.90-92 Other risk factors are decreased polyclonal Ig and renal failure. Grampositive infections are common before chemotherapy, while Gram-negative organisms predominate after chemotherapy.92

Multiple defects in the immune system have been identified. The deficiencies of the uninvolved poly-clonal Ig correlate with higher infection risks and are likely to be the major cause of infection.93 This secondary antibody deficiency (or functional hypogammaglob-ulinemic state) is mainly due to defective antibody production in the immune responses to antigenic stimulation, particularly in the primary immune responses,90 94 though the accelerated concentration-dependent catabolism of IgG may also be a factor.95 The underlying mechanism has been extensively studied in patients and in a murine plasmacytoma model. In human disease, lower numbers of peripheral blood and bone marrow B lymphocytes and plasma cell precursors, repeatedly observed in myeloma patients, indicate a suppression of B-cell proliferation and maturation. This suppression appears reversible when myeloma is effectively treated.9697

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