Plasma cell disorders in HIV-infected patients: epidemiology and molecular mechanisms

Abstract

Highly active antiretroviral therapy (HAART) has significantly improved the outcome and survival of human immunodeficiency virus (HIV)-infected patients. Subsequently, long-term morbidities including cancer have become of major public health and clinical interest for this patient population. Plasma cell disorders occur at higher incidence in HIV-infected patients; however, the molecular mechanisms driving the plasma cell disease process and the optimal management for these patients remain to be defined. This article provides an up-to-date review of the characteristics and management of HIV-infected patients with plasma cell disorders. We first present 3 cases of plasma cell disorders in HIV-infected patients, ranging from polyclonal hypergammaglobulinemia to symptomatic multiple myeloma. We then discuss the epidemiology, clinical presentation, and management of each of these plasma cell disorders, with an emphasis on the molecular events underlying the progression of plasma cell diseases from monoclonal gammopathy to symptomatic multiple myeloma. We propose a three-step hypothesis for the development of multiple myeloma. Finally, we discuss the use of high dose chemotherapy and autologous hematopoietic stem cell transplantation in the treatment of HIV-infected patients with multiple myeloma. Our review includes the care of HIV-infected patients with plasma cell disorders in the current era of HAART and novel agents available for the treatment of multiple myeloma.

Figure 1

A 3-step working hypothesis for the development of multiple myeloma. HIV infection contributes to the development of MM likely through several different mechanisms: 1) HIV infection increases the risk for somatic hypermutation; 2) HIV infection activates cell survival pathways; 3) HIV infection alters bone marrow niche microenvironement; and 4) HIV infection causes persistent antigen stimulation.