title: Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry.
abstract: Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8(+) T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance.
authors: Hospital Universitario de Salamanca, Salamanca, Spain.
authors: Roberto J
authors: RJ
authors: Pessoa de Magalhães
authors: María-Belén
authors: MB
authors: Vidriales
authors: Bruno
authors: B
authors: Paiva
authors: Carlos
authors: C
authors: Fernandez-Gimenez
authors: Ramón
authors: R
authors: García-Sanz
authors: Maria-Victoria
authors: MV
authors: Mateos
authors: Norma C
authors: NC
authors: Gutierrez
authors: Quentin
authors: Q
authors: Lecrevisse
authors: Juan F
authors: JF
authors: Blanco
authors: Jose
authors: J
authors: Hernández
authors: Natalia
authors: N
authors: de las Heras
authors: Joaquin
authors: J
authors: Martinez-Lopez
authors: Monica
authors: M
authors: Roig
authors: Elaine Sobral
authors: ES
authors: Costa
authors: Enrique M
authors: EM
authors: Ocio
authors: Martin
authors: M
authors: Perez-Andres
authors: Angelo
authors: A
authors: Maiolino
authors: Marcio
authors: M
authors: Nucci
authors: Javier
authors: J
authors: De La Rubia
authors: Juan-Jose
authors: JJ
authors: Lahuerta
authors: Jesús F
authors: JF
authors: San-Miguel
authors: Alberto
authors: A
authors: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods / Q000639:trends*; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D011446:Prospective Studies; D013997:Time Factors