Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry.

Data de publicació: 01/01/2013

Autors de IIS La Fe

Abelardo Garcia De Lorenzo Mateos

Autor
Julio Hernández Jaras

Autor
Marta Roig Pons

Autor
Javier De La Rubia Comos

Autor

Autors aliens a IIS La Fe

Pessoa de Magalhães RJ
Vidriales MB
Paiva B
Fernandez-Gimenez C
García-Sanz R
Gutierrez NC
Lecrevisse Q
Blanco JF
de las Heras N
Martinez-Lopez J
Costa ES
Ocio EM
Perez-Andres M
Maiolino A
Nucci M
Lahuerta JJ
San-Miguel JF
Orfao A
Spanish Myeloma Group (GEM)
Grupo Castellano-Leones de Gammapatias Monoclonales, cooperative study groups

Grups d'Investigació

Farmacogenética

Investigador Principal

María José Herrero Cervera
Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

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.

Dades de la publicació

ISSN/ISSNe:: 0390-6078, 1592-8721
Tipus:: Article
Pàgines:: 79-86
DOI:: 10.3324/haematol.2012.067272
PubMed:: 22773604
Factor d'Impacte:: 2,496 SCImago ℠
Quartil:: Q1 SCImago ℠

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Keywords

REGULATORY T-CELLS; PERIPHERAL-BLOOD; BONE-MARROW; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; TUMOR-IMMUNITY; ONCOLOGY-GROUP; PLASMA-CELLS; EXPRESSION; SURVIVAL