title: The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network.
abstract: Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance.
authors.affiliation: Department of Hematology, University Medical Center Utrecht, The Netherlands n.w.c.j.vandedonk@umcutrecht.nl.
authors.forename: Niels W C J
authors.initials: NW
authors.lastname: van de Donk
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Johnsen
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Engelhardt
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gay
authors.affiliation: Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Gregersen
authors.affiliation: Department of Haemato-oncology, University Hospital Ostrava and Faculty of Medicine, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kleber
authors.affiliation: Department of Medicine I, Wilhelminenspital Wien, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: Institute of Cancer Research, Royal Marsden Hospital, London, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Morgan
authors.affiliation: Scientific Direction, Centro di Riferimento Oncologico della Basilicata, Istituto di Ricovero e Cura a Carattere Scientifico, Rionero in Vulture, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.affiliation: Department of hematology at Vejle Hospital, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.affiliation: Department of Hematology, Memorial Hospital, Istanbul, Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Sezer
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Department of Hematology, St. Olavs Hospital, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.affiliation: Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Department of Hematology, University Medical Center Utrecht, The Netherlands.
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
mesh_terms: D002471:Cell Transformation, Neoplastic; D003937:Diagnosis, Differential; D019468:Disease Management; D018450:Disease Progression; D006801:Humans; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications / Q000175:diagnosis* / Q000209:etiology; D011230:Precancerous Conditions; D011379:Prognosis; D057832:Watchful Waiting