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International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

Abstract

The serum immunoglobulin-free light chain (FLC) assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.

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Correspondence to A Dispenzieri.

Appendix

Appendix

International Myeloma Working Group

Ray Alexanian, MD Anderson, Houston, TX, USA; Kenneth Anderson, DFCI, Boston, MA, USA; Michael Attal, Purpan Hospital, Toulouse, France; Herve Avet-Loiseau, Institute de Biologie, Nantes, France; Ashraf Badros, University of Maryland, Baltimore, MD, USA; Leif Bergsagel, Mayo Clinic Scottsdale, Scottsdale, AZ, USA; Joan Bladé, Hospital Clinica, Barcelona, Spain; Bart Barlogie, MIRT UAMS Little Rock, AR, USA; Regis Batille, Institute de Biologie, Nantes, France; Meral Beksac, Ankara University, Ankara, Turkey; Andrew Belch, Cross Cancer Institute, Alberta, Canada; Bill Bensinger, Fred Hutchinson Cancer Center, Seattle, Washington, USA; Mario Boccadoro, University of Torino, Torino, Italy; Michele Cavo, Universita di Bologna, Bologna, Italy; Wen Ming Chen, MM Research Center of Beijing, Beijing, China; Tony Child, Leeds General Hospital, Leeds, United Kingdom; James Chim, Department of Medicine, Queen Mary Hospital, Hong Kong; Ray Comenzo, Memorial Sloane-Kettering, New York City, NY, USA; John Crowley, Cancer Research and Biostatistics, Seattle, WA, USA; William Dalton, H Lee Moffitt, Tampa, FL, USA; Faith Davies, Royal Marsden Hospital, London, England; Cármino de Souza, Univeridade de Campinas, Caminas, Brazil; Michel Delforge, University Hospital Gasthuisberg, Leuven, Belgium; Meletios Dimipoulous, Alexandra Hospital, Athens, Greece; Angela Dispenzieri, Mayo Clinic, Rochester, MN, USA; Hermann Einsele, Universitätsklinik Würzburg, Würzburg, Germany; Theirry Facon, Centre Hospitalier Regional Universitaire de Lille, Lille, France; Dorotea Fantl, Socieded Argentinade Hematolgia, Buenos Aires, Argentina; Jean-Paul Fermand, Hopitaux de Paris, Paris, France; Rafael Fonseca, Mayo Clinic Scottsdale, Scottsdale, AZ, USA; Gosta Gahrton, Karolinska Institute for Medicine, Huddinge, Sweden; Morie Gertz, Mayo Clinic, Rochester, MN, USA; John Gibson, Royal Prince Alfred Hospital, Sydney, Australia; Hartmut Goldschmidt, University Hospital Heidelberg, Heidelberg, Germany; Philip Greipp, Mayo Clinic, Rochester, MN, USA; Roman Hajek, Brno University, Brno, Czech Republic; Izhar Hardan, Tel Aviv University, Tel Aviv, Israel; Jean-Luc Harousseau, Institute de Biologie, Nantes, France; Hiroyuki Hata, Kumamoto University Hospital, Kumamoto, Japan; Yutaka Hattori, Keio University School of Medicine, Tokyo, Japan; Joy Ho, Royal Prince Alfred Hospital, Sydney, Australia; Vania Hungria, Clinica San Germano, Sao Paolo, Brazil; Mohamad Hussein, Cleveland Clinic Taussig Cancer Center, Cleveland, OH, USA; Shinsuke Ida, Nagoya City University Medical School, Nagoya, Japan; Peter Jacobs, Constantiaberg Medi-Clinic, Plumstead, South Africa; Sundar Jagannath, St Vincent's Comprehensive Cancer Center, New York, NY, USA; Hou Jian, Shanghai Chang Zheng Hospital, Shanghai, China; Douglas Joshua, Royal Prince Alfred Hospital, Sydney, Australia; Michio Kawano, Yamaguchi University, Ube, Japan; Shaji Kumar, Department of Hematology, Mayo Clinic, MN, USA; Robert Kyle, Department of Laboratory Med. and Pathology, Mayo Clinic, MN, USA; Juan Lahuerta, Grupo Espanol di Mieloma, Hospital Universitario, Madrid, Spain; Jae Hoon Lee, Gachon University Gil Hospital, Incheon, Korea; Henk Lokhorst, University Medical CenterUtrecht, Utrecht, The Netherlands; Heinz Ludwig, Wilhelminenspital Der Stat Wien, Vienna, Austria; Xavier LeLeu, Hospital Huriez, CHRU Lille, France; Angelo Maiolino, Rua fonte da Saudade, Rio de Janeiro, Brazil; Jayesh Mehta, Northwestern University, Chicago, IL, USA; GianPaolo Merlini, University of Pavia, Pavia, Italy; Philippe Moreau, University Hospital, Nantes, France; Gareth Morgan, Royal Marsden Hospital, London, England; Nikhil Munshi, Diane Farber Cancer Institute, Boston, MA, USA; Antonio Palumbo, Cathedra Ematologia, Torino, Italy; Santiago Pavlovsky, Fundaleu, Buenos Aires, Argentina; Ruben Niesvizky, Weill Medical College of Cornell University, New York, NY, USA; Yana Novis, Hospital SírioLibanês, Bela Vista, Brazil; Amara Nouel, Hospital Rutz y Paez, Bolivar, Venezuela; Raymond Powles, Leukaemia & Myeloma, Wimbledon, England; Linda Pilarski, University of Alberta, Alberta, Canada; S Vincent Rajkumar, Mayo Clinic, Rochester, MN, USA; Donna Reece, Princess Margaret, Toronto, Canada; Tony Reiman, Cross Cancer Institute, Alberta, Canada; Paul Richardson, Dana Farber Cancer Institute, Boston, MA, USA; Angelina Rodriquez Morales, Bonco Metro Politano de Sangre, Caracas, Venezuela; Orhan Sezer, Department of Hem/Onc, Universitatsklinikum Charite, Berlin, Germany; John Shaughnessy, M.I.R.T. UAMS, Little Rock, AR, USA; Kazayuki Shimizu, Nagoya City Midori General Hospital, Nagoya, Japan; David Siegel, Hackensack, Cancer Center, Hackensack, NJ, USA; Guido Tricot, M.I.R.T. UAMS, Little Rock, AR, USA; Jesus San Miguel, University of Salamanca, Salamanca, Spain; Seema Singhal, Northwestern University, Chicago, IL, USA; Pieter Sonneveld, Erasmus MC, Rotterdam, The Netherlands; Chaim Shustik, McGill, Toronto, Canada; Andrew Spencer, The Alfred Hospital, Melbourne, Australia; Keith Stewart, Mayo Clinic Scottsdale, Scottsdale, AR, USA; Patrizia Tosi, Italian Cooperative Group, Istituto di Ematologia Seragnoli, Bologna, Italy; Ingemar Turesson, Department of Hematology, Malmo University, Malmo, Sweden; Brian Van Ness, University of Minnesota, Minneapolis, MN, USA; Ivan Van Riet, Brussels Vrija University, Brussels, Belgium; Robert Vescio, Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA, USA; David Vesole, St Vincent's Comprehensive Cancer Center, New York, NY, USA; Anders Waage, University Hospital, Trondheim, Norway NSMG; Michael Wang, MD Anderson, Houston, TX, USA; Donna Weber, MD Anderson, Houston, TX, USA; Jan Westin, University of Lund, Lund, Sweden; Keith Wheatley, University of Birmingham, Birmingham, United Kingdom; Dina B Yehuda, Department of Hematology, Hadassah University Hospital, Hadassah, Israel; Jeffrey Zonder, SWOG, Department of Hem/Onc., Karmanos Cancer Institute, MI, USA.

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Dispenzieri, A., Kyle, R., Merlini, G. et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 23, 215–224 (2009). https://doi.org/10.1038/leu.2008.307

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