Advertisement

Annals of Hematology

, Volume 91, Issue 2, pp 243–248 | Cite as

Prevalence and progression of monoclonal gammopathy of undetermined significance and light-chain MGUS in Germany

  • Lewin Eisele
  • Jan Dürig
  • Andreas Hüttmann
  • Ulrich Dührsen
  • Roland Assert
  • Beate Bokhof
  • Raimund Erbel
  • Klaus Mann
  • Karl-Heinz Jöckel
  • Susanne Moebus
  • on behalf of the Heinz Nixdorf Recall Study Investigative Group
Original Article

Abstract

We determined the prevalence and progression rate of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS (LCMGUS) in Germany utilizing the biobank of the population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45–75 years. To detect monoclonal proteins, standard serum electrophoresis was combined with parallel screening immunofixation using pentavalent antisera. Additionally, free light chains (FLC) were measured in all samples. Definition of MGUS included M-protein concentration, laboratory results, and disease history. LCMGUS was defined as abnormal FLC ratio, increase in FLC causing the abnormal ratio, and lack of intact immunoglobulin. One hundred sixty-five MGUS cases were identified among 4,702 screened samples (prevalence 3.5%, 95% confidence interval (CI) 3.0–4.1; median age 63 years, range 47–75 years; 103 (62%) male; IgG 59%, IgA 17%, IgM 17%, biclonal 4.8%, kappa 56%, and lambda 44%). Five cases progressed (0.6%/year, 95% CI 0.2–1.4). An abnormal FLC ratio was detected in 220 samples. Thirty-nine of these showed intact immunoglobulin. Thirty-four of the remaining met LCMGUS criteria (prevalence 0.7%, 95% CI 0.5–1.0). None of the LCMGUS cases progressed. We demonstrate a MGUS prevalence of 3.5% and a LCMGUS prevalence of 0.7% in the general population aged 45–75 years in Germany using a sensitive screening approach.

Keywords

MGUS LCMGUS Prevalence Germany Population-based 

Notes

Acknowledgments

We thank Anja Führer and Sabrina Kieruzel for expert technical assistance. Furthermore, we thank the Heinz Nixdorf Stiftung (Chairman: Dr. jur. G. Schmidt (deceased), Essen, Germany) for the sponsoring of the Heinz Nixdorf Recall study. We also thank the investigative group and the study personnel of the Heinz Nixdorf Study. We gratefully acknowledge the collaboration with D. Grönemeyer, R. Seibel, L. Volbracht, and M. Bröcker-Preuss. This study was supported by an internal research grant to L.E. from the Faculty of Medicine of the University Hospital of Essen (IFORES). Parts of the study were funded by a research grant from Celgene, Munich, Germany. The Heinz Nixdorf Recall Study was supported by the Heinz Nixdorf Foundation and a research grant from the German Ministry of Education and Science (BMBF).

Heinz Nixdorf Recall Study advisory board: T. Meinertz, Germany (Chair); M. Blettner, Germany; C. Bode, Germany; PJ. de Feyter, the Netherlands; B. Güntert, Austria; F. Gutzwiller, Switzerland; H. Heinen, Germany; O. Hess, Switzerland; B. Klein, Germany; H. Löwel, Germany; M. Reiser, Germany; G. Schmidt, Germany; M. Schwaiger, Germany; C. Steinmüller, Germany; T. Theorell, Sweden; S.N. Willich, Germany.

Supplementary material

277_2011_1293_MOESM1_ESM.doc (8.3 mb)
ESMdoc (DOC 8479 kb)

References

  1. 1.
    International Myeloma Working Group (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121(5):749–757CrossRefGoogle Scholar
  2. 2.
    Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd (2006) Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 354(13):1362–1369. doi: 10.1056/NEJMoa054494 PubMedCrossRefGoogle Scholar
  3. 3.
    Blade J, Rosinol L, Cibeira MT, de Larrea CF (2008) Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia 22:1651–1657. doi: 10.1038/leu.2008.203 PubMedCrossRefGoogle Scholar
  4. 4.
    Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, Melton LJ 3rd (2002) A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 346(8):564–569. doi: 10.1056/NEJMoa01133202 PubMedCrossRefGoogle Scholar
  5. 5.
    Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV (2009) Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 113(22):5412–5417. doi: 10.1182/blood-2008-12-194241 PubMedCrossRefGoogle Scholar
  6. 6.
    Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM (2009) A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 113(22):5418–5422. doi: 10.1182/blood-2008-12-195008 PubMedCrossRefGoogle Scholar
  7. 7.
    Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, Therneau TM, Clark R, Kumar SK, Bradwell A, Fonseca R, Jelinek DF, Rajkumar SV (2010) Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet 375(9727):1721–1728. doi: 10.1016/S0140-6736(10)60482-5 PubMedCrossRefGoogle Scholar
  8. 8.
    Schmermund A, Möhlenkamp S, Stang A, Grönemeyer D, Seibel R, Hirche H, Mann K, Siffert W, Lauterbach K, Siegrist J, Jöckel KH, Erbel R (2002) Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Risk Factors, Evaluation of Coronary Calcium and Lifestyle. Am Heart J 144(2):212–218PubMedCrossRefGoogle Scholar
  9. 9.
    Stang A, Moebus S, Dragano N, Beck EM, Möhlenkamp S, Schmermund A, Siegrist J, Erbel R, Jöckel KH (2005) Baseline recruitment and analyses of nonresponse of the Heinz Nixdorf Recall Study: identifiability of phone numbers as the major determinant of response. Eur J Epidemiol 20(6):489–496PubMedCrossRefGoogle Scholar
  10. 10.
    Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA (2002) Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 48(9):1437–1444PubMedGoogle Scholar
  11. 11.
    Tate JR, Gill D, Cobcroft R, Hickman PE (2003) Practical considerations for the measurement of free light chains in serum. Clin Chem 49(8):1252–1257PubMedCrossRefGoogle Scholar
  12. 12.
    Anderson RN, Rosenberg HM (1998) Age standardization of death rates: implementation of the year 2000 standard. Natl Vital Stat Rep 47(3):1–16, 20Google Scholar
  13. 13.
    Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, Larson DR, Plevak MF, Dispenzieri A, Katzmann JA (2005) Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 106(3):812–817. doi: 10.1182/blood-2005-03-1038 PubMedCrossRefGoogle Scholar
  14. 14.
    Hill PG, Forsyth JM, Rai B, Mayne S (2006) Serum free light chains: an alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies. Clin Chem 52(9):1743–1748. doi: 10.1373/clinchem.2006.069104 PubMedCrossRefGoogle Scholar
  15. 15.
    Hutchison CA, Basnayake K, Cockwell P (2009) Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol 5(11):621–628. doi: 10.1038/nrneph.2009.151 PubMedCrossRefGoogle Scholar
  16. 16.
    Bailie GR, Uhlig K, Levey AS (2005) Clinical practice guidelines in nephrology: evaluation, classification, and stratification of chronic kidney disease. Pharmacotherapy 25(4):491–502PubMedCrossRefGoogle Scholar
  17. 17.
    Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A (2009) Screening panels for detection of monoclonal gammopathies. Clin Chem 55(8):1517–1522. doi: 10.1373/clinchem.2009.126664 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Lewin Eisele
    • 1
  • Jan Dürig
    • 1
  • Andreas Hüttmann
    • 1
  • Ulrich Dührsen
    • 1
  • Roland Assert
    • 2
  • Beate Bokhof
    • 3
  • Raimund Erbel
    • 4
  • Klaus Mann
    • 2
  • Karl-Heinz Jöckel
    • 3
  • Susanne Moebus
    • 3
  • on behalf of the Heinz Nixdorf Recall Study Investigative Group
  1. 1.Department of HematologyUniversity Hospital EssenEssenGermany
  2. 2.Division of Laboratory Medicine, Department of EndocrinologyUniversity Hospital EssenEssenGermany
  3. 3.Institute of Medical Informatics, Biometry and EpidemiologyUniversity Hospital EssenEssenGermany
  4. 4.West German Heart CenterUniversity Hospital EssenEssenGermany

Personalised recommendations