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Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma

A Corrigendum to this article was published on 09 April 2014


New systems have emerged for diagnosis, staging and response assessment in multiple myeloma (MM). The diagnostic and response criteria recommended are primarily derived from the International Myeloma Working Group, with certain updates and clarifications. The International Staging System is the current standard for staging of myeloma. A new risk stratification model is provided to specifically define high-risk patients who may benefit from novel therapeutic strategies. This paper provides the current criteria for diagnosis, staging, risk stratification and response assessment of MM.

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  1. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clinic Proc 2003; 78: 21–33.

    Article  Google Scholar 

  2. Snozek CLH, Katzmann JA, Kyle RA, Dispenzieri A, Larson D, Therneau TM et al. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the International Staging System. Leukemia 2008; 22: 1933–1937.

    CAS  Article  Google Scholar 

  3. Rajkumar SV, Kyle RA, Therneau TM, Melton III LJ, Bradwell AR, Clark RJ et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance (MGUS). Blood 2005; 106: 812–817.

    CAS  Article  Google Scholar 

  4. Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008; 111: 785–789.

    CAS  Article  Google Scholar 

  5. Dingli D, Kyle RA, Rajkumar SV, Nowakowski GS, Larson DR, Bida JP et al. Immunoglobulin free light chains and solitary plasmacytoma of bone. Blood 2006; 108: 1979–1983.

    CAS  Article  Google Scholar 

  6. The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121: 749–757.

    Article  Google Scholar 

  7. Rajkumar SV, Kyle RA . Multiple myeloma: diagnosis and treatment.[see comment]. Mayo Clinic Proc 2005; 80: 1371–1382.

    Article  Google Scholar 

  8. Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 2003; 102: 3759–3764.

    CAS  Article  Google Scholar 

  9. Gobbi PG, Baldini L, Broglia C, Goldaniga M, Comelli M, Morel P et al. Prognostic validation of the international classification of immunoglobulin M gammopathies: a survival advantage for patients with immunoglobulin M monoclonal gammopathy of undetermined significance? Clin Cancer Res 2005; 11: 1786–1790.

    CAS  Article  Google Scholar 

  10. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Semin Oncol 2003; 30: 169–171.

    CAS  Article  Google Scholar 

  11. Baldini L, Goldaniga M, Guffanti A, Broglia C, Cortelazzo S, Rossi A et al. Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system. J Clin Oncol 2005; 23: 4662–4668.

    Article  Google Scholar 

  12. Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al. Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol 2003; 30: 110–115.

    Article  Google Scholar 

  13. Dimopoulos MA, Moulopoulos LA, Maniatis A, Alexanian R . Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood 2000; 96: 2037–2044.

    CAS  PubMed  Google Scholar 

  14. Dimopoulos MA, Kiamouris C, Moulopoulos LA . Solitary plasmacytoma of bone and extramedullary plasmacytoma. Hematol Oncol Clin North Am 1999; 13: 1249–1257.

    CAS  Article  Google Scholar 

  15. Rajkumar SV, Dispenzieri A, Kyle RA . Monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin Proc 2006; 81: 693–703.

    Article  Google Scholar 

  16. Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV, Therneau TM, Larson DR et al. POEMS syndrome: definitions and long-term outcome. Blood 2003; 101: 2496–2506.

    CAS  Article  Google Scholar 

  17. Durie BG, Salmon SE . A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975; 36: 842–854.

    CAS  Article  Google Scholar 

  18. Bataille R, Durie BG, Grenier J . Serum beta2 microglobulin and survival duration in multiple myeloma: a simple reliable marker for staging. Br J Haematol 1983; 55: 439–447.

    CAS  Article  Google Scholar 

  19. Greipp PR, San Miguel JF, Durie BG, Crowley JJ, Barlogie B, Blade J et al. International Staging System for multiple myeloma. J Clin Oncol 2005; 23: 3412–3420.

    Article  Google Scholar 

  20. Tricot G, Barlogie B, Jagannath S, Bracy D, Mattox S, Vesole DH et al. Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities. Blood 1995; 86: 4250–4256.

    CAS  PubMed  Google Scholar 

  21. Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C, Groupe Francais de Cytogenetique H . Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 2001; 98: 2229–2238.

    CAS  Article  Google Scholar 

  22. Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64: 1546–1558.

    CAS  Article  Google Scholar 

  23. Fassas AB, Spencer T, Sawyer J, Zangari M, Lee CK, Anaissie E et al. Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma. Br J Haematol 2002; 118: 1041–1047.

    CAS  Article  Google Scholar 

  24. Rajkumar SV, Kyle RA . Multiple myeloma: diagnosis and treatment. Mayo Clin Proc 2005; 80: 1371–1382.

    Article  Google Scholar 

  25. Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101: 4569–4575.

    CAS  Article  Google Scholar 

  26. Facon T, Avet-Loiseau H, Guillerm G, Moreau P, Genevieve F, Zandecki M et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001; 97: 1566–1571.

    CAS  Article  Google Scholar 

  27. Greipp PR, Lust JA, WM OF, Katzmann JA, Witzig TE, Kyle RA . Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma [see comments]. Blood 1993; 81: 3382–3387.

    CAS  PubMed  Google Scholar 

  28. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123.

    CAS  Article  Google Scholar 

  29. Durie BGM, Harousseau J-L, Miguel JS, Blade J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.

    CAS  Article  Google Scholar 

  30. Anderson KC, Kyle RA, Rajkumar SV, Stewart AK, Weber D, Richardson P . Clinically relevant end points and new drug approvals for myeloma. Leukemia 2008; 22: 231–239.

    CAS  Article  Google Scholar 

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This study was supported by Grants CA62242 and CA107476 from the National Cancer Institute.

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Correspondence to R A Kyle.

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Kyle, R., Rajkumar, S. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 23, 3–9 (2009).

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  • diagnosis
  • myeloma
  • prognosis
  • response
  • staging
  • treatment

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