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Biology-Based Classification and Staging of Multiple Myeloma

  • Wee Joo Chng
  • Peter Leif Bergsagel
Part of the Contemporary Hematology book series (CH)

Introduction

While staging in solid tumor describes the anatomical spread of the tumor, for example, to the lymph nodes or distant sites, this concept is not applicable to hematological malignancies as the malignant cells by default are already distributed throughout the body. In hematological malignancies such as multiple myeloma (MM), an incurable late B-cell malignancy characterized by bone marrow infiltration with malignant plasma cells (PCs), and lytic bone lesions, staging provides a measure of how advance the tumor is and often reflects tumor burden.

There is a close link between disease stage and prognosis, and in hema-tological malignancies, prognostic systems are often built around factors that reflect disease stage. As such staging system and prognostic system are synonymous. Ultimately, the importance of staging and classification is in the ability to define clinically relevant heterogeneity within a tumor type and their clinical utility as guide to treatment decision and...

Keywords

Multiple Myeloma Median Overall Survival 17p13 Deletion Centrosome Amplification International Stage System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    Durie BG, Stock-Novack D, Salmon SE, et al. Prognostic value of pretreatment serum beta 2 microglobulin in myeloma: A Southwest Oncology Group Study.Blood.1990;75:823–830.PubMedGoogle Scholar
  3. 3.
    Facon T, Avet-Loiseau H, Guillerm G, 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.PubMedCrossRefGoogle Scholar
  4. 4.
    Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med.2003;349:2495–2502.PubMedCrossRefGoogle Scholar
  5. 5.
    Desikan R, Barlogie B, Sawyer J, et al. Results of high-dose therapy for 1000 patients with multiple myeloma: Durable complete remissions and superior survival in the absence of chromosome 13 abnormalities.Blood.2000;95:4008–4010.PubMedGoogle Scholar
  6. 6.
    Tricot G, Spencer T, Sawyer J, et al. Predicting long-term (> or = 5 years) event-free survival in multiple myeloma patients following planned tandem autotrans-plants. Br J Haematol.2002;116:211–217.PubMedCrossRefGoogle Scholar
  7. 7.
    Shaughnessy J, Jr., Tian E, Sawyer J, et al. Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: Early results of total therapy II. Br J Haematol.2003;120:44–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Bensinger WI, Buckner CD, Anasetti C, et al. Allogeneic marrow transplantation for multiple myeloma: An analysis of risk factors on outcome.Blood.1996;88:2787–2793.PubMedGoogle Scholar
  9. 9.
    Gahrton G, Tura S, Ljungman P, et al. Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol.1995;13:1312–1322.PubMedGoogle Scholar
  10. 10.
    Barlogie B, Smallwood L, Smith T, Alexanian R. High serum levels of lactic dehydrogenase identify a high-grade lymphoma-like myeloma. Ann Intern Med.1989;110:521–525.PubMedGoogle Scholar
  11. 11.
    Dimopoulos MA, Barlogie B, Smith TL, Alexanian R. High serum lactate dehydro-genase level as a marker for drug resistance and short survival in multiple myeloma. Ann Intern Med.1991;115:931–935.PubMedGoogle Scholar
  12. 12.
    Bataille R, Durie BG, Grenier J, Sany J. Prognostic factors and staging in multiple myeloma: A reappraisal. J Clin Oncol.1986;4:80–87.PubMedGoogle Scholar
  13. 13.
    Jacobson JL, Hussein MA, Barlogie B, Durie BG, Crowley JJ. A new staging system for multiple myeloma patients based on the Southwest Oncology Group (SWOG) experience. Br J Haematol.2003;122:441–450.PubMedCrossRefGoogle Scholar
  14. 14.
    Bataille R, Jourdan M, Zhang XG, Klein B. Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscra-sias. J Clin Invest.1989;84:2008–2011.PubMedCrossRefGoogle Scholar
  15. 15.
    Greipp PR, Lust JA, O'Fallon WM, 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.Blood.1993;81:3382–3387.PubMedGoogle Scholar
  16. 16.
    San Miguel JF, Garcia-Sanz R, Gonzalez M, et al. A new staging system for multiple myeloma based on the number of S-phase plasma cells.Blood.1995;85:448–455.PubMedGoogle Scholar
  17. 17.
    Fonseca R, Conte G, Greipp PR. Laboratory correlates in multiple myeloma: How useful for prognosis? Blood Rev.2001;15:97–102.PubMedCrossRefGoogle Scholar
  18. 18.
    Garcia-Sanz R, Gonzalez-Fraile MI, Mateo G, et al. Proliferative activity of plasma cells is the most relevant prognostic factor in elderly multiple myeloma patients. Int J Cancer.2004;112:884–889.PubMedCrossRefGoogle Scholar
  19. 19.
    Witzig TE, Gertz MA, Lust JA, Kyle RA, O'Fallon WM, Greipp PR. Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma.Blood.1996;88:1780–1787.PubMedGoogle Scholar
  20. 20.
    Rawstron AC, Owen RG, Davies FE, et al. Circulating plasma cells in multiple myeloma: Characterization and correlation with disease stage. Br J Haematol.1997;97:46–55.PubMedCrossRefGoogle Scholar
  21. 21.
    Witzig TE, Kimlinger TK, Ahmann GJ, Katzmann JA, Greipp PR. Detection of myeloma cells in the peripheral blood by flow cytometry.Cytometry.1996;26:113–120.PubMedCrossRefGoogle Scholar
  22. 22.
    Nowakowski GS, Witzig TE, Dingli D, et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma.Blood.2005;106(7):2276–2279.PubMedCrossRefGoogle Scholar
  23. 23.
    Greipp PR, Leong T, Bennett JM, et al. Plasmablastic morphology — an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group.Blood.1998;91:2501–2507.PubMedGoogle Scholar
  24. 24.
    Rajkumar SV, Fonseca R, Lacy MQ, et al. Plasmablastic morphology is an independent predictor of poor survival after autologous stem-cell transplantation for multiple myeloma. J Clin Oncol.1999;17:1551–1557.PubMedGoogle Scholar
  25. 25.
    Goasguen JE, Zandecki M, Mathiot C, et al. Mature plasma cells as indicator of better prognosis in multiple myeloma. New methodology for the assessment of plasma cell morphology. Leuk Res.1999;23:1133–1140.PubMedCrossRefGoogle Scholar
  26. 26.
    Walker R, Barlogie B, Haessler J, et al. Magnetic resonance imaging in multiple myeloma: Diagnostic and clinical implications. J Clin Oncol.2007;25:1121–1128.PubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar
  28. 28.
    Baur A, Stabler A, Nagel D, et al. Magnetic resonance imaging as a supplement for the clinical staging system of Durie and Salmon? Cancer.2002;95:1334–1345.PubMedCrossRefGoogle Scholar
  29. 29.
    Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol.2005;23:3412–3420.PubMedCrossRefGoogle Scholar
  30. 30.
    Dewald GW, Kyle RA, Hicks GA, Greipp PR. The clinical significance of cytoge-netic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis.Blood.1985;66:380–390.PubMedGoogle Scholar
  31. 31.
    Sawyer JR, Waldron JA, Jagannath S, Barlogie B. Cytogenetic findings in 200 patients with multiple myeloma. Cancer Genet Cytogenet.1995;82:41–49.PubMedCrossRefGoogle Scholar
  32. 32.
    Rajkumar SV, Fonseca R, Dewald GW, et al. Cytogenetic abnormalities correlate with the plasma cell labeling index and extent of bone marrow involvement in myeloma. Cancer Genet Cytogenet.1999;113:73–77.PubMedCrossRefGoogle Scholar
  33. 33.
    Rajkumar S, Fonseca R, Lacy M, et al. Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma. Bone Marrow Transplant.1999;24:497–503.PubMedCrossRefGoogle Scholar
  34. 34.
    Tricot G, Sawyer JR, Jagannath S, et al. Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants. J Clin Oncol.1997;15:2659–2666.PubMedGoogle Scholar
  35. 35.
    Tricot G, Barlogie B, Jagannath S, 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.PubMedGoogle Scholar
  36. 36.
    Seong C, Delasalle K, Hayes K, et al. Prognostic value of cytogenetics in multiple myeloma. Br J Haematol.1998;101:189–194.PubMedCrossRefGoogle Scholar
  37. 37.
    Debes-Marun CS, Dewald GW, Bryant S, et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma.Leukemia.2003;17:427–436.PubMedCrossRefGoogle Scholar
  38. 38.
    Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C. Hypodiploidy is a major prognostic factor in multiple myeloma.Blood.2001;98:2229–2238.PubMedCrossRefGoogle Scholar
  39. 39.
    Fassas AB, Spencer T, Sawyer J, et al. Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma. Br J Haematol.2002;118:1041–1047.PubMedCrossRefGoogle Scholar
  40. 40.
    Shaughnessy J, Jacobson J, Sawyer J, et al. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: Interpretation in the context of global gene expression.Blood.2003;101:3849–3856.PubMedCrossRefGoogle Scholar
  41. 41.
    Dewald G, Therneau T, Larson D, et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma.Blood.2005;106(10):3553–3558.PubMedCrossRefGoogle Scholar
  42. 42.
    Chang H, Sloan S, Li D, et al. The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant. Br J Haematol.2004;125:64–68.PubMedCrossRefGoogle Scholar
  43. 43.
    Fonseca R, Blood E, Rue M, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma.Blood.2003;101:4569–4575.PubMedCrossRefGoogle Scholar
  44. 44.
    Keats JJ, Reiman T, Maxwell CA, et al. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression.Blood.2003;101:1520–1529.PubMedCrossRefGoogle Scholar
  45. 45.
    Gertz MA, Lacy MQ, Dispenzieri A, et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy.Blood.2005;106(8):2837–2840.PubMedCrossRefGoogle Scholar
  46. 46.
    Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: A workshop report. Cancer Res.2004;64:1546–1558.PubMedCrossRefGoogle Scholar
  47. 47.
    Chang H, Qi C, Yi QL, Reece D, Stewart AK.p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation.Blood.2005;105:358–360.PubMedCrossRefGoogle Scholar
  48. 48.
    Drach J, Ackermann J, Fritz E, et al. Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy.Blood.1998;92:802–809.PubMedGoogle Scholar
  49. 49.
    Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: The experience of the Intergroupe Francophone du Myelome.Blood.2007;109(8):3489–3495.PubMedCrossRefGoogle Scholar
  50. 50.
    Fonseca R, Oken MM, Greipp PR. The t(4;14)(p16.3;q32) is strongly associated with chromosome 13 abnormalities in both multiple myeloma and monoclonal gammopathy of undetermined significance.Blood.2001;98:1271–1272.PubMedCrossRefGoogle Scholar
  51. 51.
    Avet-Loiseau H, Facon T, Grosbois B, et al. Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation.Blood.2002;99:2185–2191.PubMedCrossRefGoogle Scholar
  52. 52.
    Fonseca R, Debes-Marun CS, Picken EB, et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma.Blood.2003;102:2562–2567.PubMedCrossRefGoogle Scholar
  53. 53.
    Chng WJ, Santana-Davila R, Van Wier SA, et al. Prognostic factors for hyper-diploid-myeloma: Effects of chromosome 13 deletions and IgH translocations.Leukemia.2006;20:807–813.PubMedCrossRefGoogle Scholar
  54. 54.
    Zhan F, Sawyer J, Gupta S, et al. Elevated expression of CKS1B at 1q21 is highly correlated with short survival in myeloma.Blood.2004;104:77a.Google Scholar
  55. 55.
    Zhan F, Colla S, Wu X, et al.CKS1B, over expressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-depend-ent and independent mechanisms.Blood.2007;109(11):4995–5001.PubMedCrossRefGoogle Scholar
  56. 56.
    Fonseca R, Van Wier SA, Chng WJ, et al. Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma.Leukemia.2006;20:2034–2040.PubMedCrossRefGoogle Scholar
  57. 57.
    Shaughnessy JD Jr., Zhan F, Burington BE, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1.Blood.2006;109:2276–2284.PubMedCrossRefGoogle Scholar
  58. 58.
    Zhan F, Barlogie B, Arzoumanian V, et al.Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis.Blood.2007;109:1692–1700.PubMedCrossRefGoogle Scholar
  59. 59.
    Chng WJ, Ahmann GJ, Henderson K, et al. Clinical implication of centrosome amplification in plasma cell neoplasm.Blood.2006;107:3669–3675.PubMedCrossRefGoogle Scholar
  60. 60.
    Maxwell CA, Keats JJ, Belch AR, Pilarski LM, Reiman T. Receptor for hyaluro-nan-mediated motility correlates with centrosome abnormalities in multiple myeloma and maintains mitotic integrity. Cancer Res.2005;65:850–860.PubMedGoogle Scholar
  61. 61.
    Carrasco DR, Tonon G, Huang Y, et al.High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell.2006;9:313–325.PubMedCrossRefGoogle Scholar
  62. 62.
    Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J Jr. Cyclin D dysregulation: An early and unifying pathogenic event in multiple myeloma.Blood.2005;106:296–303.PubMedCrossRefGoogle Scholar
  63. 63.
    Zhan F, Huang Y, Colla S, et al. The molecular classification of multiple myeloma.Blood.2006;108:2020–2028.PubMedCrossRefGoogle Scholar
  64. 64.
    Tian E, Zhan F, Walker R, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med.2003;349:2483–2494.PubMedCrossRefGoogle Scholar
  65. 65.
    Chng WJ, Kumar S, Vanwier S, et al. Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling. Cancer Res.2007;67:2982–2989.PubMedCrossRefGoogle Scholar
  66. 66.
    Stewart AK, Bergsagel PL, Greipp PR, et al. A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy.Leukemia.2007;21:529–534.PubMedCrossRefGoogle Scholar
  67. 67.
    Chang H, Trieu Y, Qi X, Xu W, Stewart KA, Reece D. Bortezomib therapy response is independent of cytogenetic abnormalities in relapsed/refractory multiple myeloma. Leuk Res.2007;31(6):779–782.PubMedCrossRefGoogle Scholar
  68. 68.
    Mateos MV, Hernandez JM, Hernandez MT, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: Results of a mul-ticenter phase 1/2 study.Blood.2006;108:2165–2172.PubMedCrossRefGoogle Scholar
  69. 69.
    Dispenzieri A, Rajkumar SV, Gertz MA, et al. Treatment of newly diagnosed multiple myeloma based on mayo stratification of myeloma and risk-adapted therapy (mSMART): Consensus statement. Mayo Clin Proc.2007;82:323–341.PubMedCrossRefGoogle Scholar
  70. 70.
    Paterson JL, Li Z, Wen X Y, et al. Preclinical studies of fibroblast growth factor receptor 3 as a therapeutic target in multiple myeloma. Br J Haematol.2004;124:595–603.PubMedCrossRefGoogle Scholar
  71. 71.
    Trudel S, Ely S, Farooqi Y, et al. Inhibition of fibroblast growth factor receptor 3 induces differentiation and apoptosis in t(4;14) myeloma.Blood.2004;103:3521–3528.PubMedCrossRefGoogle Scholar
  72. 72.
    Trudel S, Li ZH, Wei E, et al.CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma.Blood.2005;105:2941–2948.PubMedCrossRefGoogle Scholar
  73. 73.
    Trudel S, Stewart AK, Rom E, et al. The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells.Blood.2006;107:4039–4046.PubMedCrossRefGoogle Scholar
  74. 74.
    Bischoff JR, Kirn DH, Williams A, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells.Science.1996;274:373–376.PubMedCrossRefGoogle Scholar
  75. 75.
    Zhang WW, Fang X, Mazur W, French BA, Georges RN, Roth JA.High-efficiency gene transfer and high-level expression of wild-type p53 in human lung cancer cells mediated by recombinant adenovirus. Cancer Gene Ther.1994;1:5–13.PubMedGoogle Scholar
  76. 76.
    Kirn D, Hermiston T, McCormick F.ONYX-015: Clinical data are encouraging. Nat Med.1998;4:1341–1342.PubMedCrossRefGoogle Scholar
  77. 77.
    Tolcher AW, Hao D, de Bono J, et al. Phase I, pharmacokinetic, and pharmaco-dynamic study of intravenously administered Ad5CMV-p53, an adenoviral vector containing the wild-type p53 gene, in patients with advanced cancer. J Clin Oncol.2006;24:2052–2058.PubMedCrossRefGoogle Scholar
  78. 78.
    Shi Y, Reiman T, Li W, et al. Targeting aurora kinases as therapy in multiple myeloma.Blood.2007;109:3915–3921.PubMedCrossRefGoogle Scholar
  79. 79.
    Chng WJ, Kuehl WM, Bergsagel PL, Fonseca R. Translocation t(4;14) retains prognostic significance even in the setting of high-risk molecular signature. Leukemia 2008;22(2):459–461.PubMedCrossRefGoogle Scholar
  80. 80.
    Chng WJ, Braggio E, Mulligan G et al. The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood 2008;111(3):1603–1609.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Wee Joo Chng
    • 1
  • Peter Leif Bergsagel
    • 1
  1. 1.Mayo Clinic Comprehensive Cancer CenterScottsdaleUSA

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