Multiple myeloma (pathogenesis, clinical features, diagnosis, differential diagnosis). Part I

S.S. Bessmeltsev,

DOI:

https://doi.org/10.21320/2500-2139-2013-6-3-237-257

Multiple myeloma (MM) is a malignancy characterized by bone marrow infiltration with plasma cell and extensive skeletal bone destruction resulting in bone pain and fractures. This review presents typical laboratory findings and clinical presentation of multiple myeloma. Multiple myeloma is definite when the following hallmarks are present: ³ 10% of clonal plasma cells in the bone marrow, M protein in serum or urine (except nonsecretory myeloma), hypercalcemia, renal insufficiency, anemia, or osteolytic lesions in skeletal bones. Monoclonal (M) proteins are detected using serum protein electrophoresis and immunofixation. In addition, urine protein electrophoresis and immunofixation or a serum free light-chain assay are essential. The International Staging System classifies MM patients into three groups of risk — standard, intermediate, or high — depending on the b2-microglobulin and albumin serum levels. The presence of any one of the following indicates high-risk myeloma: a 13q deletion or hypodiploidy on metaphase cytogenetic studies, a 17p deletion, immunoglobulin heavy-chain translocations t(4;14) or t(14;16), or a plasma cell labeling index ³ 3%.

This review presents laboratory findings and clinical manifestations of monoclonal gammopathy of undetermined significance, asymptomatic myeloma (‘smouldering myeloma’), nonsecretory myeloma, solitary bone plasmacytoma, extramedullary plasmacytoma, plasma cell leukemia, Waldenstrom’s macroglobulinemia, amyloidosis, and other diseases.

  • S.S. Bessmeltsev Russian Research Institute of Hematology and Transfusiology, Saint Petersburg, Russian Federation ; Российский научно-исследовательский институт гематологии и трансфузиологии, Санкт-Петербург, Российская Федерация
  1. Harousseau J.-L., Dreyling M., on behalf of the ESMO Guidelines Working Group. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Oncology 2010; 21(Suppl. 5): v155–7. DOI: https://doi.org/10.1093/annonc/mdq178
  2. Бессмельцев С.С., Абдукадыров К.М. Множественная миелома. Современный взгляд на проблему. Алматы, 2007. [Bessmeltsev S.S., Abdukadyrov K.M. Mnozhestvennaya miyeloma. Sovremennyy vzglyad na problemu (Multiple myeloma. Current view of the problem). Almaty, 2007.]
  3. Kyle R.A., Rajkumar S.V. Multiple myeloma. Engl. J. Med. 2004; 351(18): 1860–73. DOI: https://doi.org/10.1056/NEJMra041875
  4. Fonseca R., Bergsagel P.L., Drach J. et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009; 23(12): 2210–21. DOI: https://doi.org/10.1038/leu.2009.174
  5. Anderson K.C. Targeted therapy for multiple myeloma. Hematol. 2001; 38: 286–94. DOI: https://doi.org/10.1053/shem.2001.26010
  6. Barker H.F., Ball J., Drew M. et al. The role of adhesion molecules in multiple myeloma. Lymphoma 1992; 8: 189–96. DOI: https://doi.org/10.3109/10428199209054904
  7. Харченко М.Ф., Бессмельцев С.С. Значение протеогликанов в патоге- незе множественной миеломы. Биомед. журн. Medline.ru. 2010; 11: 404–23. [Kharchenko M.F., Bessmeltsev S.S. Znacheniye proteoglikanov v patogeneze mnozhestvennoy miyelomy (Significance of proteoglycans in pathogenesis of multiple myeloma. In: Biomed. journ.). Biomed. zhurn. Medline.ru. 2010; 11: 404–23.]
  8. Stringer S.E. The role of heparan sulfate proteoglycans in angiogenesis. Soc. Trans. 2006; 34: 451–3. DOI: https://doi.org/10.1042/BST0340451
  9. Andersen N., Standal T., Nielsen J. et al. Syndecan-1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival. J. Haemat. 2004; 128: 210–7. DOI: https://doi.org/10.1111/j.1365-2141.2004.05299.x
  10. Klein B., Tarte K., Jourdan M. et al. Survival and proliferation factors of normal and malignant plasma cells. J. Hematol. 2003; 78: 106–13. DOI: https://doi.org/10.1007/BF02983377
  11. Mahtouk K., Cremer F., Reme T. et al. Heparan sulfate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma. Oncogene 2006; 25: 7180–91. DOI: https://doi.org/10.1038/sj.onc.1209699
  12. Purushothaman A., Uyama T., Kobayashi F. Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis. Blood 2010; 115: 2449–57. DOI: https://doi.org/10.1182/blood-2009-07-234757
  13. Damiano J.S., Gress A.E., Hazlehurst L.A. et al. Cell adhesion mediated drug resistance: Role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 1999; 93: 1658–67. DOI: https://doi.org/10.1182/blood.V93.5.1658
  14. Damiano J.S., Dalton W.S. Integrin-mediated drug resistance in multiple myeloma. Lymphoma 2000; 38: 71–81. DOI: https://doi.org/10.3109/10428190009060320
  15. Shain K., Landowski T., Dalton W.S. Cellular adhesion via Beta 1 integrins increases c-FLIPL levels and inhibits CD95/Fas-mediated apoptosis in hematologic malignancies: A mechanism of immune evasion. 2001.
  16. Davies F.E., Anderson K.C. Novel therapeutic targets in multiple myeloma. J. Hematol. 2000; 64: 359–67. DOI: https://doi.org/10.1034/j.1600-0609.2000.9r233.x
  17. Anderson K.C. Targeted therapy for multiple myeloma. Hematol. 2001; 38: 286–94. DOI: https://doi.org/10.1053/shem.2001.26010
  18. Klein B., Zhang X., Lu Z. Interleukin-6 in multiple myeloma. Blood 1995; 85: 863–7. DOI: https://doi.org/10.1182/blood.V85.4.863.bloodjournal854863
  19. Karin M., Cao Y., Greten F.R., Li Z.W. NF-kappaB in cancer: from innocent bystander to major culprit. Rev. Cancer 2002; 2: 301–10. DOI: https://doi.org/10.1038/nrc780
  20. Barlogie B., Epstein J., Selvanayagam P., Alexanian R. Plasma cell myeloma — new biological insights and advances in therapy. Blood 1998; 73: 865–70. DOI: https://doi.org/10.1182/blood.V73.4.865.bloodjournal734865
  21. Fonseca R., Oken M.H., Harrington D. et al. deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia 2001; 15: 981–6. DOI: https://doi.org/10.1038/sj.leu.2402125
  22. Fonseca R., Debes-Marun C.S., Picken E.B. et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood 2003; 102(7): 2562–7. DOI: https://doi.org/10.1182/blood-2003-02-0493
  23. Mohamed A.N., Bentley G., Bonnett M.L. et al. Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes. J. Hematol. 2007; 82: 1080–7. DOI: https://doi.org/10.1002/ajh.20998
  24. Chesi M., Nardini E., Lim R.C. et al. The t(4;14) translocation in multiple myeloma disregulates both FGFR 3 and novel gene, MMSET, resulting in IgH/ MMSET hybrid transcripts. Blood 1998; 92: 3025–34. DOI: https://doi.org/10.1182/blood.V92.9.3025.421k53_3025_3034
  25. Avet-Loiseau H., Attal M., Campion L. et al. Long-term analysis of the IFM 99 trials for myeloma: Cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. Clin. Oncol. 2012; 30: 1949–52. DOI: https://doi.org/10.1200/JCO.2011.36.5726
  26. Avet-Loiseau H., Minvielle S., Mellerin M.P. et al. 14q32 chromosomal translocations: A hallmark of plasma cell dyscrasias? J. 2000; 1: 292–4. DOI: https://doi.org/10.1038/sj.thj.6200045
  27. Fonseca R., Debes-Marun C.S., Picken E.B. et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood 2003; 102(7): 2562–7. DOI: https://doi.org/10.1182/blood-2003-02-0493
  28. Avet-Loiseau H., Facon T., Daviet A. et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myelome. Cancer Res. 1999; 59: 4546–50.
  29. Shaughnessy J.Jr., Cabren A.Q. Cyclin D3 at 6h21 is deregulated by recurrent chromosome translocation to immunoglobulin loci in multiple myeloma. Blood 2001; 98: 217–23. DOI: https://doi.org/10.1182/blood.V98.1.217
  30. Santra M., Zhan F., Tian E. et al. A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. Blood 2003; 101: 2374–6. DOI: https://doi.org/10.1182/blood-2002-09-2801
  31. Broyl A., Hose D., Lokhorst H. et al. Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood 2010; 116: 2543–6. DOI: https://doi.org/10.1182/blood-2009-12-261032
  32. Sawyer J.R., Lukacs J.L., Thomas E.L. et al. Multicolour spectral karyotyping identifies new translocation and a recurring pathway for chromosome loss in multiple myeloma. J. Haematol. 2000; 112: 1–9. DOI: https://doi.org/10.1046/j.1365-2141.2001.02546.x
  33. Bednarek A.K., Keck-Waggoner C.L., Daniel R.L. et al. WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res. 2001; 61: 8068–73.
  34. Shou Y., Martelli M.L., Gabrea A. et al. Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma. Natl. Acad. Sci. USA 2000; 97: 228–33. DOI: https://doi.org/10.1073/pnas.97.1.228
  35. Shaughnessy J.Jr., Tian E., Sawyer J. et al. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 2000; 96: 1505–11. DOI: https://doi.org/10.1182/blood.V96.4.1505.h8001505_1505_1511
  36. Fonseca R., Oken M.H., Harrington D. et al. deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia 2001; 15: 981–6. DOI: https://doi.org/10.1038/sj.leu.2402125
  37. Boersma-Vreugdenhill G.R., Kuipers J., Bast B.J. Breakpoint analysis of a novel recurrent chromosomal translocation t(14;20)(q32;q12) in a human multiple myeloma cell line. VIIIth International Myeloma Workshop. Banff, Alberta, Canada, 2001: 124.
  38. Fonseca R., Bergsagel P.L., Drach J. et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009; 23: 2210–21. DOI: https://doi.org/10.1038/leu.2009.174
  39. Walker B.A., Leone P.E., Chiecchio L. et al. A compendium of myelomaassociated chromosomal copy number abnormalities and their prognostic value. Blood 2010; 116: e56–65. DOI: https://doi.org/10.1182/blood-2010-04-279596
  40. Hanamura I., Stewart J.P., Huang Y. et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood 2006; 108: 1724–32. DOI: https://doi.org/10.1182/blood-2006-03-009910
  41. Liu P.C., Leong T., Quam L. et al. Activating mutations of N- and K-ras in multiple myeloma show different clinical associations — analysis of the Eastern Cooperative Oncology Group phase III trial. Blood 1996; 88: 2699–706. DOI: https://doi.org/10.1182/blood.V88.7.2699.bloodjournal8872699
  42. Urashima M., Teoh G., Ogata A. et al. Characterization of p16(INK4A) expression in multiple myeloma and plasma cell leukemia. Cancer Res. 1997; 3: 2173–9.
  43. Dimopoulos M., Kyle R., Fermand J.-P. et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus. Panel 3. Blood 2011; 117(18): 4701–5. DOI: https://doi.org/10.1182/blood-2010-10-299529
  44. Baur-Melnyk A., Buhmann S., Durr H.R., Reiser M. Role of MRI for the diagnosis and prognosis of multiple myeloma. J. Radiol. 2005; 55(1): 56–63. DOI: https://doi.org/10.1016/j.ejrad.2005.01.017
  45. Moulopoulos L.A., Gika D., Anagnostopoulos A. et al. Prognostic significance of magnetic resonance imaging of bone marrow in previously untreated patients with multiple myeloma. Oncol. 2005; 16(11): 1824–8. DOI: https://doi.org/10.1093/annonc/mdi362
  46. Walker R., Barlogie B., Haessler J. et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. Clin. Oncol. 2007; 25(9): 1121–8. DOI: https://doi.org/10.1200/JCO.2006.08.5803
  47. Durie B.G., Waxman A.D., D’Angolo A., Williams C.M. Whole-body FDG PET identifies high-risk myeloma. Nucl. Med. 2002; 43(11): 1457–63.
  48. Sezer O. Myeloma bone disease. Hematology 2005; 10(Suppl. 1): 19–24. DOI: https://doi.org/10.1080/10245330512331389782
  49. Piarse R.N., Sordillo E.M., Yaccoby S. et al. Multiple myeloma disrupts the TRANCE/osteoprotegerin cytocine axons to trigger bone destruction and promote tumor progression. Natl. Acad. Sci. USA 2001; 98: 11581–6. DOI: https://doi.org/10.1073/pnas.201394498
  50. Heider U., Langelotz C., Jakob C. et al. Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma. Cancer Res. 2003; 9: 1436–40.
  51. Seidel C., Hirtner O., Abildgaard N. et al. Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease. Blood 2001; 98: 2269–71. DOI: https://doi.org/10.1182/blood.V98.7.2269
  52. Abe M., Hiura K., Wilde J. et al. Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma. Blood 2002; 100: 2195–202. DOI: https://doi.org/10.1182/blood.V100.6.2195.h81802002195_2195_2202
  53. Zannettino A.C., Farrugia A.N., Kortesidis A. et al. Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients. Cancer Res. 2005; 65: 1700–9. DOI: https://doi.org/10.1158/0008-5472.CAN-04-1687
  54. 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. Engl. J. Med. 2003; 349: 2483–6. DOI: https://doi.org/10.1056/NEJMoa030847
  55. Бессмельцев С.С., Карягина Е.В., Стельмашенко Л.В. и др. Частота, характеристика и методы лечения периферической нейропатии у больных множественной миеломой, получающих бортезомиб (велкейд). Онкогема- тология 2008; 3: 52–62. [Bessmeltsev S.S., Karyagina Ye.V., Stelmashenko L.V. i dr. Chastota, kharakteristika i metody lecheniya perifericheskoy neyropatii u bolnykh mnozhestvennoy miyelomoy, poluchayushchikh bortezomib (velkeyd) (Incidence, characteristics, and methods of therapy for peripheral neuropathy in patients with multiple myeloma treated with bortezomib (Velcade). In: Oncohematology). Onkogematologiya 2008; 3: 52–62.]
  56. Rajkumar S.V., Fonseca R., Dispenzieri A. et al. Methods for estimation of bone marrow plasma cell involvement in myeloma: predictive value for response and survival in patients undergoing autologous stem cell transplantation. J. Hematol. 2001; 68(4): 269–75. DOI: https://doi.org/10.1002/ajh.10003
  57. Ругаль В.И., Бессмельцев С.С. Оценка опухолевой инфильтрации костного мозга при множественной миеломе по результатам исследования трепанобиоптатов. Вестн. гематол. 2009; 5(1): 49–50. [Rugal V.I., Bessmeltsev S.S. Otsenka opukholevoy infiltratsii kostnogo mozga pri mnozhestvennoy miyelome po rezultatam issledovaniya trepanobioptatov (Assessment of bone marrow tumor infiltration based on trephine biopsy findings. In: Hematol. bullet.). Vestn. gematol. 2009; 5(1): 49–50.]
  58. Людвиг Х., Остерборг А. Анемия и терапия эритропоэтином при множе- ственной миеломе. Анемия у онкологических больных. 2002; 1(Вып. 1): 3–10. [Lyudvig Kh., Osterborg A. Anemiya i terapiya eritropoetinom pri mnozhestvennoy miyelome (Anemia and erythropoietin therapy in multiple myeloma. In: Anemia in cancer patients). Anemiya u onkologicheskikh bolnykh. 2002; 1(Vyp. 1): 3–10.]
  59. Бессмельцев С.С., Гусева С.А. Современные принципы лечения анемии у пациентов с онкогематологическими заболеваниями. Украiн. журн. гематол. та трансфузiол. 2009; 1: 5–17. [Bessmeltsev S.S., Guseva S.A. Sovremennye printsipy lecheniya anemii u patsientov s onkogematologicheskimi zabolevaniyami (Current principles of therapy for anemia in patients with hematological malignancies. In: Ukraine journal of hematol. & transfusiol.). Ukrain. zhurn. gematol. ta transfuziol. 2009; 1: 5–17.]
  60. Abdulkadyrov K.M., Bessmeltsev S.S. Renal insufficiency in multiple myeloma: Basic mechanisms in its development and methods for treatment. Renal Fail. 1996; 18(1): 139–46. DOI: https://doi.org/10.3109/08860229609052784
  61. Faiman B.M., Spong J., Tariman J.D. Renal Complications in Multiple Myeloma and Related Disorders: Survivorship Care Plan of the International Myeloma Foundation Nurse Leadership Board. J. Oncol. Nurs. 2011; 15(4): 66–76. DOI: https://doi.org/10.1188/11.CJON.S1.66-76
  62. Бессмельцев С.С. Бисфосфонаты и их роль в лечении множественной миеломы. Украiн. журн. гематол. та трансфузiол. 2011; 1: 5–18. [Bessmeltsev S.S. Bisfosfonaty i ikh rol v lechenii mnozhestvennoy miyelomy (Bisphosphonates and their role in therapy for multiple myeloma. In: Ukraine journ. of hematol. & transfusiol.). Ukrain. zhurn. gematol. ta transfuziol. 2011; 1: 5–18.]
  63. Чубукина Ж.В., Бубнова Л.Н., Бессмельцев С.С. и др. Неспецифические факторы защиты и гуморальный иммунитет у больных множественной миеломой. Мед. экстрем. ситуаций 2012; 2: 93–8. [Chubukina Zh.V., Bubnova L.N., Bessmeltsev S.S. i dr. Nespetsificheskiye faktory zashchity i gumoralnyy immunitet u bolnykh mnozhestvennoy miyelomoy (Non-specific protective factors and humoral immunity in patients with multiple myeloma. In: Med. of extr. situations). Med. ekstrem. situatsiy 2012; 2: 93–8.]
  64. Бессмельцев С.С., Стельмашено Л.В., Степанова Н.В. и др. Бортезомиб (велкейд) и мелфалан с преднизолоном в лечении множественной миеломы у пожилых больных. Онкогематология 2010; 2: 40–5. [Bessmeltsev S.S., Stelmasheno L.V., Stepanova N.V. i dr. Bortezomib (velkeyd) i melfalan s prednizolonom v lechenii mnozhestvennoy miyelomy u pozhilykh bolnykh (Bortezomib (Velcade) and melphalan combined with prednisolone in therapy for multiple myeloma in older patients. In: Oncohematology). Onkogematologiya 2010; 2: 40–5.]
  65. Noel C., Ales D.O., Jasmine T. et al. Multiple Myeloma-Associated Amyloidosis Manifesting as Fulminant Hepatic Failure. South Med. J. 2001; 94(10) http://www.medscape.com/viewarticle/415092_5 DOI: https://doi.org/10.1097/00007611-200194100-00021
  66. 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 2009; 23(2): 215–24. DOI: https://doi.org/10.1038/leu.2008.307
  67. Blade J., Lust J.A., Kyle R.A. Immunoglobulin D multiple myeloma: presenting features, response to therapy, and survival in a series of 53 cases. Clin. Oncol. 1994; 12: 2398–404. DOI: https://doi.org/10.1200/JCO.1994.12.11.2398
  68. Reece D.E., Vesole D.H. Outcome of Patients With IgD and IgM Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Retrospective CIBMTR Study Clinical Lymphoma. Leuk. 2010; 10(6): 458–63. DOI: https://doi.org/10.3816/CLML.2010.n.078
  69. Avet-Loiseau H., Garand R., Lode L. et al. Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants. Blood 2003; 101: 1570–1. DOI: https://doi.org/10.1182/blood-2002-08-2436
  70. Durie B.G.M., Salmon S.E. 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: 842–54. DOI: https://doi.org/10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U
  71. Greipp P.R., San Miguel J., Durie B.G.M. et al. International Staging System for Multiple Myeloma. Clin. Oncol. 2005; 23: 3412–20. DOI: https://doi.org/10.1200/JCO.2005.04.242
  72. Tuchman S.A., Sagar Lonial. High-Risk Multiple Myeloma: Does it Still Exist? Lymph. Myel. Leuk. 2011; 11(1): S70–6. DOI: https://doi.org/10.1016/j.clml.2011.02.008
  73. Kyle R.A., Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23: 3–9. DOI: https://doi.org/10.1038/leu.2008.291
  74. Hari P.N., Zhang M.J., Roy V. et al. Is the international staging system superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous transplant. Leukemia 2009; 23: 1528–34. DOI: https://doi.org/10.1038/leu.2009.61
  75. 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: 3489–95. DOI: https://doi.org/10.1182/blood-2006-08-040410
  76. Dimopoulos M.A., Kastritis E., Christoulas D. et al. Treatment of patients with relapsed/refractory multiple myeloma (MM) with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities. Blood (ASH Annual Meeting Abstracts) 2009; 114: Abstract 958. DOI: https://doi.org/10.1182/blood.V114.22.958.958
  77. Sawyer J., Shaughnessy J.D., Haussler J. et al. Gene expression profiling (GEP) in multiple myeloma (MM): Distinguishing relapses with high-risk transformation from those with sustained low risk. Clin. Oncol. 2010; 28: 15s (suppl; abstr. 8122). DOI: https://doi.org/10.1200/jco.2010.28.15_suppl.8122
  78. Kumar S.K., Mikhael J.R. Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines. Mayo Clin. Proc. 2009; 84(12): 1095–110. DOI: https://doi.org/10.4065/mcp.2009.0603
  79. Fonseca R., Blood E., Rue M. et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101(11): 4569–75. DOI: https://doi.org/10.1182/blood-2002-10-3017
  80. Gertz M.A., Lacy M.Q., 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): 2837–40. DOI: https://doi.org/10.1182/blood-2005-04-1411
  81. Dispenzieri A., Rajkumar S.V., Gertz M.A. et al. Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-Adapted therapy (mSMART). Mayo Clin. Proc. 2007; 82: 323–41. DOI: https://doi.org/10.4065/82.3.323
  82. Бессмельцев С.С. Диагностика и дифференциальная диагностика множественной миеломы. Вопр. онкол. 2004; 4: 406–16. [Bessmeltsev S.S. Diagnostika i differentsialnaya diagnostika mnozhestvennoy miyelomy (Detection and differential diagnosis of multiple myeloma. In: Issues of oncol.). Vopr. onkol. 2004; 4: 406–16.]
  83. Kyle R.A. Sequence of testing for monoclonal gammopathies: serum and urine assays. Pathol. Lab. Med. 1999; 123(2): 114–8. DOI: https://doi.org/10.5858/1999-123-0114-SOTFMG
  84. Drayson M., Tang L.X., Drew R. et al. Serum free light chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97(9): 2900–2. DOI: https://doi.org/10.1182/blood.V97.9.2900
  85. Dingli D., Kyle R.A., Rajkumar S.V. et al. Immunoglobulin free light chains and solitary plasmacytoma of bone. Blood 2006; 108(6): 1979–83. DOI: https://doi.org/10.1182/blood-2006-04-015784
  86. Dispenzieri A., Kyle R.A., Katzmann J.A. et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008; 111(2): 785–9. DOI: https://doi.org/10.1182/blood-2007-08-108357
  87. Katzmann J.A., Clark R.J., Abrahman R.S. et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Chem. 2002; 48: 1437–44. DOI: https://doi.org/10.1093/clinchem/48.9.1437
  88. Smith A., Wisloff F., Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. J. Haematol. 2006; 132(4): 410–51. DOI: https://doi.org/10.1111/j.1365-2141.2005.05867.x
  89. Kyle R.A., Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23(1): 3–9. DOI: https://doi.org/10.1038/leu.2008.291
  90. Rajkumar S.V., Dispenzieri A., Kyle R. Monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin. Proc. 2006; 81: 693–703. DOI: https://doi.org/10.4065/81.5.693
  91. Drayson M., Tang L.X., Drew R. et al. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97: 2900–2. DOI: https://doi.org/10.1182/blood.V97.9.2900
  92. Rajkumar S.V., Kyle R.A., Therneau T.M. et al. Serum free light ration is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005; 106(3): 812–7. DOI: https://doi.org/10.1182/blood-2005-03-1038
  93. Kyle R.A. Monoclonal gammopathy of undetermined significance and solitary plasmacytoma: implications for progression to overt multiple myeloma. Oncol. Clin. N. Am. 1997; 11: 71–87. DOI: https://doi.org/10.1016/S0889-8588(05)70416-0
  94. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. J. Haematol. 2003; 121(5): 749–57. DOI: https://doi.org/10.1046/j.1365-2141.2003.04355.x
  95. Kyle R.A., Greipp P.R. ‘Idiopathic’ Bence Jones proteinuria: long-term follow-up in seven patients. Engl. J. Med. 1982; 306: 564–7. DOI: https://doi.org/10.1056/NEJM198203113061002
  96. Diop P.A., Haudrechy D., Sylla-Niang M. et al. Laboratory diagnosis of monoclonal gammopathies. Prospective study of 14 cases in Dakar, Senegal. Bull. Soc. Pathol. 1998; 91: 242–6.
  97. Sezer O., Heider U., Zavrski I., Possinger K. Differentiation of monoclonal gammopathy of undetermined significance and multiple myeloma using flow cytometric characteristics of plasma cells. Haematologica 2001; 86: 837–43.
  98. Gandara D.R., Mackenzie M.R. Differential diagnosis of monoclonal gammopathy. Clin. N. Am. 1988; 72(5): 1155–68. DOI: https://doi.org/10.1016/S0025-7125(16)30734-9
  99. Weber D., Wang L.M., Delasalle K. et al. Risk factors for early progression of asymptomatic multiple myeloma. Hematology J. 2003; 4(Suppl. 1): S31.
  100. Cesana C., Klersy C., Barbarano L. et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J. Clin. Oncol. 2002; 20: 1625–34. DOI: https://doi.org/10.1200/JCO.2002.20.6.1625
  101. Vachon C.M., Kyle R.A., Therneau N.M. et al. Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood 2009; 114: 785–7. DOI: https://doi.org/10.1182/blood-2008-12-192575
  102. Rajkumar S.V., Kyle R.A., Buadj F.K. Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence. Mayo Clin. Proc. 2010; 85(10): 945–8. DOI: https://doi.org/10.4065/mcp.2010.0520
  103. Kyle R.A., Therneau T.M., Rajkumar S.V. et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N. Engl. J. Med. 2002; 346: 564–9. DOI: https://doi.org/10.1056/NEJMoa01133202
  104. Landgren O., Kyle R.A., Pfeiffer R.M. et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009; 113(22): 5412–5. DOI: https://doi.org/10.1182/blood-2008-12-194241
  105. Weiss B.M., Abadie J., Verma P. et al. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 2009; 113(22): 5418–21. DOI: https://doi.org/10.1182/blood-2008-12-195008
  106. Kyle R.A., Remstein E., Therneau T.M. et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N. Engl. J. Med. 2007; 356: 2582–90. DOI: https://doi.org/10.1056/NEJMoa070389
  107. Moulopoulos L.A., Dimopoulos M.A., Weber D. et al. Magnetic resonance imaging in the staging of solitary plasmacytoma of bone. J. Clin. Oncol. 1993; 11: 1311–5. DOI: https://doi.org/10.1200/JCO.1993.11.7.1311
  108. Tsang R.W., Gospodarowicz M.K., Pintilie M. et al. Solitary plasmacytoma treated with radiotherapy: Impact of tumor size on outcome. Intern. J. Rad. Oncol. Biol. Phys. 2011; 50: 113–20. DOI: https://doi.org/10.1016/S0360-3016(00)01572-8
  109. Knowling M.A., Harwood A.R., Bergsagel D.E. Comparison of extramedullary plasmacytomas with solitary and multiple plasma cell tumors of bone. J. Clin. Oncol. 1983; 1: 255–62. DOI: https://doi.org/10.1200/JCO.1983.1.4.255
  110. Alexiou C., Kau R.J., Dietzfelbinger H. et al. Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts. Cancer 1999; 85: 2305–14. DOI: https://doi.org/10.1002/(SICI)1097-0142(19990601)85:11<2305::AID-CNCR2>3.0.CO;2-3
  111. McKenna R.W., Kyle R.A., Kuehl W.M. et al. Plasma cell neoplasms. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Ed. by S.H. Swerdlow, E. Campo, N.L. Harris et al., 4th ed. Lyon: IARC Press, 2008: 200–13.
  112. Costello R., Sainty D., Bouabdallah R. et al. Primary plasma cell leuukemia: a report of 18 cases. Leuk. Res. 2001; 25: 103–7. DOI: https://doi.org/10.1016/S0145-2126(00)00102-8
  113. Vela-Ojeda J., Garcia-Ruiz Esparza M.A., Rosas-Cabral A. et al. Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. Ann. Hematol. 2002; 81: 362–7. DOI: https://doi.org/10.1007/s00277-002-0480-5
  114. Lebovic D., Zhang L., Alsina M. et al. Clinical Outcomes of Patients With Plasma Cell Leukemia in the Era of Novel Therapies and Hematopoietic Stem Cell Transplantation Strategies: A Single-Institution Experience. Clin. Lymph. Myel. Leuk. 2012; 11(6): 507–11. DOI: https://doi.org/10.1016/j.clml.2011.06.010
  115. Gutierez N.C., Hernandez J.M., Garcia J.L. et al. Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization. Leukemia 2001; 5: 840–5. DOI: https://doi.org/10.1038/sj.leu.2402116
  116. Tiedemann R.E., Gonzalez-Paz N., Kyle R.A. et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 2008; 22: 1044–52. DOI: https://doi.org/10.1038/leu.2008.4
  117. Chang H., Qi X., Yeung J. et al. Genetic aberrations including chromosome 1 abnormalities and clinical features of plasma cell leukemia. Leuk. Res. 2009; 33: 259–62. DOI: https://doi.org/10.1016/j.leukres.2008.06.027
  118. Dierlamm T., Laack E., Dierlamm J. IgM myeloma: a report of four cases. Ann. Hematol. 2002; 81: 136–9. DOI: https://doi.org/10.1007/s00277-001-0420-9
  119. Owen R.G., Treon S.P., Al-Katib A. et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin. Oncol. 2003; 30(2): 110–5. DOI: https://doi.org/10.1053/sonc.2003.50082
  120. Gertz M.A. Waldenstrom macroglobulinemia: 2011 update on diagnosis, risk stratification, and management. J. Hematol. 2011; 86(5): 411–6. DOI: https://doi.org/10.1002/ajh.22014
  121. Криволапов Ю.А., Леенман Е.Е. Морфологическая диагностика лимфом. СПб.: Издательско-полиграфическая компания «Коста», 2006.
  122. Krivolapov Yu.A., Leyenman Ye.Ye. Morfologicheskaya diagnostika limfom (Morphologic diagnosis of lymphomas). Spb.: Izdatelskopoligraficheskaya kompaniya «Kosta», 2006.
  123. Kyle R.A., Treon S.P., Alexanian R. et al. Prognostic markers and criteria to initiate therapy in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia [review]. Oncol. 2003; 30(2): 116–20. DOI: https://doi.org/10.1053/sonc.2003.50038
  124. Михайлов А.М., Бессмельцев С.С., Пожарисский К.М. и др. Болезнь Кастлемана и POEMS-синдром, их проявления и взаимосвязь. В кн.: Редкие гематологические болезни и синдромы. Под ред. М.А. Волковой. М.: Практическая медицина, 2011: 360–83. [Mikhaylov A.M., Bessmeltsev S.S., Pozharisskiy K.M. i dr. Bolezn Kastlemana i POEMS-sindrom, ikh proyavleniya i vzaimosvyaz. V kn.: Redkiye gematologicheskiye bolezni i sindromy. Pod red. M.A. Volkovoy (Castleman’s disease and POEMS syndrome, their presentation and interrelations. In: Rare hematological disorders and syndromes. Ed. by M.A. Volkova). : Prakticheskaya meditsina, 2011: 360–83.]
  125. Алексеев В.В. Диагностика и лечение болей в пояснице, вызванных компрессионной радикулопатией. Справ. поликлин. врача 2002; 4: 28–32. Alekseyev V.V. Diagnostika i lecheniye boley v poyasnitse, vyzvannykh kompressionnoy radikulopatiyey [Diagnosis and treatment of lower back pain caused by compression radiculopathy. In: Desk book of polycl. doctor]. Sprav. poliklin. vracha 2002; 4: 28–32.
  126. Балаболкин М.И. Эндокринология. М.: Универсум паблишинг, 1998. [Balabolkin M.I. Endokrinologiya (Endocrinology). : Universum pablishing, 1998.]
  127. Колондаев А.Ф., Балберкин А.Ф. Болезнь Педжета (деформиру- ющий остит). Врач 2003; 4: 13–6. [Kolondayev A.F., Balberkin A.F. Bolezn Pedzheta (deformiruyushchiy ostit) (Paget’s disease (osteitis deformans). In: Medical practitioner). Vrach 2003; 4: 13–6.]
  128. Васильев Ю.В. Боль за грудиной: дифференциальная диагностика и лечение. Consilium medicum (Приложение). 2002; 3: 3–5. [Vasilyev Yu.V. Bol za grudinoy: differentsialnaya diagnostika i lecheniye (Retrosternal pain, differential diagnosis and treatment. In: Consilium medicum (Addendum)). Consilium medicum (Prilozheniye). 2002; 3: 3–5.]
  129. Бессмельцев С.С. Клиническая трактовка увеличенной скорости оседания эритроцитов практикующим врачом (Часть 1). Вестн. гематол. 2005; 2: 54–62. [Bessmeltsev S.S. Klinicheskaya traktovka uvelichennoy skorosti osedaniya eritrotsitov praktikuyushchim vrachom (Chast 1) (Clinical interpretation of elevated erythrocyte sedimentation rate by medical practitioner (Part I). In: Hematol. bullet.). Vestn. gematol. 2005; 2: 54–62.]
  130. Coleman R.E. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat. Rev. 2001; 27: 165–76. 131. Mundy G.R. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2002; 2: 584–93. 132. Fukutomi M. Increased incidence of bone metastases in hepatocellular carcinoma. J. Gastroenterol. Hepatol. 2001; 13: 1083–8. DOI: https://doi.org/10.1053/ctrv.2000.0210

Keywords:

multiple myeloma, monoclonal gammopathy of undetermined significance, asymptomatic myeloma, M protein, clonal plasma cells

License

Copyright (c) 2013 Clinical Oncohematology

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Downloads

Download data is not yet available.
2013-3

Downloads

Published

01.07.2013

Issue

Vol. 6 No. 3 (2013)
REVIEWS

How to Cite

Bessmeltsev S.S. Multiple myeloma (pathogenesis, clinical features, diagnosis, differential diagnosis). Part I. Clinical Oncohematology. 2013;6(3):237–257. doi:10.21320/2500-2139-2013-6-3-237-257.

Most read articles by the same author(s)

1 2 > >>