clonal plasma cells

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

REVIEWS , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, Saint Petersburg, Russian Federation

ABSTRACT

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.

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

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REFERENCES

  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.
  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.
  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.
  5. Anderson K.C. Targeted therapy for multiple myeloma. Hematol. 2001; 38: 286–94.
  6. Barker H.F., Ball J., Drew M. et al. The role of adhesion molecules in multiple myeloma. Lymphoma 1992; 8: 189–96.
  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.
  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.
  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.
  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.
  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.
  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.
  14. Damiano J.S., Dalton W.S. Integrin-mediated drug resistance in multiple myeloma. Lymphoma 2000; 38: 71–81.
  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.
  17. Anderson K.C. Targeted therapy for multiple myeloma. Hematol. 2001; 38: 286–94.
  18. Klein B., Zhang X., Lu Z. Interleukin-6 in multiple myeloma. Blood 1995; 85: 863–7.
  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.
  20. Barlogie B., Epstein J., Selvanayagam P., Alexanian R. Plasma cell myeloma — new biological insights and advances in therapy. Blood 1998; 73: 865–70.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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
  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.
  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.
  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.
  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.
  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.
  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.
  72. Tuchman S.A., Sagar Lonial. High-Risk Multiple Myeloma: Does it Still Exist? Lymph. Myel. Leuk. 2011; 11(1): S70–6.
  73. Kyle R.A., Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23: 3–9.
  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.
  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.
  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.
  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).
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  88. Smith A., Wisloff F., Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. J. Haematol. 2006; 132(4): 410–51.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  110. Alexiou C., Kau R.J., Dietzfelbinger H. et al. Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts. Cancer 1999; 85: 2305–14.
  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.
  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.
  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.
  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.
  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.
  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.
  118. Dierlamm T., Laack E., Dierlamm J. IgM myeloma: a report of four cases. Ann. Hematol. 2002; 81: 136–9.
  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.
  120. Gertz M.A. Waldenstrom macroglobulinemia: 2011 update on diagnosis, risk stratification, and management. J. Hematol. 2011; 86(5): 411–6.
  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.
  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.