Blood Reviews
Volume 23, Issue 6 , Pages 257-265 , November 2009

The incidental monoclonal protein: Current approach to management of monoclonal gammopathy of undetermined significance (MGUS)

  • Sumit Madan

      Affiliations

    • Tel.: +1 507 776 2040; fax: +1 507 266 9277.
  • ,
  • Philip R. Greipp

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1 507 284 9094; fax: +1 507 266 9277.

References 

  1. Dispenzieri A, Gertz MA, Therneau TM, Kyle RA. Retrospective cohort study of 148 patients with polyclonal gammopathy. Mayo Clin Proc. 2001;76:476–487
  2. Kyle RA. Monoclonal gammopathy of undetermined significance. Natural history in 241 cases. Am J Med. 1978;64:814–826
  3. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. New Engl J Med. 2002;346:564–569
  4. 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
  5. Rajkumar SV, Lacy MQ, Kyle RA. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Blood Rev. 2007;21:255–265
  6. 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
  7. Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. New Engl J Med. 2007;356:2582–2590
  8. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. New Engl J Med. 2006;354:1362–1369
  9. Iwanaga M, Tagawa M, Tsukasaki K, Kamihira S, Tomonaga M. Prevalence of monoclonal gammopathy of undetermined significance. study of 52, 802 persons in Nagasaki City, Japan. Mayo Clin Proc. 2007;82:1474–1479
  10. Kyle RA, Finkelstein S, Elveback LR, Kurland LT. Incidence of monoclonal proteins in a Minnesota community with a cluster of multiple myeloma. Blood. 1972;40:719–724
  11. Saleun JP, Vicariot M, Deroff P, Morin JF. Monoclonal gammopathies in the adult population of Finistere, France. J Clin Pathol. 1982;35:63–68
  12. Axelsson U, Bachmann R, Hallen J. Frequency of pathological proteins (M-components) om 6, 995 sera from an adult population. Acta Med Scand. 1966;179:235–247
  13. Giraldo MP, Rubio-Felix D, Perella M, Gracia JA, Bergua JM, Giralt M. Monoclonal gammopathies of undetermined significance. Clinical course and biological aspects of 397 cases. Sangre (Barc). 1991;36:377–382
  14. Landgren O, Gridley G, Turesson I, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood. 2006;107:904–906
  15. Cohen HJ, Crawford J, Rao MK, Pieper CF, Currie MS. Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly. Am J Med. 1998;104:439–444
  16. Munshi NC. Monoclonal gammopathy of undetermined significance. genetic vs. environmental etiologies. Mayo Clin Proc. 2007;82:1457–1459
  17. Blade J. Clinical practice. Monoclonal gammopathy of undetermined significance. New Engl J Med. 2006;355:2765–2770
  18. Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Hematol Oncol Clin North Am. 2007;21:1093–1113ix
  19. Landgren O, Katzmann JA, Hsing AW, et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc. 2007;82:1468–1473
  20. Brown LM, Linet MS, Greenberg RS, et al. Multiple myeloma and family history of cancer among blacks and whites in the US. Cancer. 1999;85:2385–2390
  21. Eriksson M, Hallberg B. Familial occurrence of hematologic malignancies and other diseases in multiple myeloma: a case-control study. Cancer Causes Control. 1992;3:63–67
  22. Landgren O, Linet MS, McMaster ML, Gridley G, Hemminki K, Goldin LR. Familial characteristics of autoimmune and hematologic disorders in 8, 406 multiple myeloma patients: a population-based case-control study. Int J Cancer. 2006;118:3095–3098
  23. Ogmundsdottir HM, Haraldsdottirm V, Johannesson GM, et al. Familiarity of benign and malignant paraproteinemias. A population-based cancer-registry study of multiple myeloma families. Haematologica. 2005;90:66–71
  24. Vachon CM, Kyle RA, Therneau TM, et al. Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood. 2009;114:785–790
  25. Brown LM, Gridley G, Check D, Landgren O. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood. 2008;111:3388–3394
  26. Linet MS, McLaughlin JK, Harlow SD, Fraumeni JF. Family history of autoimmune disorders and cancer in multiple myeloma. Int J Epidemiol. 1988;17:512–513
  27. Hsing AW, Hansson LE, McLaughlin JK, et al. Pernicious anemia and subsequent cancer. A population-based cohort study. Cancer. 1993;71:745–750
  28. Brinton LA, Gridley G, Hrubec Z, Hoover R, Fraumeni JF. Cancer risk following pernicious anaemia. Br J Cancer. 1989;59:810–813
  29. Landgren O, Kyle RA, Hoppin JA, et al. Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study. Blood. 2009;113:6386–6391
  30. Bergsagel PL, Kuehl WM. The molecular biology of multiple myeloma. In:  Malpas JS,  Bergsagel DE,  Kyle RA,  Anderson KC editor. Myeloma: Biology and Management. 3rd ed.. Philadelphia: Saunders; 2004;p. 35–58
  31. Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64:1546–1558
  32. Blade J, Rosinol L, Cibeira MT, de Larrea CF. Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia. 2008;22:1651–1657
  33. Brousseau M, Leleu X, Gerard J, et al. Hyperdiploidy is a common finding in monoclonal gammopathy of undetermined significance and monosomy 13 is restricted to these hyperdiploid patients. Clin Cancer Res. 2007;13:6026–6031
  34. Avet-Loiseau H, Li JY, Facon T, et al. High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies. Cancer Res. 1998;58:5640–5645
  35. Nishida K, Tamura A, Nakazawa N, et al. The Ig heavy chain gene is frequently involved in chromosomal translocations in multiple myeloma and plasma cell leukemia as detected by in situ hybridization. Blood. 1997;90:526–534
  36. 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;59:4546–4550
  37. Fonseca R, Bailey RJ, Ahmann GJ, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood. 2002;100:1417–1424
  38. Chng WJ, Van Wier SA, Ahmann GJ, et al. A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS. Blood. 2005;106:2156–2161
  39. Konigsberg R, Ackermann J, Kaufmann H, et al. Deletions of chromosome 13q in monoclonal gammopathy of undetermined significance. Leukemia. 2000;14:1975–1979
  40. Ackermann J, Meidlinger P, Zojer N, et al. Absence of p53 deletions in bone marrow plasma cells of patients with monoclonal gammopathy of undetermined significance. Br J Haematol. 1998;103:1161–1163
  41. Corradini P, Inghirami G, Astolfi M, et al. Inactivation of tumor suppressor genes, p53 and Rb1, in plasma cell dyscrasias. Leukemia. 1994;8:758–767
  42. 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
  43. Harada H, Kawano MM, Huang N, et al. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993;81:2658–2663
  44. Ocqueteau M, Orfao A, Almeida J, et al. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol. 1998;152:1655–1665
  45. Kumar S, Rajkumar SV, Kimlinger T, Greipp PR, Witzig TE. CD45 expression by bone marrow plasma cells in multiple myeloma: clinical and biological correlations. Leukemia. 2005;19:1466–1470
  46. Vacca A, Ribatti D, Roncali L, Dammacco F. Angiogenesis in B cell lymphoproliferative diseases. Biological and clinical studies. Leuk Lymphoma. 1995;20:27–38
  47. Vacca A, Ribatti D, Roncali L, et al. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol. 1994;87:503–508
  48. Aguayo A, Kantarjian H, Manshouri T, et al. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood. 2000;96:2240–2245
  49. Rajkumar SV, Mesa RA, Fonseca R, et al. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res. 2002;8:2210–2216
  50. Kumar S, Witzig TE, Timm M, et al. Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression. Blood. 2004;104:1159–1165
  51. Vacca A, Ribatti D, Presta M, et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood. 1999;93:3064–3073
  52. van de Donk NW, Lokhorst HM, Bloem AC. Growth factors and antiapoptotic signaling pathways in multiple myeloma. Leukemia. 2005;19:2177–2185
  53. Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332:83–85
  54. Ogata A, Anderson KC. Therapeutic strategies for inhibition of interleukin-6 mediated multiple myeloma cell growth. Leuk Res. 1996;20:303–307
  55. Rawstron AC, Fenton JA, Ashcroft J, et al. The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells. Blood. 2000;96:3880–3886
  56. Lust JA, Donovan KA. The role of interleukin-1 beta in the pathogenesis of multiple myeloma. Hematol Oncol Clin North Am. 1999;13:1117–1125
  57. Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson KC. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene. 2001;20:4519–4527
  58. Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer. 2002;2:175–187
  59. Hanamura I, Stewart JP, 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;108:1724–1732
  60. Liu P, 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;88:2699–2706
  61. Bezieau S, Devilder MC, Avet-Loiseau H, et al. High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis. Hum Mutat. 2001;18:212–224
  62. Corradini P, Ladetto M, Voena C, et al. Mutational activation of N- and K-ras oncogenes in plasma cell dyscrasias. Blood. 1993;81:2708–2713
  63. Blade J, Lopez-Guillermo A, Rozman C, et al. Malignant transformation and life expectancy in monoclonal gammopathy of undetermined significance. Br J Haematol. 1992;81:391–394
  64. Gregersen H, Mellemkjaer L, Ibsen JS, Dahlerup JF, Thomassen L, Sorensen HT. The impact of M-component type and immunoglobulin concentration on the risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance. Haematologica. 2001;86:1172–1179
  65. 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;20:1625–1634
  66. Rosinol L, Cibeira MT, Montoto S, et al. Monoclonal gammopathy of undetermined significance. predictors of malignant transformation and recognition of an evolving type characterized by a progressive increase in M protein size. Mayo Clin Proc. 2007;82:428–434
  67. Baldini L, Guffanti A, Cesana BM, et al. Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy. Blood. 1996;87:912–918
  68. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton LJ. Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance. the original Mayo Clinic series 25 years later. Mayo Clin Proc. 2004;79:859–866
  69. Kyle RA. “Benign” monoclonal gammopathy – after 20 to 35 years of follow-up. Mayo Clin Proc. 1993;68:26–36
  70. Rajkumar SV, Kyle RA, Therneau TM, et al. Presence of monoclonal free light chains in the serum predicts risk of progression in monoclonal gammopathy of undetermined significance. Br J Haematol. 2004;127:308–310
  71. Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106:812–817
  72. Katzmann JA, Clark RJ, Abraham RS, 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. Clin Chem. 2002;48:1437–1444
  73. 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
  74. Kumar S, Rajkumar SV, Kyle RA, et al. Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance. J Clin Oncol. 2005;23:5668–5674
  75. Kyle RA. ‘Benign’ monoclonal gammopathy. A misnomer?. JAMA. 1984;251:1849–1854
  76. Montoto S, Blade J, Montserrat E. Monoclonal gammopathy of undetermined significance. New Engl J Med. 2002;346:2087–2088(author reply 2087–2088)
  77. Blade J. On the “significance” of monoclonal gammopathy of undetermined significance. Mayo Clin Proc. 2004;79:855–856
  78. Terpos E, Szydlo R, Apperley JF, et al. Soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index. Blood. 2003;102:1064–1069
  79. Politou M, Terpos E, Anagnostopoulos A, et al. Role of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol. 2004;126:686–689
  80. Lust JA, Donovan KA. Biology of the transition of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma. Cancer Control. 1998;5:209–217
  81. Rajkumar SV. MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management hematology. Am Soc Hematol Educ Program. 2005;340–345
  82. Pecherstorfer M, Seibel MJ, Woitge HW, et al. Bone resorption in multiple myeloma and in monoclonal gammopathy of undetermined significance. quantification by urinary pyridinium cross-links of collagen. Blood. 1997;90:3743–3750
  83. Vejlgaard T, Abildgaard N, Jans H, Nielsen JL, Heickendorff L. Abnormal bone turnover in monoclonal gammopathy of undetermined significance. analyses of type I collagen telopeptide, osteocalcin, bone-specific alkaline phosphatase and propeptides of type I and type III procollagens. Eur J Haematol. 1997;58:104–108
  84. Gregersen H, Jensen P, Gislum M, Jorgensen B, Sorensen HT, Norgaard M. Fracture risk in patients with monoclonal gammopathy of undetermined significance. Br J Haematol. 2006;135:62–67
  85. Jakob C, Zavrski I, Heider U, et al. Bone resorption parameters [carboxy-terminal telopeptide of type-I collagen (ICTP), amino-terminal collagen type-I telopeptide (NTx), and deoxypyridinoline (Dpd)] in MGUS and multiple myeloma. Eur J Haematol. 2002;69:37–42
  86. Hernandez JM, Suquia B, Queizan JA, et al. Bone remodelation markers are useful in the management of monoclonal gammopathies. Hematol J. 2004;5:480–488
  87. Laroche M, Attal M, Dromer C. Bone remodelling in monoclonal gammopathies of uncertain significance, symptomatic and nonsymptomatic myeloma. Clin Rheumatol. 1996;15:347–352
  88. Diamond T, Levy S, Smith A, Day P, Manoharan A. Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance. Intern Med J. 2001;31:272–278
  89. Melton LJ, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA. Fracture risk in monoclonal gammopathy of undetermined significance. J Bone Miner Res. 2004;19:25–30
  90. Pepe J, Petrucci MT, Nofroni I, et al. Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance. Br J Haematol. 2006;134:485–490
  91. Golombick T, Diamond T. Prevalence of monoclonal gammopathy of undetermined significance/myeloma in patients with acute osteoporotic vertebral fractures. Acta Haematol. 2008;120:87–90
  92. Pongchaiyakul C, Nguyen ND, Jones G, Center JR, Eisman JA, Nguyen TV. Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study. J Bone Miner Res. 2005;20:1349–1355
  93. Pepe J, Petrucci MT, Mascia ML, et al. The effects of alendronate treatment in osteoporotic patients affected by monoclonal gammopathy of undetermined significance. Calcif Tissue Int. 2008;82:418–426
  94. Berenson JR, Yellin O, Boccia RV, et al. Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss. Clin Cancer Res. 2008;14:6289–6295
  95. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63:1567–1575
  96. Kristinsson SY, Fears TR, Gridley G, et al. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood. 2008;112:3582–3586
  97. Srkalovic G, Cameron MG, Rybicki L, Deitcher SR, Kattke-Marchant K, Hussein MA. Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer. 2004;101:558–566
  98. Sallah S, Husain A, Wan J, Vos P, Nguyen NP. The risk of venous thromboembolic disease in patients with monoclonal gammopathy of undetermined significance. Ann Oncol. 2004;15:1490–1494
  99. Auwerda JJ, Sonneveld P, de Maat MP, Leebeek FW. Prothrombotic coagulation abnormalities in patients with paraprotein-producing B-cell disorders. Clin Lymphoma Myeloma. 2007;7:462–466
  100. Dispenzieri A. POEMS syndrome. Blood Rev. 2007;21:285–299
  101. Dispenzieri A, Kyle RA, Lacy MQ, et al. POEMS syndrome: definitions and long-term outcome. Blood. 2003;101:2496–2506
  102. James K, Fudenberg H, Epstein WL, Shuster J. Studies on a unique diagnostic serum globulin in papular mucinosis (lichen myxedematosus). Clin Exp Immunol. 1967;2:153–166
  103. Powell FC, Greipp PR, Su WP. Discoid lupus erythematosus and monoclonal gammopathy. Br J Dermatol. 1983;109:355–360
  104. Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance. Br J Haematol. 2006;134:573–589
  105. Pomann JJ, Rudner EJ. Scleromyxedema revisited. Int J Dermatol. 2003;42:31–35
  106. Kovary PM, Dhonau H, Happle R. Paraproteinaemia in erythema elevatum diutinum. Arch Dermatol Res. 1977;260:155–158
  107. Chowdhury MM, Inaloz HS, Motley RJ, Knight AG. Erythema elevatum diutinum and IgA paraproteinaemia: ‘a preclinical iceberg’. Int J Dermatol. 2002;41:368–370
  108. Zent CS, Wilson CS, Tricot G, et al. Oligoclonal protein bands and Ig isotype switching in multiple myeloma treated with high-dose therapy and hematopoietic cell transplantation. Blood. 1998;91:3518–3523
  109. Badley AD, Portela DF, Patel R, et al. Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder. Liver Transpl Surg. 1996;2:375–382
  110. Gosselin S, Kyle RA, Dyck PJ. Neuropathy associated with monoclonal gammopathies of undetermined significance. Ann Neurol. 1991;30:54–61
  111. Dingli D, Larson DR, Plevak MF, Grande JP, Kyle RA. Focal and segmental glomerulosclerosis and plasma cell proliferative disorders. Am J Kidney Dis. 2005;46:278–282
  112. Czarnecki PG, Lager DJ, Leung N, Dispenzieri A, Cosio FG, Fervenza FC. Long-term outcome of kidney transplantation in patients with fibrillary glomerulonephritis or monoclonal gammopathy with fibrillary deposits. Kidney Int. 2009;75:420–427
  113. Esparza AR, Chazan JA, Nayak RN, Cavallo T. Fibrillary (immunotactoid) glomerulopathy. A possible role for kappa light chain in its etiology and/or pathogenesis. Am J Surg Pathol. 1991;15:632–643
  114. Rollino C, Coppo R, Mazzucco G, et al. Monoclonal gammopathy and glomerulonephritis with organized microtubular deposits. Am J Kidney Dis. 1990;15:276–280
  115. Malik AA, Ganti AK, Potti A, Levitt R, Hanley JF. Role of Helicobacter pylori infection in the incidence and clinical course of monoclonal gammopathy of undetermined significance. Am J Gastroenterol. 2002;97:1371–1374
  116. Rajkumar SV, Kyle RA, Plevak MF, Murray JA, Therneau TM. Helicobacter pylori infection and monoclonal gammopathy of undetermined significance. Br J Haematol. 2002;119:706–708
  117. Alexanian R. Monoclonal gammopathy in lymphoma. Arch Intern Med. 1975;135:62–66
  118. Kyle RA, Garton JP. The spectrum of IgM monoclonal gammopathy in 430 cases. Mayo Clin Proc. 1987;62:719–731
  119. Noel P, Kyle RA. Monoclonal proteins in chronic lymphocytic leukemia. Am J Clin Pathol. 1987;87:385–388
  120. Zawadzki ZA, Benedek TG. Rheumatoid arthritis, dysproteinemic arthropathy, and paraproteinemia. Arthritis Rheum. 1969;12:555–568
  121. Renier G, Renier JC, Gardembas-Pain M, Chevailler A, Boasson M, Hurez D. Ankylosing spondylitis and monoclonal gammopathies. Ann Rheum Dis. 1992;51:951–954
  122. Ilfeld D, Barzilay J, Vana D, Ben-Bassat M, Joshua H, Pick I. IgG monoclonal gammopathy in four patients with polymyalgia rheumatica. Ann Rheum Dis. 1985;44:501
  123. Porcel JM, Ordi J, Tolosa C, Selva A, Castro-Salomo A, Vilardell M. Monoclonal gammopathy in systemic lupus erythematosus. Lupus. 1992;1:263–264
  124. Mussini C, Ghini M, Mascia MT. Et al. HCV and monoclonal gammopathies. Clin Exp Rheumatol. 1995;13(Suppl. 13):S45–49
  125. Pascual M, Widmann JJ, Schifferli JA. Recurrent febrile panniculitis and hepatitis in two patients with acquired complement deficiency and paraproteinemia. Am J Med. 1987;83:959–962
  126. Droder RM, Kyle RA, Greipp PR. Control of systemic capillary leak syndrome with aminophylline and terbutaline. Am J Med. 1992;92:523–526
  127. Lamboley V, Zabraniecki L, Sie P, Pourrat J, Fournie B. Myeloma and monoclonal gammopathy of uncertain significance associated with acquired von Willebrand’s syndrome. Seven new cases with a literature review. Joint Bone Spine. 2002;69:62–67
  128. Fremeaux-Bacchi V, Guinnepain MT, Cacoub P, et al. Prevalence of monoclonal gammopathy in patients presenting with acquired angioedema type 2. Am J Med. 2002;113:194–199

PII: S0268-960X(09)00042-3

doi: 10.1016/j.blre.2009.07.004

Blood Reviews
Volume 23, Issue 6 , Pages 257-265 , November 2009