Multiple Myeloma and Plasma Cell Dyscrasias

  • Pietro Zucchelli
  • Sonia Pasquali

Abstract

The term plasma cell dyscrasias includes a number of diseases characterized by a single clone expansion of plasma cells and their immediate precursors, the activated B cells. The result of that proliferation is a qualitative and quantitative alteration in immunoglobulin synthesis, with a production of a single type of whole immunoglobulin and/or a variety of immunoglobulin fragments, all antigenically similar (M component). Plasma cell dyscrasias particularly comprise multiple myeloma, Waldenstrom’s macroglobulinemia, monoclonal gammopathy of undetermined significance (also called benign monoclonal gammopathy), and (rarely) lymphoma or lymphocytic leukemia. Multiple myeloma (MM) is a B-cell cancer characterized by proliferation of mature plasma cells and B lymphocytes in different evolution stages (frequently expressing the pre-B-cell antigen called CALLA) (1). MM represents one of the relatively common hematologic malignancies whose incidence rises with age to approximately 7 per 100,000 at age 50 and to more than 20 per 100,000 at age 80 (2).

Keywords

Multiple Myeloma Light Chain Peritoneal Dialysis Familial Mediterranean Fever Deposition Disease 
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.

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References

  1. 1.
    Epstein J, Xiao H, He XJ: Markers of multiple hematopoietic-cell lineages in multiple myeloma. N Engl J Med 322: 664–668, 1990.PubMedCrossRefGoogle Scholar
  2. 2.
    Crawford JC, Cohen HJ: An approach to monoclonal gammopathies in the elderly. Geriatrics 37: 97–112, 1982.PubMedGoogle Scholar
  3. 3.
    Solomon A, Weiss DT: Ominous consequences of immunoglobulin deposition. N Engl J Med 329: 1422–1423, 1993.PubMedCrossRefGoogle Scholar
  4. 4.
    Gallo G: Renal complications of B-cell dyscrasia. N Engl J Med 324: 1889–1890, 1991.PubMedCrossRefGoogle Scholar
  5. 5.
    Jvanyi B, Varga G, Berkessy S: Renal disease in multiple myeloma. Geriatr Nephrol Urol 2: 25–34, 1992.CrossRefGoogle Scholar
  6. 6.
    Wochner RD, Strober W, Waldmann TA: The role of the kidney in the catabolism of Bence Jones proteins and immunoglobulin fragments. J Exp Med 126: 207–221, 1967.PubMedCrossRefGoogle Scholar
  7. 7.
    Fang LST: Light-chain nephropathy. Kidney Int 27: 582–592, 1985.PubMedCrossRefGoogle Scholar
  8. 8.
    Mazzucco G, Casanova S, Donini U, Rollino C, Zucchelli P, Piccoli G, Monga G: Glomerulonephritis with organized deposits: a new clinicopathological entity? Light-Electron- Microscope and immunofluorescence study of 12 cases. Am J Nephrol 10: 21–30, 1990.PubMedCrossRefGoogle Scholar
  9. 9.
    Alpers CE: Immunotactoid (microtubular) glomerulopathy: an entity distinct from fibrillary glomerulonephritis. Am J Kidney Dis 19: 185–191, 1992.PubMedGoogle Scholar
  10. 10.
    Fogo A, Quieshi N, Horn RG: Morphological and clinical features of fibrillary glomerulonephritis (FGN) vs. immunotactoid glomerulopathy (IT) (abstract). Mod Pathol 6:117-A, 1993.Google Scholar
  11. 11.
    Kyle RA: Amyloidosis. J Int Med 232: 507–508, 1992.CrossRefGoogle Scholar
  12. 12.
    Husby G: Nomenclature and classification of amyloid and amyloidosis. J Int Med 232: 511–512, 1992.CrossRefGoogle Scholar
  13. 13.
    Kyle RA: Multiple myeloma: Review of 869 cases. Mayo Clin Proc 50: 29–40, 1975.PubMedGoogle Scholar
  14. 14.
    Feiner HD: Pathology of dysprotidemia: Light-chain amyloidosis, non-amyloid immunoglobulin deposition disease, cryoglobulinemia syndromes, and macroglobulinemia of Waldestrom. Hum Pathol 19: 1255–1272, 1988.PubMedCrossRefGoogle Scholar
  15. 15.
    Gallo G, Picken M, Buxbaum J, Frangione B: The spectrum of monoclonal immunoglobulin deposition disease associated with immunocytic dyscrasias. Sem Hematol 26: 234–245, 1989.Google Scholar
  16. 16.
    Ganeval D, Noel LH, Preud’homme JL, Droz D, Grunfeld JP: Light-chain deposition disease: its relation with AL-type amyloidosis. Kidney Int 26: 1–9, 1984.PubMedCrossRefGoogle Scholar
  17. 17.
    Buxbaum J: Aberrant immunoglobulin synthesis in light chain amyloidosis. J Clin Invest 78: 789–806, 1986.CrossRefGoogle Scholar
  18. 18.
    Shirohama T, Miura K, Ju ST, Kisilevsky R, Gruys E, Cohen AS: Amyloyd enhancing factor-loaded macrophages in amyloid fibril formation. Lab Invest 61: 61–68, 1990.Google Scholar
  19. 19.
    Sanders PW, Herrera GA: Monoclonal immunoglobulin light chain-related renal disease. Semin Nephrol 13: 324–341, 1993.PubMedGoogle Scholar
  20. 20.
    Donini U, Casanova S, Zucchelli P, Linke RP: Immunohis-tochemical classification of amyloidosis and immunohis-tochemistry of fibrillar nephropathy on routinely processed plastic-embedded tissues. In: T Isobe, S Araki, F Uchino, S Kito, F Tsubura, eds, Amyloid and Amyloidosis. Plenum, New York, pp 789–794, 1988.Google Scholar
  21. 21.
    Dikman SH, Churg J, Kalin T: Morphologic and clinical correlates in renal amyloidosis. Hum Pathol 12: 160–169, 1981.PubMedCrossRefGoogle Scholar
  22. 22.
    Falk HM, Tornroth T, Wegelius O: Predominantly vascular amyloid deposition in the kidney in patients with minimal or no proteinuria. Clin Nephrol 19: 137–142, 1983.Google Scholar
  23. 23.
    Gertz MA, Kyle RA: Primary systemic amyloidosis. A diagnostic primer. Mayo Clin Proc 64: 1505–1519, 1989.PubMedCrossRefGoogle Scholar
  24. 24.
    Torres VE, Donadio JV: Clinical aspects of the nephrotic syndrome in systemic disease. In: S Cameron, R Glassock, eds, The Nephrotic Syndrome. Marcel Dekker, New York and Basel, pp 555–651, 1988.Google Scholar
  25. 25.
    Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J: Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med 314: 1001–1005, 1986.PubMedCrossRefGoogle Scholar
  26. 26.
    Kyle RA, Greipp PR, Garton JP, Gertz MA: Primary systemic amyloidosis. Comparison of melphalan/prednisone versus colchicine. Am J Med 79: 708–716, 1985.PubMedCrossRefGoogle Scholar
  27. 27.
    Cohen AS, Rubinow A, Anderson JJ, Skinner M, Mason JH, Libbey C, Kayne H: Survival of patients with primary (AL) amyloidosis. Am J Med 82: 1182–1190, 1987.PubMedCrossRefGoogle Scholar
  28. 28.
    Fielder K, Durie BGM: Primary amyloidosis associated with multiple myeloma. Predictors of successful therapy. Am J Med 80: 413–418, 1986.PubMedCrossRefGoogle Scholar
  29. 29.
    Gertz MA, Kyle RA, Greipp PR: Response rates and survival in primary systemic amyloidosis. Blood 77: 257–262, 1991.PubMedGoogle Scholar
  30. 30.
    Banfi G, Moriggi M, Confalonieri R, Minetti E, Ferrario F, Bucci A, Pasquali S, Donini U, Schiaffino E, Barbiano di Belgiojoso G, Bertani T, Pozzi C, Ravelli M, Furci L, Lupo A, Comotti C, Volpi A, Schena EP: Renal amyloidosis. Retrospective collaborative study. In: L Minetti, G D’Amico, C Ponticelli, eds, The Kidney in Plasma Cell Dyscrasias. Kluwer, Dordrecht, pp 211–219, 1988.CrossRefGoogle Scholar
  31. 31.
    Ganeval D: Kidney involvement in light-chain deposition disease. In: L Minetti, G D’Amico, C Ponticelli, eds, The Kidney in Plasma Cell Dyscrasias. Kluwer, Dordrecht, pp 221–228, 1988.CrossRefGoogle Scholar
  32. 32.
    Pirani CL, Silva F, D’agati V: Renal lesions in plasma cell dyscrasias: ultrastructural observations. Am J Kidney Dis 10: 208–221, 1987.PubMedGoogle Scholar
  33. 33.
    Gallo G: Renal amyloid and nonamyloidotic monoclonal immunoglobulin deposition diseases. An overview and update. J Nephrol 3: 137–143, 1991.Google Scholar
  34. 34.
    Confalonieri R, Barbiano di Belgiojoso G, Banfi G, Ferrario F, Casanova S, Bertani T, Pozzi C, Lupo A, Minetti L: Light chain nephropathy. Histological and clinical aspects in 15 cases. Nephrol Dial Transplant 3: 150–156, 1986.Google Scholar
  35. 35.
    Heilman RL, Velosa JA, Holley KE, Offord KP, Kyle RA: Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease. Am J Kidney Dis 20: 34–41, 1992.PubMedGoogle Scholar
  36. 36.
    Mallick NP, Dosa S, Acheson EJ: Detection significance and treatment of paraprotein in patients presenting with “idiopathic” proteinuria without myeloma. Q J Med 47: 145–175, 1978.PubMedGoogle Scholar
  37. 37.
    Bradley JR, Thiru S, Evans BD: Light-chains and the kidney. J Clin Pathol 40: 53–60, 1987.PubMedCrossRefGoogle Scholar
  38. 38.
    Randall RE, Williamson WC Jr, Mullinax F, Tung MJ, Still WJS: Manifestations of systemic light chain deposition. Am J Med 60: 293–299, 1976.PubMedCrossRefGoogle Scholar
  39. 39.
    Silver MM, Hearm SA, Ritchie S, Slinger RP, Sholdice JA, Cordy PS, Hodsman AB: Renal and systemic kappa light chain deposits and their plasma cell origin identified by immunoelectron microscopy. Am J Pathol 122: 17–27, 1986.PubMedGoogle Scholar
  40. 40.
    Tubbs RR, Gephardt GN, McMahon JT, Hall PM, Valenzuela R, Vidt DG: Light chain nephropathy. Am J Med 71: 263–269, 1981.PubMedCrossRefGoogle Scholar
  41. 41.
    Cogne M, Preud’homme JL, Bauwens M, Touchard G, Ancontuzier P: Structure of a monoclonal kappa chain of the VK-IV subgroup chain deposition disease. J Clin Invest 87: 2188–2190, 1991.CrossRefGoogle Scholar
  42. 42.
    McLaughlin H, Hobbs JR: Clinical significance of Bence Jones proteinuria. Protides of biologic fluids. In: H Petters, ed, Proceedings of the 20th Colloquium. Oxford, Pergamon Press, pp 251–254, 1973.Google Scholar
  43. 43.
    Kyle RA, Maldonado JE, Bayrd ED: Idiopathic Bence Jones proteinuria. A distinct entity. Am J Med 55: 222–226, 1973.PubMedCrossRefGoogle Scholar
  44. 44.
    Coward RA, Mallick NP, Delamore IW: Tubular function in multiple myeloma. Clin Nephrol 24: 180–185, 1985.PubMedGoogle Scholar
  45. 45.
    Pasquali S, Zucchelli P, Casanova S, Cagnoli L, Confalonieri R, Pozzi C, Banfi G, Lupo A, Bertani T: Renal histological lesions and clinical syndromes in multiple myeloma. Clin Nephrol 2: 222–228, 1987.Google Scholar
  46. 46.
    Pirani CL: Histological, histochemical and ultrastructural features of myeloma kidney. In: L Minetti, G D’Amico, C Ponticelli, eds, The Kidney in Plasma Cell Dyscrasias. Kluwer, Dordrecht, pp 154–169, 1988.Google Scholar
  47. 47.
    Cohen AH, Border WA: Myeloma kidney. An im-munomorphogenetic study of renal biopsies. Lab Invest 42: 248–256, 1980.PubMedGoogle Scholar
  48. 48.
    Clyne DH, Pesce AJ, Thompson RE: Nephrotoxicity of Bence Jones proteins: the importance of isoelectric point. Kidney Int 16: 345–352, 1979.PubMedCrossRefGoogle Scholar
  49. 49.
    Baylis C, Falconer-Smith J, Ross B: Glomerular and tubular handling of differently charged human immunoglobulin light chains by the rat kidney. Clin Science 74: 639–644, 1988.Google Scholar
  50. 50.
    Coward RA, Delamore IW, Mallick NP, Robinson EL: The importance of urinary immunoglobulin light chain isoelectric point in nephrotoxicity in multiple myeloma. Clin Science 66: 229–232, 1984.Google Scholar
  51. 51.
    Rota S, Mougenot B, Boudouin B, De Meyer Brasseur M, Lemaitre V, Michel C, Mignon F, Rondeau E, Vanhille P, Verroust P, Ronco P: Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients. Medicine 66: 126–137, 1987.PubMedCrossRefGoogle Scholar
  52. 52.
    Melcion C, Mougenot B, Baudouin B, Ronco P, Moulonguet- Doleris L, Vanhille P, Beaufils M, Morel-Maroger L, Verrout P, Richet G: Renal failure in myeloma: relationship with isoelectric point of immunoglobulin light chains. Clin Nephrol 22: 138–143, 1984.PubMedGoogle Scholar
  53. 53.
    Pasquali S, Casanova S, Zucchelli A, Zucchelli P: Long-term survival patients with acute and severe renal failure due to multiple myeloma. Clin Nephrol 34: 247–254, 1990.PubMedGoogle Scholar
  54. 54.
    Johns EA, Turner R, Cooper EH, Mac Lennan ICM: Isoelectric points of urinary light chain in myelomatosis: analysis in relation to nephrotoxicity. J Clin Pathol 36: 833–837, 1986.CrossRefGoogle Scholar
  55. 55.
    Solomon A, Weiss DT: A prospective of plasma cell dyscrasias: clinical implication of monoclonal light chain in renal disease. In: L Minetti, G D’Amico, C Ponticelli, eds, The Kidney in Plasma Cell Dyscrasias. Kluwer, Dordrecht, pp 3–18, 1988.CrossRefGoogle Scholar
  56. 56.
    Martinez-Maldonado M, Jium J, Suki WN, Eknoyan G: Renal complication in multiple myeloma. Pathophysiology and some aspects of clinical management. J Chron Dis 24:221— 227, 1971.Google Scholar
  57. 57.
    De Fronzo RA, Coke CR, Wright JR, Humphrey RL: Renal function in patients with multiple myeloma. Medicine 57: 151–166, 1978.Google Scholar
  58. 58.
    Rees ED, Waugh WH: Factors in renal failure of multiple myeloma. Arch Intern Med 116: 400–405, 1966.CrossRefGoogle Scholar
  59. 59.
    De Fronzo RA, Humphrey RL, Wright JR, Cooke CR: Acute renal failure in multiple myeloma. Medicine 54: 209–223, 1975.CrossRefGoogle Scholar
  60. 60.
    Mundy GR, Raisz LG: Big and little forms of osteoclast activating factor. J Clin Invest 60: 122–128, 1977.PubMedCrossRefGoogle Scholar
  61. 61.
    Ganeval D, Cathomen M, Noel LH, Grunfeld JP: Kidney involvement in multiple myeloma and related disorders. Contrib Nephrol 33: 210–222, 1982.PubMedGoogle Scholar
  62. 62.
    Kapadia SB: Multiple myeloma: a clinicopathologic study of 62 consecutively autopsied cases. Medicine 59: 380–392, 1980.PubMedCrossRefGoogle Scholar
  63. 63.
    Bryan CW, Healy JK: Acute renal failure in multiple myeloma. Am J Med 44: 128–135, 1968.PubMedCrossRefGoogle Scholar
  64. 64.
    Bartels ED, Brun GC, Gammeltoft A, Gjorub PA: Acute anuria following intravenous pyelography in patients with myelomatosis. Acta Med Scand 150: 297–302, 1954.PubMedCrossRefGoogle Scholar
  65. 65.
    Leucutta T: Multiple myeloma and intravenous pyelography (editorial). Am J Roent Radiat Ther Nucl Med 85: 187–189, 1961.Google Scholar
  66. 66.
    Lasser EC, Lang JH, Zawalski ZA: Contrast media: myeloma protein precipitates in urography. JAMA 198: 945–947, 1966.PubMedCrossRefGoogle Scholar
  67. 67.
    Morgan C, Hammack WJ: Intravenous urography in multiple myeloma. N Engl J Med 275: 77–79, 1966.PubMedCrossRefGoogle Scholar
  68. 68.
    Vix VA: Intravenous pyelography in multiple myeloma: a review of 52 studies in 40 patients. Radiology 87: 896–902, 1966.PubMedGoogle Scholar
  69. 69.
    Osgood EE: The survival time of patients with plasmocytic myeloma. Cancer Chemother Rep 9: 1–10, 1960.PubMedGoogle Scholar
  70. 70.
    Alexanian R, Bonnet J, Gehan E: Combination chemo-theraphy for multiple myeloma. Cancer 30: 382–389, 1972.PubMedCrossRefGoogle Scholar
  71. 71.
    Rivers SL: Cyclophosphamide versus melphalan in the treatment of plasma cell myeloma. JAMA 207: 1328–1330, 1969.PubMedCrossRefGoogle Scholar
  72. 72.
    Medical Research Council: Medical Research Council’s working party for therapeutic trials in leukemia myelomatosis: comparison of melphalan and cyclophosphamide therapy. Br Med J 1: 640–642, 1971.CrossRefGoogle Scholar
  73. 73.
    Chronich Leukemia-Myeloma Task Force: Proposed guidelines for protocol studies. II. Plasma cell myeloma. Cancer Chemother Rep 4: 145–158, 1973.Google Scholar
  74. 74.
    Salmon SE, Haut A, Bonnett JD: Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group study. J Clin Oncol 1: 453–461, 1983.PubMedGoogle Scholar
  75. 75.
    Powis G: Effect of human renal and hepatic disease on the pharmacokinetics of anticancer drugs. Cancer Treat Rev 9: 85–124, 1982.PubMedCrossRefGoogle Scholar
  76. 76.
    Cornwell GG III, Pajak JF, Mclntyre OR, Kochwa S, Dosik H: Influence of renal failure on myelosuppressive effects of melphalan: Cancer and leukemia Group B experience. Cancer Treat Rep 66:475-181, 1982.Google Scholar
  77. 77.
    Zucchelli P, Pasquali S, Cagnoli L, Ferrari G: Controlled plasma exchange trial in acute renal failure due to multiple myeloma. Kidney Int 33: 1175–1180, 1988.PubMedCrossRefGoogle Scholar
  78. 78.
    Reich SD: Clinical correlation of adriamycin pharmacology Pharmacol Ther Part C 2: 239–249, 1978.Google Scholar
  79. 79.
    Mac Lennan ICM, Chapman C, Dunn J, Kelly K: Combined chemotheraphy with AB CM versus melphalan for treatment of myelomatosis. Lancet 339: 200–205, 1992.CrossRefGoogle Scholar
  80. 80.
    Samson D, Newland A, Kearney J, Jayner M, Mitchell T, Barrett AJ, Gaminara E, Van De Pette J, McCarthy D, Aston L, Hamon M, Evans M: Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma. Lancet 2: 882–885, 1989.PubMedCrossRefGoogle Scholar
  81. 81.
    Bergsagel DE: Melphalan/prednisone versus drug combinations for plasma cell myeloma. Eur J Haematol 43:117–123Google Scholar
  82. 82.
    Gregory WM, Richards MA, Malpas JS: Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myelona: an overview of published trials./Clin Oncol 10: 334–342, 1992.Google Scholar
  83. 83.
    Niesvizky R, Siegel D, Michaeli J: Biology and treatment of multiple myeloma. Blood Rev 7: 24–33, 1993.PubMedCrossRefGoogle Scholar
  84. 84.
    Clyne DH, Pesce AJ, Thompson RE: Nephrotoxicity of Bence Jones proteins in the rat: importance of protein isoelectric point. Kidney Int 16: 345–352, 1979.PubMedCrossRefGoogle Scholar
  85. 85.
    MRC Working Party on Leukaemia in Adults: Analysis and management of renal failure in fourth MRC myelomatosis trial. Br Med J 288: 1411–1416, 1984.CrossRefGoogle Scholar
  86. 86.
    Minetti L: Kidney involvement in plasma cell dyscrasias. In: S Cameron, AM Davison, JP Grünfeld, D Kerr, E Ritz, eds, Oxford Textbook of Clinical Nephrology. Oxford University Press, Oxford, pp 562–576, 1992.Google Scholar
  87. 87.
    Raisz LG: New diphosphonates to block bone resorption. N Engl J Med 302: 347–348, 1980.PubMedCrossRefGoogle Scholar
  88. 88.
    Alexanian R, Barlogie B, Dixon D: Renal failure in multiple myeloma pathogenesis and prognostic implications. Arch Intern Med 150: 1683–1695, 1990.CrossRefGoogle Scholar
  89. 89.
    Rosansky SJ, Richards FW: Use of peritoneal dialysis in the treatment of patients with renal failure and paraproteinemia. Am J Nephrol 5: 361–365, 1985.PubMedCrossRefGoogle Scholar
  90. 90.
    Perri RT, Hebbel RP, Oken MM: Influence of treatment and response status on infection risk in multiple myeloma. Am J Med 71: 935–940, 1981.PubMedCrossRefGoogle Scholar
  91. 91.
    Iggo N, Palmer ABD, Severn A: Chronic dialysis in patients with multiple myeloma and renal failure. A worthwhile treatment. Q J Med 73: 903–910, 1989.PubMedGoogle Scholar
  92. 92.
    Rayner HC, Haynes AP, Thompson JR: Perspectives in multiple myeloma: survival, prognostic factors and disease complications in a single centre between 1975 and 1988. Q J Med 79: 517–525, 1991.PubMedGoogle Scholar
  93. 93.
    Tapson JS, Mansy H, Wickinson R: End stage renal failure due to multiple myeloma. Poor survival on peritoneal dialysis. Int J Artif Organs 11: 38–42, 1988.Google Scholar
  94. 94.
    Korzets A, Tam F, Russell G, Feehally J, Walls J: The role of continuous ambulatory peritoneal dialysis in end-stage renal failure due to multiple myeloma. Am J Kidney Dis 16:216–223Google Scholar
  95. 95.
    Walker F, Bear RA: Renal transplantation in light chain myeloma. Am J Nephrol 3: 34–37, 1983.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Pietro Zucchelli
    • 1
  • Sonia Pasquali
    • 1
  1. 1.Malpighi Department of NephrologyPoliclinico S. Orsola-MalpighiBolognaItaly

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