Skip to main content Accessibility help
×
Hostname: page-component-7c8c6479df-r7xzm Total loading time: 0 Render date: 2024-03-29T10:07:21.381Z Has data issue: false hasContentIssue false

13 - MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE AND SMOLDERING MULTIPLE MYELOMA

Published online by Cambridge University Press:  11 July 2009

S. Vincent Rajkumar
Affiliation:
Mayo Clinic, Minnesota
Robert A. Kyle
Affiliation:
Mayo Clinic, Minnesota
Get access

Summary

INTRODUCTION

In 1952, Jan Waldenström introduced the term “essential hyperglobulinemia” to describe patients with a small spike in the electrophoretic pattern but no evidence of multiple myeloma (MM), Waldenström macroglobulinemia (WM), amyloidosis (AL), or related disorders. Benign, idiopathic, asymptomatic, nonmyelomatous, cryptogenic, lanthanic, and rudimentary monoclonalgammopathy; dysimmunoglobulinemia; idiopathic paraproteinemia; and asymptomatic paraimmunoglobulinemia have been used to describe the entity. According to Waldenström, the protein spike remained constant in size in contrast to the increasing protein spike of the protein in MM. The entity became known as “benign monoclonal gammopathy,” but this is misleading because a monoclonal (M) protein may remain stable or it may increase and develop into symptomatic MM, WM, AL, or a related disorder. Because of this, the term “monoclonal gammopathy of undetermined significance” is a more appropriate term.

Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the proliferation of a single clone of plasma cells that produces a homogeneous monoclonal (M) protein. Each M protein consists of two heavy polypeptide chains of the same class and subclass and two light chain polypeptide chains of the same type. In contrast, polyclonal immunoglobulins are produced by many clones of plasma cells. They contain all heavy chain classes and both light chain types. Each M protein consists of two heavy polypeptide chains of the same class: gamma (γ) constitutes immunoglobulin G (IgG), alpha (α) is found in IgA, mu (μ) is present in IgM, delta (δ) occurs in IgD, and epsilon (ε) is present in IgE.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

WaldenströM, J.Studies on conditions associated with disturbed gamma globulin formation (gammopathies). Harvey Lectures 1960–1961;56:211–31.Google Scholar
Kyle, RA.Monoclonal gammopathy of undetermined significance. Natural history in 241 cases. Am J Med 1978;64(5):814–26.CrossRefGoogle ScholarPubMed
,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(5):749–57.CrossRef
Katzmann, JA, Kyle, RA. Immunochemical characterization of immunoglobulins in serum, urine, and cerebrospinal fluid. In: Detrick, B., Hamilton, R., Folds, J., eds. Manual of molecular and clinical laboratory immunology. 7th ed. Washington DC, ASM Press 2006:88–100.
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. Clinical Chemistry 2002;48(9):1437–44.Google ScholarPubMed
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(3):812–17.CrossRefGoogle ScholarPubMed
Dingli, D, Kyle, RA, Rajkumar, SV, et al. Immunoglobulin free light chains and solitary plasmacytoma of bone. Blood 2006;108(6):1979–83.CrossRefGoogle ScholarPubMed
Dispenzieri, A, Kyle, RA, Katzmann, JA, 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.CrossRefGoogle ScholarPubMed
Katzmann, JA, Dispenzieri, A, Kyle, RA, et al. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc 2006;81(12):1575–8.CrossRefGoogle ScholarPubMed
Axelsson, U, Bachmann, R, Hallen, J.Frequency of pathological proteins (m-components) om 6,995 sera from an adult population. Acta Medica Scandinavica 1966;179(2):235–47.CrossRefGoogle ScholarPubMed
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(5):719–24.Google Scholar
Saleun, JP, Vicariot, M, Deroff, P, Morin, JF.Monoclonal gammopathies in the adult population of finistere, France. J Clin Pathol 1982;35(1):63–8.CrossRefGoogle ScholarPubMed
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(3):904–6.CrossRefGoogle ScholarPubMed
Landgren, O, Katzmann, JA, Hsing, AW, et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc 2007;82(12):1468–73.CrossRefGoogle ScholarPubMed
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(12):1474–9.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Melton Iii, LJ, et al. Monoclonal gammopathy of undetermined significance: estimated incidence and duration prior to recognition. Blood 2007;10(11):79a (Abstract #246).Google Scholar
Kyle, RA, Therneau, TM, Rajkumar, SV, Larson, DR, Plevak, MF, Melton Lj, III.Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: The original Mayo Clinic series 25 years later [see comment]. Mayo Clin Proc 2004;79(7):859–66.CrossRefGoogle Scholar
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance [see comment]. N Engl J Med 2002;346(8):564–9.CrossRefGoogle Scholar
Surveillance, Epidemiology, and End Results (SEER) Program public-use data CD ROM (1973–1998). Bethesda, MD, National Cancer Institute, Cancer Statistics Branch, 2001.
Kyle, RA, Gertz, MA, Witzig, TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma [see comment]. Mayo Clin Proc 2003;78(1):21–33.CrossRefGoogle Scholar
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(3): 391–4.CrossRefGoogle ScholarPubMed
Poel, MH, Coebergh, JW, Hillen, HF.Malignant transformation of monoclonal gammopathy of undetermined significance among out-patients of a community hospital in southeastern Netherlands. Br J Haematol 1995;91(1):121–5.CrossRefGoogle ScholarPubMed
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(3):912–18.Google ScholarPubMed
Pasqualetti, P, Festuccia, V, Collacciani, A, Casale, R.The natural history of monoclonal gammopathy of undetermined significance. A 5- to 20-year follow-up of 263 cases. Acta Haematol 1997;97(3):174–9.CrossRefGoogle ScholarPubMed
Gregersen, H, Ibsen, J, Mellemkjoer, L, Dahlerup, J, Olsen, J, Sorensen, H.Mortality and causes of death in patients with monoclonal gammopathy of undetermined significance. Br J Haematol 2001;112(2):353–7.CrossRefGoogle ScholarPubMed
Gregersen, H, Mellemkjaer, L, Salling Ibsen, J, et al. Cancer risk in patients with monoclonal gammopathy of undetermined significance. Am J Hematol 2000;63(1):1–6.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
Ogmundsdottir, HM, Haraldsdottir, V, G, MJ, et al. Monoclonal gammopathy in Iceland: a population-based registry and follow-up. Br J Haematol 2002;118(1):166–73.CrossRefGoogle ScholarPubMed
Kyle, RA, Rajkumar, SV.Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: emphasis on risk factors for progression. Br J Haematol 2007;139(5):730–43.CrossRefGoogle ScholarPubMed
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(24):5640–5.Google Scholar
Fonseca, R, Bailey, RJ, Ahmann, GJ, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood 2002;100(4):1417–24.Google ScholarPubMed
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(6):2156–61.CrossRefGoogle ScholarPubMed
Avet-Loiseau, H, Li, JY, Morineau, N, et al. Monosomy 13 is associated with the transition of monoclonal gammopathy of undetermined significance to multiple myeloma. Intergroupe francophone du myelome. Blood 1999;94(8):2583–9.Google ScholarPubMed
Rasmussen, T, Kuehl, M, Lodahl, M, Johnsen, HE, Dahl I, MS.Possible roles for activating ras mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumors. Blood 2005;105(1)317–23.CrossRefGoogle Scholar
Vacca, A, Ribatti, D, Roncali, L, et al. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 1994;87(3):503–8.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Mesa, RA, Fonseca, R.Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 2002;8(7):2210–16.Google ScholarPubMed
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(9):3064–73.Google ScholarPubMed
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(4):1159–65.CrossRefGoogle ScholarPubMed
Melton, LJ III, Rajkumar, SV, Khosla, S, et al. Fracture risk in monoclonal gammopathy of undetermined significance. J Bone Miner Res 2004;19(1):25–30.CrossRefGoogle ScholarPubMed
Roodman, GD, Biology of myeloma bone disease. In: VC Broudy, JL.Abkowitz, JM Vose, eds. Hematology 2002: American society of hematology education program book. Washington, DC: 2002; 227–32.Google Scholar
Croucher, PI, Shipman, CM, Lippitt, J, et al. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 2001;98(13):3534–40.CrossRefGoogle ScholarPubMed
Lust, JA, Donovan Ka, . Biology of the transition of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma. Cancer Control 1998;5(3):209–17.CrossRefGoogle Scholar
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(6):1371–4.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Kyle, RA, Plevak, MF, Murray, JA, Therneau, TM.Helicobacter pyloriinfection and monoclonal gammopathy of undetermined significance. Br J Haematol 2002;119(3):706–8.CrossRefGoogle ScholarPubMed
Kyle, RA.“Benign” monoclonal gammopathy-after 20 to 35 years of follow-up. Mayo Clin Proc 1993;68(1):26–36.CrossRefGoogle ScholarPubMed
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(4):428–34.CrossRefGoogle ScholarPubMed
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(6):1625–34.CrossRefGoogle ScholarPubMed
Kyle, RA, Greipp, PR.Smoldering multiple myeloma. N Engl J Med 1980;302(24):1347–9.CrossRefGoogle ScholarPubMed
Bellaiche, L, Laredo, JD, Liote, F, et al. Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI study group. Spine 1997;22(21):2551–7.CrossRefGoogle ScholarPubMed
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(24):5668–74.CrossRefGoogle ScholarPubMed
Nowakowski, GS, Witzig, TE, Dingli, D, et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 2005;106(7):2276–9.CrossRefGoogle ScholarPubMed
Kyle, RA, Robinson, RA, Katzmann, JA.The clinical aspects of biclonal gammopathies. Review of 57 cases. Am J Med 1981;71(6):999–1008.CrossRefGoogle ScholarPubMed
Grosbois, B, Jego, P, Rosa, H, et al. [Triclonal gammopathy and malignant immunoproliferative syndrome]. [review] [25 refs] [in French]. Revue de Medecine Interne 1997;18(6):470–3.CrossRefGoogle Scholar
Tirelli, A, Guastafierro, S, Cava, B, Lucivero, G.Triclonal gammopathy in an extranodal non-Hodgkin lymphoma patient. Am J Hematol 2003;73(4):273–5.CrossRefGoogle Scholar
Kyle, RA, Maldonado, JE, Bayrd, ED.Idiopathic Bence Jones proteinuria-a distinct entity? Am J Med 1973;55(2):222–6.CrossRefGoogle Scholar
Kyle, RA, Greipp, PR.“Idiopathic” Bence Jones proteinuria: long-term follow-up in seven patients. N Engl J Med 1982; 306(10):564–7.CrossRefGoogle ScholarPubMed
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(5):693–703.CrossRefGoogle ScholarPubMed
Kyle, RA, Garton, JP.The spectrum of IgM monoclonal gammopathy in 430 cases. Mayo Clin Proc 1987;62(8):719–31.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 2003;102(10):3759–64.CrossRefGoogle ScholarPubMed
Morra, E, Cesana, C, Klersy, C, et al. Prognostic factors for transformation in asymptomatic immunoglobulin M monoclonal gammopathies. Clin Lymphoma 2005;5(4):265–9.CrossRefGoogle ScholarPubMed
Cesana, C, Barbarano, L, Miqueleiz, S, et al. Clinical characteristics and outcome of immunoglobulin M-related disorders. Clin Lymphoma 2005;5(4):261–4.CrossRefGoogle ScholarPubMed
Baldini, L, Goldaniga, M, Guffanti, A, et al. Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system. J Clin Oncol 2005;23(21):4662–8.CrossRefGoogle ScholarPubMed
Ayto, RM, Lambert, C, Lampert, I, Salooja, N.Monoclonal gammopathy of undetermined significance with an IgE paraprotein. Blood 2007;110(11):259b (Abstract #4744).Google Scholar
Kyle, RA, Rajkumar, SV. Monoclonal gammopathies of undetermined significance. In:Malpas, J. and Al, E., eds. Myeloma: biology and management. 3rd ed. Philadelphia, PS: Saunders, 2004:315–52.Google Scholar
Kyle, RA, Rajkumar, SV.Monoclonal gammopathy of undetermined significance. Br J Haematol 2006;134(6):573–89.CrossRefGoogle ScholarPubMed
Azar, HA, Hill, WT, Osserman, EF.Malignant lymphoma and lymphatic leukemia. Am J Med 1957;23:239–49.CrossRefGoogle ScholarPubMed
Kyle, RA, Bayrd, ED, Mckenzie, BF, Heck, FJ.Diagnostic criteria for electrophoretic patterns of serum and urinary proteins in multiple myeloma: study of one hundred and sixty-five multiple myeloma patients with similar electrophoretic patterns. J Am Med Assoc 1960;174:245–51.CrossRefGoogle Scholar
Alexanian, R.Monoclonal gammopathy in lymphoma. Arch Intern Med 1975;135(1):62–6.CrossRefGoogle ScholarPubMed
Lin, P, Hao, S, Handy, BC, Bueso-Ramos, CE, Medeiros, LJ.Lymphoid neoplasms associated with IgM paraprotein: a study of 382 patients. Am J Clin Pathol 2005;123(2):200–5.CrossRefGoogle ScholarPubMed
Asatiani, E, Cohen, P, Ozdemirli, M, Kessler, CM, Mavromatis, B, Cheson, BD.Monoclonal gammopathy in extranodal marginal zone lymphoma (ENMZL) correlates with advanced disease and bone marrow involvement. Am J Hematol 2004;77(2): 144–6.CrossRefGoogle ScholarPubMed
Noel, P, Kyle, RA.Monoclonal proteins in chronic lymphocytic leukemia. Am J Clin Pathol 1987;87(3):385–8.CrossRefGoogle ScholarPubMed
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: Revue du Rhumatisme 2002;69(1):62–7.CrossRefGoogle ScholarPubMed
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(10):1490–4.CrossRefGoogle ScholarPubMed
Kelly Jj, Jr, Kyle, RA, O'brien, PC, Dyck, PJ.Prevalence of monoclonal protein in peripheral neuropathy. Neurology 1981; 31(11):1480–3.CrossRefGoogle ScholarPubMed
Quarles, RH, Weiss, MD.Autoantibodies associated with peripheral neuropathy. [review] [197 refs]. Muscle Nerve 1999;22(7):800–22.3.0.CO;2-F>CrossRefGoogle Scholar
Gosselin, S, Kyle, RA, Dyck, PJ.Neuropathy associated with monoclonal gammopathies of undetermined significance [see comment]. Ann Neurol 1991;30(1):54–61.CrossRefGoogle Scholar
Nobile-Orazio, E.Treatment of dys-immune neuropathies. J Neurol 2005;252(4):385–95.CrossRefGoogle ScholarPubMed
Dispenzieri, A, Kyle, RA, Lacy, MQ, et al. Poems syndrome: definitions and long-term outcome. Blood 2003;101(7):2496–506.CrossRefGoogle ScholarPubMed
Dispenzieri, A, Moreno-Aspitia, A, Suarez, GA, et al. Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature. Blood 2004;104(10):3400–7.CrossRefGoogle Scholar
Mundis, RJ, Kyle, RA.Primary hyperparathyroidism and monoclonal gammopathy of undetermined significance. Am J Clin Pathol 1982;77(5):619–21.CrossRefGoogle ScholarPubMed
Arnulf, B, Bengoufa, D, Sarfati, E, et al. Prevalence of monoclonal gammopathy in patients with primary hyperparathyroidism: a prospective study. Arch Intern Med 2002;162(4):464–7.CrossRefGoogle ScholarPubMed
Daoud, MS, Lust, JA, Kyle, RA, Pittelkow, MR.Monoclonal gammopathies and associated skin disorders. [review] [214 refs]. J Am Acad Dermatol 1999;40(4):507–35; quiz 536–8.CrossRefGoogle Scholar
Rostaing, L, Modesto, A, Abbal, M, Durand, D.Long-term follow-up of monoclonal gammopathy of undetermined significance in transplant patients. Am J Nephrol 1994;14(3):187–91.CrossRefGoogle ScholarPubMed
Droder, RM, Kyle, RA, Greipp, PR.Control of systemic capillary leak syndrome with aminophylline and terbutaline. Am J Med 1992;92(5):523–6.CrossRefGoogle ScholarPubMed
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(5):959–62.CrossRefGoogle ScholarPubMed
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(2):278–82.CrossRefGoogle ScholarPubMed
Karlson, EW, Tanasijevic, M, Hankinson, SE, et al. Monoclonal gammopathy of undetermined significance and exposure to breast implants. Arch Intern Med 2001;161(6):864–7.CrossRefGoogle ScholarPubMed
Merlini, G, Farhangi, M, Osserman, EF.Monoclonal immunoglobulins with antibody activity in myeloma, macroglobulinemia and related plasma cell dyscrasias. [review] [202 refs]. Semin Oncol 1986;13(3):350–65.Google Scholar
Alexanian, R, Barlogie, B, Dixon, D.Prognosis of asymptomatic multiple myeloma. Arch Intern Med 1988;148(9):1963–5.CrossRefGoogle ScholarPubMed
Dimopoulos, MA, Moulopoulos, A, Smith, T, Delasalle, KB, Alexanian, R.Risk of disease progression in asymptomatic multiple myeloma. Am J Med 1993;94(1):57–61.CrossRefGoogle ScholarPubMed
Facon, T, Menard, JF, Michaux, JL, et al. Prognostic factors in low tumour mass asymptomatic multiple myeloma: a report on 91 patients. The groupe d'etudes et de recherche sur le myelome (germ). Am J Hematol 1995;48(2):71–5.CrossRefGoogle Scholar
Rosinol, L, Blade, J, Esteve, J, et al. Smoldering multiple myeloma: natural history and recognition of an evolving type. Br J Haematol 2003;123(4):631–6.CrossRefGoogle ScholarPubMed
Weber, DM, Dimopoulos, MA, Moulopoulos, , Delasalle, KB, Smith, T, Alexanian, R.Prognostic features of asymptomatic multiple myeloma. Br J Haematol 1997;97(4):810–14.CrossRefGoogle ScholarPubMed
Kyle, RA, Remstein, ED, Therneau, TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007;356(25):2582–90.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×