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12 - Plasma cell neoplasms

from Part 2 - Hematological malignancies

Published online by Cambridge University Press:  06 December 2010

Wendy N. Erber
Affiliation:
University of Western Australia, Perth
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Summary

Introduction

Plasma cell neoplasms result from the clonal expansion of terminally differentiated B-cells that have the capacity to secrete a monoclonal immunoglobulin (Ig). This chapter will discuss the appropriate use of diagnostic techniques in the diagnosis and assessment of multiple myeloma, monoclonal gammopathy of undetermined significance, smoldering myeloma, plasma cell leukemia and Waldenström macroglobulinemia.

Multiple myeloma

Multiple myeloma (MM) is a plasma cell malignancy characterized by the proliferation of plasma cells (PC), mostly within the bone marrow (BM). The disease peaks in incidence in the seventh decade of life. While still considered an incurable diagnosis for most patients, patients are surviving longer due to the availability of new treatments. In a subset of patients, mostly those treated with more aggressive interventions such as combinations of novel agents and autologous stem cell transplant (SCT), the disease may be curable. MM is part of a spectrum of disorders characterized by this proliferation of clonal PC which includes monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). In MGUS, patients have a minimal plasmacytosis and the monoclonal PCs cause no harm to the individual; it is usually detected incidentally. Patients with MGUS can go on for years, often decades, without ever having further expansion of the monoclonal PCs. Patients with SMM have a more advanced plasmacytosis, yet have no discernible evidence of end organ damage due to this expansion.

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Publisher: Cambridge University Press
Print publication year: 2010

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References

Harousseau, JL, Shaughnessy, J, Richardson, P. Multiple myeloma. Hematology 2004:1:237–56.CrossRefGoogle Scholar
Rajkumar, SV, Kyle, RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc 2005;80(10):1371–82.CrossRefGoogle ScholarPubMed
Kastritis, E, Zervas, K, Symeonidis, Aet al. Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia 2009;23(6):1152–7.CrossRefGoogle Scholar
Kumar, SK, Rajkumar, SV, Dispenzieri, Aet al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111(5):2516–20.CrossRefGoogle ScholarPubMed
Barlogie, B, Tricot, G, Anaissie, Eet al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. New Engl J Med 2006;354(10):1021–30.CrossRefGoogle ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SVet al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. New Engl J Med 2002;346(8):564–9.CrossRefGoogle ScholarPubMed
Kyle, RA, Remstein, ED, Therneau, TMet al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. New Engl J Med 2007;356(25):2582–90.CrossRefGoogle ScholarPubMed
Kyle, RA, Rajkumar, SV. Multiple myeloma. New Engl J Med 2004;351(18):1860–73.CrossRefGoogle ScholarPubMed
San Miguel, JF, Lahuerta, JJ, Garcia-Sanz, Ret al. Are myeloma patients with renal failure candidates for autologous stem cell transplantation?Hematol J 2000;1(1):28–36.CrossRefGoogle ScholarPubMed
Durie, BG, Harousseau, JL, Miguel, JSet al. International uniform response criteria for multiple myeloma. Leukemia 2006;20(9):1467–73.CrossRefGoogle ScholarPubMed
Greipp, PR, Bennett, JM, Gaillard, JPet al. Poor survival in plasmablastic myeloma in Eastern Cooperative Oncology Group study E9487: cell kinetic, ploidy, biological marker, and clinical correlations (Meeting abstract). Proc Annu Meet Am Soc Clin Oncol 1995;14.Google Scholar
San Miguel, JF, Almeida, J, Mateo, Get al. Immunophenotypic evaluation of the plasma cell compartment in multiple myeloma: a tool for comparing the efficacy of different treatment strategies and predicting outcome. Blood 2002;99(5):1853–6.CrossRefGoogle ScholarPubMed
Paiva, B, Vidriales, MB, Perez, JJet al. Multiparameter flow cytometry quantification of bone marrow plasma cells at diagnosis provides more prognostic information than morphological assessment in myeloma patients. Haematologica 2009;94(11):1599–602.CrossRefGoogle ScholarPubMed
Paiva, B, Vidriales, MB, Mateo, Get al. The persistence of immunophenotypically normal residual bone marrow plasma cells at diagnosis identifies a good prognostic subgroup of symptomatic multiple myeloma patients. Blood 2009;114(20):4369–72.CrossRefGoogle ScholarPubMed
Diez-Campelo, M, Perez-Simon, JA, Perez, Jet al. Minimal residual disease monitoring after allogeneic transplantation may help to individualize post-transplant therapeutic strategies in acute myeloid malignancies. Am J Hematol 2009;84(3):149–52.CrossRefGoogle ScholarPubMed
Shaughnessy, JD, Zhan, F, Burington, BEet al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood 2007;109(6):2276–84.CrossRefGoogle ScholarPubMed
Dewald, GW, Kyle, RA, Hicks, GA, Greipp, PR. The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis. Blood 1985;66(2):380–90.Google ScholarPubMed
Tricot, G, Barlogie, B, Jagannath, Set al. Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities. Blood 1995;86(11):4250–6.Google Scholar
Smadja, NV, Bastard, C, Brigaudeau, C, Leroux, D, Fruchart, C. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 2001;98(7):2229–38.CrossRefGoogle ScholarPubMed
Sawyer, JR, Waldron, JA, Jagannath, S, Barlogie, B. Cytogenetic findings in 200 patients with multiple myeloma. Cancer Genet Cytogenet 1995;82(1):41–9.CrossRefGoogle ScholarPubMed
Rajkumar, SV, Fonseca, R, Dewald, GWet al. Cytogenetic abnormalities correlate with the plasma cell labeling index and extent of bone marrow involvement in myeloma. Cancer Genet Cytogenet 1999;113(1):73–7.CrossRefGoogle Scholar
Chesi, M, Nardini, E, Brents, et al. Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nature Genetics 1997;16(3):260–4.CrossRefGoogle Scholar
Ahmann, GJ, Jalal, SM, Juneau, ALet al. A novel three-color, clone-specific fluorescence in situ hybridization procedure for monoclonal gammopathies. Cancer Genet Cytogenet 1998;101(1):7–11.CrossRefGoogle ScholarPubMed
Avet-Loiseau, H, Andree-Ashley, , Moore, D 2nd et al. Molecular cytogenetic abnormalities in multiple myeloma and plasma cell leukemia measured using comparative genomic hybridization. Genes Chromosomes Cancer 1997;19(2):124–33.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Fonseca, R, Bergsagel, PL, Drach, Jet al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009;23(12):2210–21.CrossRefGoogle Scholar
Garand, R, Avet-Loiseau, H, Accard, Fet al. t(11;14) and t(4;14) translocations correlated with mature lymphoplasmacytoid and immature morphology, respectively, in multiple myeloma. Leukemia 2003;17:2032–5.CrossRefGoogle Scholar
Avet-Loiseau, H, Garand, R, Lode, L, Harousseau, J-L, Bataille, R. Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants. Blood 2003;101(4):1570–1.CrossRefGoogle Scholar
Schop, RF, Kuehl, WM, Wier, SAet al. Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood 2002;100(8):2996–3001.CrossRefGoogle ScholarPubMed
Fonseca, R, Blood, E, Rue, Met al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003;101(11):4569–75.CrossRefGoogle Scholar
Keats, JJ, Fonseca, R, Chesi, Met al. Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell 2007;12(2):131–44.CrossRefGoogle ScholarPubMed
Annunziata, CM, Davis, RE, Demchenko, Yet al. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell 2007;12(2):115–30.CrossRefGoogle ScholarPubMed
Carrasco, DR, Tonon, G, Huang, Yet al. High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell 2006;9(4):313–25.CrossRefGoogle ScholarPubMed
Zhan, F, Huang, Y, Colla, Set al. The molecular classification of multiple myeloma. Blood 2006;108(6):2020–8.CrossRefGoogle ScholarPubMed
Katzmann, JA, Clark, R, Sanders, E, Landers, JP, Kyle, RA. Prospective study of serum protein capillary zone electrophoresis and immunotyping of monoclonal proteins by immunosubtraction. Am J Clin Pathol 1998;110(4):503–9.CrossRefGoogle ScholarPubMed
Katzmann, JA, Clark, R, Wiegert, Eet al. Identification of monoclonal proteins in serum: a quantitative comparison of acetate, agarose gel, and capillary electrophoresis. Electrophoresis 1997;18(10):1775–80.CrossRefGoogle ScholarPubMed
Bradwell, AR, Carr-Smith, HD, Mead, GP, Harvey, TC, Drayson, MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003;361(9356):489–91.CrossRefGoogle ScholarPubMed
Abraham, RS, Clark, RJ, Bryant, SCet al. Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma. Clin Chem 2002;48(4):655–7.Google ScholarPubMed
Durie, BG, Salmon, SE. 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(3):842–54.3.0.CO;2-U>CrossRefGoogle Scholar
Greipp, PR, San Miguel, J, Durie, BGet al. International staging system for multiple myeloma. J Clin Oncol 2005;23(15):3412–20.CrossRefGoogle ScholarPubMed
Stewart, AK, Bergsagel, PL, Greipp, PRet al. A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy. Leukemia 2007;21(3):529–34.CrossRefGoogle ScholarPubMed
San Miguel, JF, Schlag, R, Khuageva, NKet al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. New Engl J Med 2008;359(9):906–17.CrossRefGoogle ScholarPubMed
Jagannath, S, Richardson, PG, Sonneveld, Pet al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia 2007;21(1):151–7.CrossRefGoogle ScholarPubMed
Chng, WJ, Braggio, E, Mulligan, Get al. The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood 2008;111(3):1603–9.CrossRefGoogle ScholarPubMed
Durie, BG. Is magnitude of initial response predictive for survival in multiple myeloma?Ann Oncol 1991;2(3):166.CrossRefGoogle ScholarPubMed
Blade, J, Samson, D, Reece, Det al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998;102(5):1115–23.CrossRefGoogle Scholar
Greipp, PR, Kyle, RA. Clinical, morphological, and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma. Blood 1983;62(1):166–71.Google ScholarPubMed
Avet-Loiseau, H, Facon, T, Daviet, Aet 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(18):4546–50.Google ScholarPubMed
Fonseca, R, Bailey, RJ, Ahmann, GJet al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood 2002;100(4):1417–24.Google ScholarPubMed
Kyle, RA, Therneau, TM, Rajkumar, SVet al. Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: the original Mayo Clinic series 25 years later.[see comment]. Mayo Clinic Proceedings 2004;79(7):859–66.CrossRefGoogle Scholar
Perez-Persona, E, Mateo, G, Garcia-Sanz, Ret al. Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells. Br J Haematol 2009;148(1):110–4.CrossRefGoogle ScholarPubMed
Noel, P, Kyle, RA. Plasma cell leukemia: an evaluation of response to therapy. Am J Med 1987;83(6):1062–8.CrossRefGoogle ScholarPubMed
Tiedemann, RE, Gonzalez-Paz, N, Kyle, RAet al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 2008;22(5):1044–52.CrossRefGoogle ScholarPubMed
Avet-Loiseau, H, Daviet, A, Brigaudeau, Cet al. Cytogenetic, interphase, and multicolor fluorescence in situ hybridization analyses in primary plasma cell leukemia: a study of 40 patients at diagnosis, on behalf of the Intergroupe Francophone du Myelome and the Groupe Francais de Cytogenetique Hematologique. Blood 2001;97(3):822–5.CrossRefGoogle Scholar
Garcia-Sanz, R, Orfao, A, Gonzalez, Met al. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. Blood 1999;93(3):1032–7.Google ScholarPubMed
Fonseca, R, Hayman, S. Waldenström macroglobulinaemia. Br J Haematol 2007;138(6):700–20.CrossRefGoogle ScholarPubMed
Owen, RG, Johnson, SA, Morgan, GJ. Waldenström's macroglobulinemia: laboratory diagnosis and treatment. Hematol Oncol 2000;18(2):41–9.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Treon, SP, Dimopoulos, M, Kyle, RA. Defining Waldenström's macroglobulinemia. Semin Oncol 2003;30(2):107–9.CrossRefGoogle ScholarPubMed
Schop, RF, Jalal, SM, Wier, SAet al. Deletions of 17p13.1 and 13q14 are uncommon in Waldenström macroglobulinemia clonal cells and mostly seen at the time of disease progression. Cancer Genet Cytogenet 2002;132(1):55–60.CrossRefGoogle Scholar
Schop, RF, Wier, SA, Xu, Ret al. 6q deletion discriminates Waldenström macroglobulinemia from IgM monoclonal gammopathy of undetermined significance. Cancer Genet Cytogenet 2006;169(2):150–3.CrossRefGoogle ScholarPubMed
Braggio, E, Keats, JJ, Leleu, Xet al. Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenström's macroglobulinemia. Cancer Res 2009;69(8):3579–88.CrossRefGoogle ScholarPubMed
Ocio, EM, Schop, RF, Gonzalez, Bet al. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis. Br J Haematol 2007;136(1):80–6.CrossRefGoogle ScholarPubMed

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