Abstract
Multiple myeloma is the second most common hematologic malignancy, with approximately 15,000 new cases each year in the United States. Our understanding of the pathophysiology underlying myeloma continues to expand, but the etiology of this plasma-cell dyscrasia remains unclear. Although controversy remains regarding a possible viral etiology of myeloma, evidence suggesting a role for the human herpesvirus-8 (HHV-8) is mounting. The roles of cytogenetic abnormalities, as well as aberrant angiogenesis and cytokine expression in the etiology of myeloma continue to be explored, and may lead to future therapeutic strategies. Transplantation in myeloma is rarely curative, but offers clinical benefit for young and possibly older myeloma patients as well. Newer bisphosphonates may offer greater ease of administration, improved efficacy, and possibly even enhanced anti-tumor effect. Finally, thalidomide and other new agents offer new therapeutic alternatives to myeloma patients who were previously refractory to multiple agents.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Vescio RA and Berenson JR. Myeloma, macroglobulinemia and amyloidosis. In: Haskell, CM, ed. Cancer Treatment, 5th ed., WB Saunders Company, Philadelphia, PA, pp. 1503–1539.
Billadeau D, Ahmann G, Greipp P, et al. The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell. J Exp Med 1993; 178: 1023.
Corradini P, Boccadoro M, Voena C, et al. Evidence for a bone marrow B cell transcribing malignant plasma cell VDJ joined to C mu sequence in immunoglobulin (IgG)- and IgAsecreting multiple myelomas. J Exp Med 1993; 178: 1091.
Bakkus MH, Heirman C, Van Riet I, et al. Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation. Blood 1992; 80: 2326.
Vescio RA, Cao J, Hong CH, et al. Myeloma Ig heavy chain V region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity. J Immunol 1995; 155: 2487.
Pilarski LM, Jensen GS. Monoclonal circulating B cells in multiple myeloma: a continuously differentiating, possibly invasive, population as defined by expression of CD45 isoforms and adhesion molecules. Hematol Oncol Clin NAm 1992; 6: 297.
Tricot G. New insights into role of microenvironment in multiple myeloma. Lancet 2000; 355: 248.
Rettig MB, Vescio RA, Cao J, et al. VH gene usage is multiple myeloma: complete absence of the VH4.21 (VH4–34) gene. Blood 1996; 87: 2846.
Hsu FJ, Levy R. Preferential use of the VH4 Ig gene family by diffuse large-cell lymphoma. Blood 1995; 86: 3072.
Vescio RA, Hong CH, Cao J, et al. The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma. Blood 1994; 84: 3283.
Szczepek AJ, Bergsagel PL, Axelsson L, et al. CD34+ cells in the blood of patients with multiple myeloma express CD19 and IgH mRNA and have patient-specific IgH VDJ gene rearrangements. Blood 1997; 89: 1824.
Schiller G, Vescio R, Freytes C, et al. Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma. Blood 1995; 86: 390.
Vescio R, Schiller G, Stewart AK, et al. Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood 1999; 93: 1858.
Lemoli RM, Martinelli G, Zamagni E, et al. Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy. Blood 2000; 95: 2234.
Cao J, Vescio RA, Rettig MB, et al. A CD10-positive subset of malignant cells is identified in multiple myeloma using PCR with patient-specific immunoglobulin gene primers. Leukemia 1995; 9: 1948.
Ruiz-Arguelles GJ, Katzmann JA, Greipp PR, et al. Multiple myeloma: circulating lymphocytes that express plasma cell antigens. Blood 1984; 64: 352.
Harada H, Kawano MM, Huang N, et al. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood 1993; 81: 2658.
Rawstron AC, Davies FE, Owen RG, et al. B-lymphocyte suppression in multiple myeloma is a reversible phenomenon specific to normal B-cell progenitors and plasma cell precursors. Br J Haematol 1998; 100: 176.
Bergsagel PL, Smith AM, Szczepek A, et al. In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain [published erratum appears in Blood 1995 Jun 1;85(11):3365]. Blood 1995; 85: 436.
Rawstron AC, Owen RG, Davies FE, et al. Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage. Br J Haematol 1997; 97: 46.
Luque R, Brieva JA, Moreno A, et al. Normal and clonal B lineage cells can be distinguished by their differential expression of B cell antigens and adhesion molecules in peripheral blood from multiple myeloma (MM) patients-diagnostic and clinical implications. Clin Exp Immunol 1998; 112: 410.
Zandecki M, Bernardi F, Genevieve F, et al. Involvement of peripheral blood cells in multiple myeloma: chromosome changes are the rule within circulating plasma cells but not within B lymphocytes. Leukemia 1997; 11: 1034.
Mahmoud MS, Fujii R, Ishikawa H, Kawano MM. Enforced CD19 expression leads to growth inhibition and reduced tumorigenicity. Blood 1999; 94: 3551.
Kay NE, Leong TL, Bone N, et al. Blood levels of immune cells predict survival in myeloma patients: results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients. Blood 2001; 98: 23.
Pellat-Deceunynck C, Bataille R, Robillard N, et al. Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood 1994; 84: 2597.
Robillard N, Jego G, Pellat-Deceunynck C, et al. CD28, a marker associated with tumoral expansion in multiple myeloma. Clin Cancer Res 1998; 4: 1521.
Pope B, Brown RD, Gibson J, et al. B7–2-positive myeloma: incidence, clinical characteristics, prognostic significance, and implications for tumor immunotherapy. Blood 2000; 96: 1274.
Shapiro VS, Mollenauer MN, Weiss A. Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression. Blood 2001; 98: 187.
Berenson JR, Vescio RA, Hong CH, et al. Multiple myeloma clones are derived from a cell late in B lymphoid development. Curr Top Microbiol Immunol 1995; 194: 25.
Pellat-Deceunynck C, Barille S, Jego G, et al. The absence of CD56 (NCAM) on malignant plasma cells is a hallmark of plasma cell leukemia and of a special subset of multiple myeloma. Leukemia 1998; 12: 1977.
Rawstron A, Barrans S, Blythe D, et al. Distribution of myeloma plasma cells in peripheral blood and bone marrow correlates with CD56 expression. Br J Haematol 1999; 104: 138.
Sonneveld P, Durie BG, Lokhorst HM, et al. Analysis of multidrug-resistance (MDR-1) glycoprotein and CD56 expression to separate monoclonal gammopathy from multiple myeloma. Br J Haematol 1993; 83: 63.
Ong F, Kaiser U, Seelen PJ, et al. Serum neural cell adhesion molecule differentiates multiple myeloma from paraproteinemias due to other causes. Blood 1996; 87: 712.
Hirano T, Yasukawa K, Harada H, et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 1986; 324: 73.
Kawano MM, Mihara K, Huang N, et al. Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis. Blood 1995; 85: 487.
Jego G, Robillard N, Puthier D, et al. Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells. Blood 1999; 94: 701.
Rawstron AC, Fenton JA, Ashcroft J, et al. The interleukin-6 receptor alpha-chain (CD 126) is expressed by neoplastic but not normal plasma cells. Blood 2000; 96: 3880.
Wijdenes J, Vooijs WC, Clement C, et al. A plasmocyte selective monoclonal antibody (B-B4) recognizes syndecan-1. Br J Haematol 1996; 94: 318–323;
Ridley RC, Xiao H, Hata H, et al. Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen. Blood 1993; 81: 767–774.
Borset M, Hjertner O, Yaccoby S, et al. Syndecan-1 is targeted to the uropods of polarized myeloma cells where it promotes adhesion and sequesters heparin-binding proteins. Blood 2000; 96: 2528–2536.
Dhodapkar MV, Abe E, Theus E, et al. Syndecan-1 is a multifunctional regulator of myeloma pathobiology: control of tumor cell survival, growth, and bone cell differentiation. Blood 1998; 91: 2679–2688.
Seidel C, Sundan A, Hjorth M, et al. Serum syndecan-1: a new independent prognostic marker in multiple myeloma. Blood 2000; 95: 388–392.
Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL6 for human multiple myelomas. Nature 1988; 332: 83–85.
Klein B, Zhang XG, Jourdan M, et al. Paracrine rather than autocrine regulation of myelomacell growth and differentiation by interleukin-6 Blood 1989; 73: 517–526.
Klein B, Zhang XG, Lu ZY, et al. Interleukin-6 in human multiple myeloma. Blood 1995; 85: 863–872.
Uchiyama H, Barut BA, Mohrbacher AF, et al. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood 1993; 82: 3712–3720.
Zhang XG, Bataille R, Jourdan M, et al. Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells. Blood 1990; 76: 2599–2605.
Jernberg H, Pettersson M, Kishimoto T, Nilsson K. Heterogeneity in response to interleukin 6 (IL-6), expression of IL-6 and IL-6 receptor mRNA in a panel of established human multiple myeloma cell lines [published erratum appears in Leukemia 1991 Jun;5(6):following 530]. Leukemia 1991; 5: 255–265.
Suematsu S, Matsuda T, Aozasa K, et al. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 1989; 86: 7547–7551.
Bataille R, Jourdan M, Zhang XG, et al. Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. J Clin Invest 1989; 84: 2008–2011.
Ludwig H, Nachbaur DM, Fritz E, et al. Interleukin-6 is a prognostic factor in multiple myeloma. Blood 1991; 77:2794–2795.
Lichtenstein A, Tu Y, Fady C, et al. Interleukin-6 inhibits apoptosis of malignant plasma cells. Cell Immunol 1995; 162: 248–255.
Xu FH, Sharma S, Gardner A, et al. Interleukin-6-induced inhibition of multiple myeloma cell apoptosis: support for the hypothesis that protection is mediated via inhibition of the JNK/SAPK pathway. Blood 1998; 92: 241–251.
Chauhan D, Pandey P, Ogata A, et al. Dexamethasone induces apoptosis of multiple myeloma cells in a INK/SAP kinase independent mechanism. Oncogene 1997; 15: 837–843.
Klein B, Wijdenes J, Zhang XG, et al. Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood 1991; 78: 1198–1204.
Bataille R, Barlogie B, Lu ZY, et al. Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma. Blood 1995; 86: 685–691.
Cozzolino F, Torcia M, Aldinucci D, et al. Production of interleukin-1 by bone marrow myeloma cells. Blood 1989; 74: 380–387.
Carter A, Merchav S, Silvian-Draxler I, et al. The role of interleukin-1 and tumour necrosis factor-alpha in human multiple myeloma. Br J Haematol 1990; 74: 424–431.
Donovan KA, Lacy MQ, Kline MP, et al. Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma. Leukemia 1998; 12: 593–600.
Lacy MQ, Donovan KA, Heimbach JK, et al. Comparison of interleukin-1 beta expression by in situ hybridization in monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 1999; 93: 300–305.
Jourdan M, Tarte K, Legouffe E, et al. Tumor necrosis factor is a survival and proliferation factor for human myeloma cells. Eur Cytokine Netw 1999; 10: 65–70.
Borset M, Waage A, Brekke OL, et al. TNF and IL-6 are potent growth factors for OH-2, a novel human myeloma cell line. Eur J Haematol 1994; 53: 31–37.
Filella X, Blade J, Montoto S, et al. Impaired production of interleukin 6 and tumour necrosis factor alpha in whole blood cell cultures of patients with multiple myeloma. Cytokine 1998; 10: 993–996.
Filella X, Blade J, Guillermo AL, et al. Cytokines (IL-6, TNF-alpha, IL-1 alpha) and soluble interleukin-2 receptor as serum tumor markers in multiple myeloma. Cancer Detect Prey 1996; 20: 52–56.
Jourdan M, Zhang XG, Portier M, et al. IFN-alpha induces autocrine production of IL-6 in myeloma cell lines. J Immunol 1991; 147: 4402–4407.
Vacca A, Ribatti D, Roncalli L, et al. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 1994; 87: 505–508.
Bellamy WT, Richer L, Frutiger, et al. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res 1999; 59: 728–733.
Dankbar B, Padro T, Leo R, et al. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood 2000; 95: 2630–2636.
Nuda S, Kaku M, Amano H, et al. Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption. J Exp Med 1999; 190: 293–298.
Hofbauer LC. Osteoprotegerin ligand and osteoprotegerin: novel implications for osteoclast biology and bone metabolism. Soc Eur J Endocrinol 1999; 141: 195–210.
Kobayashi K, Takahashi N, Jimi E, et al. Tumor necrosis factor a stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 2000; 191: 275–285.
Altamirano CV, Ma HJ, Parker KM, et al. RANKL is expressed in malignant multiple myeloma (MM) cell lines. Blood 2000; 96: 365a.
Shipman CM, Holen I, Lippitt JM, et al. Tumour cells isolated from patients with multiple myeloma express the critical osteoclastogenic factor, RANKL. Blood 2000; 96: 360a.
Bucay N, Saroosi I, Dunstan CR, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dey 1998; 12: 1260–1268
Capparelli C, Kostenuik PJ, Morony S, et al. Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypecalcemia of malignancy. Cancer Res 2000; 60: 783–787.
Honore P, Luger NM, Sabino MAC, et al. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 2000; 6: 521–528.
Altamirano CV, Neeser JA, Manyak S, et al. Malignant multiple myeloma cells expressing RANKL induce the formation or TRAP positive multinucleated cells. Blood 2001; 98: 637a.
Yaccoby S, Pearse R, Epstein J, et al. Reciprocal relationship between myeloma-induced changes in the bone marrow microenvironment and myeloma cell growth. Blood 2000; 96: 549a.
Pearse RN, Sordillo EM, Yaccoby S, et al. Administration of the TRANCE-antagonist TRFc limits myeloma-induced bone destruction. Blood 2000; 96: 549a.
Beg AA, Baldwin AS, Jr: The I kappa B proteins: multifunctional regulators of Rel/NFkappa B transcription factors. Genes Dey 1993; 7: 2064–2070
Brown K, Park S, et al. Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc Natl Acad Sci USA 1993; 90: 2532–2536
Henkel T, et al. Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B. Nature 1993; 365: 182–185.
Mellits KH, Hay RT, Goodboum S. Proteolytic degradation of MAD3 (I kappa B alpha) and enhanced processing of the NF-kappa B precursor p105 are obligatory steps in the activation of NF-kappa B. Nucleic Acids Res 1993; 21: 5059–5066
Palombella VJ, Rando OJ, Goldberg AL, et al. The ubiquitin-proteasome pathway is required for processing the NF- kappa B1 precursor protein and the activation of NF-kappa B. Cell 1994; 78: 773–785.
Feinman R, et al. Role of NF-kappaB in the recue of multiple myeloma cells from glucocorticoid-induced apoptosis by bc1–2. Blood 1999; 93: 3011 3052.
Ma H, Parker K, Manyak S, et al. The proteasome inhibitor enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. (Submitted.)
Hideshima T, et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61: 3071–3076.
LeBlanc R, Catley L, Hideshima T, et al. Proteasome inhibitor PS-341 inhibits multiple myeloma growth in a murine model. Blood 2001; 98: 774a.
Jelinek DF, Witzig TE, Arendt BK. A role for insulin-like growth factor in the regulation of IL-6-responsive human myeloma cell line growth. J Immunol 1997; 159: 487–496.
Georgii-Hemming P, Wiklund HJ, Ljunggren O, Nilsson K. Insulin-like growth factor I is a growth and survival factor in human multiple myeloma cell lines. Blood 1996; 88: 2250–2258.
Jelinek DF. Mechanisms of myeloma cell growth control. Hematol Oncol Clin NAm 1999; 13: 1145–1157.
Xu F, Gardner A, Tu Y, Michl P, et al. Multiple myeloma cells are protected against dexamethasone-induced apoptosis by insulin-like growth factors. Br J Haematol 1997; 97: 429–440.
Lu ZY, Zhang XG, Rodriguez C, et al. Interleukin-10 is a proliferation factor but not a differentiation factor for human myeloma cells. Blood 1995; 85: 2521–2527.
Seidel C, Borset M, Turesson I, Abildgaard N, et al. Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. The Nordic Myeloma Study Group. Blood 1998; 91: 806–812.
Celsing F, Hast R, Stenke L, Hansson H, Pisa P. Extramedullary progression of multiple myeloma following GM-CSF treatment-grounds for caution ? Eur JHaematol 1992; 49: 108.
Schwabe M, Brini AT, Bosco MC, et al. Disruption by interferon-alpha of an autocrine interleukin-6 growth loop in IL-6-dependent U266 myeloma cells by homologous and heterologous down-regulation of the IL-6 receptor alpha-and beta-chains. J Clin Invest 1994; 94: 2317–2325.
Choi SJ, Cruz JC, Craig F, et al. Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood 2000; 96: 671–675.
Choi SJ, Alsina M, Oba Y, et al. Antisense construct to MIP-1-alpha blocks bone destruction in an in vivo model of myeloma. Blood 2000; 96: 549a.
Nakamura M, Merchav S, Carter A, et al. Expression of a novel 3–5-kb macrophage colony-stimulating factor transcript in human myeloma cells. J Immunol 1989; 143: 3543–3547.
Janowska-Wieczorek A, Belch AR, Jacobs A, et al. Increased circulating colony-stimulating factor-1 in patients with preleukemia, leukemia, and lymphoid malignancies. Blood 1991; 77: 1796–1803.
MacDonald BR, Mundy GR, Clark S, et al. Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term marrow cultures. J Bone Mineral Res 1986; 1: 227–233.
Sarma U, Flanagan AM. Macrophage colony-stimulating factor induces substantial osteoclast generation and bone resorption in human bone marrow cultures. Blood 1996; 88: 2531–2540.
Fuller K, Owens JM, Jagger CJ, et al. Macrophage colony-stimulating factor stimulates survival and chemotactic behaviour in isolated osteoclasts. J Exp Med 1993; 189: 1733 1744.
Girasole G, Passeri G, Jilka RL, et al. Interleukin-11: a new cytokine critical for osteoclast development. J Clin Invest 1994; 93: 1516.
Hjertner O, Torgersen ML, Seidel C, et al. Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: a possible role for HGF in myeloma-associated osteolytic bone disease. Blood 1999; 94: 3883–3888.
Borset M, Hjorth-Hansen H, Seidel et al. Hepatocyte growth factor and its receptor c-Met in multiple myeloma. Blood 1996; 88: 3998–4004.
Fuller K, Owens J, Chambers TJ. The effect of hepatocyte growth factor on the behaviour of osteoclasts. Biochem Biophys Res Comm 1995; 212: 334–340.
Grano M, Galimi F, Zambonin G, et al. Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro. Proc Natl Acad Sci USA 1996; 93: 7644–7648.
Seidel C, Borset M, Turesson I, Abildgaard N, et al. Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. Blood 1998; 91: 806–812.
Rettig MB, Ma HJ, Vescio RA, et al. Kaposi’s sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science 1997; 276: 1851 1854.
Said JW, Rettig MR, Heppner K, et al. Localization of Kaposi’s sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. Blood 1997; 90: 4278–4282.
Rask C, Kelsen J, Olesen G, et al. Danish patients with untreated multiple myeloma do not harbour human herpesvirus 8. Br J Haematol 2000; 108: 96–98.
Bellos F, Goldschmidt H, Dorner M, et al. Bone marrow derived dendritic cells from patients with multiple myeloma cultured with three distinct protocols do not bear Kaposi’s sarcoma associated herpesvirus DNA. Ann Oncol 1999; 10: 323–327.
Chauhan D, Bharti A, Raje N, et al. Detection of Kaposi’s sarcoma herpesvirus DNA sequences in multiple myeloma bone marrow stromal cells. Blood 1999; 93: 1482–1486.
Brousset P, Meggetto F, Laharrague P, et al. Kaposi’s sarcoma-associated herpesvirus (KSHV) in bone marrow biopsy from patients with multiple myeloma: PCR amplification of orf26 but not orf72 and orf75 sequences. Br J Haematol 2000; 108: 197–198.
Raje N, Gong J, Chauhan D, et al. Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi’s sarcoma herpesvirus gene sequences. Blood 1999; 93: 1487–1495.
Belec L, Mohamed AS, Authier FJ, et al. Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman’ s disease. Blood 1999; 93: 3643–3653.
Ma HJ, Sjak-Shie NN, Vescio RA, et al. Human herpes virus 8 sequences from ORF26 and ORF65 in multiple myeloma patients show a disease specific pattern. Clinical Cancer Res 2000; 6: 4226–4233.
Vescio RA, Wu CH, Zheng L, et al. Human herpesvirus 8 (KSHV) contamination of peripheral blood and autograft products from multiple myeloma patients. Bone Marrow Transplant 2000; 25: 153–160.
Sjak-Shie NN, Vescio RA, Berenson JR. The role of human herpesvirus-8 in the pathogenesis of multiple myeloma. Hematol Oncol Clin NAm 1999; 13: 1159–1167.
MacKenzie J, Sheldon J, Morgan G, et al. HHV-8 and multiple myeloma in the UK. Lancet 1997; 350: 1144–1145.
Gao SJ, Alsina M, Deng JH, et al. Antibodies to Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in patients with multiple myeloma. J Infect Dis 1998; 178: 846–849.
Drach J, Schuster J, Nowotny H, et al. Multiple myeloma: high incidence of chromosomal aneuploidy as detected by interphase fluorescence in situ hybridization. Cancer Res 1995; 55: 3854–3859.
Perez-Simon JA, Garcia-Sanz R, Tabemero MD, et al. Prognostic value of numerical chromosome aberrations in multiple myeloma: a FISH analysis of 15 different chromosomes. Blood 1998; 91: 3366–3371.
Avet-Loiseau H, Li JY, Facon T, Brigaudeau C, 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.
Avet-Loiseau H, Brigaudeau C, Morineau N, et al. High incidence of cryptic translocations involving the Ig heavy chain gene in multiple myeloma, as shown by fluorescence in situ hybridization. Genes Chromosomes Cancer 1999; 24: 9–15.
Bergsagel PL, Chesi M, Nardini E, et al. Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma. Proc Natl Acad Sci USA 1996; 93: 13, 931.
Chesi M, Bergsagel PL, Shonukan 00, et al. Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma. Blood 1998; 91: 4457.
Chesi M, Brents LA, Ely SA, et al. Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma. Blood 2001; 97: 729.
Iida S, Rao PH, Butler M, et al. Deregulation of MUM UIRF4 by chromosomal translocation in multiple myeloma. Nat Genet 1997; 17: 226.
Shaughnessy J Jr, Gabrea A, Qi Y, et al. Cyclin D3 at 6p21 is dysregulated by recurrent chromosomal translocations to immunoglobulin loci in multiple myeloma. Blood 2001; 98: 217.
Ronchetti D, Finelli P, Richelda R, et al. Molecular analysis of l 1q 13 breakpoints in multiple myeloma. Blood 1999; 93: 1330.
Janssen JW, Vaandrager JW, Heuser T, et al. Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32). Blood 2000; 95: 2691.
Cigudosa JC, Rao PH, Calasanz M.1, et al. Characterization of nonrandom chromosomal gains and losses in multiple myeloma by comparative genomic hybridization. Blood 1998; 91: 3007.
Sawyer JR, Tricot G, Mattox S, et al. Jumping translocations of chromosome lq in multiple myeloma: evidence for a mechanism involving decondensation of pericentromeric hetero-chromatin. Blood 1998; 91: 1732.
Tricot G, Barlogie B, Jaganath S, et al. Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 1 l q and not other karyotype abnormalities. Blood 1995; 86: 4250.
Avet-Louseau H, Daviet A, Sauner S, et al. Chromosome 13 abnormalities in multiple myeloma are mostly monosomy 13. Br J Haematol 2000; 111: 1116.
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: 2583–2589.
Shaughnessy J, Tian E, Sawyer J, et al. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 2000; 96: 1505.
Schreiber S, Ackermann J, Obermair A, et al. Multiple myeloma with deletion of chromosome 13q is characterized by increased bone marrow neovascularization. Br J Haematol 2000; 110: 605.
Zojer N, Konigsberg R, Ackermann J, et al. Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization. Blood 2000; 95: 1925.
Desikan R, Barlogie B, Sawyer J, et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000; 95: 4008.
Zandecki M, Lai JL, Genevieve F, et al. Several cytogenetic subclones may be identified within plasma cells from patients with monoclonal gammopathy of undetermined significance, both at diagnosis and during the indolent course of this condition. Blood 1997; 90: 3682.
Kalakonda N, Rothwell DG, Scarffe JH, et al. Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation. Blood 2001; 98: 1555.
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.
Corradini P, Inghirami G, Astolfi M, et al. Inactivation of tumor suppressor genes, p53 and Rbl, in plasma cell dyscrasias. Leukemia 1994; 8: 758.
Tasaka T, Asou H, Munker R, et al. Methylation of the p 16INK4A gene in multiple myeloma. Br J Haematol 1998; 101: 558.
Guillerm G, Gyan E, Wolowiec D, et al. p16(INK4a) and p15(INK4b) gene methylations in plasma cells from monoclonal gammopathy of undetermined significance. Blood 2001; 98: 244.
Silvestris F, Tucci M, Cafforio P, et al. Fas-L up-regulation by highly malignant myeloma plasma cells: role in the pathogenesis of anemia and disease progression. Blood 2001; 97: 1155.
Landowski TH, Qu N, Buyuksal I, et al. Mutations in the fas antigen in patients with multiple myeloma. Blood 1997; 90: 4266.
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.
Bellamy WT, Richter L, Frutiger Y, et al. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res 1999; 59: 728–733.
Ribatti D, Vacca A, Nico B, et al. Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma. Br J Cancer 1999; 79: 45 1455.
Munshi N, Wilson CS, Penn J, et al. Angiogenesis in newly diagnosed multiple myeloma: poor prognosis with increased microvessel density (MVD) in bone marrow biopsies. Blood 1998; 92.
Rajkumar SV, Fonseca R, Witzig TE, et al. Bone marrow angiogenesis in patients achieving complete response after stem cell transplantation for multiple myeloma. Leukemia 1999; 13: 469–472.
van Hoeven KH, Reed LJ, Factor SM. Autopsy-documented cure of multiple myeloma 14 years after M2 chemotherapy. Cancer 1990; 66: 1472–1474.
Hjorth M, Hellquist L, Holmberg E, et al. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I-a randomized study. Myeloma Group of Western Sweden. Eur J Haematol 1993; 50: 95–102.
Alexanian R, Dimopoulos MA, Delasalle K, et al. Primary dexamethasone treatment in multiple myeloma. Blood 1992; 80: 887–890.
Case DC, Jr., Lee DJ, Clarkson BD. Improved survival times in multiple myeloma treated with melphalan, prednisone, cyclophosphamide, vincristine and BCNU: M-2 protocol. Am J Med 1977; 63: 897–903.
Oken MM, Harrington DP, Abramson N, et al. Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479. Cancer 1997; 79: 1561–1567.
Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984; 310: 1353–1356.
Alexanian R, Yap BS, Bodey GP. Prednisone pulse therapy for refractory myeloma. Blood 1983; 62: 572–577.
Monconduit M, Le Loet X, Bernard JF, et al. Combination chemotherapy with vincristine, doxorubicin, dexamethasone for refractory or relapsing multiple myeloma. Br J Haematol 1986; 63: 599–601.
Sheehan T, Judge M, Parker AC. The efficacy and toxicity of VAD in the treatment of myeloma and related disorders. Scand J Haematol 1986; 37: 425–428.
Buzaid AC, Durie BG. Management of refractory myeloma: a review. J Clin Oncol 1988; 6: 889–905.
Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists’ Collaborative Group. J Clin Oncol 1998; 16:3832–3842.
Osterborg A, Bjorkholm M, Bjoreman M, et al. Natural interferon-alpha in combination with melphalan/prednisone versus melphalan/prednisone in the treatment of multiple myeloma stages II and III: a randomized study from the Myeloma Group of Central Sweden. Blood 1993; 81: 1428–1434.
Cooper MR, Dear K, McIntyre OR, et al. A randomized clinical trial comparing melphalan/ prednisone with or without interferon alfa-2b in newly diagnosed patients with multiple myeloma: a Cancer and Leukemia Group B study. J Clin Oncol 1993; 11: 155–160.
Musto P, Lombardi G, Matera R, et al. The expression of the multidrug transporter P-170 glycoprotein in remission phase is associated with early and resistant relapse in multiple myeloma. Haematologica 1991; 76: 513–516.
Ludwig H, Cohen AM, Polliack A, et al. Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies. Ann Oncol 1995; 6: 467–476.
Tura S, Cavo M. Allogeneic bone marrow transplantation in multiple myeloma. Hematol Oncol Clin N Am 1992; 6: 425–435.
Gahrton G. Allogeneic bone marrow transplantation in multiple myeloma. Pathol Biol (Paris) 1999, 47: 188–191.
Gahrton G, Svensson H, Cavo, et al. Progress in allogeneic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983–1993 and 1994–1998 at European Group for Blood and Marrow Transplantation Centers. Br J Haematol 2001; 113: 209–216.
Martinelli G, Terragna C, Zamagni E, et al. Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma. J Clin Oncol 2000; 18: 2273–2281.
Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.
Badros A, Barlogie B, Morris C, et al. High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor leukocyte infusions. Blood 2001; 98: 2574–2579.
Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: Predictive factors for response and long-term outcome. J Clin Oncol 2000; 18: 3031–3037.
Gahrton G, Svensson H, Bjorkstrand B, et al. Syngeneic transplantation in multiple myeloma-a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1999; 24: 741–745.
Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.
Harousseau JL, Attal M. The role of autologous hematopoietic stem cell transplantation in multiple myeloma. Semin Hematolv 1997; 34: 61–66.
Lenhoff S, Hjorth M, Holmberg E, et al. Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Nordic Myeloma Study Group. Blood 2000; 95: 7–11.
Palumbo A, Triolo S, Argentino C, et al. Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 1999; 94: s1248–1253.
Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.
Harousseau JL, Attal M. The role of autologous hematopoietic stem cell transplantation in multiple myeloma. Semin Hematol 1997; 34: 61–66.
Bergsagel DE. Treatment of plasma cell myeloma. Annu Rev Med 1979; 30: 431–443.
Jagannath S, Tricot G, Barlogie B. Autotransplants in multiple myeloma: Pushing the envelope. Hematol Oncol Clin NAm 1997; 11: 363–381.
Goldschmidt H, Hegenbart U, Wallmeier M, et al. High-dose chemotherapy in multiple myeloma. Leukemia 1997; 11(Suppl 5):S27–31.
Vesole DH. Bone marrow and stem cell transplantation for multiple myeloma. Cancer Treat Res 1999; 99: 171–94.
Fermand JP, Brechignac S. The role of autologous stem cell transplantation in the management of multiple myeloma. Pathol Biol (Paris) 1999; 47: 199–202.
Tribalto M, Amadori S, Cudillo L, et al. Autologous peripheral blood stem cell transplantation as first line treatment of multiple myeloma: an Italian multicenter study. Haematologica 2000; 85: 52–58.
Fermand JP, Ravaud P, Chevret S, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 1998; 92: 3131–3136.
Siegel DS, Desikan KR, Mehta J, et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood 1999; 93: 51–54.
Reiffers J, Marit G, Boiron JM. Autologous blood stem cell transplantation in high-risk multiple myeloma. Br J Haematol 1989; 72: 296–297.
Fermand JP, Chevret S, Ravaud P, et al. High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients. Blood 1993; 82: 2005–2009.
Vesole DH, Jagannath S, Glenn L, et al. Autotransplantation in multiple myeloma. Hematol Oncol Clin NAm 1993; 7: 613–630.
Cunningham D, Paz-Ares L, Gore ME, et al. High-dose melphalan for multiple myeloma: long-term follow-up data. J Clin Oncol 1994; 12: 764–768.
Schiller G, Vescio R, Freytes C, et al. Autologous CD34-selected blood progenitor cell transplants for patients with advanced multiple myeloma. Bone Marrow Transplant 1998; 21: 141–145.
Vescio RA, Han EJ, Schiller GJ, et al. Quantitative comparison of multiple myeloma tumor contamination in bone marrow harvest and leukapheresis autografts. Bone Marrow Transplant 1996; 18: 103–110.
Vescio RA, Hong CH, Cao J, et al. The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma. Blood 1994; 84: 3283–3290.
Vescio R, Schiller G, Stewart AK, et al. Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood 1999; 93: 1858–1868.
Stewart K, Vescio R, Schiller G, et al. Purging of autologous peripheral blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose therapy: results of a multi-center randomized controlled trial. J Clin Oncol 2001; 19: 3771–3779.
Vescio R and Berenson J. Autologous transplantation. purging and the impact of minimal residual disease. Hematol Oncol Clin NAm 1999; 13: 969–986.
Mandelli F, Avvisati G, Amadori S, et al. Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med 1990; 20: 1430–1434.
Westin J, Rodjer S, Turesson I, et al. Interferon alfa-2b versus no maintenance therapy during the plateau phase in multiple myeloma: A randomised study. Br J Haematol 1995; 89: 561–568.
Browman GP, Bergsagel DE, Sicheri D, et al. Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1995; 13: 2354–2360.
Ludwig H, Cohen AM, Polliack A, et al. Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies. Ann Oncol 1995; 6: 467–476.
Salmon SE, Crowley JJ, Grogan TM, et al. Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: A Southwest Oncology Group study. J Clin Oncol 1994; 12: 2405–2414.
Peest D, Deicher H, Coldewey R, et al. A comparison of polychemotherapy and melphalanprednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma: a prospective trial of the German Myeloma Treatment Group. Eur J Cancer 1995; 31A: 146–150.
Mandelli F, Avvisati G, Amadori S, et al. Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med 1990; 20: 1430–1434.
Westin J, Rodjer S, Turesson I, et al. Interferon alfa-2b versus no maintenance therapy during the plateau phase in multiple myeloma: A randomised study. Br J Haematol 1995; 89: 561–568.
Browman GP, Bergsagel DE, Sicheri D, et al. Randomized trial of interferon maintenance in multiple myeloma: A study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1995; 13: 2354–2360.
Ludwig H, Cohen AM, Polliack A, et al. Interferon-alpha for induction and maintenance in multiple myeloma: Results of two multicenter randomized trials and summary of other studies. Ann Oncol 1995; 6: 467–476.
Salmon SE, Crowley JJ, Grogan TM, et al. Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: A Southwest Oncology Group study. J Clin Oncol 1994; 12: 2405–2414.
Peest D, Deicher H, Coldewey R, et al. A comparison of polychemotherapy and melphalanprednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma: A prospective trial of the German Myeloma Treatment Group. Eur J Cancer 1995; 31A: 146–150.
Palumbo A, Boccadoro M, Garino LA, et al. Interferon plus glucocorticoids as intensified maintenance therapy prolongs tumor control in relapsed myeloma. Acta Haematol 1993; 90: 71–76.
Salmon SE, Crowley JJ, Balcerzak SP, et al. Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: A Southwest Oncology Group study. J Clin Oncol 1998; 16: 890–896.
Berenson JR, Crowley JJ, Grogan T, et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 2002; 99: 3163–3168.
Dimopoulos MA, Delasalle KB, Champlin R, et al. Cyclophosphamide and etoposide therapy with GM-CSF for VAD-resistant multiple myeloma. Br J Haematol 1993; 83: 240–244.
Barlogie B, Vesole DH, Jagannath S. Salvage therapy for multiple myeloma: the University of Arkansas experience. Mayo Clin Proc 1994; 69: 787–795.
Barlogie B, Jagannath S, Dixon DO, et al. High-dose melphalan and granulocyte-macrophage colony-stimulating factor for refractory multiple myeloma. Blood 1990; 76: 677–680.
Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–1571.
Barlogie B Desikan, Eddlemon, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide; identification of prognostic factors in phase 2 study of 169 patients. Blood 2001; 98:492–494.
Zangari M, Anaissie E, et al. Increased risk of deep-venous thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Bloody 2001: 98: 1614–1615.
Sastry PS. Inhibition of TNF-alpha synthesis with thalidomide for prevention of acute exacerbations and altering the natural history of multiple sclerosis. Med Hypotheses 1999; 53: 76–77.
Moller DR, Wysocka M, Greenlee BM, et al. Inhibition of IL-12 production by thalidomide. J Immunol 1997; 159: 5157–5161.
Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001; 98: 210–216.
Keifer JA, Guttridge DC, Ashburner BP, et al. Inhibition of NF-kB activity by thalidomide through suppression of 1kB kinase activity. J Biol Chem 2001; 276:22, 382–22, 387.
Larkin M. Low-dose thalidomide seems to be effective in multiple myeloma. Lancet 1999; 354: 925.
Alexanian R. Thalidomide and prednisone in the treatment of multiple myeloma. Blood 1999; ASH 1999; 94: 604a.
Rajkumar SV, Hayman S, Fonseca R, et al. Thalidomide plus dexamethasone (Thal/Dex) and thalidomide alone as first line therapy for newly diagnosed myeloma (MM). Blood 2000; 96: 168a.
Richardson P, Berenson J, Irwin D, et al. Phase II study of PS-341, a novel proteasome inhibitor, alone or in combination with dexamethasone in patients with multiple myeloma who have relapsed following front-line therapy and are refractor to their most recent therapy. Blood 2001; 98: 774a.
Ma MH, Parker KM, Manyak S, et al. Proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma cells to chemotherapeutic agents and overcomes chemoresistance through inhibition of the NF-kB pathway. Blood 2001; 98: 11: 473a.
Ma MH, Borad MJ, Friedman J, et al. Arsenic trioxide-mediated growth inhibition of multiple myeloma cells correlated with inhibition of nuclear factor (NF)-kB activity. Blood 2001; 98: 100a.
Grad JM, Bahlis NJ, Reis I, et al. Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells. Blood 2001; 98: 805–813.
Hussein MA, Mason J, Ravandi F, et al. A phase II trial of arsenic trioxide (ATO) in patients (Pts) with relapsed or refractory multiple myeloma (MM): a preliminary report. Blood 2001; 98: 378a.
Kyle RA. Multiple myeloma: review of 869 cases. Mayo Clin Proc 1975; 50: 29–40.
Mundy GR, Bertolini DR. Bone destruction and hypercalcemia in plasma cell myeloma [published erratum appears in Semin Oncol 1986 Dec;13(4):lxiii]. Semin Oncol 1986; 13: 291–299.
Belch AR, Bergsagel DE, Wilson K, et al. Effect of daily etidronate on the osteolysis of multiple myeloma. J Clin Oncol 1991; 9: 1397–1402.
Kyle RA, Jowsey J, Kelly PJ, Taves DR. Multiple-myeloma bone disease. The comparative effect of sodium fluoride and calcium carbonate or placebo. N Engl J Med 1975; 293: 1334–1338.
Harley JB, Schilling A, Glidewell O. Ineffectiveness of fluoride therapy in multiple myeloma. N Engl J Med 1972; 286: 1283–1288.
Cohen HJ, Silberman HR, Tornyos K, Bartolucci AA. Comparison of two long-term chemotherapy regimens, with or without agents to modify skeletal repair, in multiple myeloma. Blood 1984; 63: 639–648.
van Breukelen FJ, Bijvoet OL, van Oosterom AT. Inhibition of osteolytic bone lesions by (3-amino- 1-hydroxypropylidene)-1, 1-bi sphosphonate (A.P.D.). Lancet 1979; 1: 803–805.
Siris ES, Sherman WH, Baquiran DC, et al. Effects of dichloromethylene diphosphonate on skeletal mobilization of calcium in multiple myeloma. N Engl J Med 1980; 302: 310–315.
Lahtinen R, Laakso M, Palva 1, et al. Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group [published erratum appears in Lancet 1992 Dec 5;340(8832):14201. Lancet 1992; 340: 1049–1052.
McCloskey EV, MacLennan IC, Drayson MT, et al. A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults. Br J Haematol 1998; 100: 317–325.
Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 1996; 334: 488–493.
Berenson JR, Lichtenstein A, Porter L, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998; 16: 593–602.
Brincker H, Westin J, Abildgaard N, et al. Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-blind placebo-controlled trial. Danish-Swedish co-operative study group. Br J Haematol 1998; 101: 280–286.
Troehler U, Bonjour JP, Fleisch H. Renal secretion of diphosphonates in rats. Kidney Int 1975; 8: 6–13.
Berenson JR, Rosen L, Vescio R, et al. Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function. J Clin Pharmacol 1997; 37: 285290.
Markowitz GS, Apel GB, Fine PL, et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. JAm Soc Nephrol 2000; 12: 1164–1172.
Major PP, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001; 19: 558–567.
Berenson JR, Vescio R, Henick K, et al. A Phase I, open label, dose ranging trial of intravenous bolus zoledronic acid, a novel bisphosphonate, in cancer patients with metastatic bone disease. Cancer 2001; 91: 144–154.
Berenson JR, Vescio RA, Rosen LS, et al. A Phase I dose-ranging trial of monthly infusions of zoledronic acid for the treatment of osteolytic bone metastases. Clin Can Res 2001; 7: 478–485.
Berenson JR, Rosen LS, Howell A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 2001; 91: 1191–2000.
Rosen LS, Gordon D, Kaminski M, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001; 7: 377–387.
Aparicio A, Gardner A, Tu Y, et al. In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates. Leukemia 1998; 12: 220–229.
Savage AD, Belson DJ, Vescio RA, et al. Pamidronate reduces IL-6 production by bone marrow stroma from multiple myeloma patients. Blood 1996; 88: 105a.
Kunzmann V, Bauer E, Feurle, et al. Stimulation of yS T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 2000; 96: 384–392.
Greipp P, Facon T, Williams CD, et al. A single subcutaneous dose of an osteoprotegerin (OPG) construct (AMGN-0007) causes a profound and sustained decrease of bone resorption comparable to standard intravenous bisphosphonate in patients with multiple myeloma. Blood 2001; 98: 775a.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Berenson, J.R., Vescio, R.A. (2003). Advances in the Biology and Treatment of Multiple Myeloma. In: Schiller, G.J. (eds) Chronic Leukemias and Lymphomas. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-308-8_9
Download citation
DOI: https://doi.org/10.1007/978-1-59259-308-8_9
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4684-9732-8
Online ISBN: 978-1-59259-308-8
eBook Packages: Springer Book Archive