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Neoplastic Diseases of the Blood pp 681–699Cite as

Waldenström’s Macroglobulinemia

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Abstract

Waldenström’s macroglobulinemia is a neoplastic disorder of the B lymphocytes that is characterized by the infiltration of the bone marrow by a lymphoplasmatic clone that produces a monoclonal immunoglobulin which is always of the IgM type. WM is named after Jan Waldenström, a Swedish physician who first described two patients who presented with oronasal bleeding, lymphadenopathy, anemia and thrombocytopenia, elevated erythrocyte sedimentation rate, high serum viscosity, normal bone radiographs, and bone marrow showing predominantly lymphoid cells. At that time electrophoresis of the serum proteins was not available; however, he attributed the hyperviscosity to an abnormal high-molecular-weight serum protein, which subsequently was shown to be a monoclonal immunoglobulin of the M class (IgM). Indeed, these two first patients presented with several of the most common features of WM, as have been subsequently described.

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References

  1. Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and management of Waldenstrom’s macroglobulinemia. J Clin Oncol. 2005;23(7):1564–77.

    Article  PubMed  Google Scholar 

  2. Vijay A, Gertz MA. Waldenstrom macroglobulinemia. Blood. 2007;109(12):5096–103.

    Article  PubMed  CAS  Google Scholar 

  3. Treon SP. How I treat Waldenstrom macroglobulinemia. Blood. 2009;114(12):2375–85.

    Article  PubMed  CAS  Google Scholar 

  4. Kastritis E, Zervas K, Repoussis P, Michali E, Katodrytou E, Zomas A, et al. Prognostication in young and old patients with Waldenstrom’s macroglobulinemia: importance of the International Prognostic Scoring System and of serum lactate dehydrogenase. Clin Lymphoma Myeloma. 2009;9(1):50–2.

    Article  PubMed  CAS  Google Scholar 

  5. Treon SP, Hunter ZR, Aggarwal A, Ewen EP, Masota S, Lee C, et al. Characterization of familial Waldenstrom’s macroglobulinemia. Ann Oncol. 2006;17(3):488–94.

    Article  PubMed  CAS  Google Scholar 

  6. Goldin LR, Pfeiffer RM, Li X, Hemminki K. Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database. Blood. 2004;104(6):1850–4.

    Article  PubMed  CAS  Google Scholar 

  7. Kristinsson SY, Bjorkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O. Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. Blood. 2008;112(8):3052–6.

    Article  PubMed  CAS  Google Scholar 

  8. Royer RH, Koshiol J, Giambarresi TR, Vasquez LG, Pfeiffer RM, McMaster ML. Differential characteristics of Waldenstrom macroglobulinemia according to patterns of familial aggregation. Blood. 2010;115(22):4464–71.

    Article  PubMed  CAS  Google Scholar 

  9. Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O. Chronic immune stimulation and subsequent Waldenstrom macroglobulinemia. Arch Intern Med. 2008;168(17):1903–9.

    Article  PubMed  Google Scholar 

  10. Silvestri F, Barillari G, Fanin R, Zaja F, Infanti L, Patriarca F, et al. Risk of hepatitis C virus infection, Waldenstrom’s macroglobulinemia, and monoclonal gammopathies. Blood. 1996;88(3):1125–6.

    PubMed  CAS  Google Scholar 

  11. Mussini C, Ghini M, Mascia MT, Giovanardi P, Zanni G, Lattuada I, et al. Monoclonal gammopathies and hepatitis C virus infection. Blood. 1995;85(4):1144–5.

    PubMed  CAS  Google Scholar 

  12. Andreone P, Gramenzi A, Cursaro C, Bernardi M. Hepatitis C virus infection and lymphoproliferative disorders. Blood. 1995;86(9):3610–1.

    PubMed  CAS  Google Scholar 

  13. Izumi T, Sasaki R, Shimizu R, Miyazato A, Hoshino Y, Miura Y, et al. Hepatitis C virus infection in Waldenstrom’s macroglobulinemia. Am J Hematol. 1996;52(3):238–9.

    Article  PubMed  CAS  Google Scholar 

  14. Schollkopf C, Smedby KE, Hjalgrim H, Rostgaard K, Panum I, Vinner L, et al. Hepatitis C infection and risk of malignant lymphoma. Int J Cancer. 2008;122(8):1885–90.

    Article  PubMed  CAS  Google Scholar 

  15. Santini GF, Crovatto M, Modolo ML, Martelli P, Silvia C, Mazzi G, et al. Waldenstrom macroglobulinemia: a role of HCV infection? Blood. 1993;82(9):2932.

    PubMed  CAS  Google Scholar 

  16. Custodi P, Cerutti A, Cassani P, Perazzi C, Ravanini P, Fortina G. Familial occurrence of IgMk gammapathy: no involvement of HCV infection. Haematologica. 1995;80(5):484–5.

    PubMed  CAS  Google Scholar 

  17. Leleu X, O’Connor K, Ho AW, Santos DD, Manning R, Xu L, et al. Hepatitis C viral infection is not associated with Waldenstrom’s macroglobulinemia. Am J Hematol. 2007;82(1):83–4.

    Article  PubMed  Google Scholar 

  18. Mikala G, Xie J, Berencsi G, Kiss C, Marton I, Domjan G, et al. Human herpesvirus 8 in hematologic diseases. Pathol Oncol Res. 1999;5(1):73–9.

    Article  PubMed  CAS  Google Scholar 

  19. Adamia S, Reichert AA, Kuppusamy H, Kriangkum J, Ghosh A, Hodges JJ, et al. Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia. Blood. 2008;112(13):5111–21.

    Article  PubMed  CAS  Google Scholar 

  20. Kristinsson SY, Koshiol J, Goldin LR, Bjorkholm M, Turesson I, Gridley G, et al. Genetics- and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia. Clin Lymphoma Myeloma. 2009;9(1):23–6.

    Article  PubMed  CAS  Google Scholar 

  21. Roccaro AM, Sacco A, Chen C, Runnels J, Leleu X, Azab F, et al. microRNA expression in the biology, prognosis, and therapy of Waldenstrom macroglobulinemia. Blood. 2009;113(18):4391–402.

    Article  PubMed  CAS  Google Scholar 

  22. McMaster ML, Goldin LR, Bai Y, Ter-Minassian M, Boehringer S, Giambarresi TR, et al. Genomewide linkage screen for Waldenstrom macroglobulinemia susceptibility loci in high-risk families. Am J Hum Genet. 2006;79(4):695–701.

    Article  PubMed  CAS  Google Scholar 

  23. Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, et al. Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS. J Biol Chem. 2000;275(45):35478–85.

    Article  PubMed  CAS  Google Scholar 

  24. Hunter ZR, Leleu X, Santos DD, Hamilton S, Verselis S, Fox EA et al. (2005) Sequence analysis in the BLYS and APRIL receptor TACI reveals novel variants with a potential pathogenetic role in Waldenstrom’s macroglobulinemia (WM). ASH Annual Meeting Abstracts 2005 November 16, 2005;106(11):991

    Google Scholar 

  25. Hunter ZR, Manning RJ, Hanzis C, Ciccarelli BT, Ioakimidis L, Patterson CJ, et al. IgA and IgG hypogammaglobulinemia in Waldenstrom’s macroglobulinemia. Haematologica. 2010;95(3):470–5.

    Article  PubMed  CAS  Google Scholar 

  26. Braggio E, Keats JJ, Leleu X, Van Wier S, Jimenez-Zepeda VH, Valdez R, et al. Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom’s macroglobulinemia. Cancer Res. 2009;69(8):3579–88.

    Article  PubMed  CAS  Google Scholar 

  27. Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF, et al. Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. Blood. 2006;108(8):2755–63.

    Article  PubMed  CAS  Google Scholar 

  28. Gutierrez NC, Ocio EM, de Las Rivas J, Maiso P, Delgado M, Ferminan E, et al. Gene expression profiling of B lymphocytes and plasma cells from Waldenstrom’s macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals. Leukemia. 2007;21(3):541–9.

    Article  PubMed  CAS  Google Scholar 

  29. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Semin Oncol. 2003;30(2):169–71.

    Article  PubMed  CAS  Google Scholar 

  30. Morra E, Cesana C, Klersy C, Barbarano L, Varettoni M, Cavanna L, et al. Clinical characteristics and factors predicting evolution of asymptomatic IgM monoclonal gammopathies and IgM-related disorders. Leukemia. 2004;18(9):1512–7.

    Article  PubMed  CAS  Google Scholar 

  31. Garcia-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A, et al. Waldenstrom macroglobulinaemia: presenting features and outcome in a series with 217 cases. Br J Haematol. 2001;115(3):575–82.

    Article  PubMed  CAS  Google Scholar 

  32. Gertz MA, Merlini G, Treon SP. Amyloidosis and Waldenstrom’s macroglobulinemia. Hematology Am Soc Hematol Educ Program 2004:257–82.

    Google Scholar 

  33. Kyle RA, Treon SP, Alexanian R, Barlogie B, Bjorkholm M, Dhodapkar M, et al. Prognostic markers and criteria to initiate therapy in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol. 2003;30(2):116–20.

    Article  PubMed  Google Scholar 

  34. Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M. Waldenstrom’s macroglobulinemia: clinical features, complications, and management. J Clin Oncol. 2000;18(1):214–26.

    PubMed  CAS  Google Scholar 

  35. Kyrtsonis MC, Angelopoulou MK, Kontopidou FN, Siakantaris MP, Dimopoulou MN, Mitropoulos F, et al. Primary lung involvement in Waldenstrom’s macroglobulinaemia: report of two cases and review of the literature. Acta Haematol. 2001;105(2):92–6.

    Article  PubMed  CAS  Google Scholar 

  36. Lin P, Bueso-Ramos C, Wilson CS, Mansoor A, Medeiros LJ. Waldenstrom macroglobulinemia involving extramedullary sites: morphologic and immunophenotypic findings in 44 patients. Am J Surg Pathol. 2003;27(8):1104–13.

    Article  PubMed  Google Scholar 

  37. Fadil A, Taylor DE. The lung and Waldenstrom’s macroglobulinemia. South Med J. 1998;91(7):681–5.

    Article  PubMed  CAS  Google Scholar 

  38. Corless JA, Allsup DJ, Deeble TJ, Delaney JC. A pulmonary mass and hyperviscosity. Postgrad Med J. 2000;76(899):582.

    Article  PubMed  CAS  Google Scholar 

  39. Cline WS, Imbeau SA, Morrissey JF. Involvement of the stomach with Waldenstrom’s macroglobulinemia. Gastrointest Endosc. 1975;21(4):166–7.

    Article  PubMed  CAS  Google Scholar 

  40. Yap JC, Poh SC. Waldenstrom’s macroglobulinemia presenting with pleuropulmonary and gastric manifestations. Singapore Med J. 1990;31(4):405–8.

    PubMed  CAS  Google Scholar 

  41. Moore Jr DF, Moulopoulos LA, Dimopoulos MA. Waldenstrom macroglobulinemia presenting as a renal or perirenal mass: clinical and radiographic features. Leuk Lymphoma. 1995;17(3–4):331–4.

    Article  PubMed  Google Scholar 

  42. Daoud MS, Lust JA, Kyle RA, Pittelkow MR. Monoclonal gammopathies and associated skin disorders. J Am Acad Dermatol. 1999;40(4):507–35. quiz 36–8.

    Article  PubMed  CAS  Google Scholar 

  43. Abdallah-Lotf M, Bourgeois-Droin C, Perronne V, Fouchard N, Michel S, Launay-Russ E, et al. Cutaneous manifestations as initial presentation of Waldenstrom’s macroglobulinemia. Eur J Dermatol. 2003;13(1):90–2.

    PubMed  Google Scholar 

  44. Yokote T, Akioka T, Oka S, Hara S, Kobayashi K, Hirata Y, et al. Cutaneous infiltration with Waldenstrom macroglobulinemia. Leuk Res. 2006;30(9):1207–10.

    Article  PubMed  CAS  Google Scholar 

  45. Giarelli L, Melato M, Falconieri G. Eye involvement in Waldenstroms’s macroglobulinaemia. Ophthalmologica. 1982;185(4):214–9.

    Article  PubMed  CAS  Google Scholar 

  46. Klapper SR, Jordan DR, Pelletier C, Brownstein S, Punja K. Ptosis in Waldenstrom’s macroglobulinemia. Am J Ophthalmol. 1998;126(2):315–7.

    Article  PubMed  CAS  Google Scholar 

  47. Drappatz J, Akar S, Fisher DC, Samuels MA, Kesari S. Imaging of Bing-Neel syndrome. Neurology. 2008;70(16):1364.

    Article  PubMed  CAS  Google Scholar 

  48. Grewal JS, Brar PK, Sahijdak WM, Tworek JA, Chottiner EG. Bing-Neel syndrome: a case report and systematic review of clinical manifestations, diagnosis, and treatment options. Clin Lymphoma Myeloma. 2009;9(6):462–6.

    Article  PubMed  Google Scholar 

  49. Zhang S, Gottardi-Littell NR, Nayar R, De Frias D. Cytology features of Bing-Neel syndrome. Acta Cytol. 2009;53(2):240–3.

    Article  PubMed  Google Scholar 

  50. Fintelmann F, Forghani R, Schaefer PW, Hochberg EP, Hochberg FH. Bing-Neel syndrome revisited. Clin Lymphoma Myeloma. 2009;9(1):104–6.

    Article  PubMed  Google Scholar 

  51. Kolbaske S, Grossmann A, Benecke R, Wittstock M. Progressive gait ataxia and intention tremor in a case of Bing-Neel syndrome. J Neurol. 2009;256(8):1366–8.

    Article  PubMed  Google Scholar 

  52. Leschziner GD, Roncaroli F, Moss J, Guiloff RJ. Nineteen-year follow-up of Waldenstrom’s-associated neuropathy and Bing-Neel syndrome. Muscle Nerve. 2009;39(1):95–100.

    Article  PubMed  Google Scholar 

  53. Malkani RG, Tallman M, Gottardi-Littell N, Karpus W, Marszalek L, Variakojis D, et al. Bing-Neel syndrome: an illustrative case and a comprehensive review of the published literature. J Neurooncol. 2010;96(3):301–12.

    Article  PubMed  Google Scholar 

  54. Stone MJ. Waldenstrom’s macroglobulinemia: hyperviscosity syndrome and cryoglobulinemia. Clin Lymphoma Myeloma. 2009;9(1):97–9.

    Article  PubMed  Google Scholar 

  55. Menke MN, Feke GT, McMeel JW, Treon SP. Ophthalmologic techniques to assess the severity of hyperviscosity syndrome and the effect of plasmapheresis in patients with Waldenstrom’s macroglobulinemia. Clin Lymphoma Myeloma. 2009;9(1):100–3.

    Article  PubMed  Google Scholar 

  56. Siami GA, Siami FS. Plasmapheresis and paraproteinemia: cryoprotein-induced diseases, monoclonal gammopathy, Waldenstrom’s macroglobulinemia, hyperviscosity syndrome, multiple myeloma, light chain disease, and amyloidosis. Ther Apher. 1999;3(1):8–19.

    Article  PubMed  CAS  Google Scholar 

  57. Drew MJ. Plasmapheresis in the dysproteinemias. Ther Apher. 2002;6(1):45–52.

    Article  PubMed  Google Scholar 

  58. Thiagarajan P, Shapiro SS, De Marco L. Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant. J Clin Invest. 1980;66(3):397–405.

    Article  PubMed  CAS  Google Scholar 

  59. Michiels JJ, van Vliet HH. Acquired von Willebrand disease in monoclonal gammapathies: effectiveness of high-dose intravenous gamma globulin. Clin Appl Thromb Hemost. 1999;5(3):152–7.

    Article  PubMed  CAS  Google Scholar 

  60. Zangari M, Elice F, Fink L, Tricot G. Hemostatic dysfunction in paraproteinemias and amyloidosis. Semin Thromb Hemost. 2007;33(4):339–49.

    Article  PubMed  Google Scholar 

  61. Harada Y, Ido N, Okada T, Otani M, Shirota T, Nakao T, et al. Nephrotic syndrome caused by protein thrombi in glomerulocapillary lumen in Waldenstrom’s macroglobulinaemia. Br J Haematol. 2000;110(4):880–3.

    Article  PubMed  CAS  Google Scholar 

  62. Yonemura K, Suzuki T, Sano K, Fujigaki Y, Ikegaya N, Hishida A. A case with acute renal failure complicated by Waldenstrom’s macroglobulinemia and cryoglobulinemia. Ren Fail. 2000;22(4):511–5.

    Article  PubMed  CAS  Google Scholar 

  63. Merlini G, Pozzi C. Mechanisms of renal damage in plasma cell dyscrasias: an overview. Contrib Nephrol. 2007;153:66–86.

    Article  PubMed  CAS  Google Scholar 

  64. Isaac J, Herrera GA. Cast nephropathy in a case of Waldenstrom’s macroglobulinemia. Nephron. 2002;91(3):512–5.

    Article  PubMed  Google Scholar 

  65. Spillane EL, Xia Y, Turiansky GW. Atypical cutaneous presentation of Waldenstrom macroglobulinemia: an extensive erythematous patch mimicking an angiosarcoma. Cutis. 2008;81(1):67–8.

    PubMed  Google Scholar 

  66. Hanke CW, Steck WD, Bergfeld WF, Valenzuela R, Weick JK, Young JR, et al. Cutaneous macroglobulinosis. Arch Dermatol. 1980;116(5):575–7.

    Article  PubMed  CAS  Google Scholar 

  67. Tichenor RE, Rau JM, Mantz FA. Macroglobulinemia cutis. Arch Dermatol. 1978;114(2):280–1.

    Article  PubMed  CAS  Google Scholar 

  68. Brandt LJ, Davidoff A, Bernstein LH, Biempica L, Rindfleisch B, Goldstein ML. Small-intestine involvement in Waldenstrom’s macroglobulinemia. Case report and review of the literature. Dig Dis Sci. 1981;26(2):174–80.

    Article  PubMed  CAS  Google Scholar 

  69. Mattila J, Alavaikko M, Jarventie G, Lehtinen M, Pitkanen R. Macroglobulinemia with abdominal symptoms caused by intestinal extracellular macroglobulin. Virchows Arch A Pathol Anat Histol. 1980;389(2):241–51.

    Article  PubMed  CAS  Google Scholar 

  70. Gertz MA, Kyle RA, Noel P. Primary systemic amyloidosis: a rare complication of immunoglobulin M monoclonal gammopathies and Waldenstrom’s macroglobulinemia. J Clin Oncol. 1993;11(5):914–20.

    PubMed  CAS  Google Scholar 

  71. Palladini G, Russo P, Bosoni T, Sarais G, Lavatelli F, Foli A, et al. AL amyloidosis associated with IgM monoclonal protein: a distinct clinical entity. Clin Lymphoma Myeloma. 2009;9(1):80–3.

    Article  PubMed  CAS  Google Scholar 

  72. Gardyn J, Schwartz A, Gal R, Lewinski U, Kristt D, Cohen AM. Waldenstrom’s macroglobulinemia associated with AA amyloidosis. Int J Hematol. 2001;74(1):76–8.

    Article  PubMed  CAS  Google Scholar 

  73. Moyner K, Sletten K, Husby G, Natvig JB. An unusually large (83 amino acid residues) amyloid fibril protein AA from a patient with Waldenstrom’s macroglobulinaemia and amyloidosis. Scand J Immunol. 1980;11(5):549–54.

    Article  PubMed  CAS  Google Scholar 

  74. Nobile-Orazio E, Marmiroli P, Baldini L, Spagnol G, Barbieri S, Moggio M, et al. Peripheral neuropathy in macroglobulinemia: incidence and antigen-specificity of M proteins. Neurology. 1987;37(9):1506–14.

    Article  PubMed  CAS  Google Scholar 

  75. Nobile-Orazio E, Francomano E, Daverio R, Barbieri S, Marmiroli P, Manfredini E, et al. Anti-myelin-associated glycoprotein IgM antibody titers in neuropathy associated with macroglobulinemia. Ann Neurol. 1989;26(4):543–50.

    Article  PubMed  CAS  Google Scholar 

  76. Nobile-Orazio E. IgM paraproteinaemic neuropathies. Curr Opin Neurol. 2004;17(5):599–605.

    Article  PubMed  CAS  Google Scholar 

  77. Mauermann ML, Ryan ML, Moon JS, Klein CJ. Case of mononeuritis multiplex onset with rituximab therapy for Waldenstrom’s macroglobulinemia. J Neurol Sci. 2007;260(1–2):240–3.

    Article  PubMed  Google Scholar 

  78. Stone MJ, Merlini G, Pascual V. Autoantibody activity in Waldenstrom’s macroglobulinemia. Clin Lymphoma. 2005;5(4):225–9.

    Article  PubMed  CAS  Google Scholar 

  79. Crisp D, Pruzanski W. B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins). Am J Med. 1982;72(6):915–22.

    Article  PubMed  CAS  Google Scholar 

  80. Meier C. Polyneuropathy in paraproteinaemia. J Neurol. 1985;232(4):204–14.

    Article  PubMed  CAS  Google Scholar 

  81. Berentsen S. Cold agglutinin-mediated autoimmune hemolytic anemia in Waldenstrom’s macroglobulinemia. Clin Lymphoma Myeloma. 2009;9(1):110–2.

    Article  PubMed  CAS  Google Scholar 

  82. Gandhi S, Little MA, Farrington K. Waldenstrom’s macroglobulinemia presenting as Goodpasture’s syndrome. Ren Fail. 2004;26(5):591–6.

    Article  PubMed  Google Scholar 

  83. Tsuji M, Ochiai S, Taka T, Hishitani Y, Nagareda T, Mori H. Nonamyloidotic nephrotic syndrome in Waldenstrom’s macroglobulinemia. Nephron. 1990;54(2):176–8.

    Article  PubMed  CAS  Google Scholar 

  84. Perera GK, Devereux S, Mufti G, Salisbury J, Creamer D. PNP with Waldenstrom’s macroglobulinaemia. Clin Exp Dermatol. 2005;30(1):27–9.

    Article  PubMed  CAS  Google Scholar 

  85. Schadlow MB, Anhalt GJ, Sinha AA. Using rituximab (anti-CD20 antibody) in a patient with paraneoplastic pemphigus. J Drugs Dermatol. 2003;2(5):564–7.

    PubMed  Google Scholar 

  86. Desai RG. An unusual case of Hansen’s disease (lepromatous ­leprosy) with circulating anticoagulant and macroglobulinemia. Int J Lepr Other Mycobact Dis. 1990;58(3):462–5.

    PubMed  CAS  Google Scholar 

  87. Tait RC, Oogarah PK, Houghton JB, Farrand SE, Haeney MR. Waldenstrom’s macroglobulinaemia secreting a paraprotein with lupus anticoagulant activity: possible association with gastrointestinal tract disease and malabsorption. J Clin Pathol. 1993;46(7):678–80.

    Article  PubMed  CAS  Google Scholar 

  88. Wisloff F, Michaelsen TE, Godal HC. Monoclonal IgM with lupus anticoagulant activity in a case of Waldenstrom’s macroglobulinaemia. Eur J Haematol. 1987;38(5):456–60.

    Article  PubMed  CAS  Google Scholar 

  89. Whittaker SJ, Bhogal BS, Black MM. Acquired immunobullous disease: a cutaneous manifestation of IgM macroglobulinaemia. Br J Dermatol. 1996;135(2):283–6.

    Article  PubMed  CAS  Google Scholar 

  90. Kastritis E, Katoulis A, Terpos E, Panayiotides I, Gavriatopoulopu M, Dimopopoulos MA. Schnitzler’s syndrome: increased levels of bone formation and angiogenesis factors are reduced after successful pefloxacin treatment. Clin Lymphoma Myeloma. 2008;8(6):359–62.

    Article  PubMed  Google Scholar 

  91. de Koning HD, Bodar EJ, van der Meer JW, Simon A. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. 2007;37(3):137–48.

    Article  PubMed  Google Scholar 

  92. Dimopoulos MA, Gertz MA, Kastritis E, Garcia-Sanz R, Kimby EK, Leblond V, et al. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom’s Macroglobulinemia. J Clin Oncol. 2009;27(1):120–6.

    Article  PubMed  Google Scholar 

  93. Varticovski L, Pick AI, Schattner A, Shoenfeld Y. Anti-platelet and anti-DNA IgM in Waldenstrom macroglobulinemia and ITP. Am J Hematol. 1987;24(4):351–5.

    Article  PubMed  CAS  Google Scholar 

  94. Yamamoto K, Nagata K, Hamaguchi H. Elevated platelet-associated IgG in immune thrombocytopenic purpura associated with Waldenstrom’s macroglobulinemia. Am J Hematol. 2002;69(1):85–6.

    Article  PubMed  Google Scholar 

  95. Owen RG, Lubenko A, Savage J, Parapia LA, Jack AS, Morgan GJ. Autoimmune thrombocytopenia in Waldenstrom’s macroglobulinemia. Am J Hematol. 2001;66(2):116–9.

    Article  PubMed  CAS  Google Scholar 

  96. O’Connell TX, Horita TJ, Kasravi B. Understanding and interpreting serum protein electrophoresis. Am Fam Physician. 2005;71(1):105–12.

    PubMed  Google Scholar 

  97. Jellum E, Thorsrud AK. High resolution two-dimensional protein electrophoresis in clinical chemistry. Scand J Clin Lab Invest Suppl. 1986;184:71–6.

    PubMed  CAS  Google Scholar 

  98. Morita K, Okamoto Y. The discrepancy between electrophoretic and nephelometric determinations of serum gamma-globulin level. Clin Lab. 2004;50(7–8):415–8.

    PubMed  CAS  Google Scholar 

  99. Jonsson M, Carlson J, Jeppsson JO, Simonsson P. Computer-supported detection of M-components and evaluation of immunoglobulins after capillary electrophoresis. Clin Chem. 2001;47(1):110–7.

    PubMed  CAS  Google Scholar 

  100. Sinclair D, Ballantyne F, Shanley S, Caine E, O’Reilly D, Shenkin A. Estimation of paraproteins by immunoturbidimetry and electrophoresis followed by scanning densitometry. Ann Clin Biochem. 1990;27(Pt 4):335–7.

    PubMed  Google Scholar 

  101. Shihabi ZK. Cryoglobulins: an important but neglected clinical test. Ann Clin Lab Sci. 2006;36(4):395–408.

    PubMed  CAS  Google Scholar 

  102. Anagnostopoulos A, Zervas K, Kyrtsonis M, Symeonidis A, Gika D, Bourantas K, et al. Prognostic value of serum beta2-microglobulin in patients with Waldenstrom’s macroglobulinemia requiring treatment. Clin Lymphoma Myeloma. 2006;7(3):205–9.

    Article  PubMed  CAS  Google Scholar 

  103. Kastritis E, Kyrtsonis MC, Hadjiharissi E, Symeonidis A, Michalis E, Repoussis P, et al. Validation of the International Prognostic Scoring System (IPSS) for Waldenstrom’s macroglobulinemia (WM) and the importance of serum lactate dehydrogenase (LDH). Leuk Res. 2010;34(10):1340–3.

    Article  PubMed  CAS  Google Scholar 

  104. Menke MN, Feke GT, McMeel JW, Treon SP. Effect of plasmapheresis on hyperviscosity-related retinopathy and retinal hemodynamics in patients with Waldenstrom’s macroglobulinemia. Invest Ophthalmol Vis Sci. 2008;49(3):1157–60.

    Article  PubMed  Google Scholar 

  105. Tedeschi A, Barate C, Minola E, Morra E. Cryoglobulinemia. Blood Rev. 2007;21(4):183–200.

    Article  PubMed  CAS  Google Scholar 

  106. Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol. 2003;30(2):110–5.

    Article  PubMed  Google Scholar 

  107. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17(12):3835–49.

    PubMed  CAS  Google Scholar 

  108. Pangalis GA, Angelopoulou MK, Vassilakopoulos TP, Siakantaris MP, Kittas C. B-chronic lymphocytic leukemia, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma, including Waldenstrom’s macroglobulinemia: a clinical, morphologic, and biologic spectrum of similar disorders. Semin Hematol. 1999;36(2):104–14.

    PubMed  CAS  Google Scholar 

  109. Remstein ED, Hanson CA, Kyle RA, Hodnefield JM, Kurtin PJ. Despite apparent morphologic and immunophenotypic heterogeneity, Waldenstrom’s macroglobulinemia is consistently composed of cells along a morphologic continuum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. Semin Oncol. 2003;30(2):182–6.

    Article  PubMed  Google Scholar 

  110. Owen RG. Developing diagnostic criteria in Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):196–200.

    Article  PubMed  Google Scholar 

  111. Konoplev S, Medeiros LJ, Bueso-Ramos CE, Jorgensen JL, Lin P. Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. Am J Clin Pathol. 2005;124(3):414–20.

    Article  PubMed  Google Scholar 

  112. Pangalis GA, Kyrtsonis MC, Kontopidou FN, Vassilakopoulos TP, Siakantaris MP, Dimopoulou MN, et al. Differential diagnosis of Waldenstrom’s macroglobulinemia from other low-grade B-cell lymphoproliferative disorders. Semin Oncol. 2003;30(2):201–5.

    Article  PubMed  Google Scholar 

  113. San Miguel JF, Vidriales MB, Ocio E, Mateo G, Sanchez-Guijo F, Sanchez ML, et al. Immunophenotypic analysis of Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):187–95.

    Article  PubMed  CAS  Google Scholar 

  114. Santos DD, Hatjiharissi E, Tournilhac O, Chemaly MZ, Leleu X, Xu L, et al. CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom’s Macroglobulinemia and mast cell disorders. Clin Lymphoma Myeloma. 2006;6(6):478–83.

    Article  PubMed  CAS  Google Scholar 

  115. Tournilhac O, Santos DD, Xu L, Kutok J, Tai YT, Le Gouill S, et al. Mast cells in Waldenstrom’s macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling. Ann Oncol. 2006;17(8):1275–82.

    Article  PubMed  CAS  Google Scholar 

  116. Owen RG, Hillmen P, Rawstron AC. CD52 expression in Waldenstrom’s macroglobulinemia: implications for alemtuzumab therapy and response assessment. Clin Lymphoma. 2005;5(4):278–81.

    Article  PubMed  CAS  Google Scholar 

  117. Owen RG, Barrans SL, Richards SJ, O’Connor SJ, Child JA, Parapia LA, et al. Waldenstrom macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors. Am J Clin Pathol. 2001;116(3):420–8.

    Article  PubMed  CAS  Google Scholar 

  118. Matutes E, Owusu-Ankomah K, Morilla R, Garcia Marco J, Houlihan A, Que TH, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 1994;8(10):1640–5.

    PubMed  CAS  Google Scholar 

  119. Chang H, Samiee S, Li D, Patterson B, Chen CI, Stewart AK. Analysis of IgH translocations, chromosome 13q14 and 17p13.1(p53) deletions by fluorescence in situ hybridization in Waldenstrom’s macroglobulinemia: a single center study of 22 cases. Leukemia. 2004;18(6):1160–2.

    Article  PubMed  CAS  Google Scholar 

  120. Hunter ZR, Branagan AR, Manning R, Patterson CJ, Santos DD, Tournilhac O, et al. CD5, CD10, and CD23 expression in Waldenstrom’s macroglobulinemia. Clin Lymphoma. 2005;5(4):246–9.

    Article  PubMed  CAS  Google Scholar 

  121. Schop RF, Kuehl WM, Van Wier SA, Ahmann GJ, Price-Troska T, Bailey RJ, et al. Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood. 2002;100(8):2996–3001.

    Article  PubMed  CAS  Google Scholar 

  122. Schop RF, Fonseca R. Genetics and cytogenetics of Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):142–5.

    Article  PubMed  CAS  Google Scholar 

  123. Schop RF, Jalal SM, Van Wier SA, Ahmann GJ, Bailey RJ, Kyle RA, et al. Deletions of 17p13.1 and 13q14 are uncommon in Waldenstrom macroglobulinemia clonal cells and mostly seen at the time of disease progression. Cancer Genet Cytogenet. 2002;132(1):55–60.

    Article  PubMed  CAS  Google Scholar 

  124. Schop RF, Van Wier SA, Xu R, Ghobrial I, Ahmann GJ, Greipp PR, et al. 6q deletion discriminates Waldenstrom macroglobulinemia from IgM monoclonal gammopathy of undetermined significance. Cancer Genet Cytogenet. 2006;169(2):150–3.

    Article  PubMed  CAS  Google Scholar 

  125. Terre C, Nguyen-Khac F, Barin C, Mozziconacci MJ, Eclache V, Leonard C, et al. Trisomy 4, a new chromosomal abnormality in Waldenstrom’s macroglobulinemia: a study of 39 cases. Leukemia. 2006;20(9):1634–6.

    Article  PubMed  CAS  Google Scholar 

  126. Mansoor A, Medeiros LJ, Weber DM, Alexanian R, Hayes K, Jones D, et al. Cytogenetic findings in lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. Chromosomal abnormalities are associated with the polymorphous subtype and an aggressive clinical course. Am J Clin Pathol. 2001;116(4):543–9.

    Article  PubMed  CAS  Google Scholar 

  127. Chang H, Qi X, Xu W, Reader JC, Ning Y. Analysis of 6q deletion in Waldenstrom macroglobulinemia. Eur J Haematol. 2007;79(3):244–7.

    Article  PubMed  CAS  Google Scholar 

  128. Liu YC, Miyazawa K, Sashida G, Kodama A, Ohyashiki K. Deletion (20q) as the sole abnormality in Waldenstrom macroglobulinemia suggests distinct pathogenesis of 20q11 anomaly. Cancer Genet Cytogenet. 2006;169(1):69–72.

    Article  PubMed  CAS  Google Scholar 

  129. Chang H, Qi C, Trieu Y, Jiang A, Young KH, Chesney A, et al. Prognostic relevance of 6q deletion in Waldenstrom’s macroglobulinemia: a multicenter study. Clin Lymphoma Myeloma. 2009;9(1):36–8.

    Article  PubMed  CAS  Google Scholar 

  130. Ocio EM, Schop RF, Gonzalez B, Van Wier SA, Hernandez-Rivas JM, Gutierrez NC, et al. 6q deletion in Waldenstrom macroglobulinemia is associated with features of adverse prognosis. Br J Haematol. 2007;136(1):80–6.

    Article  PubMed  CAS  Google Scholar 

  131. Thieblemont C, Felman P, Callet-Bauchu E, Traverse-Glehen A, Salles G, Berger F, et al. Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. Lancet Oncol. 2003;4(2):95–103.

    Article  PubMed  CAS  Google Scholar 

  132. Avet-Loiseau H, Garand R, Lode L, Robillard N, Bataille R. 14q32 Translocations discriminate IgM multiple myeloma from Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):153–5.

    Article  PubMed  CAS  Google Scholar 

  133. Avet-Loiseau H, Garand R, Lode L, Harousseau JL, 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.

    Article  PubMed  CAS  Google Scholar 

  134. Schuster S, Dispenzieri A, Rajkumar SV, Aspitia AM, Kyle R, Mikhael JR (2009) IgM multiple Myeloma: disease definition, prognosis, and differentiation from Waldenstrom’s macroglobulinemia. ASH Annual Meeting Abstracts 2009 November 20, 2009;114(22):1828.

    Google Scholar 

  135. Lin P, Mansoor A, Bueso-Ramos C, Hao S, Lai R, Medeiros LJ. Diffuse large B-cell lymphoma occurring in patients with lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. Clinicopathologic features of 12 cases. Am J Clin Pathol. 2003;120(2):246–53.

    Article  PubMed  Google Scholar 

  136. Leleu X, Manning R, Soumerai J, Hunter ZR, Moreau AS, Hatjiharissi E, Roccaro A, Sacco A, Adamia S, Patterson CJ, Ghobrial IM, Treaon SP. Increased incidence of disease transformation and development of MDS/AML in Waldenstrom’s Macroglobulinemia patients (WM) treated with nucleoside analogs. Haematologica. 2007;92(s2):WM 3.10.

    Google Scholar 

  137. Kimby E, Treon SP, Anagnostopoulos A, Dimopoulos M, Garcia-Sanz R, Gertz MA, et al. Update on recommendations for assessing response from the Third International Workshop on Waldenstrom’s Macroglobulinemia. Clin Lymphoma Myeloma. 2006;6(5):380–3.

    Article  PubMed  Google Scholar 

  138. Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood. 2003;102(10):3759–64.

    Article  PubMed  CAS  Google Scholar 

  139. Hoffkes HG, Heemann UW, Teschendorf C, Uppenkamp M, Philipp T. Hyperviscosity syndrome: efficacy and comparison of plasma exchange by plasma separation and cascade filtration in patients with immunocytoma of Waldenstrom’s type. Clin Nephrol. 1995;43(5):335–8.

    PubMed  CAS  Google Scholar 

  140. Reinhart WH, Lutolf O, Nydegger UR, Mahler F, Straub PW. Plasmapheresis for hyperviscosity syndrome in macroglobulinemia Waldenstrom and multiple myeloma: influence on blood ­rheology and the microcirculation. J Lab Clin Med. 1992;119(1):69–76.

    PubMed  CAS  Google Scholar 

  141. Kuenn JW, Weber R, Teague PO, Keitt AS. Cryopathic gangrene with an IgM lambda cryoprecipitating cold agglutinin. Cancer. 1978;42(4):1826–33.

    Article  PubMed  CAS  Google Scholar 

  142. Kyle RA, Greipp PR, Gertz MA, Witzig TE, Lust JA, Lacy MQ, et al. Waldenstrom’s macroglobulinaemia: a prospective study comparing daily with intermittent oral chlorambucil. Br J Haematol. 2000;108(4):737–42.

    Article  PubMed  CAS  Google Scholar 

  143. Dimopoulos MA, O’Brien S, Kantarjian H, Pierce S, Delasalle K, Barlogie B, et al. Fludarabine therapy in Waldenstrom’s macroglobulinemia. Am J Med. 1993;95(1):49–52.

    Article  PubMed  CAS  Google Scholar 

  144. Dhodapkar MV, Jacobson JL, Gertz MA, Crowley JJ, Barlogie B. Prognostic factors and response to fludarabine therapy in Waldenstrom’s macroglobulinemia: an update of a US intergroup trial (SW0G S9003). Semin Oncol. 2003;30(2):220–5.

    Article  PubMed  Google Scholar 

  145. Dhodapkar MV, Hoering A, Gertz MA, Rivkin S, Szymonifka J, Crowley J, et al. Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group-directed intergroup trial S9003. Blood. 2009;113(4):793–6.

    Article  PubMed  CAS  Google Scholar 

  146. Dimopoulos MA, Kantarjian H, Estey E, O’Brien S, Delasalle K, Keating MJ, et al. Treatment of Waldenstrom macroglobulinemia with 2-chlorodeoxyadenosine. Ann Intern Med. 1993;118(3):195–8.

    PubMed  CAS  Google Scholar 

  147. O’Brien S, Kantarjian H, Keating MJ. Purine analogs in chronic lymphocytic leukemia and Waldenstrom’s macroglobulinemia. Ann Oncol. 1996;7 Suppl 6:S27–33.

    Article  PubMed  Google Scholar 

  148. Laurencet FM, Zulian GB, Guetty-Alberto M, Iten PA, Betticher DC, Alberto P. Cladribine with cyclophosphamide and prednisone in the management of low-grade lymphoproliferative malignancies. Br J Cancer. 1999;79(7–8):1215–9.

    Article  PubMed  CAS  Google Scholar 

  149. Van Den Neste E, Louviaux I, Michaux JL, Delannoy A, Michaux L, Sonet A, et al. Phase I/II study of 2-chloro-2′-deoxyadenosine with cyclophosphamide in patients with pretreated B cell chronic lymphocytic leukemia and indolent non-Hodgkin’s lymphoma. Leukemia. 2000;14(6):1136–42.

    Article  CAS  Google Scholar 

  150. Weber DM, Dimopoulos MA, Delasalle K, Rankin K, Gavino M, Alexanian R. 2-Chlorodeoxyadenosine alone and in combination for previously untreated Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):243–7.

    Article  PubMed  CAS  Google Scholar 

  151. Zinzani PL, Gherlinzoni F, Bendandi M, Zaccaria A, Aitini E, Salvucci M, et al. Fludarabine treatment in resistant Waldenstrom’s macroglobulinemia. Eur J Haematol. 1995;54(2):120–3.

    Article  PubMed  CAS  Google Scholar 

  152. Leblond V, Ben-Othman T, Deconinck E, Taksin AL, Harousseau JL, Delgado MA, et al. Activity of fludarabine in previously treated Waldenstrom’s macroglobulinemia: a report of 71 cases. Groupe Cooperatif Macroglobulinemie. J Clin Oncol. 1998;16(6):2060–4.

    PubMed  CAS  Google Scholar 

  153. Leblond V, Levy V, Maloisel F, Cazin B, Fermand JP, Harousseau JL, et al. Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenstrom macroglobulinemia in first relapse or with primary refractory disease. Blood. 2001;98(9):2640–4.

    Article  PubMed  CAS  Google Scholar 

  154. Tam CS, Wolf M, Prince HM, Januszewicz EH, Westerman D, Lin KI, et al. Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma. Cancer. 2006;106(11):2412–20.

    Article  PubMed  CAS  Google Scholar 

  155. Tedeschi A, Miqueleiz S, Ricci F, Luraschi A, Schiavone M, Andriani A et al. Fludarabine, Cyclophosphamide and Rituximab in Waldenstrom’s Macroglobulinemia: An effective regimen requiring a new category of response criteria and a delayed assessment of results. ASH Annual Meeting Abstracts 2007 November 16, 2007;110(11):1290.

    Google Scholar 

  156. Vargaftig J, Pegourie-Bandelier B, Mahe B, Le Gouill S, Brottier-Mancini E, Delarue R, Buzyn A, Maigre M, Gardin C, Choquet S, Leblond V. Fludarabine plus cyclophosphamide and rituximab (RFC) in Waldenstrom’s macroglobulinemia (WM): Results in 25 patients. Haematologica. 2007;92(s2):PO-1226.

    Google Scholar 

  157. Treon SP, Branagan AR, Ioakimidis L, Soumerai JD, Patterson CJ, Turnbull B, et al. Long-term outcomes to fludarabine and rituximab in Waldenstrom macroglobulinemia. Blood. 2009;113(16):3673–8.

    Article  PubMed  CAS  Google Scholar 

  158. Cheson BD. Rituximab: clinical development and future directions. Expert Opin Biol Ther. 2002;2(1):97–110.

    Article  PubMed  CAS  Google Scholar 

  159. Dimopoulos MA, Kastritis E, Roussou M, Eleutherakis-Papaiakovou E, Migkou M, Gavriatopoulou M, et al. Rituximab-based treatments in Waldenstrom’s macroglobulinemia. Clin Lymphoma Myeloma. 2009;9(1):59–61.

    Article  PubMed  CAS  Google Scholar 

  160. Gertz MA, Rue M, Blood E, Kaminer LS, Vesole DH, Greipp PR. Multicenter phase 2 trial of rituximab for Waldenstrom macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma. 2004;45(10):2047–55.

    Article  PubMed  CAS  Google Scholar 

  161. Dimopoulos MA, Zervas C, Zomas A, Kiamouris C, Viniou NA, Grigoraki V, et al. Treatment of Waldenstrom’s macroglobulinemia with rituximab. J Clin Oncol. 2002;20(9):2327–33.

    Article  PubMed  CAS  Google Scholar 

  162. Treon SP, Emmanouilides C, Kimby E, Kelliher A, Preffer F, Branagan AR, et al. Extended rituximab therapy in Waldenstrom’s macroglobulinemia. Ann Oncol. 2005;16(1):132–8.

    Article  PubMed  CAS  Google Scholar 

  163. Treon SP, Hansen M, Branagan AR, Verselis S, Emmanouilides C, Kimby E, et al. Polymorphisms in FcgammaRIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstrom’s macroglobulinemia. J Clin Oncol. 2005;23(3):474–81.

    Article  PubMed  CAS  Google Scholar 

  164. Dimopoulos MA, Zervas C, Zomas A, Hamilos G, Gika D, Efstathiou E, et al. Extended rituximab therapy for previously untreated patients with Waldenstrom’s macroglobulinemia. Clin Lymphoma. 2002;3(3):163–6.

    Article  PubMed  CAS  Google Scholar 

  165. Ghobrial IM, Fonseca R, Greipp PR, Blood E, Rue M, Vesole DH, et al. Initial immunoglobulin M ‘flare’ after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia: an Eastern Cooperative Oncology Group Study. Cancer. 2004;101(11):2593–8.

    Article  PubMed  CAS  Google Scholar 

  166. Kilidireas C, Anagnostopoulos A, Karandreas N, Mouselimi L, Dimopoulos MA. Rituximab therapy in monoclonal IgM-related neuropathies. Leuk Lymphoma. 2006;47(5):859–64.

    Article  PubMed  CAS  Google Scholar 

  167. Thomas SK, DKB, Gavino M, Alexanian R, Weber DM. 2-CDA-Cyclophosphamide ± Rituximab for Symptomatic WM. Haematologica. [Abstract] 2007;92(s2):PO-1227.

    Google Scholar 

  168. Laszlo D, Rabascio C, Andreola G, Saronni L, Calabrese L, Rigacci L et al. Expression of the human concentrative nucleotide transporter (hCNT1) gene correlates with clinical response in patients affected by Waldenstrom’s macroglobulinemia (WM), undergoing a combination treatment with cladribine (2-CdA) and rituximab. ASH Annual Meeting Abstracts 2007 November 16, 2007;110(11):1357.

    Google Scholar 

  169. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, Zervas K, Tsatalas C, Kokkinis G, et al. Primary treatment of Waldenstrom macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide. J Clin Oncol. 2007;25(22):3344–9.

    Article  PubMed  CAS  Google Scholar 

  170. Abonour R, Zhang LA, Rajkumar V, Srkalovic G, Greipp PR, Fonseca R et al. Phase II pilot study of rituximab  +  CHOP in patients with newly diagnosed Waldenstrom’s macroglobulinemia, an Eastren Cooperative Oncology Group Trial (Study E1A02). ASH Annual Meeting Abstracts 2007 November 16, 2007;110(11):3616.

    Google Scholar 

  171. Buske C, Hoster E, Dreyling M, Eimermacher H, Wandt H, Metzner B, et al. The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia. 2008;23(1):153–61.

    Article  PubMed  CAS  Google Scholar 

  172. Mitsiades CS, Mitsiades N, Richardson PG, Treon SP, Anderson KC. Novel biologically based therapies for Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):309–12.

    Article  PubMed  CAS  Google Scholar 

  173. Roccaro AM, Leleu X, Sacco A, Jia X, Melhem M, Moreau AS, et al. Dual targeting of the proteasome regulates survival and homing in Waldenstrom macroglobulinemia. Blood. 2008;111(9):4752–63.

    Article  PubMed  CAS  Google Scholar 

  174. Leleu X, Xu L, Jia X, Sacco A, Farag M, Hunter ZR, et al. Endoplasmic reticulum stress is a target for therapy in Waldenstrom macroglobulinemia. Blood. 2009;113(3):626–34.

    Article  PubMed  CAS  Google Scholar 

  175. Roccaro AM, Sacco A, Aujay M, Ngo HT, Azab AK, Azab F, et al. Selective inhibition of chymotrypsin-like activity of the immunoproteasome and constitutive proteasome in Waldenstrom macroglobulinemia. Blood. 2010;115(20):4051–60.

    Article  PubMed  CAS  Google Scholar 

  176. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, Castritis E, Bitsaktsis A, Pangalis GA. Treatment of relapsed or refractory Waldenstrom’s macroglobulinemia with bortezomib. Haematologica. 2005;90(12):1655–8.

    PubMed  CAS  Google Scholar 

  177. Treon SP, Hunter ZR, Matous J, Joyce RM, Mannion B, Advani R, et al. Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom’s macroglobulinemia: results of WMCTG Trial 03-248. Clin Cancer Res. 2007;13(11):3320–5.

    Article  PubMed  CAS  Google Scholar 

  178. Chen CI, Kouroukis CT, White D, Voralia M, Stadtmauer E, Stewart AK, et al. Bortezomib is active in patients with untreated or relapsed Waldenstrom’s macroglobulinemia: a Phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(12):1570–5.

    Article  PubMed  CAS  Google Scholar 

  179. Ghobrial IM, Hong F, Padmanabhan S, Badros A, Rourke M, Leduc R, et al. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010;28(8):1422–8.

    Article  PubMed  CAS  Google Scholar 

  180. Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, et al. Primary therapy of Waldenstrom macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009;27(23):3830–5.

    Article  PubMed  CAS  Google Scholar 

  181. Agathocleous A, Rule S, Johnson P, Radford JA, Lafon N, Hunter H, et al. Preliminary results of a phase I/II study of weekly or twice weekly bortezomib in combination with rituximab, in patients with follicular lymphoma, mantle cell lymphoma and Waldenstrom’s macroglobulinaemia. ASH Annual Meeting Abstracts 2007 November 16, 2007;110(11):2559.

    Google Scholar 

  182. Dimopoulos MA, Zomas A, Viniou NA, Grigoraki V, Galani E, Matsouka C, et al. Treatment of Waldenstrom’s macroglobulinemia with thalidomide. J Clin Oncol. 2001;19(16):3596–601.

    PubMed  CAS  Google Scholar 

  183. Coleman M, Leonard J, Lyons L, Pekle K, Nahum K, Pearse R, et al. BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenstrom’s macroglobulinemia. Leuk Lymphoma. 2002;43(9):1777–82.

    Article  PubMed  CAS  Google Scholar 

  184. Dimopoulos MA, Tsatalas C, Zomas A, Hamilos G, Panayiotidis P, Margaritis D, et al. Treatment of Waldenstrom’s macroglobulinemia with single-agent thalidomide or with the combination of clarithromycin, thalidomide and dexamethasone. Semin Oncol. 2003;30(2):265–9.

    Article  PubMed  CAS  Google Scholar 

  185. Wu L, Adams M, Carter T, Chen R, Muller G, Stirling D, et al. lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res. 2008;14(14):4650–7.

    Article  PubMed  CAS  Google Scholar 

  186. Hernandez-Ilizaliturri FJ, Reddy N, Holkova B, Ottman E, Czuczman MS. Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res. 2005;11(16):5984–92.

    Article  PubMed  CAS  Google Scholar 

  187. Treon SP, Soumerai JD, Branagan AR, Hunter ZR, Patterson CJ, Ioakimidis L, et al. Thalidomide and rituximab in Waldenstrom macroglobulinemia. Blood. 2008;112(12):4452–7.

    Article  PubMed  CAS  Google Scholar 

  188. Treon SP, Soumerai JD, Branagan AR, Hunter ZR, Patterson CJ, Ioakimidis L, et al. Lenalidomide and rituximab in Waldenstrom’s macroglobulinemia. Clin Cancer Res. 2009;15(1):355–60.

    Article  PubMed  CAS  Google Scholar 

  189. Witzig TE, Kaufmann SH. Inhibition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in hematologic malignancies. Curr Treat Options Oncol. 2006;7(4):285–94.

    Article  PubMed  Google Scholar 

  190. Leleu X, Jia X, Runnels J, Ngo HT, Moreau AS, Farag M, et al. The Akt pathway regulates survival and homing in Waldenstrom Macroglobulinemia. Blood. 2007;110(13):4417–26.

    Article  PubMed  CAS  Google Scholar 

  191. Roccaro AM, Sacco A, Husu EN, Pitsillides C, Vesole S, Azab AK, et al. Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia. Blood. 2010;115(3):559–69.

    Article  PubMed  CAS  Google Scholar 

  192. Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P, et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol. 2005;23(23):5347–56.

    Article  PubMed  CAS  Google Scholar 

  193. Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, et al. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009;27(23):3822–9.

    Article  PubMed  CAS  Google Scholar 

  194. Ghobrial IM, Gertz M, Laplant B, Camoriano J, Hayman S, Lacy M, et al. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol. 2010;28(8):1408–14.

    Article  PubMed  CAS  Google Scholar 

  195. Ghobrial IM, Roccaro A, Hong F, Weller E, Rubin N, Leduc R, et al. Clinical and translational studies of a phase II trial of the novel oral Akt inhibitor perifosine in relapsed or relapsed/refractory Waldenstrom’s macroglobulinemia. Clin Cancer Res. 2010;16(3):1033–41.

    Article  PubMed  CAS  Google Scholar 

  196. Treon SP, Kelliher A, Keele B, Frankel S, Emmanouilides C, Kimby E, et al. Expression of serotherapy target antigens in Waldenstrom’s macroglobulinemia: therapeutic applications and considerations. Semin Oncol. 2003;30(2):248–52.

    Article  PubMed  CAS  Google Scholar 

  197. Gertz MA, Anagnostopoulos A, Anderson K, Branagan AR, Coleman M, Frankel SR, et al. Treatment recommendations in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol. 2003;30(2):121–6.

    Article  PubMed  Google Scholar 

  198. Ghobrial IM, Fonseca R, Gertz MA, Plevak MF, Larson DR, Therneau TM, et al. Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstrom macroglobulinaemia. Br J Haematol. 2006;133(2):158–64.

    Article  PubMed  Google Scholar 

  199. Kastritis E, Kyrtsonis MC, Hatjiharissi E, Symeonidis A, Michalis E, Repoussis P, et al. No significant improvement in the outcome of patients with Waldenstrom’s macroglobulinemia treated over the last 25 years. Am J Hematol. 2011;86(6):479–83.

    Article  PubMed  Google Scholar 

  200. Dimopoulos MA, Alexanian R, Gika D, Anagnostopoulos A, Zervas C, Zomas A, et al. Treatment of Waldenstrom’s macroglobulinemia with rituximab: prognostic factors for response and progression. Leuk Lymphoma. 2004;45(10):2057–61.

    Article  PubMed  CAS  Google Scholar 

  201. Dimopoulos MA, Hamilos G, Zervas K, Symeonidis A, Kouvatseas G, Roussou P, et al. Survival and prognostic factors after initiation of treatment in Waldenstrom’s macroglobulinemia. Ann Oncol. 2003;14(8):1299–305.

    Article  PubMed  CAS  Google Scholar 

  202. Dimopoulos MA, Kastritis E, Delimpassi S, Zomas A, Kyrtsonis MC, Zervas K. The international prognostic scoring system for Waldenstrom’s macroglobulinemia is applicable in patients treated with rituximab-based regimens. Haematologica. 2008;93(9):1420–2.

    Article  PubMed  CAS  Google Scholar 

  203. Facon T, Brouillard M, Duhamel A, Morel P, Simon M, Jouet JP, et al. Prognostic factors in Waldenstrom’s macroglobulinemia: a report of 167 cases. J Clin Oncol. 1993;11(8):1553–8.

    PubMed  CAS  Google Scholar 

  204. Gobbi PG, Bettini R, Montecucco C, Cavanna L, Morandi S, Pieresca C, et al. Study of prognosis in Waldenstrom’s macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility. Blood. 1994;83(10):2939–45.

    PubMed  CAS  Google Scholar 

  205. Kyrtsonis MC, Vassilakopoulos TP, Angelopoulou MK, Siakantaris P, Kontopidou FN, Dimopoulou MN, et al. Waldenstrom’s macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit. Ann Hematol. 2001;80(12):722–7.

    Article  PubMed  CAS  Google Scholar 

  206. Merlini G, Baldini L, Broglia C, Comelli M, Goldaniga M, Palladini G, et al. Prognostic factors in symptomatic Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):211–5.

    Article  PubMed  Google Scholar 

  207. Morel P, Duhamel A, Gobbi P, Dimopoulos MA, Dhodapkar MV, McCoy J, et al. International prognostic scoring system for Waldenstrom macroglobulinemia. Blood. 2009;113(18):4163–70.

    Article  PubMed  CAS  Google Scholar 

  208. Dimopoulos MA, Hamilos G, Efstathiou E, Siapkaras I, Matsouka C, Gika D, et al. Treatment of Waldenstrom’s macroglobulinemia with the combination of fludarabine and cyclophosphamide. Leuk Lymphoma. 2003;44(6):993–6.

    Article  PubMed  CAS  Google Scholar 

  209. Tamburini J, Levy V, Chaleteix C, Fermand JP, Delmer A, Stalniewicz L, et al. Fludarabine plus cyclophosphamide in Waldenstrom’s macroglobulinemia: results in 49 patients. Leukemia. 2005;19(10):1831–4.

    Article  PubMed  CAS  Google Scholar 

  210. Cervetti G, Galimberti S, Cecconi N, Caracciolo F, Petrini M. Role of low-dose 2-CdA in refractory or resistant lymphoplasmocytic lymphoma. J Chemother (Florence, Italy). 2004;16(4):388–91.

    CAS  Google Scholar 

  211. Dimopoulos MA, Kantarjian H, Weber D, O’Brien S, Estey E, Delasalle K, et al. Primary therapy of Waldenstrom’s macroglobulinemia with 2-chlorodeoxyadenosine. J Clin Oncol. 1994;12(12):2694–8.

    PubMed  CAS  Google Scholar 

  212. Dimopoulos MA, Anagnostopoulos A, Zervas C, Kyrtsonis MC, Zomas A, Bourantas C, et al. Predictive factors for response to rituximab in Waldenstrom’s macroglobulinemia. Clin Lymphoma. 2005;5(4):270–2.

    Article  PubMed  CAS  Google Scholar 

  213. Gertz MA, Abonour R, Heffner LT, Greipp PR, Uno H, Rajkumar SV. Clinical value of minor responses after 4 doses of rituximab in Waldenstrom macroglobulinaemia: a follow-up of the Eastern Cooperative Oncology Group E3A98 trial. Br J Haematol. 2009;147(5):677–80.

    Article  PubMed  CAS  Google Scholar 

  214. Buske C, Hoster E, Dreyling M, Eimermacher H, Wandt H, Metzner B, et al. The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia. 2009;23(1):153–61.

    Article  PubMed  CAS  Google Scholar 

  215. Treon SP, Hunter Z, Barnagan AR. CHOP plus rituximab therapy in Waldenstrom’s macroglobulinemia. Clin Lymphoma. 2005;5(4):273–7.

    Article  PubMed  CAS  Google Scholar 

  216. Chen C, Kouroukis CT, White D, Voralia M, Stadtmauer E, Stewart AK, et al. Bortezomib in relapsed or refractory Waldenstrom’s macroglobulinemia. Clin Lymphoma Myeloma. 2009;9(1):74–6.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Therapeutics, University of Athens School of Medicine, 80 Vas Sofias Ave, Athens, 11528, Greece

    Efstathios Kastritis M.D. & Meletios A. Dimopoulos M.D.

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  1. Efstathios Kastritis M.D.
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  2. Meletios A. Dimopoulos M.D.
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Correspondence to Efstathios Kastritis M.D. .

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Editors and Affiliations

  1. Beth Israel Hospital, Cancer Center, St. Lukes-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Peter H. Wiernik

  2. , Department of Hematology, Imperial College of London, Du Cane Road 150, London, W12 0NN, United Kingdom

    John M. Goldman

  3. Continuum Cancer Centers, Department of Medicine, St. Luke's-Roosevelt Hospital Center, 10th Avenue 1000, New York, 10019, New York, USA

    Janice P. Dutcher

  4. , Division of Hematology, Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    Robert A. Kyle

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Kastritis, E., Dimopoulos, M.A. (2013). Waldenström’s Macroglobulinemia. In: Wiernik, P., Goldman, J., Dutcher, J., Kyle, R. (eds) Neoplastic Diseases of the Blood. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3764-2_35

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