Abstract
Waldenström’s macroglobulinemia (WM) is a lymphoid neoplasm resulting from the accumulation, predominantly in the marrow, of a clonal population of lymphocytes, lymphoplasmacytic cells, and plasma cells, which secrete a monoclonal immunoglobulin (Ig) M (Owen et al., Semin Oncol 30:110, 2003). WM corresponds to lymphoplasmacytic lymphoma (LPL) as defined in the Revised European-American Lymphoma (REAL) and World Health Organization classification systems (Harris et al., Blood 84:1361, 1994; Harris et al., Ann Oncol 10:1419, 1999). Most cases of LPL are WM; less than 5% of cases are IgA-secreting, IgG-secreting, or nonsecreting LPL.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ackroyd S, O’Connor SJM, Owen RG (2005) Rarity of IgH translocations in Waldenström macroglobulinemia. Cancer Genet Cytogenet 163:77
Agathocleous A, Rohatiner A, Rule S et al (2010) Weekly versus twice weekly bortezomib given in conjunction with rituximab in patients with recurrent follicular lymphoma, mantle cell lymphoma, and Waldenström macroglobulinemia. Br J Haematol 151:346
Amrein PC, Compton CC (1990) Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 3–1990. A 66-year-old woman with Waldenström’s macroglobulinemia, diarrhea, anemia, and persistent gastrointestinal bleeding. N Engl J Med 322:183
Anagnostopoulos A, Zervas K, Kyrtsonis M et al (2006) Prognostic value of serum beta 2-microglobulin in patients with Waldenström’s macroglobulinemia requiring therapy. Clin Lymphoma Myeloma 7:205
Ansell SM, Hodge LS, Secreto FJ et al (2014) Activation of TAK1 by MYD88 L265P drives malignant B-cell growth in non-Hodgkin lymphoma. Blood Cancer J 4:e183. https://doi.org/10.1038/bcj.2014.4
Aoki H, Takishita M, Kosaka M, Saito S (1995) Frequent somatic mutations in D and/or JH segments of Ig gene in Waldenström’s macroglobulinemia and chronic lymphocytic leukemia (CLL) with Richter’s syndrome but not in common CLL. Blood 85:1913
Avet-Loiseau H, Garand R, Lode L, Robillard N, Bataille R (2003) 14q32 translocations discriminate IgM multiple myeloma from Waldenstrom’s macroglobulinemia. Semin Oncol 30:153
Betticher DC, Hsu Schmitz SF, Ratschiller D et al (1997) Cladribine (2-CDA) given as subcutaneous bolus injections is active in pretreated Waldenström’s macroglobulinaemia. Swiss Group for Clinical Cancer Research (SAKK). Br J Haematol 99:358
Bjornsson OG, Arnason A, Gudmunosson S et al (1978) Macroglobulinaemia in an Icelandic family. Acta Med Scand 203:283
Braggio E, Keats JJ, Leleu X et al (2009a) High-resolution genomic analysis in Waldenström’s macroglobulinemia identifies disease-specific and common abnormalities with marginal zone lymphomas. Clin Lymphoma Myeloma 9:39
Braggio E, Keats JJ, Leleu X et al (2009b) Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom’s macroglobulinemia. Cancer Res 69:3579
Busillo JM, Amando S, Sengupta R et al (2010) Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases and results in differential modulation of CXCR4 signaling. J Biol Chem 285:7805
Buske C, Hoster E, Dreyling MH et al (2009) 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 23:153
Cao Y, Hunter ZR, Liu X et al (2014) The WHIM-like CXCR4S338X somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom’s Macroglobulinemia. Leukemia 29(1):169–176. https://doi.org/10.1038/leu.2014.187
Cao Y, Hunter ZR, Liu X et al (2015) CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88 L265P directed signaling in Waldenstrom macroglobulinaemia cells. Br J Haematol 168:701
Case DC Jr, Ervin TJ, Boyd MA, Redfield DL (1991) Waldenström’s macroglobulinemia: long-term results with the M-2 protocol. Cancer Investig 9:1
Castillo JJ, Olszewski A, Cronin AM et al (2014) Survival trends in Waldenstrom macroglobulinemia: an analysis of the Surveillance, Epidemiology and End Results database. Blood 123:3999
Chang H, Qi C, Trieu Y et al (2009) Prognostic relevance of 6q deletion in Waldenström's macroglobulinemia: a multicenter study. Clin Lymphoma Myeloma 9(1):36
Chassande B, Leger JM, Younes-Chennoufi AB et al (1998) Peripheral neuropathy associated with IgM monoclonal gammopathy: correlations between M-protein antibody activity and clinical/electrophysiological features in 40 cases. Muscle Nerve 21:55
Chen CI, Kouroukis CT, White D et al (2007) Bortezomib is active in patients with untreated or relapsed Waldenström’s macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:1570
Ciccarelli BT, Yang G, Hatjiharissi E et al (2009) Soluble CD27 is a faithful marker of disease burden and is unaffected by the rituximab induced IgM flare, as well as plasmapheresis in patients with Waldenström’s macroglobulinemia. Clin Lymphoma Myeloma 9:56
Ciccarelli BT, Patterson CJ, Hunter ZR et al (2011) Hepcidin is produced by lymphoplasmacytic cells and is associated with anemia in Waldenström's Macroglobulinemia. Clin Lymphoma Myeloma Leuk 11:160
Cohen L, Henzel WJ, Baeuerie PA (1998) IKAP is a scaffold protein of the IkappaB kinase complex. Nature 395:292
Crisp D, Pruzanski W (1982) B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins). Am J Med 72:915
Dalakas MC, Quarles RH (1996) Autoimmune ataxic neuropathies (sensory ganglionopathies): are glycolipids the responsible autoantigens? Ann Neurol 39:419
Daoud MS, Lust JA, Kyle RA, Pittelkow MR (1999) Monoclonal gammopathies and associated skin disorders. J Am Acad Dermatol 40:507
Delannoy A, Ferrant A, Martiat P et al (1994) 2-Chlorodeoxyadenosine therapy in Waldenström’s macroglobulinaemia. Nouv Rev Fr Hematol 36:317
Dellagi K, Dupouey P, Brouet JC et al (1983) Waldenström’s macroglobulinemia and peripheral neuropathy: a clinical and immunologic study of 25 patients. Blood 62:280
Dhodapkar MV, Jacobson JL, Gertz MA et al (2001) Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003). Blood 98:41
Dimopoulos M, Gika D, Zervas K et al (2004) The international staging system for multiple myeloma is applicable in symptomatic Waldenström’s macroglobulinemia. Leuk Lymphoma 45:1809
Dimopoulos MA, Alexanian R (1994) Waldenström’s macroglobulinemia. Blood 83:1452
Dimopoulos MA, O’Brien S, Kantarjian H et al (1993) Fludarabine therapy in Waldenström’s macroglobulinemia. Am J Med 95:49
Dimopoulos MA, Kantarjian H, Weber D et al (1994a) Primary therapy of Waldenström’s macroglobulinemia with 2-chlorodeoxyadenosine. J Clin Oncol 12:2694
Dimopoulos MA, Weber DM, Kantarjian H et al (1994b) 2-Chlorodeoxyadenosine therapy of patients with Waldenström macroglobulinemia previously treated with fludarabine. Ann Oncol 5:288
Dimopoulos MA, Weber D, Delasalle KB et al (1995) Treatment of Waldenström’s macroglobulinemia resistant to standard therapy with 2-chlorodeoxyadenosine: identification of prognostic factors. Ann Oncol 6:49
Dimopoulos MA, Zervas C, Zomas A et al (2002) Treatment of Waldenström’s macroglobulinemia with rituximab. J Clin Oncol 20:2327
Dimopoulos MA, Hamilos G, Efstathiou E et al (2003) Treatment of Waldenström’s macroglobulinemia with the combination of fludarabine and cyclophosphamide. Leuk Lymphoma 44:993
Dimopoulos MA, Anagnostopoulos A, Zervas C et al (2005a) Predictive factors for response to rituximab in Waldenström’s macroglobulinemia. Clin Lymphoma 5:270
Dimopoulos MA, Anagnostopulos A, Kyrtsonis MC et al (2005b) Treatment of relapsed or refractory Waldenstrom’s macroglobulinemia with bortezomib. Haematologica 90:1655
Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC et al (2007) Primary treatment of Waldenström’s macroglobulinemia with dexamethasone, rituximab and cyclophosphamide. J Clin Oncol 25:3344
Dimopoulos MA, García-Sanz R, Gavriatopoulou M et al (2013) Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN). Blood 122:3276
Dimopoulos MA, Trotman J, Tedeschi A et al (2016) Single agent ibrutinib in rituximab-refractory patients with Waldenström’s macroglobulinemia: results from a multicenter, open-label phase 3 substudy (iNNOVATE™). Lancet Oncol 18(2):241
Dotta L, Tassone L, Badolato R (2011) Clinical and genetic features of Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome. Curr Mol Med 11:317
Dussol B, Kaplanski G, Daniel L et al (1998) Simultaneous occurrence of fibrillary glomerulopathy and AL amyloid. Nephrol Dial Transplant 13:2630
Dutcher TF, Fahey JL (1959) The histopathology of macroglobulinemia of Waldenström. J Natl Cancer Inst 22:887
Ettl AR, Birbamer GG, Philipp W (1992) Orbital involvement in Waldenström’s macroglobulinemia: ultrasound, computed tomography and magnetic resonance findings. Ophthalmologica 205:40
Eurelings M, Ang CW, Notermans NC et al (2001) Antiganglioside antibodies in polyneuropathy associated with monoclonal gammopathy. Neurology 57:1909
Facon T, Brouillard M, Duhamel A et al (1993) Prognostic factors in Waldenström’s macroglobulinemia: a report of 167 cases. J Clin Oncol 11:1553
Fadil A, Taylor DE (1998) The lung and Waldenström’s macroglobulinemia. South Med J 91:681
Farhangi M, Merlini G (1986) The clinical implications of monoclonal immunoglobulins. Semin Oncol 13:366
Feiner HD, Rizk CC, Finfer MD et al (1990) IgM monoclonal gammopathy/Waldenström’s macroglobulinemia: a morphological and immunophenotypic study of the bone marrow. Mod Pathol 3:348
Foran JM, Rohatiner AZ, Coiffier B et al (1999) Multicenter phase II study of fludarabine phosphate for patients with newly diagnosed lymphoplasmacytoid lymphoma, Waldenström’s macroglobulinemia, and mantle-cell lymphoma. J Clin Oncol 17:546
Fridrik MA, Jager G, Baldinger C et al (1997) First-line treatment of Waldenström’s disease with cladribine. Arbeitsgemeinschaft Medikamentose Tumortherapie. Ann Hematol 74:7
Gad A, Willen R, Carlen B et al (1995) Duodenal involvement in Waldenström’s macroglobulinemia. J Clin Gastroenterol 20:174
Gardyn J, Schwartz A, Gal R et al (2001) Waldenström’s macroglobulinemia associated with AA amyloidosis. Int J Hematol 74:76
Gavriatopoulou M, Garcia-Sanz R, Kastritis E et al (2017) BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow up of 6 years. Blood 129(4):456
Gertz MA, Kyle RA (1995) Hyperviscosity syndrome. J Intensive Care Med 10:128
Gertz MA, Kyle RA, Noel P (1993) Primary systemic amyloidosis: a rare complication of immunoglobulin M monoclonal gammopathies and Waldenström’s macroglobulinemia. J Clin Oncol 11:914
Gertz MA, Rue M, Blood E et al (2004) Multicenter phase 2 trial of rituximab for Waldenström macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma 45:2047
Ghobrial IM, Fonseca R, Greipp PR et al (2004) Initial immunoglobulin M “flare” after rituximab therapy in patients with Waldenström macroglobulinemia: an Eastern Cooperative Oncology Group Study. Cancer 101:2593
Ghobrial IM, Matous J, Padmanabhan S et al (2008) Phase II trial of combination of bortezomib and rituximab in relapsed and/or refractory Waldenström’s macroglobulinemia. Blood 112:832
Ghobrial IM, Witzig TE, Gertz M et al (2014) Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom Macroglobulinemia. Am J Hematol 89(3):237
Gobbi PG, Bettini R, Montecucco C et al (1994) Study of prognosis in Waldenström’s macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility. Blood 83:2939
Gordon PH, Rowland LP, Younger DS et al (1997) Lymphoproliferative disorders and motor neuron disease: an update. Neurology 48:1671
Groves FD, Travis LB, Devesa SS et al (1998) Waldenström’s macroglobulinemia: incidence patterns in the United States, 1988–1994. Cancer 82:1078
Hanzis C, Ojha RP, Hunter Z et al (2011) Associated malignancies in patients with Waldenström’s macroglobulinemia and their kin. Clin Lymphoma Myeloma Leuk 11:88
Harris NL, Jaffe ES, Stein H et al (1994) A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361
Harris NL, Jaffe ES, Diebold J et al (1999) The 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. Ann Oncol 10:1419
Hellmann A, Lewandowski K, Zaucha JM et al (1999) Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenström’s macroglobulinemia. Eur J Haematol 63:35
Hensel M, Villalobos M, Kornacker M et al (2005) Pentostatin/cyclophosphamide with or without rituximab: an effective regimen for patients with Waldenström’s macroglobulinemia/lymphoplasmacytic lymphoma. Clin Lymphoma Myeloma 6:131
Herrinton LJ, Weiss NS (1993) Incidence of Waldenström’s macroglobulinemia. Blood 82:3148
Ho AW, Hatjiharissi E, Ciccarelli BT et al (2008) CD27-CD70 interactions in the pathogenesis of Waldenstrom macroglobulinemia. Blood 112:4683
Hunter ZR, Branagan AR, Manning R et al (2005) CD5, CD10, and CD23 expression in Waldenstrom’s macroglobulinemia. Clin Lymphoma 5:246
Hunter ZR, Manning RJ, Hanzis C et al (2010) IgA and IgG hypogammaglobulinemia in Waldenstrom’s Macroglobulinemia. Haematologica 95:470
Hunter ZR, Xu L, Yang G et al (2014) The genomic landscape of Waldenstom’s Macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood 123:1637
Ilyas AA, Quarles RH, Dalakas MC et al (1985) Monoclonal IgM in a patient with paraproteinemic polyneuropathy binds to gangliosides containing disialosyl groups. Ann Neurol 18:655
Ioakimidis L, Patterson CJ, Hunter ZR et al (2009) Comparative outcomes following CP-R, CVP-R and CHOP-R in Waldenström’s macroglobulinemia. Clin Lymphoma Myeloma 9:62
Isaac J, Herrera GA (2002) Cast nephropathy in a case of Waldenström’s macroglobulinemia. Nephron 91:512
Jacobs BC, O’Hanlon GM, Breedland EG et al (1997) Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides. J Neuroimmunol 80:23
Jiménez C, Sebastián E, Del Carmen Chillón M et al (2013) MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström’s macroglobulinemia. Leukemia 27:1722
Kaila VL, el Newihi HM, Dreiling BJ et al (1996) Waldenström’s macroglobulinemia of the stomach presenting with upper gastrointestinal hemorrhage. Gastrointest Endosc 44:73
Kawagoe T, Sato S, Matsushita K et al (2008) Sequential control of Toll-like receptor dependent responses by IRAK1 and IRAK2. Nat Immunol 9:684
Kristinsson SY, Eloranta S, Dickman PW et al (2013) Patterns of survival in lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia: a population based study of 1,555 patients diagnosed in Sweden from 1980 to 2005. Am J Hematol 88:60
Kwaan HC, Bongu A (1999) The hyperviscosity syndromes. Semin Thromb Hemost 25:199
Kyle RA, Greipp PR, Gertz MA et al (2000) Waldenström’s macroglobulinaemia: a prospective study comparing daily with intermittent oral chlorambucil. Br J Haematol 108:737
Kyle RA, Treon SP, Alexanian R et al (2003) Prognostic markers and criteria to initiate therapy in Waldenström’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenström’s macroglobulinemia. Semin Oncol 30:116
Kyriakou C, Canals C, Sibon D et al (2010a) High-dose therapy and autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 28:2227
Kyriakou C, Canals C, Cornelissen JJ et al (2010b) Allogeneic stem-cell transplantation in patients with Waldenström macroglobulinemia: report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 28:4926
Kyrtsonis MC, Angelopoulou MK, Kontopidou FN et al (2001) Primary lung involvement in Waldenström’s macroglobulinaemia: report of two cases and review of the literature. Acta Haematol 105:92
Landgren O, Staudt L (2012) MYD88 L265P somatic mutation in IgM MGUS. N Engl J Med 367:2255
Latov N, Braun PE, Gross RB et al (1981) Plasma cell dyscrasia and peripheral neuropathy: identification of the myelin antigens that react with human paraproteins. Proc Natl Acad Sci U S A 78:7139
Latov N, Hays AP, Sherman WH (1988) Peripheral neuropathy and anti-MAG antibodies. Crit Rev Neurobiol 3:301
Leblond V, Ben Othman T, Deconinck E et al (1998) Activity of fludarabine in previously treated Waldenström’s macroglobulinemia: a report of 71 cases. Groupe Cooperatif Macroglobulinemie. J Clin Oncol 16:2060
Leblond V, Johnson S, Chevret S et al (2013) Results of a randomized trial of chlorambucil versus fludarabine for patients with Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol 31:301
Leblond V, Kastritis E, Advani R et al (2016) Treatment recommendations for Waldenström macroglobulinemia from the Eighth International Workshop on WM. Blood 128:1321
Leleu X, O’Connor K, Ho A et al (2007) Hepatitis C viral infection is not associated with Waldenström’s macroglobulinemia. Am J Hematol 82:83
Leleu X, Eeckhoute J, Jia X et al (2008) Targeting NF-kappaB in Waldenstrom macroglobulinemia. Blood 111:5068
Leleu XP, Manning R, Soumerai JD et al (2009a) Increased incidence of transformation and myelodysplasia/acute leukemia in patients with Waldenström macroglobulinemia treated with nucleoside analogs. J Clin Oncol 27:250
Leleu XP, Tamburini J, Roccaro A et al (2009b) Balancing risk versus benefit in the treatment of Waldenström’s macroglobulinemia patients with nucleoside analogue based therapy. Clin Lymphoma Myeloma 9:71
Lewandowski K, Halaburda K, Hellmann A (2002) Fludarabine therapy in Waldenström’s macroglobulinemia patients treated previously with 2-chlorodeoxyadenosine. Leuk Lymphoma 43:361
Lin SC, Lo YC, Wu H (2010) Helical assembly in the MYD88-IRAK4-IRAK2 complex in TLR/IL-1R signaling. Nature 465:885
Liu ES, Burian C, Miller WE, Saven A (1998) Bolus administration of cladribine in the treatment of Waldenström macroglobulinaemia. Br J Haematol 103:690
Loiarro M, Gallo G, Fanto N et al (2009) Identification of critical residues of the MYD88 death domain involved in the recruitment of downstream kinases. J Biol Chem 284:28093
Lopate G, Choksi R, Pestronk A (2002) Severe sensory ataxia and demyelinating polyneuropathy with IgM anti-GM2 and GalNAc-GD1A antibodies. Muscle Nerve 25:828
Mackenzie MR, Babcock J (1975) Studies of the hyperviscosity syndrome. II: macroglobulinemia. J Lab Clin Med 85:227
Marmont AM, Merlini G (1991) Monoclonal autoimmunity in hematology. Haematologica 76:449
Mascaro JM, Montserrat E, Estrach T et al (1982) Specific cutaneous manifestations of Waldenström’s macroglobulinaemia. A report of two cases. Br J Dermatol 106:217
Menke MN, Treon SP (2007) Hyperviscosity syndrome. In: Sekeres, Kalaycio, Bolwell (eds) Clinical malignant hematology. McGraw Hill Publishing, New York, pp 937–941
Menke MN, Feke GT, McMeel JW et al (2006) Hyperviscosity-related retinopathy in Waldenström’s macroglobulinemia. Arch Ophthalmol 124:1601
Merlini G, Farhangi M, Osserman EF (1986) Monoclonal immunoglobulins with antibody activity in myeloma, macroglobulinemia and related plasma cell dyscrasias. Semin Oncol 13:350
Minnema MC, Kimby E, D’Sa S et al (2017) Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome. Haematologica 102:43–51. https://doi.org/10.3324/haematol.2016.147728
Moore DF Jr, Moulopoulos LA, Dimopoulos MA (1995) Waldenström macroglobulinemia presenting as a renal or perirenal mass: clinical and radiographic features. Leuk Lymphoma 17:331
Morel P, Monconduit M, Jacomy D et al (2000) Prognostic factors in Waldenström macroglobulinemia: a report on 232 patients with the description of a new scoring system and its validation on 253 other patients. Blood 96:852
Morel P, Duhamel A, Gobbi P et al (2009) International prognostic scoring system for Waldenström macroglobulinemia. Blood 113:4163
Morel-Maroger L, Basch A, Danon F et al (1970) Pathology of the kidney in Waldenström’s macroglobulinemia. Study of sixteen cases. N Engl J Med 283:123
Moulopoulos LA, Dimopoulos MA, Varma DG et al (1993) Waldenström macroglobulinemia: MR imaging of the spine and CT of the abdomen and pelvis. Radiology 188:669
Moyner K, Sletten K, Husby G, Natvig JB (1980) An unusually large (83 amino acid residues) amyloid fibril protein AA from a patient with Waldenström’s macroglobulinaemia and amyloidosis. Scand J Immunol 11:549
Nemni R, Gerosa E, Piccolo G, Merlini G (1994) Neuropathies associated with monoclonal gammopathies. Haematologica 79:557
Ngo HT, Leleu X, Lee J et al (2008) SDF-1/CXCR4 and VLA-4 interaction regulates homing in Waldenstrom macroglobulinemia. Blood 112:150
Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH et al (2011) Oncogenically active MYD88 mutations in human lymphoma. Nature 470:115
Nguyen-Khac F, Lambert J, Chapiro E et al (2013) Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom’s macroglobulinemia. Haematologica 98:649
Nobile-Orazio E, Marmiroli P, Baldini L et al (1987) Peripheral neuropathy in macroglobulinemia: incidence and antigen-specificity of M proteins. Neurology 37:1506
Nobile-Orazio E, Manfredini E, Carpo M et al (1994) Frequency and clinical correlates of antineural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy. Ann Neurol 36:416
Ocio EM, Schop RF, Gonzalez B et al (2007) 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis. Br J Haematol 136(1):80
Ogmundsdottir HM, Sveinsdottir S, Sigfusson A et al (1999) Enhanced B cell survival in familial macroglobulinaemia is associated with increased expression of Bcl-2. Clin Exp Immunol 117:252
Orellana J, Friedman AH (1981) Ocular manifestations of multiple myeloma, Waldenström’s macroglobulinemia and benign monoclonal gammopathy. Surv Ophthalmol 26:157
Owen RG, Barrans SL, Richards SJ et al (2001) Waldenström macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors. Am J Clin Pathol 116:420
Owen RG, Treon SP, Al-Katib A et al (2003) Clinicopathological definition of Waldenström’s macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenström’s macroglobulinemia. Semin Oncol 30:110
Owen RG, Kyle RA, Stone MJ et al (2013) Response assessment in Waldenstrom macroglobulinemia. Br J Haematol 160(2):171
Paiva B, Montes MC, García-Sanz R et al (2013) Multiparameter flow cytometry for the identification of the Waldenström’s clone in IgM MGUS and Waldenström’s macroglobulinemia: new criteria for differential diagnosis and risk stratification. Leukemia 28:166
Pavord SR, Murphy PT, Mitchell VE (1996) POEMS syndrome and Waldenström’s macroglobulinaemia. J Clin Pathol 49:181
Petrucci MT, Avvisati G, Tribalto M et al (1989) Waldenström’s macroglobulinaemia: results of a combined oral treatment in 34 newly diagnosed patients. J Intern Med 226:443
Popat U, Saliba R, Thandi R et al (2009) Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant 15:718
Poulain S, Roumier C, Decambron A et al (2013) MYD88 L265P mutation in Waldenstrom’s macroglobulinemia. Blood 121:4504
Preud’homme JL, Seligmann M (1972) Immunoglobulins on the surface of lymphoid cells in Waldenström’s macroglobulinemia. J Clin Invest 51:701
Pruzanski W, Shumak KH (1977a) Biologic activity of cold-reacting autoantibodies (first of two parts). N Engl J Med 297:538
Pruzanski W, Shumak KH (1977b) Biologic activity of cold-reacting autoantibodies (second of two parts). N Engl J Med 297:583
Rausch PG, Herion JC (1980) Pulmonary manifestations of Waldenström macroglobulinemia. Am J Hematol 9:201
Recine MA, Perez MT, Cabello-Inchausti B et al (2001) Extranodal lymphoplasmacytoid lymphoma (immunocytoma) presenting as small intestinal obstruction. Arch Pathol Lab Med 125:677
Renier G, Ifrah N, Chevailler A et al (1989) Four brothers with Waldenström’s macroglobulinemia. Cancer 64:1554
Roccaro A, Sacco A, Jiminez C et al (2014) C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma. Blood 123:4120
Ropper AH, Gorson KC (1998) Neuropathies associated with paraproteinemia. N Engl J Med 338:1601
Rosenthal JA, Curran WJ Jr, Schuster SJ (1998) Waldenström’s macroglobulinemia resulting from localized gastric lymphoplasmacytoid lymphoma. Am J Hematol 58:244
Roux S, Fermand JP, Brechignac S et al (1996) Tumoral joint involvement in multiple myeloma and Waldenström’s macroglobulinemia—Report of 4 cases. J Rheumatol 23:2175
Rummel M, Niederle N, Maschmeyer G et al (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381:1203–1210
Rummel MJ, Lerchenmüller C, Greil R et al (2012) Bendamustine-rituximab induction followed by observation or rituximab maintenance for newly diagnosed patients with Waldenström's Macroglobulinemia: results from a prospective, randomized, multicenter study (StiL NHL 7–2008). Blood 120(21):Abstract 2739
Sahota SS, Forconi F, Ottensmeier CH et al (2002) Typical Waldenstrom macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events. Blood 100:1505
San Miguel JF, Vidriales MB, Ocio E et al (2003) Immunophenotypic analysis of Waldenstrom’s macroglobulinemia. Semin Oncol 30:187
Santini GF, Crovatto M, Modolo ML et al (1993) Waldenström macroglobulinemia: a role of HCV infection? Blood 82:2932
Schnitzler L, Schubert B, Boasson M et al (1974) Urticaire chronique, lésions osseuses, macroglobulinémie IgM: Maladie de Waldenström? Bull Soc Fr Dermatol Syphiligr 81:363
Schop RF, Kuehl WM, Van Wier SA et al (2002) Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood 100:2996
Shiokawa S, Suehiro Y, Uike N, Muta K, Nishimura J (2001) Sequence and expression analyses of mu and delta transcripts in patients with Waldenström’s macroglobulinemia. Am J Hematol 68:139
Silvestri F, Barillari G, Fanin R et al (1996) Risk of hepatitis C virus infection, Waldenström’s macroglobulinemia, and monoclonal gammopathies. Blood 88:1125
Singh A, Eckardt KU, Zimmermann A et al (1993) Increased plasma viscosity as a reason for inappropriate erythropoietin formation. J Clin Invest 91:251
Smith BR, Robert NJ, Ault KA (1983) Waldenstrom’s macroglobulinemia the quantity of detectable circulating monoclonal B lymphocytes correlates with clinical course. Blood 61:911
Stephanie Poulain S, Roumier C, Doye E, et al (2014) Genomic landscape of CXCR4 mutations in Waldenstrom’s Macroglobulinemia. Proc Am Soc Hematol: Abstract 1610
Stone MJ (2009) Waldenström’s macroglobulinemia: hyperviscosity syndrome and cryoglobulinemia. Clin Lymphoma Myeloma 9:97
Stone MJ, Bogen SA (2012) Evidence-based focused review of management of hyperviscosity syndrome. Blood 119:2205
Strauss SJ, Maharaj L, Hoare S et al (2006) Bortezomib therapy in patients with relapsed or refractory lymphoma: potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity. J Clin Oncol 24:2105
Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. IARC Press, Lyon
Tam CS, Wolf MM, Westerman D et al (2005) Fludarabine combination therapy is highly effective in first-line and salvage treatment of patients with Waldenström’s macroglobulinemia. Clin Lymphoma Myeloma 6:136
Tamburini J, Levy V, Chateilex C et al (2005) Fludarabine plus cyclophosphamide in Waldenström’s macroglobulinemia: results in 49 patients. Leukemia 19:1831
Thalhammer-Scherrer R, Geissler K, Schwarzinger I et al (2000) Fludarabine therapy in Waldenström’s macroglobulinemia. Ann Hematol 79:556
Tournilhac O, Santos DD, Xu L et al (2006) Mast cells in Waldenstrom’s macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling. Ann Oncol 17:1275
Treon SP (2009) How I treat Waldenstrom’s macroglobulinemia. Blood 114:2375
Treon SP, Agus DB, Link B et al (2001) CD20-directed antibody-mediated immunotherapy induces responses and facilitates hematologic recovery in patients with Waldenström’s macroglobulinemia. J Immunother 24:272
Treon SP, Kelliher A, Keele B et al (2003) Expression of serotherapy target antigens in Waldenström’s macroglobulinemia: therapeutic applications and considerations. Semin Oncol 30:248
Treon SP, Branagan AR, Hunter Z et al (2004) Paradoxical increases in serum IgM and viscosity levels following rituximab in Waldenström’s macroglobulinemia. Ann Oncol 15:1481
Treon SP, Emmanouilides C, Kimby E et al (2005a) Extended rituximab therapy in Waldenström’s Macroglobulinemia. Ann Oncol 16:132
Treon SP, Hansen M, Branagan AR et al (2005b) Polymorphisms in FcγRIIIA (CD16) receptor expression are associated with clinical responses to rituximab in Waldenström’s macroglobulinemia. J Clin Oncol 23:474
Treon SP, Hunter Z, Branagan A (2005c) CHOP plus rituximab therapy in Waldenström’s macroglobulinemia. Clin Lymphoma Myeloma 5:273
Treon SP, Hunter ZR, Matous J et al (2007) Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom’s macroglobulinemia: results of WMCTG Trial 03-248. Clin Cancer Res 13:3320
Treon SP, Branagan AR, Ioakimidis L et al (2009a) Long term outcomes to fludarabine and rituximab in Waldenström’s macroglobulinemia. Blood 113:3673
Treon SP, Ioakimidis L, Soumerai JD et al (2009b) Primary therapy of Waldenström’s macroglobulinemia with bortezomib, dexamethasone and rituximab. J Clin Oncol 27:3830
Treon SP, Hanzis C, Ioakimidis L et al (2010) Clinical characteristics and treatment outcome of disease-related peripheral neuropathy in Waldenstrom’s macroglobulinemia (WM). J Clin Oncol 28:15s. (Abstract 8114)
Treon SP, Hanzis C, Tripsas C et al (2011a) Bendamustine therapy in patients with relapsed or refractory Waldenstrom’s macroglobulinemia. Clin Lymphoma Myeloma Leuk 211:133–135
Treon SP, Hanzis C, Manning RJ et al (2011b) Maintenance rituximab is associated with improved clinical outcome in rituximab naïve patients with Waldenstrom’s Macroglobulinemia who respond to a Rituximab containing regimen. Br J Haematol 154:357
Treon SP, Yang G, Hanzis C et al (2011c) Attainment of complete/very good partial response following rituximab based therapy is an important determinant to progression-free survival and is impacted by polymorphisms in FCGR3A in Waldenstrom macroglobulinaemia. Br J Haematol 154:223
Treon SP, Xu L, Yang G et al (2012) MYD88 L265P somatic mutation in Waldenstrom’s macroglobulinemia. N Engl J Med 367:826
Treon SP, Tripsas C, Ciccarelli BT, Manning RJ, Patterson CJ, Sheehy P, Hunter ZR (2013) Patients with Waldenstrom macroglobulinemia commonly present with iron deficiency and those with severely depressed transferrin saturation levels show response to parenteral iron administration. Clin Lymphoma Myeloma Leuk 13:241
Treon SP, Tripsas CK, Meid K et al (2014a) Carfilzomib, rituximab and dexamethasone (CaRD) is active and offers a neuropathy-sparing approach for proteasome-inhibitor based therapy in Waldenstrom’s macroglobulinemia. Blood 124:503
Treon SP, Cao Y, Xu L et al (2014b) Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia. Blood 123:2791
Treon SP, Xu L, Hunter ZR (2015a) MYD88 mutations and response to ibrutinib in Waldenstrom’s macroglobulinemia. N Engl J Med 373:584
Treon SP, Meid K, Gustine J, et al. (2015b) Long-term outcome of a prospective study of bortezomib, dexamethasone and rituximab (BDR) in previously untreated, symptomatic patients with Waldenstrom’s macroglobulinemia. Blood 126(23):Abstract 1833
Treon SP, Tripsas CK, Meid K et al (2015c) Ibrutinib in previously treated patients with Waldenström’s Macroglobulinemia. N Engl J Med 372(15):1430
Treon SP, Tripsas CK, Meid K et al (2016) Prospective, multicenter study of everolimus as primary therapy in Waldenstrom’s Macroglobulinemia. Clin Cancer Res. https://doi.org/10.1158/1078-0432.122:1822
Varettoni M, Arcaini L, Zibellini S et al (2013) Prevalence and clinical significance of the MYD88 L265P somatic mutation in Waldenstrom macroglobulinemia, and related lymphoid neoplasms. Blood 121:2522
Varghese AM, Rawstron AC, Ashcroft J et al (2009) Assessment of bone marrow response in Waldenström’s macroglobulinemia. Clin Lymphoma Myeloma 9:53
Veltman GA, van Veen S, Kluin-Nelemans JC et al (1997) Renal disease in Waldenström’s macroglobulinaemia. Nephrol Dial Transplant 12:1256
Vital A (2001) Paraproteinemic neuropathies. Brain Pathol 11:399
Wagner SD, Martinelli V, Luzzatto L (1994) Similar patterns of V kappa gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, Waldenstrom’s macroglobulinemia, and myeloma. Blood 83:3647
Watters T, Kenny EF, O’Neill LAJ (2007) Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. Immunol Cell Biol 85:411
Weber DM, Dimopoulos MA, Delasalle K et al (2003) 2-chlorodeoxyadenosine alone and in combination for previously untreated Waldenström’s macroglobulinemia. Semin Oncol 30:243
Weiss MD, Dalakas MC, Lauter CJ et al (1999) Variability in the binding of anti-MAG and anti-SGPG antibodies to target antigens in demyelinating neuropathy and IgM paraproteinemia. J Neuroimmunol 95:174
Whittaker SJ, Bhogal BS, Black MM (1996) Acquired immunobullous disease: a cutaneous manifestation of IgM macroglobulinaemia. Br J Dermatol 135:283
Willison HJ, O’Leary CP, Veitch J et al (2001) The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies. Brain 124:1968
Xu L, Hunter Z, Yang G et al (2013) MYD88 L265P in Waldenstrom macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood 121:2051
Xu L, Hunter ZR, Yang G et al (2014) Detection of MYD88 L265P in peripheral blood of patients with Waldenström’s Macroglobulinemia and IgM Monoclonal Gammopathy by allele-specific PCR. Leukemia 28(8):1698
Xu L, Hunter ZR, Tsakmaklis N et al (2016) Clonal architecture of CXCR4 WHIM-like mutations in Waldenström macroglobulinaemia. Br J Haematol 172:735
Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ et al (2013) A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenstrom macroglobulinemia. Blood 122:1222
Yang G, Buhrlage SJ, Tan L et al (2016) HCK is a survival determinant transactivated by mutated MYD88, and a direct target of ibrutinib. Blood 127:3237
Yasui O, Tukamoto F, Sasaki N et al (1997) Malignant lymphoma of the transverse colon associated with macroglobulinemia. Am J Gastroenterol 92:2299
Zhou Y, Liu X, Xu L et al (2011) Matrix metalloproteinase-8 is overexpressed in Waldenström’s macroglobulinemi a cells, and specific inhibition of this metalloproteinase blocks release of soluble CD27. Clin Lymphoma Myeloma Leuk 11:172
Zinzani PL, Gherlinzoni F, Bendandi M et al (1995) Fludarabine treatment in resistant Waldenström’s macroglobulinemia. Eur J Haematol 54:120
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Treon, S.P., Merlini, G., Dimopoulos, M.A. (2018). Waldenström’s Macroglobulinemia. In: Dimopoulos, M., Facon, T., Terpos, E. (eds) Multiple Myeloma and Other Plasma Cell Neoplasms. Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-319-25586-6_11
Download citation
DOI: https://doi.org/10.1007/978-3-319-25586-6_11
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-25584-2
Online ISBN: 978-3-319-25586-6
eBook Packages: MedicineMedicine (R0)