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Epidemiology of Waldenström Macroglobulinemia

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Waldenström’s Macroglobulinemia

Abstract

Waldenström’s Macroglobulinemia (WM) is a rare malignancy, accounting for only 1–2 % of all hematologic tumors, with an incidence of 3–4 per million people per year. Due to the rarity of WM, acquiring epidemiological knowledge of the disease has been a challenge. In the beginning, much of the information was obtained from small clinical series but have recently been largely replaced by population-based studies. WM is a disease of the elderly, with the median age of diagnosis is around 70 years. Known risk factors for WM include family history and chronic antigen stimulation (i.e. chronic infections and autoimmune diseases), and IgM MGUS, which can be thought of as an early state of WM. Over recent decades there have been evidence of increased survival over time.

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References

  1. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117:5019–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenström’s macroglobulinemia. N Engl J Med. 2012;367:826–33.

    Article  CAS  PubMed  Google Scholar 

  3. Landgren O, Staudt L. MYD88 L265P somatic mutation in IgM MGUS. N Engl J Med. 2012;367:2255–6. author reply 6–7.

    Article  CAS  PubMed  Google Scholar 

  4. Xu L, Hunter ZR, Yang G, et al. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood. 2013;121:2051–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kyle RA, Therneau TM, Rajkumar SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood. 2003;102:3759–64.

    Article  CAS  PubMed  Google Scholar 

  6. Hunter ZR, Xu L, Yang G, et al. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood. 2014;123:1637–46.

    Article  CAS  PubMed  Google Scholar 

  7. Groves FD, Travis LB, Devesa SS, Ries LA, Fraumeni JF. Waldenström’s macroglobulinemia: incidence patterns in the United States, 1988–1994. Cancer. 1998;82:1078–81.

    Article  CAS  PubMed  Google Scholar 

  8. Herrinton LJ, Weiss NS. Incidence of Waldenström’s macroglobulinemia. Blood. 1993;82:3148–50.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Wang H, Chen Y, Li F, et al. Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a large population-based study. Cancer. 2012;118:3793–800.

    Article  PubMed  Google Scholar 

  12. Ailawadhi S, Kardosh A, Yang D, et al. Outcome disparities among ethnic subgroups of Waldenström’s macroglobulinemia: a population-based study. Oncology. 2014;86:253–62.

    Article  PubMed  Google Scholar 

  13. Iwanaga M, Chiang CJ, Soda M, et al. Incidence of lymphoplasmacytic lymphoma/Waldenström’s macroglobulinaemia in Japan and Taiwan population-based cancer registries, 1996–2003. Int J Cancer. 2014;134:174–80.

    Article  PubMed  Google Scholar 

  14. Carreon JD, Morton LM, Devesa SS, et al. Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996–2004. Cancer Causes Control. 2008;19:1171–81.

    Article  PubMed  PubMed Central  Google Scholar 

  15. The National Board of Health and Welfare. Statistikdatabas för Cancer, Antal nya cancerfall per 100 000, Kronisk lymfatisk leukemi, Riket, Ålder: 0–85+, Båda könen, 2014 [cited 2016 July 4]. Available from: http://www.socialstyrelsen.se/statistik/statistikdatabas/cancer.

  16. Fine JM, Lambin P, Massari M, Leroux P. Malignant evolution of asymptomatic monoclonal IgM after seven and fifteen years in two siblings of a patient with Waldenström’s macroglobulinemia. Acta Med Scand. 1982;211:237–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  18. Altieri A, Bermejo JL, Hemminki K. Familial aggregation of lymphoplasmacytic lymphoma with non-Hodgkin lymphoma and other neoplasms. Leukemia. 2005;19:2342–3.

    Article  CAS  PubMed  Google Scholar 

  19. Blattner WA, Garber JE, Mann DL, et al. Waldenström’s macroglobulinemia and autoimmune disease in a family. Ann Intern Med. 1980;93:830–2.

    Article  CAS  PubMed  Google Scholar 

  20. Fine JM, Muller JY, Rochu D, et al. Waldenström’s macroglobulinemia in monozygotic twins. Acta Med Scand. 1986;220:369–73.

    Article  CAS  PubMed  Google Scholar 

  21. Gétaz EP, Staples WG. Familial Waldenström’s macroglobulinaemia: a case report. S Afr Med J. 1977;51:891–2.

    PubMed  Google Scholar 

  22. Linet MS, Humphrey RL, Mehl ES, et al. A case-control and family study of Waldenstrom’s macroglobulinemia. Leukemia. 1993;7:1363–9.

    CAS  PubMed  Google Scholar 

  23. Ogmundsdóttir HM, Jóhannesson GM, Sveinsdóttir S, et al. Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function. Scand J Immunol. 1994;40:195–200.

    Article  PubMed  Google Scholar 

  24. Seligmann M, Danon F, Mihaesco C, Fudenberg HH. Immunoglobulin abnormalities in families of patients with Waldenström’s macroglobulinemia. Am J Med. 1967;43:66–83.

    Article  CAS  PubMed  Google Scholar 

  25. Taleb N, Tohme A, Abi Jirgiss D, Kattan J, Salloum E. Familial macroglobulinemia in a Lebanese family with two sisters presenting Waldenström’s disease. Acta Oncol. 1991;30:703–5.

    Article  CAS  PubMed  Google Scholar 

  26. Treon SP, Hunter ZR, Aggarwal A, et al. Characterization of familial Waldenstrom’s macroglobulinemia. Ann Oncol. 2006;17:488–94.

    Article  CAS  PubMed  Google Scholar 

  27. Youinou P, le Goff P, Saleun JP, et al. Familial occurrence of monoclonal gammapathies. Biomedicine. 1978;28:226–32.

    CAS  PubMed  Google Scholar 

  28. Jamroziak K, Balcerczak E, Smolewski P, et al. MDR1 (ABCB1) gene polymorphism C3435T is associated with P-glycoprotein activity in B-cell chronic lymphocytic leukemia. Pharmacol Rep. 2006;58:720–8.

    CAS  PubMed  Google Scholar 

  29. Rudd MF, Sellick GS, Webb EL, Catovsky D, Houlston RS. Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia. Blood. 2006;108:638–44.

    Article  CAS  PubMed  Google Scholar 

  30. Hohaus S, Massini G, D’Alo’ F, et al. Association between glutathione S-transferase genotypes and Hodgkin’s lymphoma risk and prognosis. Clin Cancer Res. 2003;9:3435–40.

    CAS  PubMed  Google Scholar 

  31. Purdue MP, Lan Q, Kricker A, et al. Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study. Carcinogenesis. 2007;28:704–12.

    Article  CAS  PubMed  Google Scholar 

  32. Shen M, Zheng T, Lan Q, et al. Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut. Hum Genet. 2006;119:659–68.

    Article  CAS  PubMed  Google Scholar 

  33. Skibola CF, Curry JD, Nieters A. Genetic susceptibility to lymphoma. Haematologica. 2007;92:960–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Giordano TP, Henderson L, Landgren O, et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA. 2007;297:2010–7.

    Article  CAS  PubMed  Google Scholar 

  35. Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst. 2006;98:51–60.

    Article  PubMed  Google Scholar 

  36. Steingrímsson V, Lund SH, Turesson I, et al. Population-based study on the impact of the familial form of Waldenström macroglobulinemia on overall survival. Blood. 2015;125:2174–5.

    Article  PubMed  PubMed Central  Google Scholar 

  37. McMaster ML. Familial Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30:146–52.

    Article  CAS  PubMed  Google Scholar 

  38. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354:1362–9.

    Article  CAS  PubMed  Google Scholar 

  39. Schop RF, Kuehl WM, Van Wier SA, et al. Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood. 2002;100:2996–3001.

    Article  CAS  PubMed  Google Scholar 

  40. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113:5412–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Aoki H, Takishita M, Kosaka M, Saito S. 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. 1995;85:1913–9.

    CAS  PubMed  Google Scholar 

  42. Wagner SD, Martinelli V, Luzzatto L. 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. 1994;83:3647–53.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Landgren O, Engels EA, Pfeiffer RM, et al. Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. J Natl Cancer Inst. 2006;98:1321–30.

    Article  PubMed  Google Scholar 

  45. Ekström K, Hjalgrim H, Brandt L, et al. Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives. Arthritis Rheum. 2003;48:963–70.

    Article  PubMed  Google Scholar 

  46. Landgren O, Kyle RA. Multiple myeloma, chronic lymphocytic leukaemia and associated precursor diseases. Br J Haematol. 2007;139:717–23.

    Article  CAS  PubMed  Google Scholar 

  47. Lindqvist EK, Goldin LR, Landgren O, et al. Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study. Blood. 2011;118:6284–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Vajdic CM, Landgren O, McMaster ML, et al. Medical history, lifestyle, family history, and occupational risk factors for lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia: the Inter Lymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014;2014:87–97.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Dimopoulos MA, Kastritis E, Owen RG, et al. Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus. Blood. 2014;124:1404–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Treon SP. How I treat Waldenström macroglobulinemia. Blood. 2009;114:2375–85.

    Article  CAS  PubMed  Google Scholar 

  51. Morel P, Duhamel A, Gobbi P, et al. International prognostic scoring system for Waldenstrom macroglobulinemia. Blood. 2009;113:4163–70.

    Article  CAS  PubMed  Google Scholar 

  52. Facon T, Brouillard M, Duhamel A, et al. Prognostic factors in Waldenström’s macroglobulinemia: a report of 167 cases. J Clin Oncol. 1993;11:1553–8.

    Article  CAS  PubMed  Google Scholar 

  53. Morel P, Monconduit M, Jacomy D, et al. 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. 2000;96(3):852–8.

    CAS  PubMed  Google Scholar 

  54. Merlini G, Baldini L, Broglia C, et al. Prognostic factors in symptomatic Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30:211–5.

    Article  PubMed  Google Scholar 

  55. García-Sanz R, Montoto S, Torrequebrada A, et al. Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases. Br J Haematol. 2001;115:575–82.

    Article  PubMed  Google Scholar 

  56. 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;30:220–5.

    Article  PubMed  Google Scholar 

  57. Gobbi PG, Bettini R, Montecucco C, et al. Study of prognosis in Waldenström’s macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility. Blood. 1994;83:2939–45.

    CAS  PubMed  Google Scholar 

  58. Björkholm M, Johansson E, Papamichael D, et al. Patterns of clinical presentation, treatment, and outcome in patients with Waldenstrom’s macroglobulinemia: a two-institution study. Semin Oncol. 2003;30:226–30.

    Article  PubMed  Google Scholar 

  59. Kyle RA, Benson JT, Larson DR, et al. Progression in smoldering Waldenstrom macroglobulinemia: long-term results. Blood. 2012;119:4462–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kastritis E, Kyrtsonis MC, Hatjiharissi E, et al. No significant improvement in the outcome of patients with Waldenström’s macroglobulinemia treated over the last 25 years. Am J Hematol. 2011;86:479–83.

    Article  PubMed  Google Scholar 

  61. Kristinsson SY, Eloranta S, Dickman PW, et al. Patterns of survival in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia: a population-based study of 1,555 patients diagnosed in Sweden from 1980 to 2005. Am J Hematol. 2013;88:60–5.

    Article  PubMed  Google Scholar 

  62. Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Björkholm M. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007;25:1993–9.

    Article  PubMed  Google Scholar 

  63. Kristinsson SY, Dickman PW, Wilson WH, Caporaso N, Björkholm M, Landgren O. Improved survival in chronic lymphocytic leukemia in the past decade: a population-based study including 11,179 patients diagnosed between 1973-2003 in Sweden. Haematologica. 2009;94:1259–65.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Castillo JJ, Olszewski AJ, Kanan S, Meid K, Hunter ZR, Treon SP. Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of the Surveillance, Epidemiology and End Results database. Br J Haematol. 2015;169:81–9.

    Article  PubMed  Google Scholar 

  65. Phekoo KJ, Jack RH, Davies E, Møller H, Schey SA, Committee STHS. The incidence and survival of Waldenström’s Macroglobulinaemia in South East England. Leuk Res. 2008;32:55–9.

    Article  CAS  PubMed  Google Scholar 

  66. Castillo JJ, Olszewski AJ, Cronin AM, Hunter ZR, Treon SP. Survival trends in Waldenström macroglobulinemia: an analysis of the Surveillance, Epidemiology and End Results database. Blood. 2014;123:3999–4000.

    Article  CAS  PubMed  Google Scholar 

  67. Hanzis C, Ojha RP, Hunter Z, et al. Associated malignancies in patients with Waldenström’s macroglobulinemia and their kin. Clin Lymphoma Myeloma Leuk. 2011;11:88–92.

    Article  PubMed  Google Scholar 

  68. Castillo JJ, Olszewski AJ, Hunter ZR, Kanan S, Meid K, Treon SP. Incidence of secondary malignancies among patients with Waldenström macroglobulinemia: an analysis of the SEER database. Cancer. 2015;121:2230–6.

    Article  PubMed  Google Scholar 

  69. Varettoni M, Tedeschi A, Arcaini L, et al. Risk of second cancers in Waldenström macroglobulinemia. Ann Oncol. 2012;23:411–5.

    Article  CAS  PubMed  Google Scholar 

  70. Ojha RP, Thertulien R. Second malignancies among Waldenstrom macroglobulinemia patients: small samples and sparse data. Ann Oncol. 2012;23:542–3.

    Article  CAS  PubMed  Google Scholar 

  71. Castillo JJ, Olszewski AJ, Kanan S, Meid K, Hunter Z, Treon SP. Incidence and survival outcomes of secondary malignancies among survivors of Waldenström macroglobulinemia. Blood. 2014;124:855.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  73. Owen RG, Bynoe AG, Varghese A, de Tute RM, Rawstron AC. Heterogeneity of histological transformation events in Waldenström’s macroglobulinemia (WM) and related disorders. Clin Lymphoma Myeloma Leuk. 2011;11:176–9.

    Article  CAS  PubMed  Google Scholar 

  74. Kristinsson SY, Goldin LR, Turesson I, Björkholm M, Landgren O. Familial aggregation of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with solid tumors and myeloid malignancies. Acta Haematol. 2012;127:173–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kristinsson SY, Pfeiffer RM, Björkholm M, et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood. 2010;115:4991–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hultcrantz M, Pfeiffer RM, Björkholm M, et al. Elevated risk of venous but not arterial thrombosis in Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. J Thromb Haemost. 2014;12:1816–21.

    Article  CAS  PubMed  Google Scholar 

  77. Hakulinen T, Isomaki H, Knekt P. Rheumatoid arthritis and cancer studies based on linking nationwide registries in Finland. Am J Med. 1985;78:29–32.

    Article  CAS  PubMed  Google Scholar 

  78. Mariette X, Cazals-Hatem D, Warszawki J, et al. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood. 2002;99:3909–15.

    Article  CAS  PubMed  Google Scholar 

  79. Toussirot E, Wendling D. The use of TNF-alpha blocking agents in rheumatoid arthritis: an update. Expert Opin Pharmacother. 2007;8:2089–107.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Faculty of Medicine, University of Iceland, Stapi v/Hringbraut, 101, Reykjavik, Iceland

    Vilhjálmur Steingrímsson & Sigurður Yngvi Kristinsson MD, PhD

  2. Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Ola Landgren

  3. Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden

    Sigurður Yngvi Kristinsson MD, PhD

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  1. Vilhjálmur Steingrímsson
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  3. Sigurður Yngvi Kristinsson MD, PhD
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  1. Haematology, Hôpital Pitié-Salpêtriêre, Paris, France

    Véronique Leblond

  2. Dana Farber Cancer Institute, Boston, Massachusetts, USA

    Steve Treon

  3. School of Medicine, University of Athens, Athens, Greece

    Meletios Dimoploulos

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Steingrímsson, V., Landgren, O., Kristinsson, S.Y. (2017). Epidemiology of Waldenström Macroglobulinemia. In: Leblond, V., Treon, S., Dimoploulos, M. (eds) Waldenström’s Macroglobulinemia. Springer, Cham. https://doi.org/10.1007/978-3-319-22584-5_9

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