Waldenström's macroglobulinemia natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2], Roukoz A. Karam, M.D.[3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]
Overview
If left untreated, patients with asymptomatic disease may progress to develop fatigue, weight loss, peripheral neuropathy, shortness of breath, purpura, raynaud's phenomenon, and vision problems. Common complications of Waldenstrom's macroglobulinemia include: hyperviscosity syndrome, cold haemagglutinin disease, cryoglobulinemia, peripheral neuropathy, primary amyloidosis, renal insufficiency, malabsorptive diarrhea, visual abnormalities, congestive heart failure, and schnitzler syndrome. Late and rare severe complications include richter syndrome, and bing-Neel syndrome. Prognosis varies depending on the various factors involved. Five year survival rate is 87% for low-risk disease and 36% for high-risk disease. A standardized scoring system known as the International PrognosticStaging System for Waldenström's Macroglobulinemia (IPSSWM) risk stratifies the patients with Waldenstrom's macroglobulinemia.
Natural History, Complications, and Prognosis
Natural History
Initial symptoms
- Symptoms of Waldenstrom's macroglobulinemia usually develop in the seventh and eighth decade of life
- It will typically start with symptoms such as:
- Fatigue
- Unexplained weight loss
- Numbness and tingling associated with peripheral neuropathy
- Shortness of breath
- Purpura
- Raynaud's phenomenon
- Vision problems such as blurred vision, vision loss or blind spots[1]
Complications
- As the disease progresses, the following complications can commonly occur in patients with Waldenstrom's macroglobulinemia:
- Hyperviscosity syndrome[2]
- Cryoglobulinemia[3]
- Peripheral neuropathy(15%)[4]
- Amyloidosis of the heart, kidney, liver, lungs, and joints[5]
- Cold haemagglutinin disease/Autoimmune hemolytic anemia(<10%)[6]
- Gastrointestinal malabsorption[7]
- Renal insufficiency[8]
- Fundoscopic abnormalities[2]
- Congestive heart failure
- Schnitzler syndrome which is an autoimmune complication associated with elevated IgM levels, that leads to fever, itchy skin lesions, and joint aches
Late and rare severe complications
- Large cell transformation (Richter syndrome):
- Dr. Richter of the University of Minnesota first recognized the blockage in maturity of the lymphoma cells at a point when they can't mature beyond the large cell stage thus, leading to large cell transformation
- Central nervous system Lymphoma (Bing-Neel syndrome):[9]
- The development of Waldenström macroglobulinemia cells in the central nervous system was first described by Drs. Bing and Neel and carries their names as the Bing-Neel syndrome. WM involves CNS in following two forms:
- Actual tumor developing in the brain substance causing seizures and paralysis
- Tumor cells invading meninges and cranial nerves without causing the actual tumors and with or without CSF cryoglobulinemia,[10] leading to the following symptoms:[11]
- The development of Waldenström macroglobulinemia cells in the central nervous system was first described by Drs. Bing and Neel and carries their names as the Bing-Neel syndrome. WM involves CNS in following two forms:
Summary of natural history and complications of Waldenstrom's macroglobulinemia
Initial symptoms
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Common complications
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Late and rare severe complications
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Prognosis
- Prognosis is generally poor
- The median survival from the time of diagnosis is 6.4 years[12]
- The median disease-specific survival is 11.2 years[12]
- Approximately 10% patients still live uptil 15 years[13][14]
- 5-year survival rate is 78%
- In the last decade (2001-2010), the median overall survival for all WM groups has improved to just over 8 years compared to 6 years in the previous decade (1991-2000)
- Cases without MYD88 mutations are associated with adenopathy and a worse outcome[15]
- After 2000, a 2-fold increased mortality is reported in patients diagnosed with WM when compared with expected population mortality[16]
- The presence of symptoms is associated with a particularly poor prognosis among patients with the disease
- Prognosis of asymptomatic patients is similar to that of the general population with a 10-year survival rate of 70-75%[17][18]
Adverse prognostic factors
- Some of the pretreatment factors associated with shorter survival in WM patients are:[19][12]
- Clinical parameters:
- Age >/=65 years
- Hyperviscosity symptoms
- Bulky organomegaly (Hepatosplenomegaly)
- Bulky lymphadenopathy
- B symptoms (weight loss, fever or night sweats)
- Presence of symptomatic or unresponsive neuropathy
- Hemolytic anemia
- Laboratory parameters:
- Hemoglobin < 10.0 g/dl)
- Platelets <100 x 10(6)/dl
- Albumin <3.5 g/dl
- Bone marrow lymphoplasmacytic infiltrate >/=50%
- Elevated beta2-microglobulin (associated with 3-fold increase in death)
- Leucopenia (<4.0 x 10(9)/l)
- Thrombocytopenia (<150 x 10(9)/l)
- Quantitative IgM < 0.4 g/l
- Serum free light chain[20]
- Serum lactate dehydrogenase[21]
- Serum soluble CD27[22]
- Clinical parameters:
- Most of the prognostic factors have defined the outcome of Waldenstrom's macroglobulinemia in patients requiring treatment, however, very few studies have evaluated the prognostic factors in patients who don't initially need the treatment
Risk Stratification Criteria
All the above prognostic data has been combined to risk stratify the WM patients and to formulate a standardized scoring system known as the International Prognostic Staging System for Waldenström's Macroglobulinemia (IPSSWM):[23]
| Risk factors | Score |
|---|---|
| Age > 65 | 1 |
| Hemoglobin ≤ 11.5g/dl | 1 |
| Platelet ≤ 100,000μl | 1 |
| β-microglobulin > 3mg/l | 1 |
| IgM > 70g/l | 1 |
| Risk group | Score | 5-year survival | Median survival |
|---|---|---|---|
| Low | 0-1 (except age) | 87% | 12 years |
| Intermediate | 2 or age>65 | 68% | 8 years |
| High | ≥3 | 36% | 3.5 years |
References
- ↑ Wang H, Chen Y, Li F, Delasalle K, Wang J, Alexanian R; et al. (2012). "Temporal and geographic variations of Waldenstrom macroglobulinemia incidence: a large population-based study". Cancer. 118 (15): 3793–800. doi:10.1002/cncr.26627. PMID 22139816.
- ↑ 2.0 2.1 García-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A; et al. (2001). "Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases". Br J Haematol. 115 (3): 575–82. PMID 11736938.
- ↑ Michael AB, Lawes M, Kamalarajan M, Huissoon A, Pratt G (2004). "Cryoglobulinaemia as an acute presentation of Waldenstrom's macroglobulinaemia". Br J Haematol. 124 (5): 565. PMID 14871241.
- ↑ Levine T, Pestronk A, Florence J, Al-Lozi MT, Lopate G, Miller T; et al. (2006). "Peripheral neuropathies in Waldenström's macroglobulinaemia". J Neurol Neurosurg Psychiatry. 77 (2): 224–8. doi:10.1136/jnnp.2005.071175. PMC 2077569. PMID 16421127.
- ↑ Zimmermann I, Gloor HJ, Rüttimann S (2001). "[General AL-amyloidosis: a rare complication in Waldenstrom macroglobulinemia]". Praxis (Bern 1994) (in German). 90 (47): 2050–5. PMID 11763619.
- ↑ Owen RG, Pratt G, Auer RL, Flatley R, Kyriakou C, Lunn MP; et al. (2014). "Guidelines on the diagnosis and management of Waldenström macroglobulinaemia". Br J Haematol. 165 (3): 316–33. doi:10.1111/bjh.12760. PMID 24528152.
- ↑ Veloso FT, Fraga J, Saleiro JV (1988). "Macroglobulinemia and small intestinal disease. A case report with review of the literature". J Clin Gastroenterol. 10 (5): 546–50. PMID 3141496.
- ↑ Vos JM, Gustine J, Rennke HG, Hunter Z, Manning RJ, Dubeau TE; et al. (2016). "Renal disease related to Waldenström macroglobulinaemia: incidence, pathology and clinical outcomes". Br J Haematol. 175 (4): 623–630. doi:10.1111/bjh.14279. PMID 27468978.
- ↑ Civit T, Coulbois S, Baylac F, Taillandier L, Auque J (1997). "[Waldenström's macroglobulinemia and cerebral lymphoplasmocytic proliferation: Bing and Neel syndrome. Apropos of a new case]". Neurochirurgie. 43 (4): 245–9. PMID 9686227.
- ↑ Fintelmann F, Forghani R, Schaefer PW, Hochberg EP, Hochberg FH (2009). "Bing-Neel Syndrome revisited". Clin Lymphoma Myeloma. 9 (1): 104–6. doi:10.3816/CLM.2009.n.028. PMID 19362988.
- ↑ Grewal JS, Brar PK, Sahijdak WM, Tworek JA, Chottiner EG (2009). "Bing-Neel syndrome: a case report and systematic review of clinical manifestations, diagnosis, and treatment options". Clin Lymphoma Myeloma. 9 (6): 462–6. doi:10.3816/CLM.2009.n.091. PMID 19951888.
- ↑ 12.0 12.1 12.2 Ghobrial IM, Fonseca R, Gertz MA, Plevak MF, Larson DR, Therneau TM; et al. (2006). "Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstrom macroglobulinaemia". Br J Haematol. 133 (2): 158–64. doi:10.1111/j.1365-2141.2006.06003.x. PMID 16611306.
- ↑ Morel, P.; Duhamel, A.; Gobbi, P.; Dimopoulos, M. A.; Dhodapkar, M. V.; McCoy, J.; Crowley, J.; Ocio, E. M.; Garcia-Sanz, R.; Treon, S. P.; Leblond, V.; Kyle, R. A.; Barlogie, B.; Merlini, G. (2009). "International prognostic scoring system for Waldenstrom macroglobulinemia". Blood. 113 (18): 4163–4170. doi:10.1182/blood-2008-08-174961. ISSN 0006-4971.
- ↑ Kyle RA, Greipp PR, Gertz MA, Witzig TE, Lust JA, Lacy MQ; et al. (2000). "Waldenström's macroglobulinaemia: a prospective study comparing daily with intermittent oral chlorambucil". Br J Haematol. 108 (4): 737–42. PMID 10792277.
- ↑ Treon SP, Cao Y, Xu L, Yang G, Liu X, Hunter ZR (2014). "Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia". Blood. 123 (18): 2791–6. doi:10.1182/blood-2014-01-550905. PMID 24553177.
- ↑ Kyle, Robert A.; Larson, Dirk R.; McPhail, Ellen D.; Therneau, Terry M.; Dispenzieri, Angela; Kumar, Shaji; Kapoor, Prashant; Cerhan, James R.; Rajkumar, S. Vincent (2018). "Fifty-Year Incidence of Waldenström Macroglobulinemia in Olmsted County, Minnesota, From 1961 Through 2010: A Population-Based Study With Complete Case Capture and Hematopathologic Review". Mayo Clinic Proceedings. 93 (6): 739–746. doi:10.1016/j.mayocp.2018.02.011. ISSN 0025-6196.
- ↑ Ansell SM, Kyle RA, Reeder CB, Fonseca R, Mikhael JR, Morice WG; et al. (2010). "Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines". Mayo Clin Proc. 85 (9): 824–33. doi:10.4065/mcp.2010.0304. PMC 2931618. PMID 20702770.
- ↑ Gobbi PG, Baldini L, Broglia C, Goldaniga M, Comelli M, Morel P; et al. (2005). "Prognostic validation of the international classification of immunoglobulin M gammopathies: a survival advantage for patients with immunoglobulin M monoclonal gammopathy of undetermined significance?". Clin Cancer Res. 11 (5): 1786–90. doi:10.1158/1078-0432.CCR-04-1899. PMID 15756000.
- ↑ Dimopoulos MA, Hamilos G, Zervas K, Symeonidis A, Kouvatseas G, Roussou P; et al. (2003). "Survival and prognostic factors after initiation of treatment in Waldenstrom's macroglobulinemia". Ann Oncol. 14 (8): 1299–305. PMID 12881396.
- ↑ Leleu X, Moreau AS, Weller E, Roccaro AM, Coiteux V, Manning R; et al. (2008). "Serum immunoglobulin free light chain correlates with tumor burden markers in Waldenstrom macroglobulinemia". Leuk Lymphoma. 49 (6): 1104–7. doi:10.1080/10428190802074619. PMID 18452095.
- ↑ Kastritis E, Zervas K, Repoussis P, Michali E, Katodrytou E, Zomas A; et al. (2009). "Prognostication in young and old patients with Waldenström's macroglobulinemia: importance of the International Prognostic Scoring System and of serum lactate dehydrogenase". Clin Lymphoma Myeloma. 9 (1): 50–2. doi:10.3816/CLM.2009.n.012. PMID 19362972.
- ↑ Ho AW, Hatjiharissi E, Ciccarelli BT, Branagan AR, Hunter ZR, Leleu X; et al. (2008). "CD27-CD70 interactions in the pathogenesis of Waldenstrom macroglobulinemia". Blood. 112 (12): 4683–9. doi:10.1182/blood-2007-04-084525. PMC 2597134. PMID 18216294.
- ↑ Morel P, Duhamel A, Gobbi P, Dimopoulos MA, Dhodapkar MV, McCoy J; et al. (2009). "International prognostic scoring system for Waldenstrom macroglobulinemia". Blood. 113 (18): 4163–70. doi:10.1182/blood-2008-08-174961. PMID 19196866.