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| {{DiseaseDisorder infobox | | | {{Waldenström's macroglobulinemia}} |
| Name = Waldenström macroglobulinemia |
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| ICD10 = {{ICD10|C|88|0|c|81}} |
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| Image = Waldenström's macroglobulinemia 001.jpg |
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| Caption = Waldenström's macroglobulinemia. Bilateral involvement of orbit and eyelid. <br> <small> [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology] </small>|
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| ICDO = {{ICDO|9761|3}} |
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| ICD9 = {{ICD9|273.3}} |
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| OMIM = 153600 |
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| MedlinePlus = 000588 |
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| DiseasesDB = 14030 |
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| MeshID = D008258 |
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| }}
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| {{SI}}
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| {{CMG}}
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| ==Overview==
| | '''For patient information on this page, click [[Waldenström's macroglobulinemia(patient information)|here]]''' |
| '''Waldenström macroglobulinemia''' (WM) is cancer involving a subtype of white blood cells called [[lymphocytes]]. The main attributing antibody is IgM. It is a type of [[lymphoproliferative disease]], and shares clinical characteristics with the indolent [[non-Hodgkin lymphoma]]s.<ref name="Cheson">{{cite book | author = Cheson BD | year = 2006 | title = ACP Medicine | chapter = Chronic Lymphoid Leukemias and Plasma Cell Disorders | editor = Dale DD, Federman DD | publisher = WebMD Professional Publishing | location = New York, NY | id = ISBN 0974832715 }}</ref> | | {{CMG}}; {{AE}} {{S.M.}}, {{RAK}}, {{MGS}}; {{GRR}} {{Nat}} |
| ==Historical Perspective==
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| WM was first described by [[Jan G. Waldenström]] (1906-1996) in 1944 in two patients with bleeding from the nose and mouth, [[anemia]], decreased levels of [[fibrinogen]] in the blood (hypofibrinogenemia), [[lymphadenopathy|swollen lymph nodes]], neoplastic plasma cells in bone marrow, and increased [[viscosity]] of the blood due to increased levels of a class of heavy proteins called [[macroglobulins]].<ref name="Waldenstrom1944">{{cite journal | author= Waldenstrom J | title=Incipient myelomatosis or "essential" hyperglobulinemia with fibrinognenopenia-a new syndrome? | journal=Acta Med Scand| year=1944 | pages=216-247 | volume=117}} </ref> | | {{SK}} Waldenstrom/Waldenstrom's macroglubulinemia (WM), Primary [[macroglobulinemia]], [[Lymphoplasmacytic lymphoma]] (LPL), [[Plasmacytoid]] [[lymphocytic lymphoma]], [[Familial]] Waldenstrom's Macroglobulinaemia, Waldenström macroglobulinaemia |
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| For a period of time, WM was considered to be related to [[multiple myeloma]] due to the presence of monoclonal gammopathy and infiltration of the bone marrow and other organs by plasmacytoid lymphocytes. The new [[World Health Organization]] (WHO) classification, however, places WM under the category of lymphoplasmacytic lymphomas, itself a subcategory of the indolent (low-grade) non-Hodgkin lymphomas. <ref name="Harris">{{cite journal | author=Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD | title=The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997 | journal=Histopathology | year=2000 | pages=69-86 | volume=36 | issue=1 | id=PMID 10632755}}</ref>
| | ==[[Waldenström's macroglobulinemia overview|Overview]]== |
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| ==Epidemiology and Demographics== | | ==[[Waldenström's macroglobulinemia historical perspective|Historical Perspective]]== |
| WM is a rare disorder, with fewer than 1,500 cases occurring in the United States annually.<ref name="Cheson"> </ref> The median age of onset of WM is between 60 and 65 years.<ref name="Raje">{{cite book | author = Raje N, Hideshima T, Anderson KC | year = 2003 | title = Holland-Frei Cancer Medicine | chapter = Plasma Cell Tumors | edition=6th edition | editor = Kufe DW, Pollock RE, Weichselbaum RR, Bast RC, Gansler TS| publisher = B.C. Decker | location = New York, NY | id = ISBN 1550092138 }}</ref><ref name="Cheson"> </ref>
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| ==Diagnosis==
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| ==Symptoms==
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| Symptoms of WM include [[weakness]], [[fatigue (physical)|fatigue]], [[weight loss]] and chronic oozing of blood from the nose and gums.<ref name="Kyle1988">{{cite book | author =Kyle RA | year = 1998 | title = Internal Medicine | chapter = Chapter 94: Multiple Myeloma and the Dysproteinemias | editor = Stein JH | edition = 5th ed. | publisher = C.V.Mosby | location = New York | id = ISBN 0815186983 }}</ref> [[Peripheral neuropathy]] can occur in 10% of patients. Lymphadenopathy, [[splenomegaly]], and/or [[hepatomegaly]] are present in 30-40% of cases.<ref name="Raje"> </ref> Some symptoms are due to the effects of the [[IgM]] [[paraprotein]], which may cause [[autoimmune]] phenomenon or [[cryoglobulinemia]]. Other symptoms of WM are due to the [[hyperviscosity syndrome]], which is present in 6-20% of patients.<ref name="Owen">{{cite journal | author=Owen RG, Barrans SL, Richards SJ, O'Connor SJ, Child JA, Parapia LA, Morgan GJ, Jack AS | title=Waldenstrom macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors | journal=Am J Clin Pathol | year=2001 | pages=420-8 | volume=116 | issue=3 | id=PMID 11554171}}</ref><ref name="SanMiguel">{{cite journal | author=San Miguel JF, Vidriales MB, Ocio E, Mateo G, Sanchez-Guijo F, Sanchez ML, Escribano L, Barez A, Moro MJ, Hernandez J, Aguilera C, Cuello R, Garcia-Frade J, Lopez R, Portero J, Orfao A | title=Immunophenotypic analysis of Waldenstrom's macroglobulinemia | journal=Semin Oncol | year=2003 | pages=187-95 | volume=30 | issue=2 | id=PMID 12720134}}</ref><ref name="Ghobrial">{{cite journal | author=Ghobrial IM, Witzig TE | title=Waldenstrom macroglobulinemia | journal=Curr Treat Options Oncol | year=2004 | pages=239-47 | volume=5 | issue=3 | id=PMID 15115652}}</ref><ref name="Dimopoulos">{{cite journal | author=Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP | title=Diagnosis and management of Waldenstrom's macroglobulinemia | journal=J Clin Oncol | year=2005 | pages=1564-77 | volume=23 | issue=7 | id=PMID 15735132}}</ref> This is attributed to the IgM monoclonal protein increasing the viscosity of the blood. Symptoms of this are mainly neurologic and can include blurring or [[loss of vision]], [[headache]], and (rarely) [[stroke]] or [[coma]].
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| ===Laboratory Tests=== | | ==[[Waldenström's macroglobulinemia classification|Classification]]== |
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| *The laboratory diagnosis of Waldenström's macroglobulinemia is contingent on demonstrating a significant monoclonal [[IgM]] spike and identifying malignant cells consistent with Waldenström's macroglobulinemia (usually found in bone marrow biopsy samples and aspirates).
| | ==[[Waldenström's macroglobulinemia pathophysiology|Pathophysiology]]== |
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| *General studies include a [[CBC]], red cell indices, [[platelet count]], and a [[peripheral smear]].
| | ==[[Waldenström's macroglobulinemia causes|Causes]]== |
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| *[[Normocytic normochromic anemia]], [[leukopenia]], and [[thrombocytopenia]] may be observed. [[Anemia]] is the most common finding, present in 80% of patients with symptomatic Waldenström's macroglobulinemia.
| | ==[[Waldenström's macroglobulinemia differential diagnosis|Differentiating Waldenström's Macroglobulinemia from other Diseases]]== |
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| *The [[peripheral smear]] may reveal plasmacytoid [[lymphocyte]]s, normocytic normochromic red cells, and rouleaux formation.
| | ==[[Waldenström's macroglobulinemia epidemiology and demographics|Epidemiology and Demographics]]== |
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| *[[Neutropenia]] can be found in some patients.
| | ==[[Waldenström's macroglobulinemia risk factors|Risk Factors]]== |
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| *[[Thrombocytopenia]] is found in approximately 50% of patients with bleeding diathesis.
| | ==[[Waldenström's macroglobulinemia screening|Screening]]== |
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| *Chemistry tests include [[lactate dehydrogenase]] ([[LDH]]) levels, [[uric acid]] levels, [[erythrocyte sedimentation rate]] ([[ESR]]), renal and [[hepatic function test]]s, [[total protein]] levels, and an [[albumin-to-globulin ratio]]. The [[ESR]] and [[uric acid]] level may be elevated.
| | ==[[Waldenström's macroglobulinemia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| *[[Creatinine]] is occasionally elevated and electrolytes are occasionally abnormal. [[Hypercalcemia]] is noted in approximately 4% of patients.
| | ==[[Diagnosis]]== |
| | | [[Waldenström's macroglobulinemia diagnostic study of choice|Diagnostic Study of Choice]] | [[Waldenström's macroglobulinemia history and symptoms|History and Symptoms]] | [[Waldenström's macroglobulinemia physical examination|Physical Examination]] | [[Waldenström's macroglobulinemia laboratory findings|Laboratory Findings]] | [[Waldenström's macroglobulinemia electrocardiogram|Electrocardiogram]] | [[Waldenström's macroglobulinemia chest x ray|Chest X Ray]] | [[Waldenström's macroglobulinemia CT|CT]] | [[Waldenström's macroglobulinemia MRI|MRI]] | [[Waldenström's macroglobulinemia Electrocardiography or Ultrasound|Electrocardiography or Ultrasound]] | [[Waldenström's macroglobulinemia PET|PET]] | [[Waldenström's macroglobulinemia Other Diagnostic Studies|Other Diagnostic Studies]] |
| *The [[LDH]] level is frequently elevated, indicating the extent of Waldenström's macroglobulinemia–related tissue involvement.
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| *[[Rheumatoid factor]], [[cryoglobulin]]s, [[direct antiglobulin test]] and [[cold agglutinin titre]] results can be positive.
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| *Beta-2-microglobulin and [[C-reactive protein]] test results are not specific for Waldenström's macroglobulinemia. Beta-2-microglobulin is elevated in proportion to tumor mass.
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| *Coagulation abnormalities may be present. Prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen tests should be performed. Platelet aggregation studies are optional.
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| *Serum [[protein electrophoresis]] results indicate evidence of a monoclonal spike but cannot establish the spike as IgM. An M component with beta-to-gamma mobility is highly suggestive of Waldenström's macroglobulinemia.
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| * A distinguishing feature of WM is the presence of an [[IgM monoclonal protein]] (or [[paraprotein]]) that is produced by the cancer cells, and a concurrent decrease in levels of uninvolved [[immunoglobulins]] (i.e., [[IgG]] and [[IgA]]).
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| *Immunoelectrophoresis and immunofixation studies help identify the type of immunoglobulin, the clonality of the light chain, and the monoclonality and quantitation of the paraprotein.
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| *High-resolution electrophoresis and serum and urine immunofixation are recommended to help identify and characterize the monoclonal IgM paraprotein.
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| *The light chain of the monoclonal protein is usually the kappa light chain. At times, patients with Waldenström's macroglobulinemia may exhibit more than one M protein.
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| *Plasma viscosity must be measured.
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| *Results from characterization studies of urinary immunoglobulins indicate that light chains ([[Bence Jones protein]]), usually of the kappa type, are found in the urine.
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| *Urine collections should be concentrated.
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| *[[Bence Jones protein|Bence Jones proteinuria]] is observed in approximately 40% of patients and exceeds 1 g/d in approximately 3% of patients.
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| *Patients with findings of [[peripheral neuropathy]] should have nerve conduction studies and [[antimyelin associated glycoprotein]] serology
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| ==Natural History, Complications and Prognosis==
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| Current medical treatments result in survival some longer than 10 years. In part this is because better diagnostic testing means early diagnosis and treatments. Older diagnosis and treatments resulted in published reports of median survival of approximately 5 years from time of diagnosis.<ref name="Cheson"> </ref> New treatments have made longer term survival a reality for many with this condition. In rare instances, WM progresses to [[multiple myeloma]].<ref name="Johansson">{{cite journal | author=Johansson B, Waldenstrom J, Hasselblom S, Mitelman F | title=Waldenstrom's macroglobulinemia with the AML/MDS-associated t(1;3)(p36;q21) | journal=Leukemia | year=1995 | pages=1136-8 | volume=9 | issue=7 | id=PMID 7630185}}</ref>
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| ==Treatment== | | ==Treatment== |
| There is no single accepted treatment for WM. Indeed, in 1991, Waldenström himself raised the question of the need for effective therapy.<ref>{{cite journal | author=Waldenstrom J | title=To treat or not to treat, this is the real question | journal=Leuk Res | year=1991 | pages=407-8 | volume=15 | issue=6 | id=PMID 1907339}}</ref> In the absence of symptoms, many clinicians will recommend simply monitoring the patient.
| | [[Waldenström's macroglobulinemia medical therapy|Medical Therapy]] | [[Waldenström's macroglobulinemia surgery| Surgery]] | [[Waldenström's macroglobulinemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Waldenström's macroglobulinemia future or investigational therapies|Future or Investigational Therapies]] |
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| In 2002, a panel at the International Workshop on Waldenström's Macroglobulinemia agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent [[fever]], [[night sweats]], [[fatigue]] due to [[anemia]], [[weight loss]], progressive symptomatic [[lymphadenopathy]] or [[splenomegaly]], and [[anemia]] due to [[bone marrow]] infiltration.
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| Complications such as [[hyperviscosity syndrome]], symptomatic sensorimotor peripheral neuropathy, systemic [[amyloidosis]], [[renal insufficiency]], or symptomatic cryoglobulinemia were also suggested as indications for therapy.<ref name="Kyel2003">{{cite journal | author=Kyle RA, Treon SP, Alexanian R, Barlogie B, Bjorkholm M, Dhodapkar M, Lister TA, Merlini G, Morel P, Stone M, Branagan AR, Leblond V | title=Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia | journal=Semin Oncol | year=2003 | pages=116-20 | volume=30 | issue=2 | id=PMID 12720119}}</ref>
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| Treatment includes the monoclonal antibody [[rituximab]], sometimes in combination with chemotherapeutic drugs such as [[chlorambucil]], [[cyclophosphamide]], or [[vincristine]]. [[Corticosteroid]]s may also be used in combination. [[Plasmapheresis]] can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease.<ref name="Gertz">{{cite journal | author=Gertz MA | title=Waldenstrom macroglobulinemia: a review of therapy | journal=Am J Hematol | year=2005 | pages=147-57 | volume=79 | issue=2 | id=PMID 15929102}}</ref>
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| Recently, [[autologous bone marrow transplantation]] has been added to the available treatment options.<ref name="Yang">{{cite journal | author=Yang L, Wen B, Li H, Yang M, Jin Y, Yang S, Tao J | title=Autologous peripheral blood stem cell transplantation for Waldenstrom's macroglobulinemia | journal=Bone Marrow Transplant | year=1999 | pages=929-30 | volume=24 | issue=8 | id=PMID 10516708}}</ref><ref name="Martino">{{cite journal | author=Martino R, Shah A, Romero P, Brunet S, Sierra J, Domingo-Albos A, Fruchtman S, Isola L | title=Allogeneic bone marrow transplantation for advanced Waldenstrom's macroglobulinemia | journal=Bone Marrow Transplant | year=1999 | pages=747-9 | volume=23 | issue=7 | id=PMID 10218857}}</ref><ref name="Anagnostopoulos">{{cite journal | author=Anagnostopoulos A, Dimopoulos MA, Aleman A, Weber D, Alexanian R, Champlin R, Giralt S | title=High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom's macroglobulinemia | journal=Bone Marrow Transplant | year=2001 | pages=1027-9 | volume=27 | issue=10 | id=PMID 11438816}}</ref><ref name="Tournilhac">{{cite journal | author=Tournilhac O, Leblond V, Tabrizi R, Gressin R, Senecal D, Milpied N, Cazin B, Divine M, Dreyfus B, Cahn JY, Pignon B, Desablens B, Perrier JF, Bay JO, Travade P | title=Transplantation in Waldenstrom's macroglobulinemia--the French experience | journal=Semin Oncol | year=2003 | pages=291-6 | volume=30 | issue=2 | id=PMID 12720155}}</ref>
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| ==References==
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| {{Reflist|2}}
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| ==External links== | | ==Case Studies== |
| *[http://www.iwmf.com/ The International Waldenström's Macroglobulinemia Foundation site]
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| *[http://www.cancer.gov/cancertopics/factsheet/Sites-Types/WM National Cancer Institute's Waldenström's Macroglobulinemia Q&A]
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| *[http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=76 American Cancer Society Detailed Guide: Waldenström's Macroglobulinemia]
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| *[http://www.waldenstromsresearch.org/ Research Fund for Waldenström's]
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| | [[Waldenström's macroglobulinemia case study one|Case #1]] |
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