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| {{CMG}}; {{AE}} {{S.M.}} | | {{CMG}}; {{AE}} {{S.M.}} |
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| {{SK}} Waldenstrom's macroglobulinemia; Waldenstrom's disease; Primary macroglobulinemia; Hyperviscosity syndrome; Lymphoplasmacytoid lymphoma | | {{SK}} Plasmacytoid lymphocytic [[lymphoma]]; Familial Waldenström's macroglobulinemia; Primary macroglobulinemia; Hyperviscosity syndrome; Lymphoplasmacytoid [[lymphoma]] |
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| ==Overview== | | ==[[Lymphoplasmacytic lymphoma overview|Overview]]== |
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| ==Differentiating Lymphoplasmacytic Lymphoma from Other B cell lymphoid neoplasms== | | ==[[Lymphoplasmacytic lymphoma historical perspective|Historical Perspective]]== |
| Waldenström macroglobulinemia must be differentiated from other B cell lymphoid neoplasms including:
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| *[[Chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]]:
| | ==[[Lymphoplasmacytic lymphoma classification|Classification]]== |
| :*Always express CD5
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| :*Usually CD23 positive<ref name="CLL">{{cite journal |vauthors=Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ |title=Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines |journal=Blood |volume=111 |issue=12 |pages=5446–56 |year=2008 |pmid=18216293 |pmc=2972576 |doi=10.1182/blood-2007-06-093906 |url=}}</ref>
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| *[[B-cell prolymphocytic leukemia]]:
| | ==[[Lymphoplasmacytic lymphoma pathophysiology|Pathophysiology]]== |
| :*Express bright surface [[Immunoglobulin M|IgM]], [[CD20]] and other B-cell antigens ([[CD19]], [[CD22]], [[CD79a]], [[FMC7]])<ref name=",m">{{cite journal |vauthors=Del Giudice I, Davis Z, Matutes E, Osuji N, Parry-Jones N, Morilla A, Brito-Babapulle V, Oscier D, Catovsky D |title=IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL) |journal=Leukemia |volume=20 |issue=7 |pages=1231–7 |year=2006 |pmid=16642047 |doi=10.1038/sj.leu.2404238 |url=}}</ref><ref name="njl">{{cite journal |vauthors=Ravandi F, O'Brien S |title=Chronic lymphoid leukemias other than chronic lymphocytic leukemia: diagnosis and treatment |journal=Mayo Clin. Proc. |volume=80 |issue=12 |pages=1660–74 |year=2005 |pmid=16342661 |doi=10.4065/80.12.1660 |url=}}</ref>
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| *[[Follicular lymphoma]]:
| | ==[[Lymphoplasmacytic lymphoma causes|Causes]]== |
| :*Express [[CD10]], [[HLA-DR]], pan B-cell antigens (CD19, CD20, CD79a), CD21, and surface IgM, [[Immunoglobulin G|IgG]], or [[IgA]]
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| :*Rearrangement of Bcl-2<ref name="FL">{{cite journal |vauthors=Karube K, Guo Y, Suzumiya J, Sugita Y, Nomura Y, Yamamoto K, Shimizu K, Yoshida S, Komatani H, Takeshita M, Kikuchi M, Nakamura N, Takasu O, Arakawa F, Tagawa H, Seto M, Ohshima K |title=CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features |journal=Blood |volume=109 |issue=7 |pages=3076–9 |year=2007 |pmid=17138820 |doi=10.1182/blood-2006-09-045989 |url=}}</ref><ref name="FL1">{{cite journal |vauthors=Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM |title=Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation |journal=Blood |volume=63 |issue=6 |pages=1424–33 |year=1984 |pmid=6609729 |doi= |url=}}
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| :*Bone marrow infiltration of small, cleaved cells that are usually paratrabecular
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| </ref>
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| *[[Multiple myeloma]]:
| | ==[[Lymphoplasmacytic lymphoma differential diagnosis|Differentiating Lymphoplasmacytic lymphoma from other Diseases]]== |
| :*Express CD138, CD38, CD79a, VS38c and CD56 (70%)
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| :*Presence of plasmacytic cell infiltration of bone marrow, osteolytic lesions, and [[renal insufficiency]]
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| :*Translocation involving chromosome 11 (t11;14)<ref name="UTD">{{cite journal |vauthors=Pangalis GA, Kyrtsonis MC, Kontopidou FN, Vassilakopoulos TP, Siakantaris MP, Dimopoulou MN, Kittas C, Angelopoulou MK |title=Differential diagnosis of Waldenstrom's macroglobulinemia from other low-grade B-cell lymphoproliferative disorders |journal=Semin. Oncol. |volume=30 |issue=2 |pages=201–5 |year=2003 |pmid=12720136 |doi=10.1053/sonc.2003.50046 |url=}}</ref>
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| *[[Mantle cell lymphoma]]:
| | ==[[Lymphoplasmacytic lymphoma epidemiology and demographics|Epidemiology and Demographics]]== |
| :* Expresses CD5+ and CD23+
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| :* Expresses surface IgM, IgD, and cyclin D1 in majority of cases
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| :*Infiltration of bone marrow by monomorphous small lymphoid cells with irregular nuclei<ref name="MCL">{{cite journal |vauthors=Dorfman DM, Pinkus GS |title=Distinction between small lymphocytic and mantle cell lymphoma by immunoreactivity for CD23 |journal=Mod. Pathol. |volume=7 |issue=3 |pages=326–31 |year=1994 |pmid=8058704 |doi= |url=}}</ref><ref name="MCL1">{{cite journal |vauthors=DiRaimondo F, Albitar M, Huh Y, O'Brien S, Montillo M, Tedeschi A, Kantarjian H, Lerner S, Giustolisi R, Keating M |title=The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease |journal=Cancer |volume=94 |issue=6 |pages=1721–30 |year=2002 |pmid=11920534 |doi= |url=}}</ref>
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| *[[Marginal zone lymphoma]]:
| | ==[[Lymphoplasmacytic lymphoma risk factors|Risk Factors]]== |
| :*Expresses B cell markers CD19, CD20, and CD22
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| :*Infiltrates the bone marrow with a characteristic intertrabecular and intrasinusoidal pattern
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| :*Most common cytogenetic abnormalities are loss of 7q (19%) along with +3q (19%) and +5q (10% )<ref name="add">{{cite journal |vauthors=Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD |title=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 |journal=J. Clin. Oncol. |volume=17 |issue=12 |pages=3835–49 |year=1999 |pmid=10577857 |doi= |url=}}</ref><ref name="asdf">{{cite journal |vauthors=Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC |title=A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group |journal=Blood |volume=84 |issue=5 |pages=1361–92 |year=1994 |pmid=8068936 |doi= |url=}}</ref>
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| ==Epidemiology and Demographics== | | ==[[Lymphoplasmacytic lymphoma screening|Screening]]== |
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| ==Risk Factors== | | ==[[Lymphoplasmacytic lymphoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| ==Screening== | | ==Diagnosis== |
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| ==Natural History, Complications, and Prognosis==
| | [[Lymphoplasmacytic lymphoma diagnostic study of choice|Diagnostic study of choice]] | [[Lymphoplasmacytic lymphoma history and symptoms|History and Symptoms]] | [[Lymphoplasmacytic lymphoma physical examination|Physical Examination]] | [[Lymphoplasmacytic lymphoma laboratory findings|Laboratory Findings]] | [[Lymphoplasmacytic lymphoma electrocardiogram|Electrocardiogram]] | [[Lymphoplasmacytic lymphoma x ray|X-Ray Findings]] | [[Lymphoplasmacytic lymphoma echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Lymphoplasmacytic lymphoma CT scan|CT-Scan Findings]] | [[Lymphoplasmacytic lymphoma MRI|MRI Findings]] | [[Lymphoplasmacytic lymphoma other imaging findings|Other Imaging Findings]] | [[Lymphoplasmacytic lymphoma other diagnostic studies|Other Diagnostic Studies]] |
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| ==Diagnosis==
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| *Not all the diagnostic tests mentioned are performed in a WM patient. A doctor takes into account the following factors before choosing diagnostic tests in a particular patient:
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| **Suspected type of cancer.
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| **Signs and symptoms.
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| **Age.
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| **Medical condition of the patient.
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| **Results of earlier medical tests.
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| ===Other Diagnostic Studies===
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| Other diagnostic studies for Waldenström macroglobulinemia include:
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| *'''[[Nerve conduction study|Nerve conduction]] study''' and '''[[electromyography]]''', which demonstrates:<ref name="ser">{{cite journal |vauthors=Nobile-Orazio E, Marmiroli P, Baldini L, Spagnol G, Barbieri S, Moggio M, Polli N, Polli E, Scarlato G |title=Peripheral neuropathy in macroglobulinemia: incidence and antigen-specificity of M proteins |journal=Neurology |volume=37 |issue=9 |pages=1506–14 |year=1987 |pmid=2442666 |doi= |url=}}</ref>
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| **[[Demyelination]] with sensory involvement more than motor
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| *'''[[Fundoscopy]]''', which demonstrates:<ref name="pmid27378193">{{cite journal| author=Castillo JJ, Garcia-Sanz R, Hatjiharissi E, Kyle RA, Leleu X, McMaster M et al.| title=Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia. | journal=Br J Haematol | year= 2016 | volume= 175 | issue= 1 | pages= 77-86 | pmid=27378193 | doi=10.1111/bjh.14196 | pmc=5154335 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27378193 }} </ref>
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| **Dilated, segmented, and tortuous [[retinal veins]] giving a "sausage link" appearance
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| ***Useful in patients with suspected [[hyperviscosity syndrome]]
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| * '''Plasma viscosity''', which demonstrates:<ref name="pmid4014299">{{cite journal| author=Crawford J, Cox EB, Cohen HJ| title=Evaluation of hyperviscosity in monoclonal gammopathies. | journal=Am J Med | year= 1985 | volume= 79 | issue= 1 | pages= 13-22 | pmid=4014299 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4014299 }} </ref>
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| **Values > 1.5 centipoise
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| ***Should be measured in patients presenting with signs and symptoms suggestive of hyperviscosity syndrome or whenever the monoclonal [[Immunoglobulin M|IgM]] protein spike is > 4 g/dL.
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| * '''Mutational analysis''' for the ''[[MYD88]]'' gene, since the MYD88 L265P mutation is found in 90% of patients with Waldenstrom's macroglobulinemia<ref name="pmid23321251">{{cite journal| author=Xu L, Hunter ZR, Yang G, Zhou Y, Cao Y, Liu X et al.| title=MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. | journal=Blood | year= 2013 | volume= 121 | issue= 11 | pages= 2051-8 | pmid=23321251 | doi=10.1182/blood-2012-09-454355 | pmc=3596964 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23321251 }} </ref>
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| ==Treatment== | | ==Treatment== |
| There are several different options for treating Waldenström macroglobulinemia depending on stage of the disease:<ref name="Tx">Lymphoplasmacytic lymphoma. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/lymphoplasmacytic-lymphoma/?region=ab Accessed on November 6 2015 </ref>
| | [[Lymphoplasmacytic lymphoma medical therapy|Medical Therapy]] | [[Lymphoplasmacytic lymphoma surgery|Surgery]] | [[Lymphoplasmacytic lymphoma primary prevention|Primary Prevention]] | [[Lymphoplasmacytic lymphoma secondary prevention|Secondary Prevention]] | [[Lymphoplasmacytic lymphoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Lymphoplasmacytic lymphoma future or investigational therapies|Future or Investigational Therapies]] |
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| ====Asymptomatic/Smoldering Waldenström's Macroglobulinemia====
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| There is no treatment for asymptomatic Waldenström macroglobulinemia. Asymptomatic waldenström's macroglobulinemia can be monitored every 3-6 months.<ref name="BM">Waldenström's macroglobulinemia. Patient (2015)http://patient.info/doctor/waldenstroms-macroglobulinaemia-pro Accessed on November 10, 2015</ref> Active surveillance includes monitoring of the following laboratory parameters:
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| *Complete blood count ([[Complete blood count|CBC]]) with differential
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| *Complete metabolic panel ([[CMP-N-acetylneuraminate monooxygenase|CMP]])
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| *Immunoglobulin levels in the serum (quantitative)
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| *Serum protein electrophoresis
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| ====Symptomatic Waldenström's Macroglobulinemia====
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| Symptomatic patients with waldenström macroglobulinemia are started on chemotherapy depending on the stage.<ref name="ADR">Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015)http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015</ref>
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| *Initial stage of waldenström's macroglobulinemia associated with:
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| :*[[Neuropathy]]
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| :*[[Anemia]] or [[cytopenias]]
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| :*Low-volume nodal involvement
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| :*Asymptomatic [[splenomegaly]]
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| *Late stage of Waldenström's macroglobulinemia associated with:
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| :*[[Adenopathy]]
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| :*Symptomatic [[splenomegaly]]
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| :*[[Cytopenia|Cytopenias]]
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| :*[[Hyperviscosity syndrome]]
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| :*[[Neuropathy]]
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| :*Constitutional symptoms
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| {| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
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| |+
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| ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Treatment Regimen<ref name="ADR">Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015)http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015</ref>
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| }}
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| ! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Drugs}}
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| ! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Side effects}}
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''[[CHOP-R regimen]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" | | |
| *[[Cyclophosphamide]]
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| *[[Doxorubicin]]
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| *[[Vincristine]]
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| *[[Prednisone]]
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| *[[Rituximab]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Nausea]]
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| *[[Alopecia]]
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| *[[Granulocytopenia]]
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| *[[Cardiotoxicity]]
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| *[[Mucositis]]
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| |- | |
| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''[[Ibrutinib]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Ibrutinib]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Fatigue]]
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| *[[Cytopenia]]
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| *[[Bleeding]]
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| *[[Atrial fibrillation]]
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| *[[Opportunistic infection]]
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''[[Rituximab]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Rituximab]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *Infusion related reaction
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| *[[Hepatitis B]] reaction
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| *Progressive multi-focal leukoencephaloptahy
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |
| '''FR regimen'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Fludarabine]]
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| *[[Rituximab]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Neutropenia]] (63%)
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| *[[Thrombocytopenia]]
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| *[[Pneumonia]]
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''BDR regimen'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Bortezomib]]
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| *[[Dexamethasone]]
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| *[[Rituximab]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Peripheral neuropathy]] - reversible in 61% of patients
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| *[[Infections]]
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |
| '''DRC regimen'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Dexamethasone]]
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| *[[Rituximab]]
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| *[[Cyclophosphamide]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Neutropenia]]
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''CR regimen'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Cladribine]]
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| *[[Rituximab]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Anemia]]
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| *Neurological symptoms
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| *Symptomatic [[cryoglobulinemia]]
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| *[[Thrombocytopenia]]
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
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| '''IR regimen'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Ibrutinib]]
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| *[[Rituximab]]
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| | style="padding: 5px 5px; background: #F5F5F5;" |
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| *[[Anemia]]
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| *Neurological symptoms
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| *Symptomatic [[cryoglobulinemia]]
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| *[[Thrombocytopenia]]
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| *[[Atrial fibrillation]]
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| |-
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| |} | |
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| ====Hyperviscosity syndrome====
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| *Waldenström macroglobulinemia complicated with [[hyperviscosity syndrome]] is a medical emergency and requires prompt treatment with plasmapheresis.<ref name="ADR">Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015)http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015</ref>
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| *[[Plasmapheresis]] temporarily lowers [[IgM]] levels by removing some of the abnormal IgM from the blood, which makes blood thinner.
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| *Plasmapheresis is usually given until chemotherapy starts to work.
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| *Plasmapheresis is combined with chemotherapy to control the disease for a longer period of time.
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| ===Surgery===
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| [[Stem cell transplant]] is usually reserved for patients with either relapse or refractory Waldenström's macroglobulinemia.<ref name="sure">Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015) http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015</ref>
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| ===Primary Prevention===
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| Primary prevention of Waldenström macroglobulinemia depends on the type of risk factor causing the disease.<ref name="PP">Waldenström's macroglobulinemia. American Cancer Society. (2015)http://www.cancer.org/cancer/waldenstrommacroglobulinemia/detailedguide/waldenstrom-macroglobulinemia-prevention Accessed on November 11, 2015</ref>
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| ===Modifiable risk factors===
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| *[[Hepatitis C]]
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| ===Non-modifiable risk factors===
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| *Age > 50
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| *Male gender
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| *Race - White
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| *Hereditary- [[Monoclonal gammopathy of undetermined significance]]
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| ===Secondary Prevention===
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| There are no established measures for the secondary prevention of Waldenström's macroglobulinemia.
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| One or more of the following treatments can be given for lymphoplasmacytic lymphoma.
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| ===Watchful waiting===
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| Watchful waiting (also called active surveillance) may be offered for lymphoplasmacytic lymphoma because it develops slowly and may not need to be treated right away. The healthcare team will carefully monitor the person with lymphoplasmacytic lymphoma and start treatment when symptoms appear, such as hyperviscosity syndrome, or there are signs that the disease is progressing more quickly.
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| ===Chemotherapy===
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| *People with lymphoplasmacytic lymphoma who have symptoms or hyperviscosity syndrome are usually given chemotherapy. Chemotherapy drugs that may be used with or without prednisone include:
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| **Chlorambucil (Leukeran)
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| **Fludarabine (Fludara)
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| **Bendamustine (Treanda)
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| **Cyclophosphamide (Cytoxan, Procytox)
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| *Combinations of chemotherapy drugs that may be used include:
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| **DRC – dexamethasone (Decadron, Dexasone), rituximab (Rituxan) and cyclophosphamide
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| **BRD – bortezomib (Velcade) and rituximab, with or without dexamethasone
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| **CVP – cyclophosphamide, vincristine (Oncovin) and prednisone
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| **R-CVP – CVP with rituximab
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| **Thalidomide (Thalomid) and rituximab
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| ===Targeted therapy===
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| *Targeted therapy uses drugs to target specific molecules (such as proteins) on the surface of cancer cells. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting harm to normal cells.
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| *Targeted therapy drugs used alone or in combination to treat lymphoplasmacytic lymphoma include rituximab, bortezomib and ibrutinib (Imbruvica).
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| ===Immunotherapy===
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| *Immunotherapy works by stimulating, boosting, restoring or acting like the body’s immune system to create a response against cancer cells. Immunomodulatory drugs are a type of immunotherapy that interferes with the growth and division of cancer cells.
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| *Thalidomide is a type of immunomodulatory drug that may be used to treat lymphoplasmacytic lymphoma.
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| ===Radiation therapy===
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| External beam radiation therapy may be used to treat lymphoplasmacytic lymphoma that develops outside of the lymphatic system (called extralymphatic disease), but this is rare.
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| ===Stem cell transplant===
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| *Some people with lymphoplasmacytic lymphoma may be offered a stem cell transplant.
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| *It may be used if the lymphoma comes back (recurs) after treatment or doesn’t respond to other treatments (called refractory disease).
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| *Many people with lymphoplasmacytic lymphoma are older or may not be in good health, so a stem cell transplant may not be a good treatment option for them.
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| | ==Case Studies== |
| | [[Lymphoplasmacytic lymphoma case study one|Case #1]] |
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| Read more: http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/more-types-of-nhl/lymphoplasmacytic-lymphoma/?region=on#ixzz5eb6iT7G6
| | [[Category: (name of the system)]] |
| ==References==
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| {{reflist|2}}
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