|
|
|
|
Waldenström macroglobulinemia
|
| |
|
| |
Waldenström's macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) 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 lymphomas.
It is named after the Swedish physician Jan G. Waldenström, who first identified the condition.
as 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), 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.
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.
Discussion
Ask a question about 'Waldenström macroglobulinemia' Start a new discussion about 'Waldenström macroglobulinemia' Answer questions from other users |
Encyclopedia
Waldenström's macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) 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 lymphomas.
It is named after the Swedish physician Jan G. Waldenström, who first identified the condition.
History and classification
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), 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.
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.
Causes
The underlying cause is not yet known but a number of risk factors have been identified. There has been an association demonstrated with the locus 6p21.3 on chromosome 6. There is a 2- to 3-fold risk increase of developing WM in people with a personal history of autoimmune diseases with autoantibodies and particularly elevated risks associated with hepatitis, human immunodeficiency virus, and rickettsiosis.
There are genetic factors, with first-degree relatives shown to have a highly increased risk of also contracting Waldenstrom's.
Biochemistry
The following pathways have been implicated:
Epidemiology
Of all cancers involving the same class of blood cell, 1% of cases are WM.
WM is a rare disorder, with fewer than 1,500 cases occurring in the United States annually. The median age of onset of WM is between 60 and 65 years, with some cases occurring in late teens.
Symptoms
Symptoms of WM include weakness, fatigue, weight loss and chronic oozing of blood from the nose and gums. Peripheral neuropathy can occur in 10% of patients. Lymphadenopathy, splenomegaly, and/or hepatomegaly are present in 30-40% of cases. 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. 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.
Diagnosis
A distinguishing feature of WM is the presence of an IgM monoclonal protein (or paraprotein) that is produced by the cancer cells.
Lab Studies:
The laboratory diagnosis of Waldenström macroglobulinemia is contingent on demonstrating a significant monoclonal IgM spike and identifying malignant cells consistent with Waldenström macroglobulinemia (usually found in bone marrow biopsy samples and aspirates).
General studies include a full blood count, red cell indices, platelet count, and a peripheral smear.
Normocytic normochromic anemia, leukopenia, and thrombocytopenia may be observed. Anemia is the most common finding, present in 80% of patients with symptomatic Waldenström macroglobulinemia.
The peripheral smear may reveal plasmacytoid lymphocytes, normocytic normochromic red cells, and rouleaux formation.
Neutropenia can be found in some patients.
Thrombocytopenia is found in approximately 50% of patients with bleeding diathesis.
Chemistry tests include lactate dehydrogenase (LDH) levels, uric acid levels, erythrocyte sedimentation rate (ESR), renal and hepatic function, total protein levels, and an albumin-to-globulin ratio.
The ESR and uric acid level may be elevated.
Creatinine is occasionally elevated and electrolytes are occasionally abnormal. Hypercalcemia is noted in approximately 4% of patients.
The LDH level is frequently elevated, indicating the extent of Waldenström macroglobulinemia–related tissue involvement.
Rheumatoid factor, cryoglobulins, direct antiglobulin test and cold agglutinin titre results can be positive.
Beta-2-microglobulin and C-reactive protein test results are not specific for Waldenström macroglobulinemia. Beta-2-microglobulin is elevated in proportion to tumor mass.
Coagulation abnormalities may be present. Prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen tests should be performed. Platelet aggregation studies are optional.
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 macroglobulinemia.
Immunoelectrophoresis and immunofixation studies help identify the type of immunoglobulin, the clonality of the light chain, and the monoclonality and quantitation of the paraprotein.
High-resolution electrophoresis and serum and urine immunofixation are recommended to help identify and characterize the monoclonal IgM paraprotein.
The light chain of the monoclonal protein is usually the kappa light chain. At times, patients with Waldenström macroglobulinemia may exhibit more than one M protein.
Plasma viscosity must be measured.
Results from characterization studies of urinary immunoglobulins indicate that light chains (Bence Jones protein), usually of the kappa type, are found in the urine.
Urine collections should be concentrated.
Bence Jones proteinuria is observed in approximately 40% of patients and exceeds 1 g/d in approximately 3% of patients.
Patients with findings of peripheral neuropathy should have nerve conduction studies and antimyelin associated glycoprotein serology
Prognosis
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. New treatments have made longer term survival a reality for many with this condition. In rare instances, WM progresses to multiple myeloma.
The International Prognostic Scoring System for Waldenström’s Macroglobulinemia (IPSSWM) is a predictive model to characterise long-term outcome.
According to the model, factors predicting survival are:
- age >65 years;
- hemoglobin =11.5 g/dL;
- platelet count =100×109/L;
- B2-microglobulin >3 mg/L;
- serum monoclonal protein concentration >70 g/L.
The risk categories are:
- Low: =1 adverse variable except age;
- Intermediate: 2 adverse characteristics or age >65 years;
- High: >2 adverse characteristics.
Five-year survival rates for these categories are 87%, 68% and 36% respectively.
The IPSSWM has been shown applicable to patients on a Rituximab-based treatment regimen.
An additional predictive factor is elevated serum lactate dehydrogenase (LDH).
Treatment
There is no single accepted treatment for WM. Indeed, in 1991, Waldenström himself raised the question of the need for effective therapy. In the absence of symptoms, many clinicians will recommend simply monitoring the patient. Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells.
In 2002, a panel at the International Workshop on Waldenstrom 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 marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, renal insufficiency, or symptomatic cryoglobulinemia were also suggested as indications for therapy.
Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. Corticosteroids 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.
Recently, autologous bone marrow transplantation has been added to the available treatment options.
Drug pipeline
A database of clinical trials investigating Waldenstrom's macroglobulinemia is maintained by the National Institutes of Health in the US.
Phase IV
Phase III
- Comparison between Chlorambucil and Fludarabine
Phase II
There are over 100 active trials studying different interventions. Interventions include either individually or combinations of Fludarabine, Perifosine, Bortezomib, Rituximab, Sildenafil citrate, CC-5013, Thalidomide, Simvastatin, Campath-1H, Dexamethasone, Antineoplaston, Beta Alethine, Dolastatin 10, Cyclophosphamide, Yttrium Y 90 Ibritumomab, ABT-263, Ofatumumab, Enzastaurin and Denileukin diftitox.
External links
|
| |
|
|
