Waldenström macroglobulinemia
Waldenström macroglobulinemia | |
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Other names | Lymphoplasmacytic lymphoma |
Specialty | Hematology and oncology |
Waldenström macroglobulinemia (
Waldenström macroglobulinemia is a rare disease, with only about 1,500 cases per year in the United States. It occurs more frequently in older adults.[7] While the disease is incurable, it is treatable. Because of its indolent nature, many patients are able to lead active lives, and when treatment is required, may experience years of symptom-free remission.[8]
Signs and symptoms
Signs and symptoms of Waldenström macroglobulinemia include
Causes
Waldenström macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. The most commonly associated mutations, based on whole-genome sequencing of 30 patients, are a
There are
Genetics
Although believed to be a sporadic disease, studies have shown increased susceptibility within families, indicating a genetic component.
The protein
MicroRNAs involved in Waldenström:[33][34]
- increased expression of miRNAs-363*,[35] -206,[36] -494,[37] -155,[38] -184,[39] -542–3p.[40]
- decreased expression of miRNA-9*.[41]
MicroRNA-155 regulates the proliferation and growth of Waldenström macroglobulinemia cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways.[citation needed]
In Waldenström macroglobulinemia cells,
Pathophysiology
Symptoms including blurring or loss of vision, headache, and (rarely)
Diagnosis
A diagnosis of Waldenström macroglobulinemia depends on a significant monoclonal IgM spike evident in blood tests and
Additional tests such as
Chemistry tests include
Criteria for diagnosis of Waldenström macroglobulinemia include:
- IgM monoclonal gammopathy that excludes chronic lymphocytic leukemia and mantle cell lymphoma
- Evidence of anemia, constitutional symptoms, hyperviscosity, swollen lymph nodes, or enlargement of the liver and spleen that can be attributed to an underlying lymphoproliferative disorder.[51]
Treatment
There is no single accepted treatment for Waldenström macroglobulinemia.
There are different treatment flowcharts: Treon[57] and mSMART.[58][clarification needed]
Patients with Waldenström macroglobulinemia are at higher risk of developing second cancers than the general population, but it is not yet clear whether treatments are contributory.[59]
Watchful waiting
In the absence of symptoms, many clinicians will recommend simply monitoring the patient;
First-line
Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells.[62]
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
Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide.[64] Corticosteroids, such as prednisone, 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.[65] Ibrutinib is another agent that has been approved for use in this condition. Combination treatment with ibrutinib and rituximab showed significantly higher disease progression free survival than with just rituximab treatment.[66]
Autologous
Zanubrutinib is indicated for the treatment of adults with Waldenström macroglobulinemia.[71]
Salvage therapy
When primary or secondary
Drug pipeline
As of October 2010, there have been a total of 44 clinical trials on Waldenström macroglobulinemia, excluding transplantation treatments. Of these, 11 were performed on previously untreated patients, 14 in patients with relapsed or refractory Waldenström.[73] A database of clinical trials investigating Waldenström macroglobulinemia is maintained by the National Institutes of Health in the US.[74]
Patient stratification
Patients with
Prognosis
Current medical treatments result in survival of 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.[4] Currently, median survival is 6.5 years.[76] In rare instances, Waldenström macroglobulinemia progresses to multiple myeloma.[77]
The International Prognostic Scoring System for Waldenström's Macroglobulinemia is a predictive model to characterise long-term outcomes.[78][79] According to the model, factors predicting reduced survival[80] 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.[81] The corresponding median survival rates are 12, 8, and 3.5 years.[82]
The International Prognostic Scoring System for Waldenström's Macroglobulinemia has been shown to be reliable.[83] It is also applicable to patients on a rituximab-based treatment regimen.[81] An additional predictive factor is elevated serum lactate dehydrogenase (LDH).[84]
Epidemiology
Of cancers involving the lymphocytes, 1% of cases are Waldenström macroglobulinemia.[85] A rare disorder, there are fewer than 1,500 cases occurring in the United States annually.
The examples and perspective in this article may not represent a worldwide view of the subject. (November 2022) |
The median age of onset is between 60 and 65 years, with some cases occurring in late teens. Notable victims of the disease include dancer/choreographer Gower Champion, who died of the disease in 1980, aged 61;[4][10] and former French President Georges Pompidou.
History
Waldenström macroglobulinemia was first described by
For a time, Waldenström macroglobulinemia was considered to be related to multiple myeloma because of 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 Waldenström macroglobulinemia under the category of lymphoplasmacytic lymphomas, itself a subcategory of the indolent (low-grade) non-Hodgkin lymphomas.[87] Since the 1990s, there have been significant advances in the understanding and treatment of Waldenström macroglobulinemia.[53]
See also
References
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