Lymphoplasmacytic Lymphoma
Disease Details
Family Health Simplified
- Description
- Lymphoplasmacytic lymphoma is a rare, slow-growing type of non-Hodgkin lymphoma characterized by the accumulation of small lymphocytes, plasmacytoid lymphocytes, and plasma cells in the bone marrow, lymph nodes, and spleen.
- Type
-
Lymphoplasmacytic lymphoma (LPL) is a type of non-Hodgkin lymphoma characterized by the presence of lymphoplasmacytic cells, which are a mixture of small lymphocytes, plasma cells, and cells that are intermediate between these types. LPL most commonly involves the bone marrow, lymph nodes, and spleen.
Regarding genetic transmission, LPL is generally not considered to be directly inherited in a Mendelian fashion. However, there can be familial predispositions due to shared genetic and environmental factors that may increase the risk for developing the disease among family members. Specific genetic mutations, such as MYD88 L265P, are often associated with LPL. - Signs And Symptoms
- Signs and symptoms of Waldenström macroglobulinemia include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums. Peripheral neuropathy occurs in 10% of patients. Enlargement of the lymph nodes, spleen, and/or liver are present in 30–40% of cases. Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma.
- 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. Currently, median survival is 6.5 years. In rare instances, Waldenström macroglobulinemia progresses to multiple myeloma.The International Prognostic Scoring System for Waldenström's Macroglobulinemia is a predictive model to characterise long-term outcomes. According to the model, factors predicting reduced 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/LThe risk categories are:
Low: ≤ 1 adverse variable except age
Intermediate: 2 adverse characteristics or age > 65 years
High: > 2 adverse characteristicsFive-year survival rates for these categories are 87%, 68% and 36%, respectively. The corresponding median survival rates are 12, 8, and 3.5 years.The International Prognostic Scoring System for Waldenström's Macroglobulinemia has been shown to be reliable. It is also applicable to patients on a rituximab-based treatment regimen. An additional predictive factor is elevated serum lactate dehydrogenase (LDH). - Onset
- Lymphoplasmacytic lymphoma (LPL) typically has an insidious onset, with symptoms that develop gradually over time. These symptoms can include fatigue, unintended weight loss, night sweats, and anemia. Some patients may also present with peripheral neuropathy or hyperviscosity syndrome due to the elevated levels of IgM in the blood.
- Prevalence
- Lymphoplasmacytic lymphoma (LPL) is a rare type of non-Hodgkin lymphoma. Its prevalence is estimated at approximately 1,000 to 1,500 new cases per year in the United States. This translates to less than 1% of all non-Hodgkin lymphoma cases.
- Epidemiology
- Of cancers involving the lymphocytes, 1% of cases are Waldenström macroglobulinemia. A rare disorder, there are fewer than 1,500 cases occurring in the United States annually. 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; and former French President Georges Pompidou.
- Intractability
- Lymphoplasmacytic lymphoma (LPL) is generally considered intractable, meaning it is not curable with current medical treatments. However, it is often manageable with therapies that can help control symptoms and maintain quality of life. Treatment typically involves a combination of chemotherapy, immunotherapy, and targeted therapies to manage disease progression and related symptoms.
- Disease Severity
- Lymphoplasmacytic lymphoma is an indolent (slow-growing) type of non-Hodgkin lymphoma often characterized by the excessive production of monoclonal IgM antibodies, and it commonly presents as Waldenström macroglobulinemia. The severity can vary widely among patients, ranging from asymptomatic cases to those with significant symptoms related to hyperviscosity, anemia, neuropathy, and other complications.
- Healthcare Professionals
- Disease Ontology ID - DOID:0060901
- Pathophysiology
- Symptoms including blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effects of the IgM paraprotein, which may cause autoimmune phenomena or cryoglobulinemia. Other symptoms of Waldenström macroglobulinemia are due to hyperviscosity syndrome, which is present in 6–20% of patients. This is attributed to the IgM monoclonal protein molecules increasing the viscosity of the blood by forming aggregates to each other, binding water through their carbohydrate component and by their interaction with blood cells.
- Carrier Status
- Lymphoplasmacytic lymphoma is a type of non-Hodgkin lymphoma. It involves mature lymphocytes and plasma cells. There is no concept of carrier status associated with lymphoplasmacytic lymphoma as it is not a hereditary condition but rather a type of cancer that develops sporadically.
- Mechanism
-
Lymphoplasmacytic lymphoma (LPL) is a type of non-Hodgkin lymphoma characterized by the presence of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. It typically affects the bone marrow, lymph nodes, and spleen.
**Mechanism:**
LPL arises due to the clonal expansion of B lymphocytes, which then differentiate into plasma cells. These cells produce an excessive amount of a monoclonal immunoglobulin protein, usually IgM, leading to hyperviscosity syndrome and other clinical symptoms. The underlying trigger for this clonal expansion is often a genetic mutation.
**Molecular Mechanisms:**
1. **MYD88 L265P Mutation:** The most common mutation in LPL, found in about 90% of cases, is the MYD88 L265P mutation. This mutation activates the NF-κB signaling pathway, leading to increased cell survival and proliferation.
2. **CXCR4 Mutations:** Mutations in the CXCR4 gene, present in about 30-40% of cases with MYD88 L265P, contribute to cell migration and adhesion, potentially affecting the tumor microenvironment and making the disease more resistant to treatment.
3. **Additional Pathways:** Aberrant signaling through other pathways, such as BTK (Bruton's tyrosine kinase) and PI3K (phosphatidylinositol-3-kinase), also supports the growth and survival of the malignant B cells.
These molecular alterations collectively drive the oncogenic process, helping the malignant B cells evade apoptosis and proliferate uncontrollably. - Treatment
- There is no single accepted treatment for Waldenström macroglobulinemia. There is marked variation in clinical outcome due to gaps in knowledge of the disease's molecular basis. Objective response rates are high (> 80%) but complete response rates are low (0–15%). The medication ibrutinib targets the MYD88 L265P mutation induced activation of Bruton's tyrosine kinase. In a cohort study of previously treated patients, ibrutinib induced responses in 91% of patients, and at 2 years 69% of patients had no progression of disease and 95% were alive. Based on this study, the Food and Drug Administration approved ibrutinib for use in Waldenström macroglobulinemia in 2015.There are different treatment flowcharts: Treon and mSMART.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.
- Compassionate Use Treatment
-
Compassionate use treatment for lymphoplasmacytic lymphoma (LPL), also known as Waldenström macroglobulinemia, involves accessing investigational drugs outside of clinical trials when no other treatments are available. Off-label or experimental treatments for LPL may include:
1. **Ibrutinib**: Primarily approved for chronic lymphocytic leukemia and mantle cell lymphoma, it is often used off-label for LPL due to its efficacy in targeting BTK pathways.
2. **Venetoclax**: Although officially approved for chronic lymphocytic leukemia, it is under investigation for potential use in treating LPL.
3. **CAR T-cell therapy**: This experimental treatment involves modifying the patient's T-cells to attack specific cancer cells and is being explored in various clinical trials for different lymphomas, including LPL.
4. **Selinexor**: A selective inhibitor of nuclear export, studied in clinical trials for its effectiveness in treating various lymphomas, including LPL.
5. **Monoclonal antibodies (e.g., Rituximab)**: While commonly used for other types of lymphoma, Rituximab and newer monoclonal antibodies are sometimes used off-label for LPL.
It's important to consult with a healthcare provider to discuss potential treatments, their availability, and suitability based on individual patient conditions. - Lifestyle Recommendations
-
For lymphoplasmacytic lymphoma (LPL):
**Lifestyle Recommendations:**
1. **Healthy Diet:** Focus on a balanced diet rich in fruits, vegetables, lean proteins, whole grains, and healthy fats to support overall health and immune function.
2. **Regular Exercise:** Engage in regular physical activity, such as walking, swimming, or yoga, to maintain physical fitness and improve well-being.
3. **Adequate Rest:** Ensure sufficient sleep and rest to help the body recover and cope with treatment.
4. **Stress Management:** Practice stress-reducing techniques like meditation, deep breathing exercises, or mindfulness to manage anxiety and improve quality of life.
5. **Avoid Infections:** Take precautions to avoid infections, such as practicing good hygiene, avoiding large crowds, and staying up to date with vaccinations.
6. **Regular Medical Follow-ups:** Keep consistent appointments with healthcare providers to monitor the condition and adjust treatments as needed.
7. **Support Systems:** Engage with support groups or counseling services for emotional and psychological support. - Medication
-
Lymphoplasmacytic lymphoma, also known as Waldenström's macroglobulinemia, is typically treated with a combination of medications. The primary categories of drugs used include:
1. **Chemotherapy Agents**: Such as bendamustine, fludarabine, and chlorambucil.
2. **Monoclonal Antibodies**: Like rituximab, used to target specific cancer cells.
3. **Proteasome Inhibitors**: Bortezomib and carfilzomib can be effective.
4. **Immunomodulatory Agents**: Examples include thalidomide or lenalidomide.
5. **BTK Inhibitors**: Ibrutinib is a targeted therapy that has shown effectiveness.
Each treatment plan is tailored to the individual based on factors including the severity of the disease, patient health, and prior treatments. - Repurposable Drugs
-
Lymphoplasmacytic lymphoma (LPL) is a type of non-Hodgkin lymphoma characterized by the malignant proliferation of B lymphocytes and an excess production of monoclonal IgM antibody. Treatment often involves specific chemotherapies, targeted therapies, and immunotherapies.
Repurposable drugs for LPL include:
1. **Rituximab**: An anti-CD20 monoclonal antibody originally used for other types of non-Hodgkin lymphoma and chronic lymphocytic leukemia.
2. **Ibrutinib**: A Bruton's tyrosine kinase (BTK) inhibitor initially approved for mantle cell lymphoma and chronic lymphocytic leukemia.
Research is ongoing to explore additional drugs that can be repurposed to treat LPL effectively. Always consult a healthcare professional for personalized medical advice and treatment options. - Metabolites
-
Lymphoplasmacytic lymphoma (LPL), including its common form Waldenström's macroglobulinemia, is associated with the abnormal production of IgM monoclonal protein by malignant B cells. Important metabolites and markers involved in LPL include:
1. **Monoclonal IgM**: Elevated levels of this immunoglobulin are a hallmark of the condition.
2. **Serum Viscosity**: Increased due to high levels of monoclonal IgM, leading to hyperviscosity syndrome.
3. **Beta-2 Microglobulin**: Often elevated, indicative of tumor burden.
4. **Lactate Dehydrogenase (LDH)**: Can be elevated and serves as a marker of cell turnover.
5. **Cryoglobulins**: Can be present, causing cryoglobulinemia.
6. **Free Light Chains**: Elevated due to overproduction of immunoglobulins.
Further metabolic alterations might be assessed during disease-specific diagnostic evaluations, including routine blood panels and specialized protein studies. - Nutraceuticals
- There is limited scientific evidence supporting the use of nutraceuticals specifically for the treatment of lymphoplasmacytic lymphoma. Always consult with a healthcare professional before adding any supplements or alternative therapies to your treatment plan.
- Peptides
- Lymphoplasmacytic lymphoma (LPL) is a type of non-Hodgkin lymphoma that typically involves an overproduction of monoclonal immunoglobulin M (IgM) by malignant B-cells. Peptide-related treatments or diagnostic markers are not standard in the context of LPL. "Nan" is an unclear term in this context; it may refer to "nanotechnology," which is not yet a standard treatment or diagnostic tool specifically for LPL. The focus for LPL is often on targeted therapies like rituximab, chemotherapy, and management of symptoms related to IgM overproduction.