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Angioimmunoblastic T-cell Lymphoma

Disease Details

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Description: Angioimmunoblastic T-cell lymphoma is a rare and aggressive type of peripheral T-cell lymphoma characterized by systemic symptoms, immune dysfunction, and frequent lymphadenopathy.
Type: Angioimmunoblastic T-cell lymphoma (AITL) is a type of non-Hodgkin lymphoma that originates from T-cells. It does not follow a specific pattern of genetic transmission or inheritance. Instead, it arises from acquired genetic mutations and environmental factors.
Signs And Symptoms: Patients with AITL usually present at an advanced stage and show systemic involvement. The clinical findings typically include a pruritic skin rash and possibly edema, ascites, pleural effusions, and arthritis.
Prognosis: Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive type of peripheral T-cell lymphoma. The prognosis for AITL varies and is generally considered poor. Factors that influence the prognosis include the stage of the disease at diagnosis, patient age, overall health, and response to treatment. Early-stage disease and younger age may be associated with a better prognosis. However, due to its aggressive nature, AITL often requires intensive treatment, such as chemotherapy and possibly stem cell transplantation. Regular follow-up is crucial for monitoring potential relapses.
Onset: Onset for angioimmunoblastic T-cell lymphoma (AITL) typically occurs in middle-aged to older adults, often in their 60s and 70s. It is characterized by generalized lymphadenopathy, systemic symptoms such as fever, weight loss, and night sweats.
Prevalence: Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma. While specific prevalence data can vary, AITL accounts for approximately 1-2% of all non-Hodgkin lymphomas. It is more commonly diagnosed in older adults and has a slightly higher prevalence in males compared to females.
Epidemiology: The typical patient with angioimmunoblastic T-cell lymphoma (AITL) is either middle-aged or elderly, and no gender preference for this disease has been observed. AITL comprises 15–20% of peripheral T-cell lymphomas and 1–2% of all non-Hodgkin lymphomas.
Intractability: Angioimmunoblastic T-cell lymphoma (AITL) is generally considered a challenging disease to treat due to its aggressive nature and tendency for relapse. While it is not labeled outright as "intractable," achieving long-term remission can be difficult. Treatment typically involves chemotherapy, immunotherapy, and sometimes stem cell transplantation. Individual responses to treatment can vary widely.
Disease Severity: Angioimmunoblastic T-cell lymphoma (AITL) is a type of peripheral T-cell lymphoma that is generally considered aggressive. It typically presents at an advanced stage and can be associated with various systemic symptoms. The disease often requires prompt and intensive treatment due to its rapid progression.
Healthcare Professionals: Disease Ontology ID - DOID:0111147
Pathophysiology: Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma characterized by aggressive behavior. The pathophysiology involves:

1. **Aberrant T-cell Proliferation**: Malignant transformation of follicular helper T-cells (TFH cells) leads to abnormal proliferation.

2. **Microenvironment Alteration**: The lymphoma creates a disrupted nodal architecture with prominent proliferation of high endothelial venules and follicular dendritic cells.

3. **Immune Dysregulation**: AITL is associated with systemic immune deregulation, including cytokine release and immune evasion.

4. **Genetic Mutations**: Common mutations include those in the RHOA, TET2, and DNMT3A genes, contributing to the malignant phenotype.

5. **Chronic Inflammation**: Often linked with chronic immune activation, which may drive some of the pathological changes seen in the tumor microenvironment.

These elements contribute collectively to the disease's clinical manifestations, including lymphadenopathy, systemic symptoms, and immunodeficiency.
Carrier Status: Angioimmunoblastic T-cell lymphoma (AITL) is not caused by a single gene mutation, so there is no carrier status associated with this disease. It is a type of peripheral T-cell lymphoma, and risk factors are not typically inherited.
Mechanism: Angioimmunoblastic T-cell lymphoma (AITL) is a type of peripheral T-cell lymphoma characterized by abnormal proliferation of T-cells and a dense network of high endothelial venules and follicular dendritic cells.

### Mechanism:
The pathogenesis of AITL involves the abnormal proliferation of follicular helper T-cells (T_FH cells). It is typically associated with immune dysregulation, presenting with generalized lymphadenopathy, systemic symptoms, and immune-related phenomena.

### Molecular Mechanisms:
1. **Genetic Mutations**:
- **TET2 (Ten-Eleven Translocation 2)**: This gene's mutations are common and affect DNA methylation.
- **DNMT3A (DNA Methyltransferase 3 Alpha)**: Mutations impact epigenetic regulation.
- **RHOA (Ras Homolog Family Member A)**: The G17V mutation leads to aberrant signal transduction affecting cellular function.
- **IDH2 (Isocitrate Dehydrogenase 2)**: Mutations influence the metabolic state of the cells.

2. **Epigenetic Alterations**: Aberrations in the DNA methylation status due to the genetic mutations listed above, altering gene expression without changing the DNA sequence.

3. **Dysregulated Immune Microenvironment**: The interaction between T_FH cells and the surrounding immune cells, and the microenvironment contributes to disease pathogenesis. Notable is the aberrant production of cytokines and chemokines.

4. **Immune Evasion and Immunosuppression**: Tumor cells evade immune surveillance and suppress normal immune function, contributing to widespread systemic symptoms.

5. **Angiogenesis and Vascular Changes**: AITL is characterized by prominent vascularization due to interactions between malignant T-cells and endothelial cells.

Understanding these molecular mechanisms provides insights into targeted therapies for AITL, focusing on the underlying genetic and epigenetic abnormalities.
Treatment: There is no proven or standard first-line chemotherapy that works for the majority of AITL patients. There are several clinical trials that offer treatment options that can fight the disease. Stem cell transplantation is the treatment of choice, with the allogeneic one being the preference because AITL tends to recur after autologous transplants.
Compassionate Use Treatment: For angioimmunoblastic T-cell lymphoma (AITL), compassionate use treatments, off-label, or experimental treatments may be considered in cases where standard therapies have not been effective. These options can include:

1. **Compassionate Use Treatments**:
- Compassionate use, also known as expanded access, involves the use of investigational drugs that are not yet approved. Patients with AITL could potentially gain access to promising treatments that are in clinical trials but not yet widely available.

2. **Off-label Treatments**:
- **Lenalidomide**: An immunomodulatory drug often used off-label for various lymphomas, including AITL.
- **Romidepsin**: A histone deacetylase inhibitor approved for other types of T-cell lymphoma but sometimes used off-label for AITL.
- **Pralatrexate**: An anti-folate chemotherapy agent approved for peripheral T-cell lymphoma, which can be used off-label for AITL.
- **Rituximab**: Although primarily used for B-cell lymphomas, rituximab has been used off-label in combination with chemotherapy for T-cell lymphomas like AITL.

3. **Experimental Treatments**:
- **Clinical Trials**: Enrollment in clinical trials can provide access to new and investigational therapies. These might include novel targeted therapies, immune checkpoint inhibitors, or other innovative treatments designed to tackle the specific molecular and genetic features of AITL.
- **Epigenetic Modifiers**: Research is ongoing into drugs that target epigenetic changes in T-cell lymphomas, including those seen in AITL.
- **CAR T-Cell Therapy**: While primarily used in B-cell malignancies, CAR T-cell therapy is being explored experimentally for T-cell lymphomas, including AITL.

Patients interested in these treatment options should discuss them with their healthcare provider to determine eligibility and potential risks and benefits. Access to these treatments often requires navigating regulatory pathways and enrollment criteria.
Lifestyle Recommendations: For Angioimmunoblastic T-cell Lymphoma (AITL), lifestyle recommendations generally focus on maintaining overall health and managing symptoms. Although lifestyle changes alone cannot treat AITL, they can support well-being and complement medical treatment:

1. **Balanced Diet**: Emphasize a diet rich in fruits, vegetables, lean proteins, and whole grains. Proper nutrition can help strengthen the immune system and maintain energy levels.

2. **Regular Exercise**: Engage in moderate physical activity as tolerated to maintain strength, reduce fatigue, and improve mood. Consult with healthcare providers before starting any new exercise routine.

3. **Avoid Infections**: Due to weakened immunity, practice good hygiene, stay away from sick individuals, and ensure vaccinations are up to date, upon advice from your healthcare provider.

4. **Stress Management**: Use techniques such as meditation, yoga, and counseling to manage stress, which can positively impact overall health.

5. **Limit Alcohol and Tobacco**: Avoid smoking and limit alcohol consumption, as these can have adverse effects on your health and interfere with treatment.

6. **Regular Medical Follow-ups**: Keep all appointments with your healthcare team to monitor your condition and adjust treatments as necessary.

These recommendations should be personalized based on individual health conditions and in consultation with healthcare providers.
Medication: For angioimmunoblastic T-cell lymphoma (AITL), medications commonly used in treatment include:

1. **Corticosteroids**: Often used in combination with other therapies to reduce inflammation and modify the immune response.
2. **Chemotherapy**: Regimens such as CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) are frequently employed.
3. **Immunotherapy**: Drugs like Brentuximab vedotin for CD30-positive cases and immune checkpoint inhibitors are being explored.
4. **Targeted Therapy**: Agents such as Ruxolitinib and PI3K inhibitors are under investigation and may be used depending on specific molecular targets.
5. **Stem Cell Transplantation**: In some cases, high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation is considered.

These treatments can vary based on the patient's overall health, disease stage, and other individual factors.
Repurposable Drugs: Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive form of non-Hodgkin lymphoma. Repurposable drugs for AITL that have shown potential include:

1. **Lenalidomide** - An immunomodulatory drug primarily used in multiple myeloma and certain types of anemia.
2. **Bortezomib** - A proteasome inhibitor used mainly in multiple myeloma and mantle cell lymphoma.
3. **Vorinostat (SAHA)** - A histone deacetylase inhibitor approved for cutaneous T-cell lymphoma.
4. **Romidepsin** - Another histone deacetylase inhibitor used for peripheral T-cell lymphoma including cutaneous T-cell lymphoma.
5. **Ruxolitinib** - A JAK1/JAK2 inhibitor initially approved for myelofibrosis and polycythemia vera.

These drugs are being studied and sometimes used off-label, but consultation with a specialist is crucial for proper management and to understand potential efficacy and side effects.
Metabolites: Angioimmunoblastic T-cell lymphoma (AITL) involves complex metabolic changes, although specific metabolite profiles are still under extensive research. Currently, no definitive or unique metabolites have been identified exclusively for AITL. Diagnosis primarily relies on clinical presentation, histopathologic examination, immunophenotyping, and genetic studies rather than specific metabolic markers.
Nutraceuticals: There is limited evidence supporting the use of nutraceuticals specifically for Angioimmunoblastic T-cell Lymphoma (AITL). Nutraceuticals are products derived from food sources that provide extra health benefits in addition to their basic nutritional value, such as vitamins, minerals, and herbal supplements. Patients should consult their healthcare provider before incorporating any nutraceuticals into their regimen, as interactions with conventional treatments and overall safety need to be carefully considered.
Peptides: Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive form of peripheral T-cell lymphoma. In the context of AITL, peptides can refer to small chains of amino acids that may be involved in the tumor microenvironment, immune response modulation, or as potential targets for therapeutic interventions. However, specific peptides associated with AITL are not well-defined in current literature, requiring further research.

The "nan" likely refers to nanoparticles, which are an area of exploration in the treatment of various cancers, including lymphomas. Nanoparticles may be used to deliver drugs more effectively to tumor cells while minimizing side effects on healthy tissues. There are ongoing studies investigating the use of nanoparticle-based therapies in AITL, but it is still a developing field.