Angioimmunoblastic T-cell lymphoma (AITL), a rare type of peripheral T-cell lymphoma, is also a form of non-Hodgkin lymphoma (NHL). Lymphomas are blood cancers that affect lymphocytes (white blood cells). Lymphomas originate in the lymphatic system, part of the immune system made up of the lymph nodes, bone marrow, spleen, thymus, and tonsils. The lymphatic system removes waste and bacteria from the body and drains excess fluid from tissue.

AITL has been called by many different names, including:

• Angioimmunoblastic lymphadenopathy
• Immunoblastic lymphadenopathy
• Angioimmunoblastic lymphadenopathy with dysproteinemia
• Lymphogranulomatosis X

Read on to find out what to know about AITL, including symptoms, causes, and what to expect from diagnosis and treatment.

What Is Angioimmunoblastic T-Cell Lymphoma?

AITL is a fast-growing type of cancer usually seen in adults older than 70 years. The cancer cells arise from T lymphocytes (or T cells) known as follicular helper T cells. The cancer primarily involves lymph nodes and bone marrow, but AITL may also affect the liver and spleen.

AITL is also closely associated with another type of T-cell lymphoma called follicular T-cell lymphoma (FTCL). AITL and FTCL have similar biological origins and are treated the same way. AITL has several unusual aspects, however:

• AITL can cause immune system dysfunction, leading to certain autoimmune disorders.
• AITL can cause proliferation (growth or multiplication) of B cells.
• AITL can sometimes result in an aggressive B-cell NHL called diffuse large B-cell lymphoma.

Signs and Symptoms of Angioimmunoblastic T-Cell Lymphoma

AITL can have many symptoms that are common in different types of NHL. The most common symptoms include:

• Swollen lymph nodes, especially in the neck, groin, and armpits
• Flat or raised lesions or nodules on the skin that can be itchy or scaly
• An increase in infections
• Autoimmune disorders such as autoimmune hemolytic anemia and immune thrombocytopenia
• B symptoms (unexplained fever, unexplained weight loss, and drenching night sweats), which may indicate a more advanced stage of AITL

Other symptoms may vary depending on the area affected by lymphoma:

• Chest and neck — Chest pain, chest pressure, chronic cough, and difficulty breathing due to enlarged lymph nodes
• Abdomen — Swollen or painful belly, bloating, loss of appetite, nausea, vomiting, and diarrhea due to an enlarged liver or spleen
• Bone marrow — Fatigue (persistent tiredness) due to anemia (low red blood cell counts) and increased bleeding due to thrombocytopenia (low platelet counts)
• Joints — Joint pain due to inflammation from autoimmune responses

Causes of Angioimmunoblastic T-Cell Lymphoma

The cause of AITL is not clear, although lymphoma seems to occur more frequently in people who have certain genetic mutations or who have had certain infections. These infections include Epstein-Barr virus (EBV), cytomegalovirus, HIV, and certain types of human herpesvirus (HHV) — HHV-6 and HHV-8. A compromised immune system (like that caused by HIV, for example) may contribute to the development of different types of lymphoma.

Gene Mutations

Genetic mutations may be risk factors in the development of AITL. Mutations of certain genes, including BCL-6, DNMT3A, TET2, IDH2, and RhoA, are linked to AITL and other types of cancer such as acute myeloid leukemia.

Epstein-Barr Virus

EBV infection is linked to other types of NHL and Hodgkin lymphoma. Evidence of infection with EBV is seen in about 90 percent of cases of AITL. However, the EBV infection is seen only in B cells and not in T cells, the cancerous cells in AITL. It is not known how EBV infection may contribute to the development of AITL.

Diagnosis of Angioimmunoblastic T-Cell Lymphoma

AITL can be difficult to diagnose because of its unusual symptoms and laboratory findings. Diagnosis of AITL typically requires a thorough medical history and physical exam followed by imaging to locate tumors throughout the body, biopsies of tumors, and other tests.

Biopsy

Surgical biopsy to remove all or part of a tumor is often the best way for a doctor to identify what kind of cancer cells are present. Biopsies using a needle (such as core needle biopsy and fine-needle aspiration) may be used if tumors are difficult to reach. Bone marrow biopsy (samples tissue) and bone marrow aspiration (samples fluid) can be used to identify cancer cells and other abnormal cells in the bone marrow.

Imaging

Imaging tests are important to identify the location of tumors and see how far disease has spread. Common imaging tests used for AITL and other lymphomas include:

• Computed tomography (CT)
• Positron emission tomography (PET or PET-CT)
• Magnetic resonance imaging (MRI)

Identifying the tumor’s location is important for diagnosis as well as for staging and selecting the best treatment plan.

Blood Tests

A complete blood count is usually the most important blood test for lymphoma and other blood cancers. Other diagnostic blood tests include standard blood tests for kidney and liver function, tests for HIV and viral hepatitis, and tests to determine lactate dehydrogenase levels.

Immunophenotyping

Immunophenotyping is a test to determine what kind of cancer is in a tumor using tests such as immunohistochemistry. Immunohistochemistry involves using antibodies to identify specific proteins inside and on the surface of cancer cells in a sample. Surface proteins that can bind to antibodies, such as CD30 seen in AITL cells, help not only identify the type of cancer but also the best types of treatment (such as targeted immunotherapy).

Staging Angioimmunoblastic T-Cell Lymphoma

Cancer staging is an important part of diagnosing lymphoma. Staging helps determine the prognosis (outlook) of the disease. Most types of lymphoma are staged using the Lugano classification system. Stages are based on whether the lymphoma is localized or widespread, especially if the lymphoma has spread from one side of the diaphragm to the other. Stages are defined further by the size (bulk) of the tumor and whether lymphoma has spread beyond the lymphatic system. Most people with AITL are diagnosed in advanced stages:

• Stages 1 and 2 — Early-stage or limited-stage cancers that involve the lymph nodes and/or one organ outside the lymphatic system on the same side of the diaphragm
• Stages 3 and 4 — Late-stage or advanced-stage cancers that have spread to both sides of the diaphragm, and cancer may include organs outside of the lymphatic system

Treatment of Angioimmunoblastic T-Cell Lymphoma

The primary treatment for AITL is chemotherapy, either alone or with targeted drug therapy. Sometimes, high-dose chemotherapy or radiation is used, usually followed by a stem cell transplant. In some cases of limited AITL, radiation may be used without chemotherapy.

Chemotherapy

First-line chemotherapy regimens for AITL include:

• CHOP — Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), Oncovin (vincristine), and prednisone (a corticosteroid)
• CHOEP — Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), Oncovin (vincristine), VP-16 (etoposide), and prednisone
• B-CHP — Adcetris (brentuximab vedotin) plus Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and prednisone

Targeted immunotherapy using Adcetris can be added to chemotherapy. This drug is a monoclonal antibody to the CD30 cell surface protein, joined to a very strong chemotherapy drug. Joining these drugs together makes it possible to deliver the chemotherapy drug directly to AITL cancer cells, minimizing the effect on healthy tissue.

Stem Cell Transplant

Stem cell transplantation is frequently used along with high-dose chemotherapy or radiation therapy. Autologous (self) stem cell transplant or allogeneic (donor) stem cell transplant are used to replace the bone marrow killed off during chemotherapy. A stem cell transplant can decrease the chance of relapse after initial treatment.

Targeted Therapy

Treatment for AITL that is relapsed or refractory (unresponsive to standard chemotherapy) may be treated using targeted drug therapy with the histone deacetylase inhibitors Istodax (romidepsin) or Beleodaq (belinostat). Other targeted therapy drugs such as Adcetris (brentuximab vedotin) and Folotyn (pralatrexate) may also be used.

Clinical Trials

Ongoing clinical trials for AITL treatment using existing and experimental drugs may be another option for treatment. Clinical trials test the effectiveness of various drugs, sometimes in conjunction with chemotherapy. Clinical trials can be a good choice for the treatment of AITL and other rare types of cancer.

Palliative Care

Another important part of any cancer treatment plan is palliative care to help deal with the complications of cancer and cancer treatment. Palliative care is focused on improving quality of life by treating symptoms caused by illness and treatment. Palliative care can also help you find emotional and spiritual support for you and your caregivers.

Prognosis for AITL

AITL is an aggressive type of lymphoma that is most often diagnosed after it has reached an advanced stage. Survival rates for AITL are low compared to other NHLs. Median survival after diagnosis is less than three years, with a five-year survival rate of 33 percent and a seven-year survival rate of 29 percent.

When AITL progresses to B-cell lymphoma, the prognosis is often worse. However, chemotherapy has a high response rate of 70 percent to 80 percent, and stem cell transplantation increases the five-year progression-free survival rate to 40 percent.

Talk With Others Who Understand

A new cancer diagnosis can be difficult, and it may help to have the support of others who understand what you’re going through. MyLymphomaTeam is the social network for people with lymphoma. On MyLymphomaTeam, more than 10,000 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

Are you or someone you care for living with angioimmunoblastic T-cell lymphoma? Share your experience in the comments below, or start a conversation by posting on MyLymphomaTeam.