Angioimmunoblastic T-cell Lymphoma
Angioimmunoblastic T-cell lymphoma is a rare and fast-growing blood cancer that affects T cells, a type of white blood cell that normally helps fight infection. This disease most commonly appears in older adults and often causes symptoms like fever, skin rash, and swollen lymph nodes throughout the body.
Table of contents
- What is Angioimmunoblastic T-cell Lymphoma?
- Symptoms of the Disease
- Causes and Risk Factors
- How the Disease is Diagnosed
- Stages and Grades
- Prognosis and Risk Assessment
- Treatment Options
What is Angioimmunoblastic T-cell Lymphoma?
Angioimmunoblastic T-cell lymphoma, often shortened to AITL, is a rare type of blood cancer that develops in T lymphocytes (T cells), which are white blood cells that normally help the body fight infections and diseases[1]. AITL belongs to a larger group of cancers called non-Hodgkin lymphoma and is specifically classified as a peripheral T-cell lymphoma[2].
Under normal circumstances, T lymphocytes destroy harmful microorganisms like viruses and bacteria, and they can even kill cancer cells. However, in AITL, a T lymphocyte transforms into a cancer cell. More T cells may follow and spread uncontrollably[2]. This cancer develops from specialized T cells called follicular helper T cells (Tfh cells)[4].
AITL is a fast-growing cancer, which doctors describe as high grade[3]. The disease can spread to other areas of the body including the liver, lungs, bone marrow, spleen, and skin[2][3].
While AITL is one of the more common subtypes of T-cell lymphoma, it remains rare overall. It accounts for about 20-30% of all peripheral T-cell lymphomas[1]. In the United States, AITL represents approximately 4% of all lymphoma cases and only 1% to 2% of all non-Hodgkin lymphoma cases[2]. The disease most commonly affects people over the age of 65, with the median age at diagnosis being 65 years, though it can also affect younger adults[1][2].
Symptoms of the Disease
Because AITL is a fast-growing cancer, symptoms can develop quickly, sometimes starting or getting worse in just a few weeks[3].
The most common symptom of AITL is one or more painless swellings, typically in the neck, armpit, or groin. These swellings are enlarged lymph nodes, and they can grow very quickly[2][3].
Many people with AITL experience a group of symptoms that doctors call B symptoms. These include heavy sweating at night, high temperatures (fever) that come and go with no obvious cause, and losing a significant amount of weight without trying[3]. Some people may also have unexplained itching[3].
AITL has several unique characteristics that set it apart from other lymphomas. Because the disease affects the immune system, many people develop symptoms related to abnormal immune system activity. These can include skin rash or itchiness, swollen joints with inflammation, and shortness of breath[1][2][3].
When the lymphoma grows in the bone marrow, it can take up the space of normal blood cells, causing low blood cell counts. This can lead to tiredness and shortness of breath from low red blood cell counts, as well as bleeding and bruising from low platelet counts[3].
Some people develop a swollen spleen or liver, which can cause bloating and stomach discomfort or pain[3]. Other symptoms may include fatigue (persistent tiredness) and poor appetite[5].
Because AITL attacks the lymphatic system (part of the immune system), many people with this cancer also develop autoimmune diseases. These are conditions where the immune system mistakenly attacks the body’s own healthy tissues. Common examples include autoimmune hemolytic anemia (where the immune system attacks red blood cells) and immune thrombocytopenia (where the immune system attacks platelets)[1][2].
Causes and Risk Factors
AITL happens when T cells become abnormal and grow out of control. Researchers are not completely sure why some people develop T-cell lymphomas like AITL and others do not[2].
There might be a connection between AITL and viral infections. Some research suggests a possible link with the Epstein-Barr virus, which is a common virus that causes infectious mononucleosis. However, scientists need more information to understand why this connection exists[2].
Studies have identified certain genetic mutations that may contribute to the development of AITL. The disease shows specific patterns of genetic changes, including mutations in genes called TET2 and DNMT3A in hematopoietic stem cells (the cells that give rise to all blood cells). Additional mutations in genes called RHOA and IDH2 are found in the follicular helper T cells themselves[4].
How the Disease is Diagnosed
Diagnosing AITL is usually done through a lymph node biopsy. This means a doctor removes a sample from the affected area, often removing part or all of a swollen lymph node. The sample is sent to a laboratory where a specialist examines it under a microscope[1][3]. Healthcare providers suspect AITL if test results show abnormal T lymphocytes[2].
Under the microscope, the tumor cells have a characteristic appearance. They appear to be surrounded by a complex network of small blood vessels, which is where the name “angio” (meaning blood vessel) comes from. There are usually large virus-infected cells scattered throughout, called immunoblasts (the source of “immunoblastic” in the name)[5].
Diagnosing AITL and all lymphomas can be difficult. The disease has a complex nature, and symptoms can come on gradually and may look like other conditions. For these reasons, most people with AITL receive their diagnosis during the late stages of the disease[2].
After confirming the diagnosis, an oncologist (a doctor who specializes in cancer) will perform a physical examination and ask about symptoms. They will also review the person’s health history, including any current or previous health conditions[2].
Additional tests are usually needed to determine how widely the lymphoma has spread through the body. This process is called staging[5]. Blood tests are commonly performed[3]. A bone marrow biopsy may be done to check if lymphoma cells are present in the bone marrow[2][3].
Several types of imaging tests may be ordered. These can include CT scans (computed tomography scans), which use X-rays and computers to create detailed pictures of the inside of the body[1][2]. An MRI scan (magnetic resonance imaging) uses magnets and radio waves to create images[1][2]. A PET scan (positron emission tomography) or PET-CT scan may also be used[1][2][3].
Stages and Grades
The grade of a lymphoma describes how the cells look under a microscope and tells the doctor how quickly the lymphoma is likely to grow and spread. Doctors divide non-Hodgkin lymphoma into two grades: low grade (slow growing) and high grade (fast growing). AITL is fast growing, so doctors call it a high grade lymphoma[3].
The stage indicates the number of places in the body affected by lymphoma and where these areas are located. Doctors use staging to plan treatment[3]. There are four main stages of non-Hodgkin lymphoma, numbered from 1 to 4[3].
Most people with AITL are diagnosed with advanced-stage disease, meaning the disease has grown and affects many areas of the body[1]. Early-stage disease (Stage I or Stage II) is rare in AITL. Stage I means localized disease that has not spread beyond one lymph node or other location. Stage II means the disease has spread only to nearby lymph nodes[1].
In Stage III, affected lymph nodes are found both above and below the diaphragm (the muscle that separates the chest from the abdomen). In Stage IV, one or more organs beyond the lymph nodes are affected, such as the bone, bone marrow, skin, or liver[1].
Prognosis and Risk Assessment
A new tool called the AITL Score was recently developed to predict outcomes in patients with AITL. This scoring system categorizes patients by level of risk: low-risk, intermediate-risk, and high-risk[1].
The risk categories are determined by several factors. These include age, ECOG performance status (a scale from 0 to 5 that describes the patient’s ability to take care of themselves and perform daily activities, like walking or working), levels of C-reactive protein (CRP, a protein made in the liver in response to inflammation or tissue damage), and β2 microglobulin (a protein that is increased in some types of cancer, like lymphoma)[1].
The overall prognosis for AITL remains challenging. The disease has an overall 5-year survival rate of approximately 30% with standard cytotoxic chemotherapy treatment[4]. Treatment can be difficult because of frequent relapses after initial and subsequent therapy[8].
Treatment Options
Treatment for AITL depends on many factors, including symptoms, severity of disease, overall health, age, and other medical conditions[2][5].
Some patients may first be treated with a steroid medication like prednisone. This can temporarily relieve symptoms caused by the immune system’s reaction to the cancer cells, such as joint inflammation or pain and skin rash[9].
The recommended first-line therapy is either enrollment in a clinical trial or treatment with a combination of chemotherapy drugs. The most commonly used combination is called CHOP, which stands for the drugs used: cyclophosphamide, doxorubicin, vincristine, and prednisone[3][5][9]. Another regimen called BV+CHP may also be used[2]. Treatment is typically done in cycles, usually every 3 weeks, and will normally include 6-8 cycles[5].
The majority of patients will have an initial response to treatment, with shrinkage of the lymph nodes and disappearance of lymphoma-related symptoms such as rash, itching, sweats, and joint pains. Some patients achieve complete remission, which means the disappearance of all signs of lymphoma[5].
For patients who achieve a response to initial treatment, doctors may consider stem cell transplantation. This is a complex procedure that uses either the patient’s own stem cells (autologous stem cell transplant) or stem cells from a donor (allogeneic stem cell transplant)[8][9]. Sometimes higher doses of chemotherapy followed by stem cell transplantation may be added to the treatment plan[9]. In the relapsed and refractory settings, allogeneic stem cell transplant offers the chance for long-term remission[8].
Several newer drugs have been tested in clinical trials and show promise for treating AITL. Agents with preferential activity in relapsed or refractory AITL include epigenetic modifiers such as histone deacetylase inhibitors and hypomethylating agents[8]. Other targeted agents that show promise include brentuximab vedotin, lenalidomide, panobinostat, and phosphoinositide-3-kinase inhibitors[8][9].
If AITL returns after initial remission or does not respond to first treatment, consultation with lymphoma and bone marrow experts is very important. They can help determine the most appropriate course of action based on the characteristics of the disease, age, other medical conditions, and the patient’s own preferences regarding risks of therapy and probability of cure[5].
Ongoing studies are evaluating new potential targets for AITL, with particular focus on identifying markers of response and resistance. Additional studies are assessing how to incorporate novel agents into the front-line treatment of AITL. These studies aim to lead to more individualized treatment approaches and, ultimately, improved outcomes for patients with AITL[8].
