Adult T cell leukemia/lymphoma

by Jason Wasserman MD PhD FRCPC
August 18, 2025

Adult T-cell leukemia/lymphoma (ATLL) is a rare type of blood cancer that develops in T cells. T cells are a type of white blood cell that plays a key role in the immune system by fighting infections and helping to regulate immune responses.

When ATLL mainly affects the blood and bone marrow, it is called leukemia. When it grows as a solid mass in lymph nodes or other tissues, it is called lymphoma. In many patients, ATLL affects both the blood and the lymph nodes, reflecting the wide range of ways this disease can appear.

This cancer occurs only in people infected with a virus called human T-cell lymphotropic virus type 1 (HTLV-1). ATLL can develop in different parts of the body, including the blood, lymph nodes, skin, liver, and spleen. Doctors classify ATLL into four main types: acute, lymphomatous, chronic, and smoldering, depending on how the disease behaves and which organs are involved.

What are the symptoms of ATLL?

The symptoms of ATLL depend on the type of disease and which parts of the body are affected. Common symptoms include swollen lymph nodes, fever, night sweats, and unexplained weight loss. Patients often feel tired or weak because the bone marrow cannot produce enough normal blood cells. Some patients develop skin changes such as rashes, lesions, or lumps. Bone pain and abdominal discomfort can occur when the spleen or liver becomes enlarged.

Another common feature of ATLL is high calcium levels in the blood. This can cause nausea, vomiting, constipation, or confusion, and if untreated, it may become life-threatening.

What causes ATLL?

ATLL is caused by long-term infection with the HTLV-1 virus. However, only a small number of people infected with HTLV-1 (about 3 to 5 percent) will ever develop ATLL. The virus is more common in some parts of the world, including southern Japan, the Caribbean, parts of South America, and parts of Africa.

Several factors increase the risk of developing ATLL, including being male, older age, and having had the infection for many years. People who are infected at a young age, such as during infancy or childhood, are also at higher risk. A high number of HTLV-1 infected cells in the blood makes the disease more likely to develop.

In people with HTLV-1, most infected T cells remain dormant and do not cause problems. Over time, however, some infected cells undergo genetic changes that make them grow uncontrollably. These abnormal cells may eventually become cancerous. Additional genetic or environmental changes are usually needed for ATLL to fully develop.

What are the four main types of ATLL?

Doctors divide ATLL into four types based on how the disease behaves and which parts of the body are affected.

• Acute ATLL is the most aggressive form. It usually involves the blood, lymph nodes, skin, liver, and spleen. Symptoms often appear suddenly and progress quickly.
• Lymphomatous ATLL mainly involves the lymph nodes and other tissues but does not have many cancer cells in the blood. It behaves aggressively, similar to acute ATLL.
• Chronic ATLL grows more slowly and usually affects the blood, skin, and lymph nodes. It may remain stable for some time, but in some patients it can transform into a more aggressive form.
• Smoldering ATLL is the least aggressive type. It often causes few or no symptoms and may only be detected through routine blood tests. However, even this type requires monitoring because it can progress over time.

How is this diagnosis made?

The diagnosis of ATLL usually requires a combination of tests. A biopsy of an affected tissue, such as a lymph node or skin lesion, is often the first step. A pathologist examines the tissue under the microscope to look for abnormal T cells. A blood test may show high numbers of abnormal lymphocytes (a type of white blood cell), and sometimes leukemia cells are seen circulating in the blood.

Additional tests are used to confirm the diagnosis and better classify the disease. Immunohistochemistry and flow cytometry are special laboratory tests that look at the proteins on the surface of the cancer cells. These tests can confirm that the cancer cells are T cells and provide information about which subtype of T cell is involved. Blood tests can also be used to confirm HTLV-1 infection, which is required for a diagnosis of ATLL.

What does ATLL look like under the microscope?

When examined under the microscope, the appearance of ATLL depends on where the tumour is located. In the lymph nodes, cancer cells usually replace the normal structure, sometimes spreading through the large spaces called sinuses. In the skin, the cancer cells may collect in the top layer of tissue and form small clusters called microabscesses. They can also be seen deeper in the skin and fat.

The cancer cells themselves come in many shapes and sizes. Some have irregular or lobed nuclei (the central part of the cell that contains genetic material). In less aggressive types of ATLL, the cells may look smaller and closer to normal, while in more aggressive types the cells are often larger, more irregular, and more abnormal in appearance.

In some cases, larger immune cells infected with another virus called Epstein-Barr virus (EBV) may also be seen alongside ATLL cells, showing that the immune system is weakened.

Immunohistochemistry and flow cytometry

Immunohistochemistry (IHC) uses special dyes that attach to proteins inside the cancer cells. In ATLL, the cells usually show proteins that confirm their T-cell origin, such as CD2, CD3, and CD5. They often lack another protein called CD7. Most cases are positive for CD4 (a helper T-cell marker) and negative for CD8 (a cytotoxic T-cell marker). The protein CD25 is also commonly present. Some cells may express CD30, and many show positivity for CCR4, which is important because it can help guide treatment.

Flow cytometry is another test that analyzes cancer cells one at a time as they pass through a laser beam. It measures which proteins are present on the surface of the cells. Aggressive forms of ATLL often show reduced levels of CD7 and increased levels of CCR4 and CADM1. These findings help doctors understand how advanced the disease is and guide treatment decisions.

Prognosis

The outlook for patients with ATLL depends on the type of disease and how early it is diagnosed. Smoldering and chronic ATLL usually grow slowly and may have better outcomes if treated appropriately. In contrast, acute and lymphomatous ATLL tend to be more aggressive and often require intensive therapy.

Some newer treatments, including drugs that target CCR4 and other immune-based therapies, are showing promise for patients with aggressive disease. Factors such as older age, high calcium levels in the blood, and a high number of cancerous cells in the blood are associated with a worse prognosis. Because ATLL can behave in many different ways, close monitoring and individualized treatment planning are essential.

Questions to ask your doctor

If you have been diagnosed with adult T-cell leukemia/lymphoma, you may find it helpful to ask your doctor the following questions:

• What type of ATLL do I have (acute, lymphomatous, chronic, or smoldering)?

• Did my tests confirm infection with HTLV-1?

• What treatments are available for my type of ATLL?

• How aggressive is my disease, and what does this mean for my prognosis?

• Are there any targeted therapies or clinical trials that may be suitable for me?