Adult T-cell leukemia/lymphoma (ATLL) is a rare type of blood cancer. It accounts for 1 percent to 2 percent of all T-cell lymphomas diagnosed in the United States and Europe. ATLL is a type of non-Hodgkin lymphoma (NHL). NHLs are cancers that affect lymphocytes — the specialized infection-fighting white blood cells in the immune system. ATLL develops when T cells become cancerous.

ATLL is linked to infection with the human T-cell lymphotropic virus type 1 (HTLV-1). Adult T-cell leukemia/lymphoma occurs in areas where this virus is more common, such as China, Japan, South and Central America, West Africa, and the Caribbean. ATLL is less common in North America and Australia, and behaves somewhat differently than in the other locations. Men are slightly more likely than women to develop ATLL.

Types of ATLL

There are four subtypes of acute T-cell leukemia/lymphoma: acute, lymphoma, chronic, and smoldering. The subtypes of ATLL are not completely separate diseases, but rather occur on a spectrum. The signs and symptoms of the different subtypes overlap. Additionally, people can transition from one subtype to another — about a quarter of people with chronic or smoldering ATLL develop the acute subtype.

Acute

Acute ATLL, which makes up 60 percent of ATLL cases, is aggressive and fast-growing. When a specific kind of abnormal T cells is found in the peripheral blood (the blood that circulates around your body in your veins), the doctor will diagnose acute T-cell leukemia.

Acute Lymphoma/Leukemia

This fast-growing subtype of lymphoma affects 20 percent of people with ATLL. If the cancer cells are found in the lymphatic system (network of organs and vessels that helps remove germs and waste from the body), the doctor will diagnose T-cell lymphoma, or it may be in the blood and will be called leukemia.

Chronic

Some people with the chronic subtype have more aggressive leukemia, and others have milder, slower-growing disease.

Smoldering

Smoldering ATLL progresses slowly and often doesn’t cause many symptoms.

What Causes ATLL?

Adult T-cell leukemia/lymphoma is generally caused by infection with the HTLV-1 virus, sometimes also called HTLV-I. It is also possible that infection with the related virus HTLV-2 can cause ATLL, but researchers don't yet know for sure.

The HTLV-1 virus may be spread through blood transfusions, sharing needles, sexual activity, and breastfeeding. HTLV-1 infection doesn’t usually cause any signs or symptoms, so you may not know you have it. Being infected with HTLV-1 does not necessarily mean you will develop cancer. Only 2 percent to 5 percent of people with these infections are diagnosed with ATLL. Experts don’t yet know why ATLL occurs in some people with HTLV-1 but not others.

Leukemias and lymphomas are generally caused by changes in a cell’s genes. ATLL cells tend to contain many different gene mutations. It’s not always clear how these mutations play a role in leading to cancer. Scientists are still learning how to use treatments to target these gene mutations.

Symptoms of Adult T-Cell Leukemia/Lymphoma

Different ATLL subtypes cause different sets of symptoms. Because acute ATLL develops quickly, symptoms usually begin early on in the disease.

Symptoms of acute ATLL include:

• Tiredness
• Rash on the skin
• Swollen lymph nodes (lymphadenopathy), which appear as lumps in the neck, armpits, or groin

Chronic ATLL also causes these same symptoms, but it grows more slowly, and symptoms may not appear until later on in the disease. People with lymphomatous ATLL also generally develop swollen lymph nodes. Smoldering ATLL usually leads to mild symptoms, such as a small rash.

Other disease signs that may be found during laboratory tests include:

• Increased levels of white blood cells
• Hypercalcemia (high levels of calcium), which can cause confusion, bone pain, and severe constipation
• Lesions on the bone, or small areas of softened, damaged bone

These signs and symptoms are also frequently caused by other, more common health conditions. If you are experiencing any of the symptoms of ATLL, talk to your doctor to learn more about what may be causing them.

Diagnosis of Adult T-Cell Leukemia/Lymphoma

When diagnosing leukemia or lymphoma, your doctor will generally perform a physical exam to help them identify signs like swollen lymph nodes. Additionally, your doctor may ask to collect samples of your blood or bone marrow (the spongy tissue found inside your bones that makes new blood cells). A bone marrow sample is collected during a procedure known as a bone marrow aspiration and biopsy, in which a small piece of tissue/fluid is removed with a needle.

Laboratory Tests

Blood and bone marrow samples can be further examined under a microscope. Most normal cells have a nucleus (compartment in the cell that contains DNA) that is circular. ATLL cells often have a characteristic appearance in which the nucleus has several round lobes in the shape of petals. ATLL cells are sometimes called “flower cells.”

Diagnosing a Viral Infection

To determine whether leukemia or lymphoma is ATLL, doctors will need to figure out whether you are infected with HTLV. Serology tests can measure whether you have antibodies designed to fight HTLV. HTLV serology tests include enzyme-linked immunosorbent assay (ELISA) and a Western blot.

Blood Tests

Doctors may use metabolic blood tests to look for signs of damage caused by leukemia. For example, ATLL often causes bone damage. In this case, the calcium that is normally stored in the bones is released into the bloodstream. High calcium levels in the blood can cause kidney damage. A comprehensive metabolic panel can measure calcium levels and kidney function and identify any problems that may be ongoing in the body.

Imaging Tests

Imaging tests can help doctors visualize whether lymph nodes around the body are swollen and examine whether any cancer cells have reached the brain. Common imaging tests for ATLL include magnetic resonance imaging (MRI), computed tomography (CT) scan, and positron emission tomography (PET) scan.

Treatment of Adult T-Cell Leukemia/Lymphoma

The various subtypes of ATLL are often treated differently. There are several approaches.

Watch and Wait

In a watch-and-wait approach, you and your doctor delay treatment until you begin to experience more serious symptoms. During this waiting period, you will likely need to see your doctor regularly for exams and tests to monitor the disease. Smoldering and chronic ATLL may justify this approach.

Chemotherapy

People with acute and lymphoma ATLL subtypes often need aggressive chemotherapy treatment plans. In one recent study, a combination of many different medications, called VCAP-AMP-VECP, helped people have better outcomes. Some of these drugs are not available in all countries. An alternative chemotherapy combination is EPOCH, which includes VP-16 (etoposide), Adriamycin (doxorubicin), Oncovin (vincristine), Cytoxan (cyclophosphamide), and Deltasone (prednisone).

Leukemic T cells may also sometimes spread to your central nervous system (brain or spinal cord). You may need chemotherapy delivered directly to these areas to prevent or treat it.

About 90 percent of ATLL cases relapse (come back) after initial treatment success. Doctors usually treat people with relapsed ATLL with additional cycles of chemotherapy. This treatment may be the same chemotherapy that was used the first time or a different regimen. Relapse can sometimes be prevented with a stem cell transplant.

Targeted Therapy

Some doctors treat ATLL with Poteligeo (mogamulizumab). It is FDA-approved for the treatment of adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy, but it also works for ATLL. This drug is a monoclonal antibody (a laboratory-made antibody that can attach to and block molecules on cancer cells). Mogamulizumab blocks C-C chemokine receptor 4 (CCR4), a protein found on abnormal T cells. Other targeted therapies are also being studied in clinical trials for the treatment of different cancers involving T cells. Some of these drugs may eventually be used to treat adult T-cell leukemia/lymphoma.

Antiviral Drugs

Doctors sometimes treat chronic or smoldering ATLL with antiviral drugs such as Retrovir (zidovudine). Antivirals may be combined with chemotherapy or drugs that boost the immune system, such as Intron A (Interferon alpha).

Stem Cell Transplant

If initial treatments with chemotherapy and antiviral medications are effective, you may go into remission (a period when all signs of ATLL disappear). In this case, you may be eligible for a stem cell transplant. An allogeneic (from another person) stem cell transplant is the only treatment that can provide a long-term ATLL cure.

Before a transplant, you will generally receive aggressive chemotherapy to kill your old, damaged blood cells and to open up space for the transplanted cells to grow. Then, you receive healthy blood stem cells from a donor. Once you receive a transplant, the new stem cells can make more healthy, noncancerous blood cells.

Other Treatments

Sometimes, ATLL can appear in specific areas of the body, requiring other treatments. For example, ATLL sometimes causes skin tumors, which may be managed with medication that is applied directly to the skin or with light treatments.

Outlook and Prognosis for Adult T-Cell Leukemia/Lymphoma

People with acute or lymphoma ATLL tend to have a worse outlook than people with most other types of non-Hodgkin lymphoma. About 14 percent of people with aggressive forms of ATLL live for five years or more after diagnosis. About 40 percent to 50 percent of people with smoldering or chronic ATLL will live for at least five years after being diagnosed.

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