What is Adult T-Cell Leukemia?
Adult T-cell leukemia (ATL) is a rapidly progressing type of cancer in certain white blood cells, connected to a virus called Human T-cell lymphotropic virus type 1 (HTLV-1). This virus currently affects about 10 million people globally. Surprisingly, only a small percentage of these people, around 1-5%, will go on to develop noticeable symptoms of ATL.
HTLV-1, the first virus of its kind discovered in humans, is most commonly found in the north and south parts of Japan, in the Caribbean region, Africa, some Middle Eastern regions, and in South and Central America. Unfortunately, this virus can be passed from mother to child through breastfeeding, sexual activity, and blood transfusions. Initial signs of ATL may include general swelling of the lymph nodes, an enlarged liver or spleen, skin conditions, and infections that occur due to a weakened immune system.
Depending on the symptoms, this disease is broken down into four categories: acute, lymphoma, chronic, and smoldering type. The more aggressive types of ATL (acute, lymphoma, and certain severe cases of the chronic type) unfortunately have a less promising outlook, with most patients living less than a year after detection. Conversely, the less severe chronic and smoldering types have a better prognosis and health professionals often adopt a “wait and see” approach, only intervening if the disease advances. Unfortunately, those with a rapidly advancing disease generally have a poor prognosis, as the cancerous cells are resistant to chemotherapy and the patient’s immune system is significantly weakened.
What Causes Adult T-Cell Leukemia?
Adult T-cell leukemia is typically caused by an infection with HTLV-1, a virus that often doesn’t show symptoms. Two proteins associated with the virus, ‘tax’ and ‘HBZ’, are crucial in the development and progression of the disease. The ‘tax’ protein plays a big part in the initial shift towards cancerous development. The ‘HBZ’ protein is found in all infected cancer cells and is responsible for promoting growth in leukemia cells.
Risk Factors and Frequency for Adult T-Cell Leukemia
There are certain parts of the world that report high occurrences of a certain illness caused by the HTLV-1 virus and ATL. These include southwestern Japan, the Caribbean region, West Africa, northeast Iran, and south and Central America. These diseases are more common in men, according to several studies. North America, on the other hand, sees very few instances of these illnesses. For example, a recent study gave a rating of 0.06 out of 100,000 people in North America between 2001 and 2015. In Japan, the yearly rate is far higher, with a rating of 60 out of 100,000 carriers and a thousand deaths each year.
- Southwestern Japan, the Caribbean, West Africa, northeast Iran, and south and Central America have high instances of HTLV-1 and ATL.
- The illnesses are slightly more common in males.
- North America rarely sees cases of these diseases.
- From 2001 to 2015, North America had a rate of 0.06 cases per 100,000 people.
- Japan has a yearly incidence of 60 cases per 100,000 carriers, resulting in 1,000 deaths each year.
Signs and Symptoms of Adult T-Cell Leukemia
Adult T cell leukemia, or ATL, is a condition that is classified into four main types based on the Shimoyama criteria. Each type has its unique characteristics and symptoms:
- The acute subtype makes up more than half of all ATL cases. It is recognized by symptoms like a high number of white blood cells, systemic symptoms (affecting the entire body), swollen lymph nodes, organs being invaded by the disease, high calcium levels, and an increased level of a substance called lactate dehydrogenase (LDH).
- The chronic ATL kind is known for affecting the skin, lungs, and liver. People with this variant often have an increased number of white blood cells but normal levels of LDH and calcium. There are two subtypes of chronic ATL: favorable and unfavorable. The unfavorable type is distinguished by poor prognosis indicators such as high LDH, high BUN (a waste product found in your blood), and low albumin (a protein made by your liver).
- The lymphoma type of ATL involves extensive swelling of the lymph nodes, enlargement of organs, very high LDH levels, elevated calcium, and very little presence of leukemia cells in the peripheral blood.
- The smoldering form typically manifests with lung or skin involvement, an average number of lymphocytes (a type of white blood cell), and either normal or slightly increased LDH levels.
All types of ATL can show varying skin symptoms. More aggressive types of ATL can exhibit tumor lysis syndrome (a rapid release of cells into the blood caused by certain treatments) and affect the central nervous system. Due to ATL causing severe weakening of the immune system, patients are more susceptible to infections, including fungal, viral, and parasitic infections, particularly an infection called strongyloidiasis.
Testing for Adult T-Cell Leukemia
Adult T cell leukemia, also known as ATL, is often diagnosed in patients from areas where HTLV-1, a specific type of virus, is common. These regions include Southwestern Japan, the Caribbean, South America, sub-Saharan Africa, parts of the Middle East and Australo-Melanesia. This virus can be passed on through sexual intercourse, long-term breastfeeding (over six months), and exposure to blood transfusions containing infected cells.
Almost 70% of patients with ATL have an unusually high level of calcium in their blood. Some severe symptoms, like kidney problems, mental disturbances, and digestive issues, are noticed when the body can’t control high calcium levels. Also, ATL patients may show signs of serious eosinophilia, a condition where too many of a specific type of white blood cells are produced, or eosinopenia, a low level of these cells, especially in patients with widespread strongyloidiasis, a parasitic infection.
In the aggressive phases of the disease, the patient might have an elevated white blood cell count, including abnormal cells. A blood smear may show a specific cell shape, often referred to as a ‘flower cell’ or ‘cloverleaf’ cell, which is typical for ATL. Blood tests can confirm HTLV-1 infection.
The typical markers to diagnose ATL include CD3, CD4, CD5, CD7, CD8, CD25, and CD30. CD30 is more commonly expressed in the lymphoma subtype of ATL. ATL is also associated with various nonspecific chromosomal changes, like trisomy 3, trisomy 7, monosomy X, and defects in chromosomes 6 and 14, especially in severe cases.
Biopsies from the lymph node, skin, and gastrointestinal tract, along with lab techniques like flow cytometry and immunohistochemistry can assist in diagnosis. Depending upon the patient’s condition, bone marrow tests might also be needed. Increased Ki-67 proliferation index is linked to aggressive ATL.
In a clinical examination, doctors also look at detailed blood test results, lactate dehydrogenase levels, and vital mineral levels. Another essential aspect is identifying a particular genetic condition (G6PD deficiency) before initiating specific treatments. Panel tests for HIV and hepatitis should also be carried out, and patients with severe ATL should be typed for specific immune system markers.
The severity and spread of ATL can be assessed through imaging tests, like CT scans or PET-CT, to look for enlarged lymph nodes, splenomegaly (enlarged spleen), organ infiltration, and bone involvement. Tests like a brain CT scan or MRI, and evaluation of the spinal fluid, should also be considered to check for brain and nervous system involvement, especially in aggressive ATL cases.
Treatment Options for Adult T-Cell Leukemia
Adult T-cell leukemia is a serious condition that typically has poor survival rates, usually measured in months. The most appropriate treatment approach depends on the type and characteristics of the disease, as well as the patient’s health. For aggressive forms, chemotherapy or antiviral treatment is usually the first step. Less aggressive forms like smoldering and favorable chronic subtypes might be managed with antiviral treatment or observation. UV-B or psoralen therapy plus UV-A can be used to treat skin lesions related to the condition.
Patients who receive a first line of treatment with antiviral therapy generally see improved results. Despite promising response rates, many patients unfortunately suffer disease relapse. A combination of antivirals and chemotherapy has demonstrated significant survival benefits in some studies, but more research is still needed to validate these results.
Chemotherapy remains a key option for treatment, with multiple drug combinations under consideration. The most effective regimen will significantly depend on the patient’s characteristics and the specifics of their disease. Elderly patients who might not withstand aggressive chemotherapy could benefit from less severe regimens.
Alongside drug treatments, transplanting healthy stem cells has shown potential for treating aggressive forms of the disease. This is due to the lower survival outcomes with standard treatments. However, the success of this approach is limited by poor survival rates and high transplant-related mortality.
Monoclonal antibody therapy, which targets specific cells, is another treatment being explored. Several promising monoclonal antibodies have shown effectiveness in clinical trials, including brentuximab vedotin, mogamulizumab, and alemtuzumab. However, these treatments are associated with various side effects and risks that need further investigation.
In addition to these established treatments, new strategies are also under investigation to improve survival. This includes drugs like lenalidomide, checkpoint inhibitors, histone deacetylase inhibitors, and denileukin diftitox. These treatments are still experimental, and more research is needed to confirm their safety and effectiveness.
What else can Adult T-Cell Leukemia be?
When doctors are trying to diagnose mature T-cell malignancies, a type of lymphoma, they have to consider several other similar conditions. These include:
- Peripheral T-cell lymphoma that cannot be further detailed (known as PTCL-NOS)
- Anaplastic large cell lymphoma (ALCL)
- Angioimmunoblastic T-cell lymphoma (AITL)
- Mycosis fungoides
- Sézary syndrome
Sometimes, the presence of specific types of cells called Reed Sternberg-like cells in peripheral T-cell lymphomas can lead to a misdiagnosis. This is because these cells can make it seem like the patient has a type of Hodgkin lymphoma known as lymphocyte-rich classical Hodgkin lymphoma.
What to expect with Adult T-Cell Leukemia
Adult T cell leukemia, generally resistant to chemotherapy, usually presents a grim outlook despite recent advancements in treatment options. On comparison, the acute and lymphoma versions of this disease generally have a worse prognosis than the chronic and smoldering types.
Briefly, a health study recorded the average survival times of the disease according to its type – 6 months for the acute type, 10 months for the lymphoma type, and 24 months for the chronic type. Another retrospective study showed improvement in survival times with an aggressive chemotherapy and stem cell transplantation treatment, achieving 8.3, 10.6, 31.5, and 55 months survival for patients with acute, lymphoma, chronic, and smoldering types, respectively.
However, for patients undergoing stem cell transplantation, the median survival time was recorded as short as 5.9 months. Measurements of 4-year survival rates across each subtype came in at 11% for acute, 16% for lymphomatous, 36% for chronic, and 52% for smoldering types.
Several factors have been associated with worse outcomes – high performance status, high lactic acid levels, age above 40, having more than three lesions involved, high calcium levels, and many others. With all these considered, the long-term prognosis of T cell leukemia remains unsatisfactory.
To enable the assessment of prognosis in patients, researchers have attempted to create an index, considering several factors – more advanced stages of the disease, age above 70, poor performance status, low levels of albumin in the blood, and high levels of a certain immune cell product.
In addition to these, certain other factors were identified as poor prognostic markers, which included bone marrow involvement, skin involvement, unusually high levels of blood monocytes, high eosinophil count, high lactic acid levels, high levels of BUN in blood, and low albumin levels. These were particularly noted in the chronic version of T cell leukemia.
Other cellular and molecular factors, including elevated levels of certain immune markers and genetic mutations, were also associated with poor prognosis and resistance to antiviral therapy.
Possible Complications When Diagnosed with Adult T-Cell Leukemia
Patients with ATL, a type of cancer, often suffer from opportunistic infections due to a weakened immune system. To prevent these infections, certain precautionary measures should be taken. Proactive treatment with a medication called trimethoprim/sulfamethoxazole can prevent a type of pneumonia caused by pneumocystis jirovecii. Tests to check for these infections can also be considered if needed. Additionally, prophylactic measures against the herpes-zoster virus, gram-negative bacterial and fungal infections, as well as the screening for a strongyloidiasis stercoralis infection, should also be contemplated.
Another serious concern for ATL patients is the tumor lysis syndrome. This is a life-threatening condition that requires immediate intervention. To manage this, a robust hydration regimen should be implemented through an IV, and medication called rasburicase should be given. Allopurinol, another medication, is generally advised to be taken 24 hours before starting cancer treatment.
- Proactive treatment with trimethoprim/sulfamethoxazole
- Screening and prevention for pneumocystis jirovecii pneumonia
- Prophylactic measures against the herpes-zoster virus, gram-negative bacterial and fungal infections
- Screening for strongyloidiasis stercoralis infection
- Proactive management against tumor lysis syndrome with vigorous hydration and rasburicase.
- Advising Allopurinol administration 24 hours before the start of cancer treatment.
Preventing Adult T-Cell Leukemia
Adult T cell leukemia, a type of cancer, is primarily caused by an infection from a virus called HTLV-1. This virus can be passed on through breastfeeding, sexual contact, and blood transfusions. Even though most people with the HTLV-1 infection don’t show any symptoms, they have a higher chance of developing this type of leukemia over their lifetime. There’s no standard screening test for this.
Still, there are ways to lower the risk. Physicians should recommend their patients to stop prolonged breastfeeding after six months and encourage the use of condoms. Additionally, education about the risks of catching infections, including HTLV-1, from intravenous drug use can be beneficial. This can help limit the spread of the virus and reduce the risk of developing Adult T cell leukemia.
