T-cell Type Acute Leukaemia

T-cell type acute leukaemia is an aggressive blood cancer affecting the bone marrow, where immature and abnormal T-cells accumulate and crowd out healthy blood cells needed to fight infection and maintain health.

Table of contents

• What is T-cell acute lymphoblastic leukaemia?
• How common is T-cell ALL?
• What causes T-cell ALL?
• Genetic changes in T-cell ALL
• Signs and symptoms
• How is T-cell ALL diagnosed?
• Treatment options
• Outlook and survival

What is T-cell acute lymphoblastic leukaemia?

T-cell acute lymphoblastic leukaemia, also called T-cell ALL or T-ALL, is a type of blood cancer that develops in the bone marrow^[1]. The bone marrow is the soft, spongy tissue inside your bones where blood cells are made^[3].

T-cell acute lymphocytic leukemia, T-cell acute lymphoblastic leukemia, precursor T-lymphoblastic leukemia

• Bone marrow
• Blood
• Thymus
• Central nervous system (brain and spinal cord)
• Liver
• Spleen
• Lymph nodes

In T-cell ALL, too many immature and abnormally shaped T-cells are produced in the bone marrow^[1]. These abnormal cells are called ‘leukaemia cells’ or ‘blasts‘ and they do not fight infections properly^[1]. T-cells are a type of white blood cell that normally help your body fight off infections by directly killing infected cells and supporting other immune cells^[2].

The large numbers of leukaemia cells prevent your bone marrow from making the other blood cells you need, including healthy white blood cells, red blood cells, and platelets (cells that help your blood clot)^[1]. This is what causes many of the symptoms of the disease.

T-cell ALL is considered an aggressive or fast-growing cancer^[1]. The word “acute” means the disease progresses rapidly and requires quick treatment^[3]. T-ALL is more aggressive compared to B-cell ALL, another form of acute lymphoblastic leukaemia^[1].

The cancer often spreads beyond the bone marrow. It commonly affects the central nervous system (the brain and spinal cord) and can cause tumors behind the breastbone in an area called the mediastinum^[2]. Around 75% of people with T-ALL develop these chest tumors, known as mediastinal masses^[11]. The cancer cells can also build up in the liver, spleen, and lymph nodes^[2].

How common is T-cell ALL?

T-cell ALL is an uncommon form of blood cancer^[1]. It represents approximately 12% to 15% of all newly diagnosed cases of acute lymphoblastic leukaemia in children^[4]. In adults, T-ALL accounts for about 25% of all acute lymphoblastic leukaemia cases^[2].

Among children who develop T-cell ALL, 15% are diagnosed, with a peak occurrence between ages 2 and 5 years^[1]. In children with T-ALL, the average age at diagnosis is around 9 years^[2]. For adults, the average age at diagnosis is around 30 years^[11].

T-cell ALL is more prevalent in the adult population compared to children, although the rate of new cases decreases as people get older^[2]. The disease affects slightly more males than females at all ages^[1]. The disease also shows marked male predominance, particularly in adolescents^[2].

What causes T-cell ALL?

The exact cause of T-cell ALL is unknown^[1]. The disease develops when changes, called mutations, occur in the genetic material (DNA) inside bone marrow cells^[3]. These genetic changes disrupt the normal development of T-cells within the thymus, a small organ behind the breastbone where T-cells mature^[11].

The mutations cause certain developmental pathways that control how T-cells grow, how tumor-suppressing genes work, and how cell growth and multiplication are controlled to become faulty^[2]. This leads T-cells to transform abnormally and become cancerous during their development^[11].

In young children with T-ALL, these gene changes may have happened before they were born^[6]. Between 60% and 80% of patients who develop T-cell ALL have abnormal changes in their chromosomes and genes^[1]. These are acquired mutations, which means they develop during a person’s lifetime and cannot be passed on to your children^[1]. The remaining patients do not have any detectable chromosome or gene abnormalities^[1].

Several factors can increase the risk of developing T-cell ALL, though having these risk factors does not mean a person will definitely develop the disease^[11]. Risk factors include:

• Family history of leukaemia, especially in siblings^[11]
• Genetic conditions, such as Down syndrome or Fanconi anemia^[6]
• Previous exposure to X-rays, radiation, or chemotherapy^[11]
• Radiation exposure during development before birth or from past radiation therapy^[6]
• Infections with certain viruses, such as Epstein-Barr virus^[6]

Genetic changes in T-cell ALL

Several specific genetic mutations have been found in people with T-cell ALL. These mutations cannot be passed on to children^[1].

The most common genetic changes found in T-ALL include:

• Up to 80% of patients have a deletion (loss) of the CDKN2A gene^[1]
• 60% of patients have deletions of the TAL1 gene^[1]
• The most common mutations occur in the NOTCH1/FBXW7 pathway, found in 60% of adult patients^[1]

Only two genes, NOTCH1 and CDKN2A/2B, are mutated in more than 50% of T-ALL cases^[1]. Many other genes are mutated at lower frequencies^[1]. Modern research has identified several groups of genetic changes that can be targeted with specific treatments, including changes in the Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK pathways^[4].

Signs and symptoms

At first, the symptoms of T-cell ALL can be vague and easily mistaken for other common illnesses like the flu^[1]. Sometimes, a routine blood test will show signs of ALL, such as high levels of white blood cells, before symptoms appear^[1]. However, most patients have symptoms when they are diagnosed^[1].

Patients with T-cell ALL produce large amounts of abnormal leukaemia cells that overwhelm the bone marrow^[1]. This prevents the bone marrow from producing adequate numbers of normal blood cells. People with T-cell ALL can present with extremely high white blood cell counts^[1].

Reduced levels of normal blood cells cause many of the main symptoms. The most common symptoms and signs of T-cell ALL include^[1]:

• Weakness or fatigue (feeling extremely tired)
• Pale skin
• Fever and/or night sweats
• Unexpected weight loss or loss of appetite
• Difficulty breathing or shortness of breath
• Easy bruising
• Bleeding gums
• Purpura (purple-colored patches on the skin that, unlike bruises, are not due to injury)
• Petechiae (flat, 2 mm red or purple spots on the skin that do not disappear when pressed beneath a glass)

Additional symptoms may include^[2]:

• Recurrent infections due to a lack of normal white blood cells
• Swelling of lymph nodes in the neck, middle of the chest, or other areas
• Unexplained fevers and chills
• Extreme tiredness

In T-cell ALL, involvement of the central nervous system is seen in about 10% of patients at diagnosis^[1]. When the cancer spreads to the brain or spinal cord, it may cause additional complications including^[6]:

• Balance problems
• Blurred vision or double vision
• Enlarged liver or spleen
• Facial muscle weakness or numbness
• Headaches
• Nausea and vomiting
• Seizures

Some individuals with T-ALL develop swollen lymph nodes in the middle of their chest, which can affect breathing or blood circulation^[7]. Abdominal pain may occur due to an enlarged liver or spleen^[11].

Having these symptoms does not necessarily mean you have T-cell ALL, as many other medical conditions can cause similar symptoms^[2]. You should always talk to a healthcare provider about changes in your body that last longer than two weeks^[6].

How is T-cell ALL diagnosed?

To diagnose T-cell ALL, your medical team will perform several tests. A healthcare provider will start with a physical exam and ask about your symptoms, including how long they have lasted and how they affect your daily life^[6].

Diagnostic tests include:

Full blood count: A blood test measures the number of red cells, different types of white cells, and platelets in your blood^[1]. High levels of T-cell white blood cells (lymphocytes) can help determine a diagnosis of T-cell ALL^[1]. A blood sample can also show abnormal-looking lymphocytes when examined under a microscope^[1]. The blood test may reveal too many or too few white blood cells, not enough red blood cells, and not enough platelets^[14].

Bone marrow aspiration or biopsy: Bone marrow samples are taken from your hip bone using a special biopsy needle^[1]. You should receive a local anesthetic to numb the area^[1]. The samples are examined under a microscope to confirm a T-cell ALL diagnosis if it is not obvious from the blood sample^[1]. Doctors in the laboratory classify the blood cells into specific types based on their size, shape, and genetic features^[14]. This test is the most common and reliable method for T-ALL diagnosis^[11].

Lumbar puncture (spinal tap): A member of your medical team inserts a fine needle in the lower back region of your spine to collect a small amount of fluid^[1]. This test reveals if leukaemia cells have entered your central nervous system^[1].

Imaging tests: These tests help determine cancer severity and locate affected lymph nodes and tumors^[11]. They can also detect enlarged organs such as the liver or spleen^[11]. Imaging tests may include:

• Chest X-rays^[11]
• Computed tomography (CT) scans^[11]
• Magnetic resonance imaging (MRI) scans^[6]
• Positron emission tomography (PET) scans^[11]
• Ultrasounds^[11]
• Echocardiograms^[11]

Genetic tests: These tests look for specific changes in chromosomes and genes that help doctors plan your treatment^[14]. They identify whether leukaemia cells began from B lymphocytes or T lymphocytes and look for certain changes in the cancer cells^[14].

Treatment options

Doctors often treat T-cell ALL with a combination of several chemotherapy drugs and steroids over a period of 2 to 3 years^[7]. Chemotherapy uses drugs that kill cancer cells or stop them from dividing^[7]. Treatment is intensive and requires careful management^[4].

Treatment for T-cell ALL is divided into different phases^[15]:

Steroid pre-phase: Most people receive steroids first, often starting up to a week before chemotherapy begins^[15]. This helps destroy as many leukaemia cells as possible and often makes people feel better quite quickly^[15]. The most common steroids are prednisolone or dexamethasone^[15]. You may also receive a chemotherapy drug and supportive medicine with the steroid^[15].

Induction phase: During induction, you receive several chemotherapy drugs over a few days^[15]. This phase usually takes about 4 to 8 weeks^[15]. You will generally need to stay in hospital until you have recovered, as chemotherapy damages healthy cells as well as leukaemia cells^[15]. You also receive supportive medicine, including fluids to protect your kidneys, antibiotics if you have an infection, and blood or platelet transfusions as needed^[15].

Consolidation phase: This phase aims to kill any remaining leukaemia cells^[8].

Intensification phase: Additional intensive chemotherapy is given during this phase^[8].

Maintenance phase: This is the longest phase, lasting about 2 years^[15]. During maintenance, many people can return to work or school^[15]. This phase involves less intensive treatment to prevent the cancer from returning^[8].

Additional treatment approaches include:

Targeted therapy: If you have a specific type called Philadelphia positive ALL, you will take a targeted cancer drug, most commonly imatinib, as a tablet every day throughout your treatment^[15].

Central nervous system treatment: Because T-cell ALL can spread to the brain and spinal cord, treatment often includes chemotherapy given directly into the spinal fluid or, less commonly now, radiation therapy to the central nervous system^[4].

Stem cell transplantation: In some cases, particularly for high-risk patients or those whose cancer returns, doctors may recommend a stem cell or bone marrow transplant^[4]. If you have a stem cell transplant, the treatment time is shorter but more intensive^[15].

Your treatment plan depends on several factors, including your type of T-ALL, general health, and age^[1]. Your medical team will explain your treatment plan and each phase to you^[1]. Before starting treatment, your doctor may discuss how treatment might affect your fertility^[15].

Outlook and survival

With modern treatment, outcomes for T-cell ALL have steadily improved^[4]. In children, treatment can cure up to 80% of cases^[11]. Around 75% of children with T-ALL remain cancer-free after five years^[11]. Event-free survival rates now exceed 85% in many contemporary clinical trials for children^[4].

For adults, outcomes are generally less favorable, with typical cure rates of less than 50%^[11]. Around 60% of adults with T-ALL remain cancer-free after three years^[11]. The five-year event-free survival for adults is approximately 70%, with overall survival around 80%^[4].

Recent advances in therapy have brought T-ALL outcomes close to those of B-cell ALL, with approximately 85% five-year event-free survival in many studies^[4].

The key factor that predicts outcome in T-ALL is minimal residual disease (MRD) response, which measures how much cancer remains after initial treatment^[4]. Unlike B-cell ALL, other factors such as age, white blood cell count at diagnosis, and the genetics of the cancer cells are not independently predictive of outcome when MRD response is considered^[4].

Around one-third of patients experience a relapse (return of the cancer) within one to two years^[11]. Unfortunately, when T-ALL returns after treatment, it is very difficult to cure^[4]. For relapsed disease, event-free survival and overall survival rates are less than 25%^[4].

Current research efforts focus on preventing relapse by strengthening therapy for high-risk patients, reducing side effects for patients with favorable responses, and developing new treatments for cancer that returns^[4].