Leukemia is a type of blood cancer, and there are many types and subtypes depending on the cells involved and the course of the disease. When we talk about T-Cell Acute Lymphoblastic Leukemia, also known as T-ALL, we are referring to a type of leukemia or blood cancer with the following characteristics:
- It involves T-cell lymphocytes, a variety of white blood cell that defends the body against bacterial infection
- It is acute, which mean it progresses very quickly and is potentially dangerous and aggressive
T-ALL shares many features of other types of leukemia, but has critical elements that allow us to identify and target T lymphocytes in the management of the disease.
What causes T-ALL?
Similar to other types of cancer, patients with T-Cell Acute lymphoblastic leukemia typically display a series of genetic alterations in cancer cells and stem cells in the bone marrow. Many types of genetic aberrations are known to cause T-ALL. For example:
- Genetic lesions of the T-cell receptor: Around 35% of patients have a lesion in the T-cell receptor, which is vital to promote T-cell differentiation, and to regulate the production of these cells. The aberration is usually located in the chromosome 7 and 14.
- Oncogene lesions: Oncogenes are normal genes in the body that turn cells into cancer when they become aberrant. The most common oncogenes that become activated in T-Cell Acute lymphoblastic leukemia are Notch1 mutations, HOXA cluster alterations, and other genetic abnormalities in TLX and TAL genes. In the majority of patients, these genetic alterations are associated with other disturbances, and they altogether cause T-ALL.
- Tyrosine kinase genetic lesions: These enzymes work as a second messenger in the body, and the aberration creates abnormal signals that cause cancer. Typical examples include the ABL1 gene, which is typically found in chronic myeloid leukemia, and JAK1 mutations, found in 18% of patients, and associated with a bad prognostic.
The most important risk factors in T-ALL include age and gender. This type of alteration is more common in children than adults, and the incidence is higher before 5 years of age. T-ALL affects a higher proportion of males than females, and even though the causes are genetic alterations, it is not an inherited disease. It is surely not contagious, either.
Symptoms of T-ALL
The symptoms of T-ALL are basically the same as those found in other types of leukemia. We can only make an appropriate diagnosis by investigating further and using additional blood tests and bone marrow aspiration.
Typical symptoms include:
– Fever of unknown origin
T-ALL is a type of leukemia affecting the immune system. Therefore, individuals are more susceptible to hidden infections and associated fever. It may be difficult sometimes to trace the source of the infection, which is why this type of fever receives the name of “fever of unknown origin.”
– Weakness and tiredness
Patients often report symptoms of fatigue and exhaustion. Depending on the severity and the stage of the disease, they may also feel palpitations as the thickness of the blood changes and affects the circulation of the body.
– Anemia
The bone marrow produces an excess aberrant and nonfunctioning white blood cells. These overpopulate and infiltrate in the bone marrow and other tissues, reducing the available space and resources to produce red blood cells. A lack of red blood cells causes anemia and intensifies the symptoms of fatigue.
– Bruises and bleeding
Similarly, another cell line that is commonly affected by excess production of blood cells is platelets. These cells are important for coagulation and wound healing, and not having them increases the risk of bleeding and spontaneous bruising.
– Lymphadenopathy
It is the clinical name of swollen lymph nodes, which can be palpable through the skin or apparent in chest X-rays. In some cases, these lymph nodes are located in the middle of the chest and may cause additional symptoms such as difficult breathing and impaired circulation.
Diagnosis
The diagnosis of T-Cell Acute lymphoblastic leukemia has different phases we can follow. In the initial phase of the diagnosis, the suspicion is made by looking at different signs and symptoms of the disease. The age of the patient and the symptoms are taken into consideration, and sometimes patients are detected by trying to figure out the cause of a case of fever of unknown origin.
Regardless of the signs and symptoms, the initial laboratory tests include a complete blood count, which shows several alterations, including an excessively high count of white blood cells, anemia, and thrombocytopenia. More alterations in the complete blood count are associated with a poor prognosis.
When the diagnosis is apparent, the next step for diagnosis is performing a bone marrow aspiration or biopsy. A sample is taken from the bone marrow, and it is analyzed through the microscope and with genetic and other specialized tests to find out the subtype of leukemia that is affecting the patient. Other tests are required, depending on the signs and symptoms of the patient and the existence of a given infection. Even if there’s no traceable problem in the kidneys and liver, tests are usually performed to evaluate their function, which will be useful to program a therapeutic protocol.
Another standard test in T-ALL is a lumbar puncture, which is done to obtain a sample of cerebrospinal fluid. This is because lymphoid cells usually enter the central nervous system, and this is more common in T-Cell Acute lymphoblastic leukemia.
After performing all of these tests, doctors will have enough information as to what type of leukemia they are facing and any additional alteration they should cover in treatment protocols.
Treatment of T-ALL
In the pediatric and adult population, T-Cell Acute lymphoblastic leukemia usually involves a higher risk than B-Cell Acute lymphoblastic leukemia. There’s a higher risk, which is translated into a higher chance of resistance to treatment, a higher tendency for relapse, and a higher chance of involvement of the central nervous system.
For this reason, it is important to treat T-ALL aggressively from the start, and treatment protocols usually include a combination of chemotherapeutic treatments and radiation therapy. According to research, the intensification of this multimodal treatment has led to significant improvement in the management of the disease. Treatment should start immediately, and any delay may further compromise the patient and lead to a poor prognosis.
Treatment modalities typically include:
– Radiotherapy
It is sometimes used, especially in cases of involvement of the central nervous system.
– Chemotherapy
It is a complex regime of medications aimed at destroying the cancer cells. Chemotherapy protocols have two different phases, an induction therapy lasting no more than 6 weeks, and then a combination therapy, where chemotherapy is combined with anti-metabolite therapy in a higher intensity for the first 8 months. This type of therapy is often combined with glucocorticoids.
– Allogeneic stem cell transplantation
It is the most effective treatment for T-ALL, but a very dangerous option for some patients. It consists of giving the diseased patient a transplant of bone marrow from a healthy donor, but it is a risky procedure. Therefore, it is imperative to choose which patients are fit for stem cell transplantation and which ones are not recommended to go through this type of therapy. It is often the treatment of choice in high-risk cases and requires constant monitoring following transplantation to evaluate relapse.
– Autologous stem cell transplantation
It is a relatively safer form of stem cell transplantation in which stem cells are collected from the patient before a high dose of therapy that will cause severe damage to the bone marrow. After treatment, healthy stem cells from the sample are returned to the patient’s bone marrow to allow for the production of blood cells.
After therapy, it is very important to keep monitoring the patient, even if the signs and symptoms are gone. In cases of relapse, new chemotherapy regimens are started similar to the ones used to treat the initial phase of the disease.
Questions to ask your doctor about T-ALL
If you were diagnosed with T-Cell Acute lymphoblastic leukemia, you probably have many questions to answer. It is essential to ask your doctor all of your questions and concerns about T-ALL. Suitable questions are as follows:
- What can I do to reduce my exposure to infections?
- What type of tests do I need to get done frequently?
- What treatment options do I have, and what happens in each one of them?
- What type of food is it better to avoid?
- Where can I find help when I feel emotionally overwhelmed?
Conclusion
T-ALL is a type of blood cancer that is neither contagious nor inherited. It affects T-cells, which are important to protect the body against infections, and has a few key genetic alterations we can find in the bone marrow and the cancer cells. Signs and symptoms are similar to those found in other types of leukemia and include a fever of unknown origin, increased frequency of infections, fatigue, anemia, bleeding and bruising. Treatment options are usually aggressive from the start to prevent relapse and include a multimodal therapy of chemotherapy, radiotherapy, and stem cell transplantation in high-risk cases.
References
Marks, D. I., & Rowntree, C. (2017). Management of adults with T-cell lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology, 129(9), 1134-1142.
Vadillo, E., Dorantes-Acosta, E., Pelayo, R., & Schnoor, M. (2018). T cell acute lymphoblastic leukemia (T-ALL): new insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies. Blood reviews, 32(1), 36-51.
Follini, E., Marchesini, M., & Roti, G. (2019). Strategies to overcome resistance mechanisms in T-cell acute lymphoblastic leukemia. International journal of molecular sciences, 20(12), 3021.
Chiaretti, S., & Foà, R. (2009). T-cell acute lymphoblastic leukemia.