What is acute lymphoblastic leukemia (ALL)?
Acute lymphoblastic leukemia (ALL) which can be divided into B-cell ALL (B-ALL) and T-cell ALL (T-ALL), is a type of blood cancer that begins in the bone marrow. The bone marrow is the soft tissue inside the bones where blood cells are made. In ALL, the bone marrow makes too many immature white blood cells called lymphoblasts. Lymphoblasts are a type of lymphocyte, which is a type of white blood cell.
ALL is defined as an aggressive neoplasm of the lymphoid lineage caused by acquired somatic defects due to either inherited factors or infections e.g. viruses in early haematopoietic blasts that impede or significantly impair differentiation leading to accumulation of undifferentiated blasts in the marrow, spilling into the peripheral blood and infiltrate other tissues. Leukemic blasts are too immature to be functional and are prone to suppress or supplant the production of normal haematopoiesis causing pancytopenia.
ALL is the most common type of cancer in children, but it can also occur in adults. It is most common in children under the age of 5 and in adults over the age of 65.
What is T-ALL?
T-cell acute lymphoblastic leukemia (T-ALL) is a subtype of acute lymphoblastic leukemia (ALL), which is the most common type of cancer in children. T-ALL is less common than B-cell ALL, but it is still the second most common type of ALL in children. T-ALL makes up roughly 15% of ALLs.
T-ALL is caused by the uncontrolled growth of immature T cells. T cells are a type of white blood cell that helps the body fight infection. When T cells become cancerous, they can crowd out healthy blood cells in the bone marrow and bloodstream. This can lead to a number of problems, including fatigue, weakness, and an increased risk of infection.
Risk factors for T-ALL
The exact cause of B-ALL is unknown, but there are a number of risk factors that may increase the risk of developing the disease. These risk factors include:
- Age: T-ALL is most common in children under the age of 5 and in adults over the age of 65. The peak incidence is at about 15 years old.
- Gender: There is a 2:1 male predominance.
- Family history: People with a family history of T-ALL are at an increased risk of developing the disease.
- Certain genetic conditions: People with certain genetic conditions, such as Down syndrome and Noonan syndrome, are at an increased risk of developing T-ALL.
- Exposure to radiation: Exposure to high levels of radiation, such as from X-rays or nuclear fallout, can increase the risk of developing T-ALL.
- Exposure to certain chemicals: Exposure to certain chemicals, such as benzene, has been linked to an increased risk of developing T-ALL.
What are the clinical features of T-ALL?
About ⅔ of T-ALLs present as mediastinal lymphomas associated with large masses in the thymus. The enlarging tumor mass often compresses structures such as major airways and blood vessels, producing cough, shortness of breath and superior vena cava syndrome which is characterized by swelling and redness of the face and upper extremities due to blockage of venous return to the heart. T-ALL has a greater tendency than B-ALL to produce organomegaly and lymphadenopathy and it often spreads to the central nervous system too.
What are the laboratory investigations for T-ALL?
Laboratory investigations play an important role in the diagnosis, staging, and monitoring of T-cell acute lymphoblastic leukemia (T-ALL). The following tests are commonly used:
Complete blood count (CBC)
A CBC measures the number of red blood cells, white blood cells, and platelets in the blood. In T-ALL, the white blood cell count is often elevated, and the differential may show a large number of immature T cells (blasts). Full blood count is similar to B-ALL.
Peripheral blood smear
A peripheral blood smear is a blood test that examines the different types of blood cells under a microscope. In T-ALL, the peripheral blood smear may show blasts and other abnormal cells. Peripheral blood smear is similar to B-ALL.

Bone marrow aspiration and biopsy
A bone marrow aspiration and biopsy are procedures that remove a sample of bone marrow for examination under a microscope. Bone marrow is the soft tissue inside the bones where blood cells are made. In T-ALL, the bone marrow is usually infiltrated with blasts. The diagnosis is based on morphologic demonstration of lymphoblasts replacing tissues such as the thymus and the bone marrow.
Immunophenotyping
Immunophenotyping is a laboratory test that uses antibodies to identify the type of white blood cells present in a sample. In T-ALL, immunophenotyping can be used to identify the specific type of T cell that is involved in the cancer. Immunotyping is essential to confirm the diagnosis and expresses a variable combination of T-lineage antigens such as CD3, CD5 and negative for CD19 which is a B-cell lineage antigen.
Cytogenetic analysis
Cytogenetic analysis is a laboratory test that examines the chromosomes in cells. Chromosomal abnormalities are common in T-ALL. Cytogenetics, however, has not proved helpful in predicting patient outcomes.
Fluorescence in situ hybridization (FISH)
FISH is a laboratory test that uses fluorescent probes to identify specific genes or chromosomal sequences. FISH can be used to detect chromosomal abnormalities and other genetic changes in T-ALL cells.
Molecular testing
Molecular testing can be used to detect the genetic changes that cause T-ALL. This includes testing for the NOTCH1 gene mutation, which is present in about 60% of adults with T-ALL. Common activating mutations include mutations in NOTCH1, chromosomal rearrangements or other aberrations that lead to increased expression of several other transcription factors.
Laboratory investigations for staging T-ALL
The following laboratory tests are used to stage T-ALL:
- Bone marrow blast count: The bone marrow blast count is the percentage of blasts in the bone marrow. A higher bone marrow blast count is associated with a worse prognosis.
- Central nervous system (CNS) involvement: CNS involvement can be detected by examining the cerebrospinal fluid (CSF) under a microscope. The presence of blasts in the CSF is a sign of CNS involvement.
- Minimal residual disease (MRD): MRD is the presence of a small number of cancer cells in the body after treatment. MRD can be detected using molecular testing.
Laboratory investigations for monitoring T-ALL
The following laboratory tests are used to monitor T-ALL:
- Complete blood count (CBC): The CBC is used to monitor the response to treatment and to detect early signs of relapse.
- Peripheral blood smear: The peripheral blood smear is used to monitor the response to treatment and to detect early signs of relapse.
- Bone marrow aspiration and biopsy: Bone marrow aspiration and biopsy are used to monitor the response to treatment and to detect early signs of relapse.
- Molecular testing: Molecular testing can be used to detect MRD and to monitor the response to treatment.
What is the treatment and management of T-ALL?
The treatment of T-cell acute lymphoblastic leukemia (T-ALL) depends on a number of factors, including the stage of the disease, the patient’s age, and their overall health. The goal of treatment is to achieve complete remission, which is the absence of detectable leukemia cells in the body.
The most common treatment for T-ALL is chemotherapy. Chemotherapy is a type of medication that kills cancer cells. Chemotherapy can be given through an IV or by mouth.
Chemotherapy drugs used to treat T-ALL include:
- Vincristine
- Prednisone
- L-asparaginase
- Doxorubicin
- Cyclophosphamide
- Methotrexate
- Nelarabine
Chemotherapy is typically given in cycles, with each cycle lasting for several weeks. The patient will have a break between cycles to allow their body to recover.
In addition to chemotherapy, other treatments may also be used, such as:
- Radiation therapy: Radiation therapy uses high-energy rays to kill cancer cells. Radiation therapy may be used to treat T-ALL that has spread to the brain or spinal cord.
- Stem cell transplant: A stem cell transplant is a procedure in which the patient’s own stem cells are harvested and then reinfused into the body after high-dose chemotherapy. Stem cell transplants can be used to treat T-ALL that is resistant to chemotherapy or that has relapsed after chemotherapy.
- Targeted therapy: Targeted therapy is a type of medication that targets specific molecules that are involved in the growth and development of cancer cells. Targeted therapy drugs are becoming increasingly important in the treatment of T-ALL.
Some examples of targeted therapy drugs used to treat T-ALL include:
- Imatinib (Gleevec)
- Dasatinib (Sprycel)
- Nilotinib (Tasigna)
- Ponatinib (Iclusig)
Targeted therapy may be used alone or in combination with chemotherapy.
Immunotherapy
Immunotherapy is a type of treatment that boosts the body’s own immune system to fight cancer. Immunotherapy is still under investigation for the treatment of T-ALL, but it has shown promising results in some clinical trials.
One example of immunotherapy that is being used to treat T-ALL is chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of immunotherapy that involves engineering the patient’s own T cells to recognize and kill cancer cells.
CAR T-cell therapy has been shown to be very effective in treating T-ALL in children and young adults. However, it is a complex and expensive treatment, and it is not yet widely available.
Below is the synopsis of T-ALL.
Definition of T-ALL
An aggressive neoplasm of the lymphoid lineage caused by acquired somatic defects due to either inherited factors or infections e.g. viruses in early hematopoietic blasts that impede or significantly impair differentiation leading to accumulation of undifferentiated blasts in the marrow, spilling into the peripheral blood and infiltrate other tissues. Leukemic blasts are too immature to be functional and are prone to suppress or supplant the production of normal hematopoiesis causing pancytopenia.
Pathogenesis of T-ALL

Image depicting the two-step oncogenic model of ALL pathogenesis, highlighting the initial genetic alterations and the subsequent epigenetic and transcriptional changes.
Acute Lymphoblastic Leukemia | ||
B-ALL | T-ALL | |
Incidence | Most common Peak at 3 y.o. Whites, Hispanics, Down syndrome | Peak at 15 y.o. Male:female 2:1 |
Signs and Symptoms | Fatigue Easy bruising Fever Spread through meninges to CNS | Mediastinal lymphoma (thymus) Cough Shortness of breath Superior vena cava syndrome e.g. swelling of the face |
Subtypes | t(12;21)(p13;q22)ETV6/RUNX1 Hyperdiploidy Hypodiploidy t(9;22)(q34;q11)BCR/ABL1 t(v;11q23) | |
Laboratory investigations | FBC: Normochromic, normocytic anemia with thrombocytopenia PBF: Presence of lymphoblasts BMAT: ≥ 20% lymphoblasts Immunophenotyping: + CD19, CD10- CD45, CD20, CD13, surface light chains | Biopsy: Replacement of thymus or bone marrow tissues with lymphoblasts Immunophenotyping: + CD3, CD5, CD7, HLA-DR – CD34, CD8, CD4, CD19 |
Prognosis | Excellent: Children Less favorable: Adults | Similar to B-ALL |
Treatment
