Acute lymphoblastic leukemia: what is it, causes, symptoms, treatment, prognosis

What is Acute Lymphoblastic Leukemia?

Acute lymphoblastic leukemia (or acute lymphocytic leukemia, abbr. ALL) Is a life-threatening disease in which cells that normally develop into lymphocytes become cancerous and quickly replace normal cells in the bone marrow.

• Due to the lack of normal blood cells, patients may experience symptoms such as fever, weakness, and pallor.
• Typically, blood tests and bone marrow tests are done in these cases.
• Chemotherapy is given and is often effective.

Acute lymphocytic leukemia (ALL) occurs in patients of any age, but is the most common type of cancer in children and accounts for 75% of all cases of leukemia in children under 15 years of age. ALL most commonly affects young children (2 to 5 years old). Among middle-aged people, this disease occurs slightly more often than in patients over 45 years old.

In ALL, very immature leukemic cells accumulate in the bone marrow, destroying and replacing cells that make normal blood cells. Leukemia cells are transported with the bloodstream to liver, spleen, lymph nodes, brain and testicles, where they can continue to grow and divide. In this case, ALL cells can accumulate in any part of the body. They can penetrate the membranes that cover the brain and spinal cord (leukemia meningitis), and lead to anemia, hepatic and renal failure and damage to other organs.

Symptoms of acute lymphoblastic leukemia

The early symptoms of ALL are caused by the inability of the bone marrow to produce enough normal blood cells.

• Fever and excessive sweating may indicate an infection. A high risk of infection is associated with too few normal white blood cells.
• Weakness, fatigue, and pallor, suggesting anemia, may be due to an insufficient number of red blood cells. Some patients may experience labored breathing, heart palpitations and chest pain.
• Rapid bruising and bleeding, sometimes in the form of nosebleeds or bleeding from the gums, is due to too few platelets. In some cases, cerebral hemorrhage or intra-abdominal bleeding may occur.

With the penetration of leukemic cells into other organs, corresponding symptoms occur.

• Leukemia cells in the brain can cause headaches, vomiting, stroke and disorders of vision, balance, hearing and facial muscles.
• Leukemia cells in the bone marrow can lead to bone and joint pain.
• If leukemic cells cause enlarged liver and spleen, there may be a feeling of fullness in the stomach and in some cases pain.

Causes of acute lymphoblastic leukemia

The underlying cause of ALL remains unknown, but there are risk factors that may be environmental or secondary to inherited and / or acquired predisposing conditions. Environmental risk factors are past exposure to ionizing radiation, chemicals (benzene, herbicides and pesticides) and chemotherapeutic agents.

To hereditary predisposing conditions relate Down syndrome, hereditary disorders characterized by a defect in the processes of DNA repair and regulation of the cell cycle (Fanconi anemia, Bloom's syndrome and ataxia-telangiectasia), hereditary disorders characterized by altered signal transmission in processes cell proliferation and apoptosis (Kostman syndrome, Schwachman-Diamond syndrome, Diamond-Blackfen anemia, and type I neurofibromatosis) and Li-Fraumeni syndrome.

There are also acquired predisposing conditions such as aplastic anemia, paroxysmal nocturnal hemoglobinuria, and myelodysplastic syndrome.

Diagnostics

The first signs of acute lymphoblastic leukemia can be detected with blood tests, such as a complete blood count. The total white blood cell count can be low, normal, or high, but the red blood cell and platelet count is almost always low. In addition, very immature white blood cells (blasts) are found in the blood.

To confirm the diagnosis and distinguish ALL from other types of leukemia, bone marrow examination is done in almost all cases. The blasts are analyzed for chromosomal abnormalities, which helps doctors determine the exact type of leukemia and the right drugs for treatment.

Blood and urine tests are done to check for other abnormalities, including electrolyte disturbances.

Imaging studies may also be required. If symptoms are detected that suggest the presence of leukemic cells in the brain, computed tomography (CT) or magnetic resonance imaging (MRI) is done. A chest CT scan may be done to look for leukemia cells around the lungs. If internal organs are enlarged, CT, MRI, or abdominal ultrasound may be done. Echocardiography (ultrasound of the heart) may be done before chemotherapy is started because sometimes chemotherapy has a negative effect on the heart.

Treatment of acute lymphoblastic leukemia

Treatment for ALL includes:

• chemotherapy;
• other drugs such as immunotherapy and / or targeted therapy;
• in rare cases, stem cell transplantation or radiation therapy.

Chemotherapy is highly effective and consists of the following phases:

• induction;
• brain treatment;
• consolidation and intensification;
• supportive therapy.

Induction chemotherapy - this is the first phase of treatment. The goal of induction therapy is to achieve a state of remission by killing leukemic cells, which restores the ability of normal cells to develop in the bone marrow. In some cases, a stay in the hospital for several days or weeks is required (this depends on how quickly the bone marrow recovers).

One of several combinations of drugs is used, the doses of which are re-administered over several days or weeks. The choice of a particular combination depends on the results of the diagnostic tests. One combination consists of oral prednisone (a corticosteroid) and weekly doses of vincristine (a chemotherapy drug), given with an anthracycline drug (usually daunorubicin), asparaginase, and sometimes cyclophosphamide, for intravenous introduction. In some patients with acute lymphocytic leukemia, new drugs, such as immunotherapy (a treatment that uses its own the human immune system to destroy tumor cells) and targeted therapy (drugs that attack the internal biological mechanisms of tumor cells).

Brain treatment usually begins during induction and can continue throughout all stages of treatment. Since ALL often spreads to the brain, this phase is also aimed at treating leukemia, already spread to the brain, or to prevent the spread of leukemic cells to the brain. Medicines are used to target leukemic cells in the layers of tissue that cover the brain and spinal cord (meninges) methotrexate, cytarabine, corticosteroids, or combinations thereof, which are usually injected directly into the cerebrospinal fluid, or high doses of these drugs may be injected intravenously. This chemotherapy can be combined with radiation therapy to the brain.

IN phase of consolidation and intensification the treatment of the bone marrow disease continues. Additional chemotherapy drugs, or the same drugs used during the induction phase, may be given multiple times over a period that lasts several weeks. Some patients at high risk of relapse due to certain chromosomal changes in leukemic cells are prescribed stem cell transplants after remission is achieved.

Further maintenance chemotherapy, which usually consists of taking fewer drugs (in some cases in smaller doses), usually lasts for 2-3 years.

Older adults with ALL may not be able to tolerate the intensive treatment regimen used in younger adults. In such patients, a more sparing treatment option can be used using only induction therapy regimens (without subsequent consolidation, intensification or maintenance therapy). Occasionally, some older people may be given immunotherapy or a more benign form of stem cell transplantation.

During all of the above phases, blood and platelet transfusions may be required to treat anemia and prevent bleeding, and antimicrobials may be required to treat infections. To help rid the body of harmful substances (such as uric acid) that are produced when broken down leukemic cells, intravenous fluids and treatment with allopurinol or rasburicase.

Relapse

The leukemic cells may start to appear again (this condition is called a relapse). They often form in the blood, bone marrow, brain, or testes. The early reappearance of such cells in the bone marrow is particularly severe. Chemotherapy is given again, and while many patients benefit from this repeated treatment, there is a high probability of repeated relapse of the disease, especially in children of the first year of life and adults. If leukemia cells reappear in the brain, chemotherapy drugs are injected into the cerebrospinal fluid once or twice a week. If leukemia cells reappear in the testicles, then along with chemotherapy, radiation therapy is given to the testicular area.

Administration of high doses of chemotherapy drugs in parallel with allogeneic stem cell transplantation ("allogeneic" means a stem cell transplant from another person) allows patients with relapse to get the best chance of cure. But transplantation can only be performed if stem cells can be obtained from a person with a compatible tissue type (with a compatible human leukocyte antigen [HLA]). The donors are usually brothers or sisters of the patient, but sometimes matching cells from donors that are not relatives (or, in rare cases, overlapping cells from family members or non-relatives donors, and umbilical stem cells). Stem cell transplantation is rarely performed in patients over 65, as there is much less the likelihood of obtaining a successful result and a high likelihood of side effects that turn out to be fatal.

Some patients with recurrent ALL are using promising new therapies using monoclonal antibodies (proteins that specifically bind to leukemic cells, labeling them for destruction). An even newer therapy that can be used in some patients with recurrent acute lymphoblastic leukemia is called chimeric antigen receptor T cell therapy (CAR-T). This therapy involves the modification of a specific type of lymphocyte (T-lymphocyte, also called T-cells) from a patient with leukemia so that these new T-lymphocytes better recognize and attack leukemic cells.

After relapse in patients unable to undergo stem cell transplant, adjunctive therapy often poorly tolerated and ineffective and usually results in severe deterioration well-being. However, remissions can occur. For patients who do not benefit from treatment, the option of caring for the terminally ill should be considered.

Life forecast

Before treatment was available, most patients with acute lymphocytic leukemia died within a few months of diagnosis. ALL can now be cured in about 80% of children and 30–40% of adults. In most patients, the first course of chemotherapy allows the disease to be brought under control (complete remission). The best prognosis for cure is available in children aged 3-9 years. Forecasts for children in the first year of life and elderly patients are less favorable. The number of leukocytes at the time of diagnosis, the presence or absence of leukemia spread to the brain, and chromosomal abnormalities in leukemic cells also affect the outcome of treatment.