Acute Lymphoblastic Leukemia Its Symptoms, Causes, Diagnosis, And Treatment

Acute lymphoblastic leukemia (ALL) appears at any age, but it is the most common cancer in children, accounting for 75% of all leukemias in children under 15 years of age. Symptoms of Acute lymphoblastic leukemia most often affect children between 2 and 5 years of age. In adults, it is relatively more frequent after 45 years of age.

In acute lymphoblastic leukemia, very immature leukemia cells accumulate in the bone marrow, destroying and replacing those that make normal blood cells, including one or more of the following:

• Red blood cells. They carry oxygen in the bloodstream
• White blood cells or leukocytes (the cells that defend us against infection)
• Platelets, small cell-like particles that are involved in the clotting process

Cancerous white blood cells don’t work like normal white blood cells, so they can’t help the body fight infection.

The bloodstream also carries leukemia cells to the liver, spleen, lymph nodes, brain, and testicles, where they can continue to grow and divide. However, acute lymphoblastic leukemia cells can accumulate anywhere in the body. They can spread to the membrane covering the brain and spinal cord (leukemic meningitis) and can also cause anemia, liver and kidney failure, and damage to other organs.

Symptoms Of Acute Lymphoblastic Leukemia

The early symptoms of acute lymphoblastic leukemia result from the bone marrow’s inability to make enough normal blood cells.

• Fever and excessive sweating may indicate an infection, which may be caused by too few normal white blood cells.
• Weakness, fatigue, and paleness may be caused by too few red blood cells (anemia). Some people may experience shortness of breath, tachycardia, or chest pain.
• Tendency to bruise and to bleed, sometimes in the form of a nose bleed or bleeding gums, may be a consequence of a low number of platelets (thrombocytopenia). In some cases, people can bleed inside their brains or abdomen.

Other symptoms of acute lymphoblastic leukemia occur when leukemia cells invade other organs.

• Leukemia cells in the brain can cause headaches, vomiting, stroke, and disturbances in vision, balance, hearing, and facial muscles.
• Leukemia cells in the bone marrow can cause bone and joint pain.
• When leukemia cells enlarge the liver and spleen, abdominal fullness and sometimes pain are experienced.

Causes Of Acute Lymphoblastic Leukemia

Acute lymphocytic leukemia occurs in the case of a ‘cell containing bone marrow. Leukemia emerges if it develops ‘changes’ called mutations in its genetic material or DNA. A cell’s DNA consists of the instructions and guides it for its roles. The DNA suggests the cell grows at a set rate normally. Further, it guides to die at a specific timelapse. The mutations direct the bone marrow cell to continue growing and dividing in acute lymphocytic leukemia.

The bone marrow produces immature cells. They develop into ‘leukemic white blood cells.’ Doctors call them lymphoblasts. The said uncommon cells could not function properly and build up and crowd out healthy cells. 

It’s unclear what causes the DNA mutations. They lead to acute lymphocytic leukemia. When it happens, we notice blood cell production becomes ‘out of control.

Diagnosis Of Acute Lymphoblastic Leukemia

Two types of tests are there to confirm these diseases: blood tests and bone marrow exams.

Blood tests, viz., a complete blood count, provide the first evidence of acute lymphoblastic leukemia. We may come across the total number of white blood cells (WBCs), which can be low, normal, or high. However, the number of red blood cells (RBCs) and platelets are almost always below their normal values. In addition, immature white blood cells (blasts) are present in the blood.

An examination of the bone marrow is almost always done to confirm the diagnosis and differentiate acute lymphoblastic leukemia from other types of leukemia. The analysis of the blasts allows for detecting chromosomal abnormalities, which helps doctors determine the exact type of leukemia and what drugs to treat it.

Doctors conduct Blood and urine tests to study for other abnormalities, including whether the leukemia cells have affected other organs.

Imaging tests may also be necessary. A computed tomography (CT) scan or magnetic resonance imaging (MRI) is done if the person has symptoms that indicate the presence of leukemia cells in the brain. They may do computed tomography (CT) scan of the chest to check for leukemia cells around the lung area. They may also perform a CT, MRI, or abdominal ultrasound when they find the ‘enlargement of internal organs.’ Before starting chemotherapy, they perform an echocardiogram (ultrasound of the heart) because chemotherapy sometimes affects the heart.

Prognosis Of Acute Lymphoblastic Leukemia

Before treatment became available, most people with acute lymphoblastic leukemia died within months of diagnosis. Currently, almost 80% of children and between 30 and 40% of adults with this disease are cured. In most cases, the first course of chemotherapy achieves control of the disease (complete remission). Children 3 to 9 years of age have the best prognosis; infants and older adults do not respond as well to treatment. The number of white blood cells (leukocytes) at diagnosis, whether or not leukemia has spread to the brain, and specific chromosomal abnormalities in the leukemia cells also influence prognosis.

Treatment Of Acute Lymphoblastic Leukemia

Treatment consists of

• Chemotherapy
• Other medications, such as immunotherapy and/or targeted therapy
• In rare cases, stem cell transplant or radiation therapy

Chemotherapy As A Treatment For Leukemia

Chemotherapy is highly effective. Doctors administer it in several phases:

• Induction
• brain treatment
• taking up the process of ‘Consolidation and intensification.’
• Maintenance

Induction of ‘chemotherapy’ is the first phase of the treatment. Inducting chemotherapy aims at achieving remission by destroying the leukemia cells so that normal cells can regrow in the bone marrow. People receiving chemotherapy may require hospitalization for a few days or weeks, depending on how quickly the bone marrow recovers.

Various combinations of drugs are commonly used, with doses repeated over several days or weeks. The specific combination depends on the results of diagnostic tests. One of these combinations involves giving prednisone by mouth and weekly doses of vincristine along with an anthracycline, asparaginase, and sometimes cyclophosphamide, given intravenously. Immunotherapy can be used in some patients with acute lymphocytic leukemia (ALL) and targeted therapy.

Brain treatment usually begins during induction and can continue during all phases of treatment. Because there is a chance that acute lymphoblastic leukemia will spread to the brain, treatment focuses on leukemia that has spread to the brain or preventing the spread of leukemia cells to the brain. When there are leukemia cells in the membranes that cover the brain and spinal cord, treatment involves injecting methotrexate, cytarabine, corticosteroids, or a combination of them directly into the spinal fluid or by giving high doses through a vein of these drugs. Doctors may combine chemotherapy with radiation therapy for the brain.

Bone marrow disease continues to be treated in the consolidation and intensification phases. Some drugs used during the induction phase, or additional drugs, may be given multiple times over many weeks. For some people at high risk of relapse due to specific chromosomal abnormalities found in their leukemia cells, stem cell transplantation is recommended once remission occurs.

Subsequent maintenance chemotherapy, which usually involves using fewer drugs, sometimes at lower doses, usually continues for 2 to 3 years.

Older people with acute lymphoblastic leukemia may not be able to tolerate the intensive regimen used for younger people. In these people, milder induction regimens alone (without subsequent consolidation, intensification, or maintenance) are an option. Sometimes immunotherapy or a milder form of stem cell transplant may be an option in some older people.

During all of the above phases, blood and platelet transfusions may be necessary to treat anemia and prevent bleeding, as well as antimicrobials to treat infections. The use of intravenous fluids and treatment with allopurinol or rasburicase can also help the body remove harmful substances, such as uric acid, that are released when leukemia cells are destroyed.

Recurrence (relapse)

Leukemia cells can return over time (relapse) in the blood, bone marrow, brain, or testicles. Its rapid reappearance in the bone marrow is particularly serious. Although most people respond positively to repeated treatment, the disease tends to recur, especially in infants and adults. In the case of relapse, chemotherapy is given again. When leukemia cells return to the brain, an anticancer (chemo) drug is injected into the spinal fluid once or twice a week. If leukemia recurs in the testicles, radiation therapy to the testicles is given in combination with chemotherapy.

For people who have relapsed, high-dose chemotherapy and an allogeneic stem cell (progenitor cell) transplant offer the best chance of cure. However, the transplant can only be done if the stem cells are obtained from a person with a compatible tissue type (HLA match )., human leukocyte antigen). The donor is usually a brother or sister, although matched cells from unrelated donors, or partially matched cells from family members or unrelated donors, or umbilical cord stem cells are sometimes used. Progenitor cell (stem cell) transplantation is rarely performed in people over 65 because it is less likely to be successful and increases the risk of fatal side effects.

Monoclonal antibody therapies (proteins that specifically bind to leukemia cells and mark them for destruction) are also being used in people with relapsed acute lymphoblastic leukemia. Chimeric antigen receptor T-cell (CAR-T) therapy may be used in some people with relapsed acute lymphocytic leukemia (ALL). This therapy involves modifying a type of lymphocytes (T lymphocytes, also called T cells) from the person with leukemia so that the new T cells recognize and attack the leukemia cells.

The additional treatment required after a relapse in people not candidates for stem cell transplantation is often poorly tolerated and ineffective, making people even sicker. Patients who do not respond to the said treatment should consider end-of-life (palliative) and other care. However, they can obtain referrals.