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Pediatric Acute Lymphoblastic Leukemia
Disease information
Overview
Leukemia is a type of cancer where the bone marrow—the body’s blood cell factory—becomes overrun by abnormal, malignant cells known as leukemic blasts. This leads to serious health issues including severe anemia, increased risk of infections, and excessive bleeding, because the bone marrow can't make enough normal blood cells—red blood cells that deliver oxygen, white blood cells that fight infections, and platelets that help stop bleeding. Leukemia is classified into different types, such as acute or chronic, and further into myeloid or lymphoblastic leukemia, based on how quickly the disease develops and the kind of malignant cells involved. These classifications influence the symptoms, treatment options, and outlook for the patient.
Acute Lymphoblastic Leukemia (ALL) is a type of blood cancer characterized by the rapid growth of immature lymphoid cells in the blood, bone marrow, and sometimes other body tissues. It's the most common type of cancer in children, typically starting around age 2, with the highest incidence occurring between ages 3 to 6. In Korea, there are about 400 new cases of childhood leukemia each year, and two-thirds of these are ALL. While some cases of ALL in children may require hematopoietic stem cell transplantation, advances in treatment mean that most children can now achieve remission with chemotherapy alone, including combination chemotherapy and intrathecal chemotherapy to prevent the disease from affecting the central nervous system.
Causes and Symptoms
While extensive research has been conducted, the exact cause of leukemia remains elusive. However, various risk factors have been identified. In certain cases, genetic mutations or chromosomal abnormalities are present, but these are not found in all patients. Other potential contributing factors include viral infections, exposure to radiation, contact with organic solvents, and other environmental influences. Despite these associations, the specific cause of leukemia in each patient is often not determined.
- In individuals with hereditary conditions e.g.) such as Down Syndrome, which is characterized by having an extra copy of chromosome 21
- In cases where past chemotherapy or radiation therapy was received
- In cases of long-term exposure to toxic chemicals such as benzene, pesticides, paint, preservatives, insecticides, etc.
- In cases of exposure to large amounts of radiation e.g.) victims of atomic bombings during World War II, victims of the Chernobyl nuclear disaster in the former Soviet Union
Acute Lymphoblastic Leukemia (ALL) is a swift-moving disease that can cause severe symptoms such as high fever, anemia, and bleeding. These symptoms are due to the rapid spread of undifferentiated immature cells, known as blasts. Given the speed at which this disease progresses, it's crucial to diagnose and treat it as soon as possible to prevent a rapid decline in the patient's health.
Sometimes, the only symptoms of ALL might be bone and joint pain. This could easily be mistaken for growing pains in children or arthritis in adults. As the leukemia cells spread through the bloodstream, they may invade organs and cause additional symptoms. These can include enlarged lymph nodes, bulging eyes, vomiting, visual impairment, facial nerve paralysis, and difficulty breathing. In the early stages of diagnosis and treatment, there's a risk of renal failure due to a condition known as tumor lysis syndrome. This happens when a large number of leukemia cells are destroyed, releasing their contents into the bloodstream, which can overload the kidneys. This underscores the need for prompt and effective treatment to manage ALL and its potential complications.
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Symptoms stemming from bone marrow failure include a reduction in neutrophils, leading to increased infection risk; anemia, which can cause feelings of fatigue and weakness; and a decrease in platelets, making bruising or bleeding more likely. Patients often experience diminished appetite and may notice unintended weight loss. These signs are important indicators of bone marrow health and should be discussed with a Doctor.
- Neutropenia Symptoms of infection and fever due to decreased immunity.
- Anemia Symptoms include dizziness, headaches, difficulty breathing during physical activity, and pallor (pale skin)
- Thrombocytopenia Hemorrhagic symptoms such as gum bleeding, epistaxis, bruising, petechiae, and retinal hemorrhage
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The fast multiplication of leukemia cells in the bone marrow can cause pain in areas such as the sternum, ribs, and long bones. If the white blood cell count, or leukocyte count, in the blood reaches very high levels, over 100,000/mm³, it can make the blood thicker. This increased blood viscosity can lead to serious conditions, including bleeding in the brain (central nervous system hemorrhage) and blood clots (thrombosis). It can also result in changes in mental state, breathing problems, and other signs of leukostasis—a medical emergency where high numbers of white blood cells block blood vessels. These symptoms are serious and require prompt medical intervention.
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Leukemia cells can spread from the bone marrow to other parts of the body, which often results in enlarged lymph nodes and an increase in the size of the liver and spleen, a condition referred to as hepatosplenomegaly. When these cells grow within the bone, it can cause bone and joint pain. If the leukemia cells reach the central nervous system, they can cause headaches, vomiting, vision problems, and symptoms resembling those of meningitis. There can also be facial nerve paralysis and issues with the cranial nerves, leading to ptosis (drooping of the eyelid) and diplopia (double vision). For male patients, the testicles may also be affected.
Treatment
Acute Lymphoblastic Leukemia (ALL) is primarily treated with chemotherapy. Hematopoietic stem cell transplantation is reserved for situations where there are negative prognostic indicators, an elevated risk of the cancer returning, or if the cancer has returned after initial treatment.
To achieve complete remission in Acute Lymphoblastic Leukemia (ALL) — which means that the symptoms present at diagnosis have subsided, normal blood cell counts have been restored in the peripheral blood, and leukemia cells make up less than 5% of cells in the bone marrow — a combination of three or more anticancer drugs is typically administered for about 4 weeks following diagnosis. This treatment approach successfully induces remission in over 95% of patients.
After induction therapy leads to primary complete remission in Acute Lymphoblastic Leukemia (ALL), there are often still leukemia cells that remain undetectable under a microscope, known as minimal residual disease. Without further treatment, relapse is almost certain.
To prevent the return of the disease, ongoing treatment is essential. The comprehensive treatment plan includes several phases: Induction, to start remission; Consolidation, to reduce the number of leukemia cells; Interim Maintenance, to control cancer growth; Delayed Intensification, to eliminate any remaining leukemia cells; and Maintenance, to prevent leukemia from returning. Central nervous system prophylaxis, which involves administering anticancer drugs directly into the spinal fluid, is also a critical component of this process. Overall, the treatment spans approximately three years.