Leukemia is a type of cancer that begins in the blood-forming tissues, such as the bone marrow. It involves the rapid production of abnormal blood cells, typically white blood cells, which do not function correctly. These abnormal cells can crowd out healthy blood cells, leading to various health issues. While leukemia primarily affects the blood and bone marrow, it can sometimes spread to other parts of the body, including the central nervous system (CNS). When leukemia cells infiltrate the CNS, it can lead to unique challenges in diagnosis and treatment.
How Leukemia Spreads to the Brain
Leukemia cells originate in the bone marrow but can travel through the bloodstream. The central nervous system is typically protected by the blood-brain barrier, a network of tightly packed cells that restrict the passage of substances from the blood into the brain and spinal cord. However, leukemia cells have developed ways to bypass or cross this barrier.
Research indicates that acute lymphoblastic leukemia (ALL) cells may not directly breach the blood-brain barrier. Instead, they can migrate along tiny blood vessels that pass directly from the vertebral bone marrow into the meninges. These cells possess specific receptors, like alpha six integrin, that allow them to attach to proteins such as laminin, which are found on these blood vessels, facilitating their entry into the cerebrospinal fluid. While less common, acute myeloid leukemia (AML) cells can also infiltrate the CNS, though the mechanisms may differ, sometimes involving trans-endothelial migration. CNS involvement is more frequent in ALL, affecting about 5% of adults at initial diagnosis, compared to AML where it is rarer.
Symptoms of Central Nervous System Leukemia
When leukemia spreads to the brain or spinal cord, it can cause a range of neurological symptoms. Symptoms often depend on the specific area of the CNS affected and the extent of the infiltration. One common set of symptoms arises from increased intracranial pressure. This can manifest as persistent headaches, nausea, and vomiting.
Focal neurological deficits can also occur, meaning problems in specific body parts due to damage to particular nerve pathways. These might include weakness or numbness in the limbs, difficulty with balance, or changes in vision. For example, a person might experience double vision or blurred vision. Cognitive changes are another possibility, leading to confusion, memory problems, or alterations in mood and behavior.
Seizures can result from the direct irritation of brain tissue by leukemia cells. The infiltration of cranial nerves, which control functions like facial movement, eye movement, hearing, and swallowing, can lead to specific palsies. For instance, facial nerve palsy, causing weakness or drooping on one side of the face, is a rare presentation. If the spinal cord is involved, symptoms may include back pain, weakness in the legs or arms, numbness, or issues with bladder or bowel control.
Diagnosis and Treatment Approaches
Diagnosing central nervous system leukemia involves a combination of methods to detect the presence of leukemia cells. A primary diagnostic tool is a lumbar puncture. During this procedure, a small needle is inserted into the lower back to collect a sample of cerebrospinal fluid (CSF). This CSF sample is then analyzed for the presence of leukemia cells, often using conventional cytology or more sensitive methods like flow cytometry.
Imaging techniques, such as magnetic resonance imaging (MRI) or computed tomography (CT) scans, are also used. These scans can help identify any masses or areas of infiltration within the brain or spinal cord, though they may have limitations in detecting subtle infiltrations. If neurological symptoms are present, radiological examination is often performed to rule out issues like bleeding or mass effects before a lumbar puncture.
Treatment for CNS leukemia aims to eliminate leukemia cells from the central nervous system and prevent their recurrence. One of the main strategies is intrathecal chemotherapy, where anti-cancer drugs are delivered directly into the cerebrospinal fluid, often during a lumbar puncture. Common chemotherapy agents used this way include methotrexate and cytarabine. Systemic chemotherapy, which is administered intravenously, is also employed, particularly with drugs that can cross the blood-brain barrier to reach the CNS. Radiation therapy, such as cranial or craniospinal irradiation, may be used, particularly in cases where intrathecal chemotherapy has not been fully effective or for overt CNS disease. While effective, radiation therapy carries potential long-term side effects, prompting efforts to reduce its use, especially in children.
Prognosis and Long-Term Management
The prognosis for individuals with central nervous system leukemia can vary significantly, depending on several factors. These factors include the specific type of leukemia, the person’s age, how well the leukemia responds to treatment, and the extent of CNS involvement at diagnosis. For example, pediatric patients with CNS leukemia often have a higher overall survival rate compared to adults. Achieving remission of systemic leukemia and having CNS leukemia diagnosed and treated before an allogeneic transplantation are also associated with better outcomes.
Ongoing monitoring is a crucial part of long-term management to detect recurrence. This typically involves regular clinical evaluations and repeat lumbar punctures to check the cerebrospinal fluid for leukemia cells. Managing potential long-term side effects of treatment is also important. These can include neurocognitive effects, such as thinking, memory, or learning issues, particularly after radiation therapy. The development of secondary cancers is another potential long-term risk associated with some treatments. A multidisciplinary team, including oncologists, neurologists, and other specialists, provides comprehensive supportive care to address these varied needs and improve the person’s quality of life.