Acute Lymphoblastic Leukemia (ALL)
Characteristics
Acute lymphoblastic leukemia (ALL) develops from early forms of lymphocytes, one of the main types of white blood cells. Genetic mutations in the DNA of these precursor cells result in an uncontrolled production of immature lymphocytes, gradually replacing the normal cells in the bone marrow.
ALL is a rare form of cancer, with about 160 new cases in Belgium in 2020. While also adults can develop ALL, it is most often diagnosed in children. In fact, ALL is the most common type of cancer in children under the age of 4.
For most patients with ALL, the cause of the disease is unclear. However, several factors have been identified that increase the risk for ALL, including certain rare inherited conditions (e.g., Down’s syndrome, Fanconi Anemia), previous treatment with chemotherapy and exposure to radiation or benzene
Symptoms
The symptoms of ALL can be vague and often mimic other, less serious conditions. In general, ALL symptoms develop quickly, within a couple of days or weeks. These symptoms can include a general feeling of weakness and fatigue, paleness, a high temperature, flu-like symptoms, weight loss, and a tendency to easily pick up infections such as coughs or colds. Patients with ALL may also be prone to bleeding (e.g., nose bleeds, swollen and bleeding gums, prolonged bleeding from minor cuts) and bruising and can suffer from joint pain, or breathlessness. In addition, lumps caused by swollen lymph nodes can occur in the neck, armpits, abdomen, or groin.
Diagnostic tests
When ALL is suspected, a blood test will be performed to measure the number of red blood cells, white blood cells and platelets in the blood. Most patients with ALL have too many immature white blood cells (lymphoblasts), and not enough red blood cells or platelets. While these findings may suggest ALL, a definite diagnosis usually requires a bone marrow test. To this end, a bone marrow sample is removed from the hipbone or sternum (breastbone) and sent to the lab for a further evaluation of the size, shape, and molecular and genetic features of the cells in the bone marrow. These tests allow physicians to determine the exact ALL subtype, which has an impact on the prognosis and the subsequent treatment plan.
In addition to this, a lumbar puncture is often performed to assess whether the ALL has spread to the brain or spinal cord. Usually, leukemia does not form tumors and, as a result, medical imaging tests (X-rays, CT-scans, MRI, ultrasound) are less important in the diagnostic work-up of ALL than for solid tumors. However, for some patients where the ALL is suspected to have spread beyond the blood and bone marrow, imaging tests can be requested.
Treatments
Patients who are diagnosed with ALL need treatment as soon as possible. The main treatment for patients with ALL consists of chemotherapy, which is usually given in three phases. The goal in the induction phase is to get the leukemia into a (complete) remission. This means that leukemia cells can no longer be found in bone marrow samples. During the consolidation phase, a short course of intensive chemotherapy is used to destroy any remaining leukemia cells in the body. In a proportion of patients, a stem cell transplantation can be used as consolidation therapy. The third phase in the first line treatment of ALL patients is referred to as maintenance therapy. In this phase, the main objective is to prevent the leukemia from growing back. This treatment phase usually takes longer (years), but the chemotherapy doses that are used are much lower than in the first 2 treatment phases.
During each treatment phase, patients may receive additional treatment to kill leukemia cells in the central nervous system. This treatment can consist of chemotherapy injected directly into the fluid that covers the spinal cord, or radiation therapy to the brain or spinal cord.
In patients harboring the so-called ‘Philadelphia chromosome’, a genetic rearrangement resulting in the creation of the BCR-ABL fusion gene, a targeted agent (e.g., imatinib, or dasatinib) can be added to chemotherapy across the different treatment phases.
Some patients have residual leukemia cells in their bone marrow after they receive intensive chemotherapy. In these cases, the disease is referred to as being “refractory”. Other patients may achieve a remission but later experience a return of leukemia cells in their bone marrow. This is referred to as a “relapse” of the disease. While relapsed/refractory ALL is generally more difficult to treat, several new treatment options have emerged in recent years. For these patients, physicians can opt for more chemotherapy (followed by a stem cell transplantation in case a remission is obtained), targeted therapy, or immunotherapy with bispecific antibodies, antibody-drug conjugates, or CAR-T cell therapy. In addition to this, enrollment into a clinical trial can be considered.
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