What is Acute Lymphocytic Leukemia?
Acute lymphocytic leukemia (ALL) is a cancer that affects B or T lymphoblasts. These are the cells responsible for creating lymphocytes, a type of white blood cell. ALL involves these cells growing uncontrollably and immaturely, eventually taking over the bone marrow and other lymphoid organs. This process creates a disease pattern that is characteristic of ALL. This type of cancer makes up about 2% of the lymphoid cancers diagnosed in the United States. ALL is slightly more common in men than in women, and occurs three times more often in Whites than in Blacks.
People with ALL usually experience symptoms relating to anemia, thrombocytopenia, and neutropenia. This happens because the growing cancer replaces the bone marrow. Common symptoms include fatigue, easy or spontaneous bruising and bleeding, and frequent infections. Some patients also have ‘B-symptoms’ such as fevers, night sweats, and unintentional weight loss, although these may be mild. Liver and spleen enlargement, along with swollen lymph nodes, can be observed in up to half of adults when they are diagnosed. Many patients also have symptoms relating to the central nervous system. These may be due to pressure on the cranial nerves or other symptoms (mostly meningeal) caused by increased pressure inside the skull.
What Causes Acute Lymphocytic Leukemia?
The exact cause of a type of cancer called acute lymphocytic leukemia isn’t clear. Some environmental factors, like exposure to benzene, radiation, or previous chemotherapy or radiotherapy, might play a role in causing it.
Some studies on our genes have found that tiny changes in certain genes (ARD5B, IKZF1, and CDKN2A) might increase the chances of getting this type of leukemia. Other less common gene changes in PAX5, ETV6, and especially p53 can also make a person more likely to develop this cancer.
Acute lymphoblastic leukemia is not generally a disease that runs in families, and there are no established screening programs to test for it in children.
Risk Factors and Frequency for Acute Lymphocytic Leukemia
Acute Lymphocytic Leukemia, or ALL, is a type of cancer that is most common in children, typically diagnosed in about 4000 people in the United States each year, most of whom are under 18. The most common age for a diagnosis of ALL is between two and ten years old.
Kids with certain genetic conditions, such as Trisomy 21 (Down syndrome), neurofibromatosis type 1, Bloom syndrome, and ataxia telangiectasia, are more likely to develop ALL, particularly between the ages of two and three.
Unfortunately, if ALL is diagnosed in babies less than one year old or in adults, the outlook isn’t as good. However, for children the prognosis is usually more positive. But if the child has a change in the MLL gene on the 11q23 chromosome, the prognosis may not be as good.
The overall incidence of ALL is low, with about 3.3 cases diagnosed per 100,000 children. But there’s good news – survival rates for ALL have improved dramatically since the 1980s. Today, more than 85 percent of people diagnosed with ALL are expected to live at least five years after diagnosis.
Signs and Symptoms of Acute Lymphocytic Leukemia
Acute lymphocytic leukemia, commonly found in children, can present symptoms that are also common in less severe illnesses. This sometimes makes it challenging to identify. Children with this condition often display signs such as an enlarged liver, an enlarged spleen, paleness, fever, or bruising. Additional symptoms may include:
- Night sweats
- Easy bruising
- Paleness
- Unexplained swollen lymph nodes
- Fatigue
- Weight loss
- Enlarged liver or spleen
- Difficulty breathing
- Superior vena cava syndrome (a condition where the large vein carrying blood to the heart is obstructed)
- Bone pain
- Changes in mental state
- Decreased urine output
- Testicular enlargement
- Musculoskeletal pain
- A mass in the chest area
- Abnormalities in a routine blood count
Testing for Acute Lymphocytic Leukemia
To investigate a possible diagnosis of Acute Lymphocytic Leukemia, initial steps include various laboratory tests. These tests could include a Complete Blood Count (CBC), checks on electrolyte levels and kidney function, and a measurement of LDH levels in the blood. Imaging might also be used, like a chest x-ray if the patient is experiencing shortness of breath. If someone exhibits symptoms such as a feeling of fullness in the abdomen, tenderness, or a detectable mass, a CT scan of the lower torso might be needed. This scan can also assist in determining the progression of the disease.
The official diagnosis guidelines from the National Comprehensive Cancer Network involve several steps:
Having more than 20% bone marrow lymphoblasts (immature white blood cells in the bone marrow) is one sign of leukemia. Additionally, a test called a biopsy will be taken of the bone marrow, and stained with a special dye to make it easier to see the cells. Morphology, or the study of the form and structure of organisms, will be applied to the bone marrow. Comprehensive analysis of the immune markers on the cells will be performed. An evaluation of the unique features of the leukemia cells will also be conducted.
If there’s worry about the disease affecting the Central Nervous System (CNS), a procedure known as a lumbar puncture might be used. This involves taking a sample of the fluid around the brain and spinal cord and then checking it for the presence of immature white blood cells.
Treatment Options for Acute Lymphocytic Leukemia
If a child is suspected of having Acute Lymphocytic Leukemia (ALL), they should be sent to a pediatric center that specializes in cancer for a thorough assessment and appropriate treatment.
The initial treatment for children with ALL involves a group of drugs called induction therapy. This includes drugs like anthracycline, vincristine, 1-asparaginase, and a type of steroid.
Once the induction therapy is completed, a variety of other drugs are then used as part of a consolidation therapy. This therapy has shown positive results.
Maintenance therapy is used to maintain these positive results, usually using oral medications, given either weekly or monthly. Typically, the entire treatment plan including induction, consolidation and maintenance therapy takes about two to three years to complete.
Additionally, therapies that target the central nervous system (CNS) are also part of the treatment plan, usually involving 8 to 16 treatments directly into the spinal canal. This is known as CNS prophylaxis.
If the ALL is associated with a change in the chromosomes called Ph-positive, certain special drugs like tyrosine kinase inhibitors are used. These might include imatinib, nilotinib, dasatinib, or ponatinib. These have shown to be very effective in trials.
In some cases, stem cell transplantation – replacing unhealthy blood cells in the bone marrow with healthy ones from a donor – may be used. But with progress in chemotherapy, stem cell transplantation has taken a back seat in ALL treatment.
A recent therapy known as CAR-T cell therapy has shown very high rates of sending the disease into remission. However, it does carry a risk of severe side effects.
All blood products given to the patient need to be irradiated beforehand to avoid a serious condition called graft versus host disease.
It is very rare that a child with ALL would need to have their spleen removed. Removal can increase the number of platelets in the blood but doesn’t directly affect the outcome of leukemia. But if the child has severe symptoms, like abdominal pain, that aren’t responding to treatment, a splenectomy might be considered. Radiation can also be used to shrink the spleen if it’s too large.
Finally, children with ALL need to be monitored for a life-threatening complication called tumor lysis syndrome. This can happen when chemotherapy treatment causes a rapid release of cell contents into the blood, potentially leading to kidney failure.
What else can Acute Lymphocytic Leukemia be?
- B cell lymphoma (a type of cancer that starts in white blood cells)
- Acute myeloid leukemia (a cancer of the blood and bone marrow cells)
- Non-Hodgkin lymphoma (a type of cancer that originates in your white blood cells)
What to expect with Acute Lymphocytic Leukemia
As of now, only 30% of adults with Acute Lymphoblastic Leukemia (ALL) can be fully cured. Some criteria might suggest a good prognosis, or a better chance of recovery, including:
* Being younger than 30 years old.
* Not having abnormal changes in your chromosomes (cytogenetics).
* Having a White Blood Cell (WBC) count of fewer than 30,000 cells.
* Achieving complete recovery from the disease within 4 weeks.
* Having a high number of extra chromosomes (51-65) in children.
* Having a specific gene arrangement (t(12;21)(p13;q22)) in children.
On the other hand, some factors point at a poor prognosis, or a greater difficulty in recovery:
* Being more than 60 years old.
* Having abnormal changes in your chromosomes, particularly t(9:22), or t(4:11).
* Not being able to achieve recovery from the disease within 4 weeks.
* Having more than 100,000 precursor B-cells (early form of a type of white blood cell).
