What You Should Know About Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. While childhood cancer rates have been increasing, the death rate has decreased. The National Cancer Institute estimates that 6,150 new cases of ALL will be diagnosed in the United States this year. This article will review what you should know about acute lymphoblastic leukemia: what it is, who is at risk and how it can be diagnosed and treated.

What is acute lymphoblastic leukemia?

Acute lymphoblastic leukemia is cancer that affects the white blood cells (WBCs). Bones have spongy tissue inside that is called bone marrow. Blood cells form in the bone marrow. These cells can become either a myeloid stem cell or a lymphoid stem cell.

Lymphoid stem cells first become lymphoblast cells and then lymphocytes, or white blood cells. These cells can become any of the following:

1. B lymphocytes create antibodies that help fight infection.
2. T lymphocytes help B lymphocytes make antibodies.
3. Natural killer cells attack cancer cells and viruses.

ALL can result from these cells growing out of control. ALL is classified by the type of WBC affected and the genetic abnormalities that occur. This childhood cancer, also known as acute lymphocytic leukemia, can also affect adults.

What are other subtypes of acute lymphocytic leukemia (ALL)?

In 1976, a group of French, American and British (FAB) leukemia cancer research experts gathered together to break ALL into subtypes based on how the cells looked under the microscope following routine staining. This FAB classification system divides acute lymphoblastic leukemia types into:

• L1: small uniform cells
• L2: large varied cells
• L3: large varied cells with vacuoles (bubble-like features)

The World Health Organization (WHO) eventually recommended that the FAB classification be rejected because it had no relationship to the prognosis. The WHO scientists created more precise subdivisions based on the type of WBC that is cancerous and other characteristics. By identifying ALL with the WHO’s system, your cancer care team can better plan treatment. There are 3 subtypes:

1. Precursor B cell ALL: Most common type in adults
2. Precursor T cell ALL: More likely to affect young adults and men
3. Mature B cell ALL (Burkitt type ALL): Identified by specific genetic changes

Philadelphia chromosome-like ALL (Ph-like ALL) is a precursor B-cell ALL that results in a change of the chromosomes on the leukemia cells. Normal cells in your body have 23 pairs of chromosomes and grow and divide at a set rate, but Ph-like ALL results in a gene breaking off chromosome 9 and sticking to chromosome 22. This new gene causes the cell to make too much of a protein that encourages leukemia cells to proliferate. The Philadelphia chromosome is present in 20-30% of ALL.

B-cell acute lymphoblastic leukemia is a fast-growing subtype where an excess of immature WBCs, known as B-cell lymphoblasts, are in the bone marrow and blood. These subtypes are differentiated by genetic differences in the leukemia cells. Normal cells have 46 chromosomes.

There are many different types of B-cell ALL with genetic changes, such as changes in the number of chromosomes or too many replications.

T-cell acute lymphoblastic leukemia (T-ALL) has features like some types of lymphoma. The National Cancer Institute defines it as a fast-growing type of blood cancer where too many immature blood cells (T-cell lymphoblasts) are in the blood and bone marrow. Early T-cell precursor lymphoblastic leukemias are a type of T-ALL that have been historically associated with a poor prognosis.

How do you get acute lymphoblastic leukemia?

ALL occurs when the bone marrow cell has DNA errors. Healthy DNA tells the cell to grow and divide until a certain point, where these DNA errors tell the cells to continue to grow and divide.

The blood cell production becomes abnormal, and the bone marrow produces too many cells called lymphoblasts. These cells do not function properly and crowd out the healthy cells. Scientists are unsure what causes these types of genetic mutations, but most cases of ALL are not inherited. Having 1 or more of the following factors increases your risk for ALL, but many people with ALL do not have any of these risk factors.

Potential risk factors for ALL include:

• Exposure to chemotherapy or radiation therapy during a prior cancer treatment
• Exposure to high levels of radiation such as that experienced during any nuclear incidents
• Genetic conditions such as Down syndrome
• Having a sibling, including a twin, with ALL

Can acute lymphoblastic leukemia be found early?

There are no tests to detect ALL early, which is why it is critical to pay attention to your body for any possible symptoms. Reporting these possible symptoms to a medical professional will get you early screening tests as soon as possible. Many of these symptoms are not specific for ALL and will need further examination.

After reporting concerns to the healthcare provider, they will perform a medical history and physical exam, lab work and blood smears. If the blood work comes back with an elevated number of WBCs and lymphoblasts in the circulating blood, it may mean the blood marrow is producing a lot of lymphoid cells.

Most patients with ALL will have a bone marrow aspiration and biopsy to confirm the diagnosis and to determine the specific type of leukemia that the patient has. A chest X-ray and scans will often be taken to look for swollen lymph nodes or cancer cells spreading to other affected sites. Sometimes the leukemia cells are in the brain and spinal cord fluid also known as cerebrospinal fluid (CSF).

Acute lymphoblastic leukemia symptoms can seem vague and nonspecific. Signs and symptoms of ALL include:

• Fatigue, weakness
• Generally feeling unwell or loss of energy
• Dizzy or lightheaded
• Shortness of breath, difficulty breathing
• Pale skin
• Recurring or persistent infections
• Bruising
• Fever or sweats
• Palpitations
• Small, reddened spots on the skin
• Increased bleeding (nosebleeds, gums, increased menstrual bleeding)
• Weight loss
• Loss of appetite
• Bone or joint pain
• Swelling or lumps in lymph nodes (neck, underarm, abdomen, groin)

Can adults get acute lymphoblastic leukemia?

Acute lymphoblastic leukemia in adults is much less likely than in children. Annually, ALL accounts for ⅕ of all cases of acute leukemia in adults older than 20 years old. In fact, 2 in 100,000 people in the United States have a lifetime risk of being diagnosed with ALL.

What is the treatment for acute lymphoblastic leukemia?

Acute lymphoblastic leukemia treatment has many options for cancer treatments. The treatment of ALL is tailored to the individual based on their age, disease progression and subtype.

The main treatment for ALL in adults is usually chemotherapy courses that have improved outcomes in this population. Chemotherapy is a cell-killing drug. Unfortunately, these intense regimens are more likely to cause problematic side effects, like low WBCs. Chemotherapy is often used in conjunction with steroids like prednisone.

Stem cell transplant may also be a treatment option. This entails infusing healthy stem cells provided by a donor into the patient’s bloodstream. The new healthy cells can help rebuild a healthy immune system in the patient.

CAR T-cell therapy is also a treatment option. This innovative approach involves extracting the patient’s T cells, reengineering them in a lab to recognize and fight cancer cells, expanding those supercharged cells, and returning them to the patient’s body.

Phases of ALL treatment

Remission induction

Induction chemotherapy aims to get ALL into remission, meaning that the cancer cells are not in bone marrow cells, the normal marrow cells return, and the WBCs normalize. This phase of treatment lasts 1 month or so and uses different combinations of chemotherapy drugs, including:

• Vincristine
• Steroids like dexamethasone or prednisone
• Anthracycline drug like doxorubicin or daunorubicin
• Other medications. For example, oncologists treat Philadelphia chromosome positive ALL with a targeted cancer drug known as imatinib or dasatinib. These drugs block the growth of the protein that encourages leukemia cells to proliferate.

Unfortunately, remission does not necessarily mean a cure, as the cancer cells can hide elsewhere in the body.

ALL often goes into remission with induction chemo, but further treatment may be needed throughout the other phases to prevent the leukemia cells from spreading.

Acute lymphoblastic leukemia treatment options include:

• Intrathecal chemotherapy: Injections directly into the spinal fluid with methotrexate or cytarabine, and it can be paired with prednisone. This type is typically given through a lumbar puncture (spinal tap).
• Intravenous drugs given in high doses: Methotrexate or cytarabine are given.
• Radiation therapy: This treatment uses high-energy radiation to kill cancer cells before a stem cell transplant or if the cancer has spread.
• Stem cell transplant, Healthy cells, often from a donor, are infused into your body to reestablish a healthy blood supply.

Consolidation or intensification

If the leukemia is in remission, next comes a course of chemotherapy with similar drugs as induction therapy. This phase lasts for a few months, but the treatment is still provided in fairly high doses. Any CNS or Philadelphia chromosome treatment continues during this phase.

Despite remission, certain subtypes of ALL are still at risk for the leukemia coming back. A stem cell transplant, also known as a blood or bone marrow transplant, may restore damaged bone marrow.

Radiation therapy may be used before a stem cell transplant. Doctors can perform the transplant using your own or donor stem cells, dependent upon the specifics of your condition. Clients should carefully weigh the risks and benefits of this procedure.

Maintenance

Maintenance lasts 2 years. The maintenance chemo program typically involves methotrexate, 6-mercaptopurine (6-MP), and may incorporate other chemo agents or steroids.

For those with CNS prophylaxis/treatment or whose leukemia cells have the Philadelphia chromosome, the drugs are continued as well.

Some people with ALL may consider participating in clinical trials, which are medical research studies, with the advice of their oncologist (cancer doctor). These clinical trials are medical research studies and may also focus on better processes for screening, diagnosing and using new or revamping existing treatments for ALL.

What is the survival rate for acute lymphoblastic leukemia?

The National Cancer Institute (NCI) estimates that 6,150 new cases of ALL will be diagnosed this year, yet 1,520 people will die from it. Because these numbers seem overwhelming, learning about the acute lymphoblastic leukemia prognosis is among the first steps newly diagnosed families take.

While acute lymphoblastic leukemia in children is more common than other types of cancer, it has high cure rates. Survival rates are lower in adults, but they are improving. The 5-year relative survival rate for ALL is 68.8%. The statistics further break down to 90% in children and 30-40% in adults.

Other factors influence survival.

• Age: The NCI determined that older adults and children have a poorer prognosis. Those with ALL have a better likelihood of survival if adults are younger than 35 years old and children are under 10 years old.
  
• Type: Some types of ALL have a higher survival rate than others.
• Treatment response: People who respond more quickly typically have a better outcome.
• WBC count: Those with a lower T-cell (less than 10,000) or B-cell (less than 30,000) count have a better prognosis.

Is acute lymphoblastic leukemia curable?

Yes. The 5-year relative survival rate describes the ratio of those alive for 5 years following their cancer diagnosis to the proportion of the general population expected to survive over the same time. The medical community considers a person cured of acute lymphocytic leukemia if they’re in total remission for 10 years.

Up to 98% of children with ALL go into remission in about a month after treatment and 9 in 10 can be cured. However, there is always a chance of the cancer returning, so it is important to follow up with the cancer care team as needed. About 80-90% of adults will have remissions during these treatments. The overall cure rate for adults is 40%.

How long can you live with acute lymphoblastic leukemia?

Some people with ALL are able to get rid of all of the cancer cells. For others, the cancer may not go away and they may need more regular treatments of chemotherapy, radiation or other therapies.

Finally, others may decide against treatment. Those who choose to forgo treatment for lymphoblastic leukemia focus on relieving their symptoms and maximizing the time they have.

Why choose The University of Kansas Cancer Center for acute lymphoblastic leukemia diagnosis and treatment?

The University of Kansas Cancer Center provides outstanding care for acute lymphoblastic leukemia. The team provides leading-edge research and world-class care. In fact, our cancer center is the only National Cancer Institute-designated cancer center in the region.