About Acute Lymphocytic Leukemia (ALL)

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What Is Acute Lymphocytic Leukemia?

ALL is a type of leukemia that starts from white blood cells in the bone marrow, the soft inner part of bones. It develops from cells called lymphocytes, a type of white blood cell central to the immune system, or from lymphoblasts, an immature type of lymphocyte.

Acute lymphoblastic leukemia invades the blood and can spread throughout the body to other organs, such as the liver, spleen, and lymph nodes. But it does not normally produce tumors as do many types of cancer. It is an acute type of leukemia, which means it can progress quickly. Without treatment, it can be fatal within a few months.

The outlook for acute lymphoblastic leukemia depends on factors such as:

  • Your age: Younger patients tend to have a better outlook.
  • Your lab test results: The prognosis is better if you have a lower white blood count when you’re diagnosed.
  • Your subtype of ALL (B-cell ALL or T-cell ALL)
  • Whether you have a chromosome abnormality called the Philadelphia chromosome; having it suggests a poorer prognosis.
  • Your response to chemotherapy: The prognosis is better if you have no evidence of leukemia four to five weeks after starting treatment.

Cancer starts when cells in the body begin to grow out of control. Cells in nearly any part of the body can become cancer, and can spread to other areas of the body. To learn more about how cancers start and spread, see What Is Cancer?

Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, is a cancer that starts from the early version of white blood cells called lymphocytes in the bone marrow (the soft inner part of the bones, where new blood cells are made).

Leukemia cells usually invade the blood fairly quickly. They can then spread to other parts of the body, including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles (in males). Other types of cancer also can start in these organs and then spread to the bone marrow, but these cancers are not leukemia.

The term “acute” means that the leukemia can progress quickly, and if not treated, would probably be fatal within a few months. Lymphocytic means it develops from early (immature) forms of lymphocytes, a type of white blood cell. This is different from acute myeloid leukemia (AML), which develops in other blood cell types found in the bone marrow. For more information on AML, see Acute Myeloid Leukemia.

Other types of cancer that start in lymphocytes are known as lymphomas (non-Hodgkin lymphoma or Hodgkin disease). The main difference between these types of cancers is that leukemias like ALL mainly affects the bone marrow and the blood, and may spread to other places, while lymphomas mainly affect the lymph nodes or other organs but may involve the bone marrow. Sometimes cancerous lymphocytes are found in both the bone marrow and lymph nodes when the cancer is first diagnosed, which can make it hard to tell if the cancer is leukemia or lymphoma. If more than 25% of the bone marrow is replaced by cancerous lymphocytes, the disease is usually considered leukemia. The size of lymph nodes is also important. The bigger they are, the more likely the disease will be considered a lymphoma. For more information on lymphomas, see Non-Hodgkin Lymphoma and Hodgkin Disease.

There are actually many types of leukemia. They differ based on what types of cells they start in, how quickly they grow, which people they affect, and how they are treated. To understand leukemia, it helps to know about the blood and lymph systems.

Normal bone marrow, blood, and lymphoid tissue

Bone marrow

Bone marrow is the soft inner part of some bones, such as the skull, shoulder blades, ribs, pelvis, and bones in the spine. The bone marrow is made up of a small number of blood stem cells, more mature blood-forming cells, fat cells, and supporting tissues that help cells grow.

Blood stem cells go through a series of changes to make new blood cells. During this process, the cells develop into 1 of the 3 main types of blood cell components:

  • Red blood cells
  • Platelets
  • White blood cells (which include lymphocytes, granulocytes, and monocytes)

Red blood cells

Red blood cells carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed.

Platelets

Platelets are actually cell fragments made by a type of bone marrow cell called a megakaryocyte. Platelets are important in plugging up holes in blood vessels caused by cuts or bruises.

White blood cells

White blood cells help the body fight infections.

Lymphocytes

These are the main cells that make up lymphoid tissue, a major part of the immune system. Lymphoid tissue is found in lymph nodes, the thymus, the spleen, the tonsils and adenoids, and is scattered throughout the digestive and respiratory systems and the bone marrow.

Lymphocytes develop from cells called lymphoblasts to become mature, infection-fighting cells. The 2 main types of lymphocytes are B lymphocytes (B cells) and T lymphocytes (T cells).

  • B lymphocytes:B lymphocytes protect the body from invading germs by maturing into plasma cells, which make proteins called antibodies. The antibodies attach to the germs (bacteria, viruses, and fungi), which helps the immune system destroy them.
  • T lymphocytes:There are several types of T cells, each with a special job. Some T cells can destroy germs directly, while others play a role in either boosting or slowing the activity of other immune system cells.

Acute lymphocytic leukemia develops from early forms of lymphocytes. It can start in either early B cells or T cells at different stages of maturity. This is discussed in How is acute lymphocytic leukemia classified?

Granulocytes

These are white blood cells that have granules in them, which are spots that can be seen under the microscope. These granules contain enzymes and other substances that can destroy germs, such as bacteria. The 3 types of granulocytes – neutrophilsbasophils, and eosinophils – are distinguished by the size and color of their granules.

Monocytes

These white blood cells, which are related to granulocytes, also help protect the body against bacteria. After circulating in the bloodstream for about a day, monocytes enter body tissues to become macrophages, which can destroy some germs by surrounding and digesting them.

Development of leukemia

Any type of early blood-forming cell of the bone marrow can turn into a leukemia cell. Once this change happens, the leukemia cells will not mature normally. The leukemia cells could reproduce quickly, and might not die when they should. Instead they survive and build up in the bone marrow. Over time, these cells spill into the bloodstream and spread to other organs, where they can keep other cells from functioning normally.

Types of leukemia

There are 4 main types of leukemia:

  • Acute myeloid (or myelogenous) leukemia (AML)
  • Chronic myeloid (or myelogenous) leukemia (CML)
  • Acute lymphocytic (or lymphoblastic) leukemia (ALL)
  • Chronic lymphocytic leukemia (CLL)

Acute leukemia versus chronic leukemia

The first factor in classifying leukemia is whether most of the abnormal cells are mature (look like normal white blood cells) or immature (look more like stem cells).

Acute leukemia: In acute leukemia, the bone marrow cells cannot mature properly. Immature leukemia cells continue to reproduce and build up. Without treatment, most people with acute leukemia would live only a few months. Some types of acute leukemia respond well to treatment, and many patients can be cured. Other types of acute leukemia have a less favorable outlook.

Chronic leukemia: In chronic leukemia, the cells can mature partly but not completely. These cells may look fairly normal, but they generally do not fight infection as well as normal white blood cells do. They also live longer, build up, and crowd out normal cells. Chronic leukemias tend to progress over a longer period of time, and most people can live for many years. But chronic leukemias are generally harder to cure than acute leukemias.

Myeloid leukemia versus lymphocytic leukemia

The second factor in classifying leukemia is the type of bone marrow cells that are affected.

Myeloid leukemia: Leukemias that start in early forms of myeloid cells – the cells that make white blood cells (other than lymphocytes), red blood cells, or platelet-making cells (megakaryocytes) – are myeloid leukemias (also known as myelocytic, myelogenous, or non-lymphocytic leukemias).

Lymphocytic leukemia: Leukemias that start in immature forms of lymphocytes are called lymphocytic leukemias (also known as lymphoid or lymphoblastic leukemias).

Risk Factors

A risk factor is something that affects your chance of getting a disease such as cancer. Some risk factors, like smoking, can be controlled. Others, like a person’s age or family history, can’t be changed.

But risk factors don’t tell us everything. Having a risk factor, or even several risk factors, does not mean that you will definitely get the disease. And many people who get the disease may have few or no known risk factors. Even if a person has one or more risk factors and develops cancer, it is often very hard to know how much they might have contributed to the cancer.

Radiation exposure

Being exposed to high levels of radiation is a risk factor for both ALL and acute myeloid leukemia (AML). Japanese atomic bomb survivors had a greatly increased risk of developing acute leukemia, usually within 6 to 8 years after exposure.

Treating cancer with radiation therapy also increases the risk of leukemia, although AML is more often seen than ALL. The risk seems to be higher if chemotherapy and radiation are both used in treatment.

The possible risks of leukemia from being exposed to lower levels of radiation, such as from medical imaging tests (such as x-rays) are not well-known. Exposure of a fetus to radiation within the first months of development may carry an increased risk of leukemia, but the extent of the risk is not clear.

If there is an increased risk from lower levels of radiation it is likely to be small, but to be safe, most doctors try to limit a person’s exposure to radiation as much as possible.

Certain chemical exposures

The risk of ALL may be increased by exposure to certain chemotherapy drugs and certain chemicals, including benzene. Benzene is a solvent used in the rubber industry, oil refineries, chemical plants, shoe manufacturing, and gasoline-related industries, and is also present in cigarette smoke, as well as some glues, cleaning products, detergents, art supplies, and paint strippers. Chemical exposure is more strongly linked to an increased risk of AML than to ALL.

Certain viral infections

Infection with the human T-cell lymphoma/leukemia virus-1 (HTLV-1) can cause a rare type of T-cell acute lymphocytic leukemia. Most cases occur in Japan and the Caribbean area. This disease is not common in the United States.

In Africa, the Epstein-Barr virus (EBV) has been linked to Burkitt lymphoma, as well as to a form of acute lymphocytic leukemia. In the United States, EBV most often causes infectious mononucleosis (“mono”).

Inherited syndromes

Acute lymphocytic leukemia does not appear to be an inherited disease. It does not seem to run in families, so a person’s risk is not increased if a family member has the disease. But there are some inherited syndromes with genetic changes that seem to raise the risk of ALL. These include:

  • Down syndrome
  • Klinefelter syndrome
  • Fanconi anemia
  • Bloom syndrome
  • Ataxia-telangiectasia
  • Neurofibromatosis

Causes

Some people with acute lymphocytic leukemia (ALL) have one or more of the known risk factors (see What are the risk factors for acute lymphocytic leukemia?), but most do not. The cause of their cancer remains unknown at this time. Even when a person has one or more risk factors, there is no way to tell whether it actually caused the cancer.

During the past few years, scientists have made great progress in understanding how certain changes in DNA can cause normal bone marrow cells to become leukemia cells. Normal human cells grow and function based mainly on the information contained in each cell’s chromosomes. Chromosomes are like bundles of long molecules of DNA in each cell. DNA is the chemical that makes up our genes – the instructions for how our cells function. We look like our parents because they are the source of our DNA. But our genes affect more than the way we look.

Some genes contain instructions for controlling when our cells grow and divide. Certain genes that help cells grow and divide are called oncogenes. Others that slow down cell growth and division or cause them to die at the right time are called tumor suppressor genes.

Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA. Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes.

Translocations are the most common type of DNA change that can lead to leukemia. Human DNA is packaged in 23 pairs of chromosomes. A translocation means that DNA from one chromosome breaks off and becomes attached to a different chromosome. The point on the chromosome where the break occurs can affect genes – for example, it can turn on oncogenes or turn off genes that would normally help a cell mature.

The most common translocation in ALL in adults is known as the Philadelphia chromosome, which is a swap of DNA between chromosomes 9 and 22, abbreviated as t(9;22). It occurs in about 1 out of 4 adult ALL cases. Other, less common translocations are those between chromosomes 4 and 11, t(4;11), or 8 and 14, t(8;14).

Other chromosome changes such as deletions (the loss of part of a chromosome) and inversions (the rearrangement of the DNA within part of a chromosome) can also affect the development of ALL, although they are less common. In many cases of ALL, the gene changes that lead to the leukemia are not known.

Doctors are trying to figure out why these changes occur and how each of them might lead to leukemia. Not all cases of ALL have the same chromosome changes. Some changes are more common than others, and some seem to have more of an effect on a person’s prognosis (outlook) than others.

Some people with certain types of cancer have inherited DNA mutations from a parent. These changes increase their risk for the disease. But ALL is very rarely caused by one of these inherited mutations.

Usually DNA mutations related to ALL occur during the person’s lifetime rather than having been inherited before birth. They may result from exposure to radiation or cancer-causing chemicals, but in most cases the reason they occur is not known.

Signs and Symptoms

Acute lymphocytic leukemia (ALL) can cause many different signs and symptoms. Most of these occur in all kinds of ALL, but some are more common with certain subtypes.

Problems caused by low blood cell counts

Most signs and symptoms of ALL result from shortages of normal blood cells, which happen when the leukemia cells crowd out the normal blood-making cells in the bone marrow. These shortages show up on blood tests, but they can also cause symptoms, including:

  • Feeling tired
  • Feeling weak
  • Feeling dizzy or lightheaded
  • Shortness of breath
  • Fever
  • Infections that don’t go away or keep coming back
  • Bruising easily
  • Bleeding, such as frequent or severe nosebleeds and bleeding gums

General symptoms

Patients with ALL also often have several non-specific symptoms. These can include:

  • Weight loss
  • Fever
  • Night sweats
  • Fatigue
  • Loss of appetite

Of course, these are not just symptoms of ALL and are more often caused by something other than leukemia.

Swelling in the abdomen

Leukemia cells may build up in the liver and spleen, causing them to enlarge. This might be noticed as a fullness or swelling of the belly or feeling full after eating only a small amount. The lower ribs usually cover these organs, but when they are enlarged the doctor can feel them.

Enlarged lymph nodes

ALL that has spread to lymph nodes close to the surface of the body (such as on the sides of the neck, in the groin, or in underarm areas), might be noticed as lumps under the skin. Lymph nodes inside the chest or abdomen may also swell, but these can be detected only by imaging tests such as CT or MRI scans.

Bone or joint pain

Sometimes leukemia cells build up near the surface of the bone or inside the joint and cause bone or joint pain.

Spread to other organs

Less often, ALL spreads to other organs:

  • If ALL spreads to the brain and spinal cord it can cause headaches, weakness, seizures, vomiting, trouble with balance, facial numbness, or blurred vision.
  • ALL may spread to the chest cavity, where it can cause fluid buildup and trouble breathing.
  • Rarely, ALL may spread to the skin, eyes, testicles, kidneys, or other organs.

Symptoms from an enlarged thymus

The T-cell subtype of ALL often affects the thymus, which is a small organ in the middle of the chest behind the sternum (breastbone) and in front of the trachea (windpipe). An enlarged thymus can press on the trachea, causing coughing or trouble breathing.

The superior vena cava (SVC), a large vein that carries blood from the head and arms back to the heart, passes next to the thymus. If the thymus is enlarged, it may press on the SVC, causing the blood to “back up” in the veins. This is known as SVC syndrome. It can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red color). It can also cause headaches, dizziness, and a change in consciousness if it affects the brain. The SVC syndrome can be life-threatening, and needs to be treated right away.

Treatment

ALL is really a group of related diseases, or subtypes. Therefore, your treatment options depend upon your subtype and other factors. You may have more than one type of treatment. These include:

  • Chemotherapy,the use of anticancer drugs in combination, generally over a couple of years. Agents used for ALL include:
  • cyclophosphamide(Cytoxan)
  • cytarabine(Cytosar)
    • daunorubicin(Cerubidine) or doxorubicin (Adriamycin)
    • etoposide(VP-16)
    • L-asparaginace (Elspar) or PEG-L-asapraginase (Oncaspar)
    • 6-mercaptopurine (6-MP, Purinethol)
    • methotrexate(Rheumatrex, Trexall)
    • methoterate oral (Xatmep)
    • steroids(prednisone, dexamethasone)
    • teniposide(Vumon
    • vincristine(Oncovin)
  • Targeted therapy,drugs that target specific parts of cancer cells and tend to have fewer or less severe side effects than chemotherapy; examples include blinatumomab (Blincyto), dasatinib (Sprycel),  imatinib (Gleevec), and nilotinib (Tasigna), ponatinib (Iclusig), which attack cells with the Philadelphia chromosome.
  • Radiation therapy, the use of high-energy radiation to kill cancercells; this is not used often for ALL, but may be used to treat leukemia in the brainor bone, for example, or before a stem cell transplant.
  • A bone marrow transplant, which involves use of high doses of chemotherapy and possibly radiation followed by a transplant of bone-forming stem cells. Stem cellsusually come from a donor, or less likely, from your own bone marrow or peripheral blood. If you cannot tolerate high doses of chemotherapy and radiation, lower doses may be used with a “mini-transplant.”

General treatment information

Adult acute lymphocytic leukemia (ALL) is not a single disease. It is really a group of related diseases, and patients with different subtypes of ALL may have different outlooks and responses to treatment.

After your cancer is diagnosed and staged, your cancer care team will discuss your treatment options with you. Choosing a treatment plan is an important decision, so it is important to take time and think about your choices. Treatment options for each patient are based on the leukemia subtype as well as certain prognostic features (described in How Is Acute Lymphocytic Leukemia Classified?).

The main types of treatment used for ALL are:

  • Chemotherapy
  • Targeted therapy
  • Stem cell transplant

Other treatments such as surgery, radiation therapy, or monoclonal antibodies, may be used in special circumstances.

Treatment of ALL typically lasts for about 2 years. It is often intense, especially in the first few months of treatment, so it is important that you are treated in a center that has experience with this disease. See Typical Treatment of Acute Lymphocytic Leukemia for information about common treatment plans.

You may have different types of doctors on your treatment team. The doctor in charge or your team will most likely be a hematologist, a doctor who specializes in treating blood diseases, including leukemia. Many other specialists may be involved in your care as well, including nurse practitioners, nurses, nutrition specialists, social workers, and other health professionals.

It is important to discuss all of your treatment options, including their goals and possible side effects, with your doctors to help make the decision that best fits your needs. It’s also very important to ask questions if there is anything you’re not sure about. You can find some good questions to ask in What Should You Ask Your Doctor About Acute Lymphocytic Leukemia?

Treatment for ALL usually needs to start very soon after it is diagnosed, but if time permits, it is often a good idea to seek a second opinion. A second opinion might give you more information and help you feel confident about your chosen treatment plan.

Thinking about taking part in a clinical trial

Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the art cancer treatment. In some cases they may be the only way to get access to newer treatments. They are also the best way for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

If you would like to learn more about clinical trials that might be right for you, start by asking your doctor if your clinic or hospital conducts clinical trials. See Clinical Trials to learn more.

Considering complementary and alternative methods

You may hear about alternative or complementary methods that your doctor hasn’t mentioned to treat your cancer or relieve symptoms. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

Complementary methods refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor’s medical treatment. Although some of these methods might be helpful in relieving symptoms or helping you feel better, many have not been proven to work. Some might even be dangerous.

Be sure to talk to your cancer care team about any method you are thinking about using. They can help you learn what is known (or not known) about the method, which can help you make an informed decision. See the Complementary and Alternative Medicine section to learn more.

Help getting through cancer treatment

Your cancer care team will be your first source of information and support, but there are other resources for help when you need it. Hospital- or clinic-based support services are an important part of your care. These might include nursing or social work services, financial aid, nutritional advice, rehab, or spiritual help.

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