What is acute lymphocytic leukemia

Acute lymphoblastic leukemia (ALL) is also known as acute lymphocytic leukemia or acute lymphoid leukemia, is a cancer of the blood and bone marrow — in which the bone marrow makes too many abnormal, immature lymphocytes called “blasts” or lymphoblasts (immature lymphocytes). These blasts (lymphoblasts) do not become healthy white blood cells. Instead, they build up in the bone marrow, so there is less room for healthy white blood cells, red blood cells, and platelets. In addition, these abnormal cells are unable to fight off infection. Acute lymphoblastic leukemia (ALL) usually develops quickly over days or weeks and the cancer usually gets worse quickly if it is not treated. The word “acute” in acute lymphocytic leukemia comes from the fact that the disease progresses rapidly and creates immature blood cells (lymphoblasts or immature lymphocytes), rather than mature ones. The word “lymphocytic” in acute lymphocytic leukemia refers to the white blood cells called lymphocytes, which acute lymphoblastic leukemia (ALL) affects.

Lymphocyte is a type of white blood cell that is made in the bone marrow and is found in the blood and in lymph tissue. Lymphocytes are involved in your immune response which produce antibodies that seek out and immobilize bacteria, viruses, and toxins which invade your body. There are two types of lymphocytes:

1. B-cells (formed in your bone marrow). B cells make antibodies as both cell-surface receptors and secreted molecules
2. T-cells (formed in your thymus gland, behind the sternum) which destroy the invading organisms that have been tagged by the B-cells as well as any cells that have become cancerous.

In children with acute lymphoblastic leukemia (childhood ALL):

• 80% to 85% of acute lymphoblastic leukemia consists of early B-cells (also called precursor B-cell)
• 15% are early T-cells. This subtype of acute lymphoblastic leukemia originates in immature cells that would normally develop into T-cell lymphocytes. This subtype is less common than B-cell acute lymphoblastic leukemia and occurs more often in adults than in children.
• Approximately 2% are mature B-cells

In adults with acute lymphoblastic leukemia (adult ALL):

• 75% of cases are early B-cells
• 25% are malignant early T-cells

Acute lymphocytic leukemia (acute lymphoblastic leukemia) starts in your bone marrow (the soft inner part of certain bones, where new blood cells are made). Most often, the leukemia cells invade your blood fairly quickly. They can also sometimes spread to other parts of your body, including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles (in males).

Other types of cancer that start in lymphocytes are known as lymphomas (either non-Hodgkin lymphoma or Hodgkin lymphoma). While leukemias like acute lymphocytic leukemia (acute lymphoblastic leukemia) mainly affect the bone marrow and the blood, lymphomas mainly affect the lymph nodes or other organs (but may also involve the bone marrow). Sometimes it can be hard to tell if a cancer of lymphocytes is a leukemia or a lymphoma. Usually, if at least 20% of the bone marrow is made up of cancerous lymphocytes (called lymphoblasts, or just blasts), the disease is considered leukemia.

Acute lymphocytic leukemia (acute lymphoblastic leukemia) is the most common type of cancer in children (around 85% of cases of acute lymphoblastic leukemia occur in children), representing approximately 25% of cancer diagnoses among children younger than 15 years (with a peak from two to five years of age) ¹ and treatments result in a good chance for a cure. Acute lymphocytic leukemia can also occur in adults (15% of acute lymphoblastic leukemia cases), , mainly aged over 50 years, though the chance of a cure is greatly reduced and most deaths from acute lymphoblastic leukemia (about 4 out of 5) occur in adults. In children, although complete
remission occurs in 97 to 99% of patients following initial multi-agent chemotherapy treatment, between 15 and 20% will have a relapse. In adults, despite complete remission rates of between 78% and 93%, relapse will occur in 60-70% of patients. Five-year survival is approximately 90% in children, but only 30% to 40% in adults and elderly patients ².

The American Cancer Society’s estimates for acute lymphoblastic leukemia (acute lymphocytic leukemia) in the United States for 2021 (including both children and adults) are ³:

• About 5,690 new cases of acute lymphoblastic leukemia (3,000 in males and 2,690 in females).
• About 1,580 deaths from acute lymphoblastic leukemia (900 in males and 680 in females).
• The risk for developing acute lymphoblastic leukemia is highest in children younger than 5 years of age. The risk then declines slowly until the mid-20s, and begins to rise again slowly after age 50. Overall, about 4 of every 10 cases of acute lymphoblastic leukemia are in adults.
• Acute lymphoblastic leukemia is not a common cancer, accounting for less than half of 1% of all cancers in the United States. The average person’s lifetime risk of getting acute lymphoblastic leukemia is about 1 in 1,000. The risk is slightly higher in males than in females, and higher in whites than in African Americans.

In the United States, acute lymphoblastic leukemia (acute lymphocytic leukemia) occurs at an annual rate of approximately 41 cases per 1 million people aged 0 to 14 years and approximately 17 cases per 1 million people aged 15 to 19 years ⁴. There are approximately 3,100 children and adolescents younger than 20 years diagnosed with acute lymphoblastic leukemia each year in the United States ⁵. Since 1975, there has been a gradual increase in the incidence of acute lymphoblastic leukemia ⁶.

A sharp peak in acute lymphoblastic leukemia incidence is observed among children aged 2 to 3 years (>90 cases per 1 million per year), with rates decreasing to fewer than 30 cases per 1 million by age 8 years ⁷. The incidence of acute lymphoblastic leukemia among children aged 2 to 3 years is approximately fourfold greater than that for infants and is likewise fourfold to fivefold greater than that for children aged 10 years and older ⁷.

The incidence of acute lymphoblastic leukemia appears to be highest in Hispanic children (43 cases per 1 million) ⁸. The incidence is substantially higher in White children than in Black children, with a nearly threefold higher incidence of acute lymphoblastic leukemia from age 2 to 3 years in White children than in Black children ⁹.

Relapsed acute lymphoblastic leukemia or relapsed ALL, refers to the return of acute lymphoblastic leukemia (acute lymphoblastic leukemia) in patients who have already undergone treatment for the disease and reached complete remission. Between 10% and 20% of patients, who have achieved complete remission after initial treatment for acute lymphoblastic leukemia, will have a relapse. In children, the relapse rate is near to 10%, while in adults relapse rate is closer to 50% ².

Normal bone marrow, blood, and lymph tissue

To understand leukemia, it helps to know about the bone marrow, blood, and lymph systems.

Bone marrow

Bone marrow is the soft inner part of certain bones. It is made up of blood-forming cells, fat cells, and supporting tissues. A small fraction of the blood-forming cells are blood stem cells.

Inside the bone marrow, blood stem cells develop into new blood cells. During this process, the cells become either lymphocytes (a kind of white blood cell) or other blood-forming cells, which are types of myeloid cells. Myeloid cells can develop into red blood cells, white blood cells (other than lymphocytes), or platelets. These myeloid cells are the ones that are abnormal in acute myeloid leukemia.

Types of blood cells

There are 3 main types of blood cells:

1. Red blood cells (RBCs) carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed.
2. Platelets are actually cell fragments made by a type of bone marrow cell called the megakaryocyte. Platelets are important in stopping bleeding. They help plug up holes in blood vessels caused by cuts or bruises.
3. White blood cells (WBCs) help the body fight infections.

There are different types of white blood cells (WBCs):

• Granulocytes are mature white blood cells that develop from myeloblasts, a type of blood-forming cell in the bone marrow. Granulocytes have granules that show up as spots under the microscope. These granules contain enzymes and other substances that can destroy germs, such as bacteria. The 3 types of granulocytes – neutrophils, basophils, and eosinophils – are distinguished by the size and color of their granules.
• Monocytes are white blood cells that develop from blood-forming monoblasts in the bone marrow. 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. Macrophages also help lymphocytes recognize germs and make antibodies to fight them.
• Lymphocytes are mature white blood cells that develop from lymphoblasts in the bone marrow. Lymphocytes are the main cells that make up lymph tissue, a major part of the immune system. Lymph tissue is found in lymph nodes, the thymus (a small organ behind the breast bone), the spleen, the tonsils and adenoids, and is scattered throughout the digestive and respiratory systems and the bone marrow. The 2 main types of lymphocytes are B cell and T cells.

Figure 1. Blood composition

Note: Blood is a complex mixture of formed elements in a liquid extracellular matrix, called blood plasma. Note that water and proteins account for 99% of the blood plasma.

Figure 2. Bone marrow anatomy

Figure 3. White blood cells development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell

Figure 4. White blood cells development

Figure 5. White blood cells

Acute lymphocytic leukemia causes

Acute lymphocytic leukemia (acute lymphoblastic leukemia) occurs when a bone marrow cell develops errors in its DNA (deoxyribonucleic acid). The errors tell the cell to continue growing and dividing, when a healthy cell would normally stop dividing and eventually die. When this happens, blood cell production becomes abnormal. The bone marrow produces immature cells that develop into leukemic white blood cells called lymphoblasts. These abnormal cells are unable to function properly, and they can build up and crowd out healthy cells.

It’s not clear what causes the DNA mutations that can lead to acute lymphocytic leukemia. But doctors have found that most cases of acute lymphocytic leukemia (acute lymphoblastic leukemia) aren’t inherited.

Great progress has been made in understanding how certain changes in the DNA in normal bone marrow cells can cause them to become leukemia cells. The DNA inside your cells makes up your genes, which control how your cells function.

Some genes control when your cells grow, divide to make new cells, and die at the right time:

• Certain genes that help cells grow, divide, or stay alive are called oncogenes.
• Genes that keep cell growth and division under control or make cells die at the right time are called tumor suppressor genes.

Each time a cell divides into 2 new cells, it must make a new copy of its chromosomes (long strands of DNA). This process isn’t perfect, and errors can occur that can affect genes within the chromosomes. Cancers (including acute lymphocytic leukemia) can be caused by mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. These types of changes can stop bone marrow cells from maturing the way they normally would, or help the cells grow out of control.

Mutations in many different genes can be found in acute lymphocytic leukemia cells, but larger changes in one or more chromosomes are also common. Even though these changes involve larger pieces of DNA, their effects are still likely to be due to changes in just one or a few genes that are on that part of the chromosome.

Several types of chromosome changes may be found in acute lymphocytic leukemia cells:

Translocations are the most common type of chomosome change that can lead to leukemia. 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 nearby genes – for example, it can turn on oncogenes or turn off genes that would normally help a cell mature.

The most common translocation in acute lymphocytic leukemia in adults is known as the Philadelphia chromosome, which is a swap of DNA between chromosomes 9 and 22, abbreviated as t(9;22). In Philadelphia chromosome positive acute lymphoblastic leukemia (also known as “Ph+ ALL” or “Ph-positive ALL”), part of chromosome 9 breaks off where the gene ABL1 is located and part of chromosome 22 breaks off where the BCR gene is located. The broken parts swap places creating a new gene called BCR-ABL1 on chromosome 22, which causes the cell to make too much of a protein called tyrosine kinase. This protein encourages leukaemia cells to grow and multiply. Doctors treat Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) with a targeted cancer drug called imatinib (tyrosine kinase blocker), which blocks this protein.

Many other, less common translocations, can occur as well, including 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) are also sometimes found in acute lymphocytic leukemia cells, although they are less common. In many cases of acute lymphocytic leukemia, 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. But there are different subtypes of acute lymphocytic leukemia, and even within a subtypes, not all cases of acute lymphocytic leukemia have the same gene or 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.

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

About 25 percent of adults with acute lymphoblastic leukemia have a subtype called “Ph-positive ALL” (also known as “Ph+ ALL” or “Philadelphia chromosome-positive ALL”). The leukemia cells of these patients have the Philadelphia chromosome, which is formed by a translocation between parts of chromosomes 9 and 22 resulting in creating a new gene called BCR-ABL1 on chromosome 22, which causes the cell to make too much of a protein called tyrosine kinase. This protein encourages leukemia cells to grow and multiply. Patients who have Ph+ ALL are typically treated with tyrosine kinase inhibitors (TKIs), combined with chemotherapy. This combination has become the standard of care for Ph+ ALL patients. New combinations of drugs for the treatment of Ph+ ALL are also being studied in clinical trials.

Philadelphia Chromosome-like (Ph-like) acute lymphoblastic leukemia

About 10 percent to 30 percent of adults have a subtype of B-cell ALL with genetic features similar to Ph+ ALL, but without the BCR-ABL1 fusion gene that defines Ph+ ALL. Instead, patients have a highly diverse range of genetic mutations that activate tyrosine kinase signaling. Findings from recent studies that analyzed the genetic profile of patients with Ph-like ALL have suggested that using tyrosine kinase inhibitors (TKIs) and other targeted therapies may help treat these types of leukemia.

Risk factors for acute lymphoblastic leukemia

A risk factor is something that increases your chance of getting a disease such as cancer. But 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.

There are only a handful of known risk factors for acute lymphocytic leukemia (acute lymphoblastic leukemia).

Factors that may increase the risk of acute lymphocytic leukemia include:

• Age: Acute lymphocytic leukemia is more likely to occur in children and in adults over the age of 50.

• Previous cancer treatment. Children and adults who’ve had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased risk of developing acute lymphocytic leukemia.

• Exposure to radiation. People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing acute lymphocytic leukemia and acute myeloid leukemia (AML). Treating cancer with radiation therapy also increases the risk of leukemia, although more for acute myeloid leukemia than acute lymphocytic leukemia (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 like x-rays or CT scans, are not well understood. Exposure to such radiation, especially very early in life, may carry an increased risk of leukemia, but this is not clear. If there is an increased risk it is likely to be small, but to be safe, most doctors try to limit radiation exposure from these tests as much as possible, especially in children and pregnant women.

• Genetic disorders. Acute lymphocytic leukemia itself doesn’t appear to have a strong inherited component. That is, it doesn’t seem to run in families, so a person’s risk is not increased if a family member (other than an identical twin – see below) has the disease. But there are some genetic syndromes (some of which can be inherited from a parent) that seem to raise the risk of acute lymphocytic leukemia. These include:
  • Down syndrome
  • Klinefelter syndrome
  • Fanconi anemia
  • Bloom syndrome
  • Ataxia-telangiectasia
  • Neurofibromatosis
  • Li-Fraumeni syndrome

• Having a brother or sister with acute lymphocytic leukemia. People who have a sibling, including a twin, with acute lymphocytic leukemia have an increased risk of acute lymphocytic leukemia.

• Certain chemical exposures: The risk of acute lymphocytic leukemia may be increased by exposure to certain chemotherapy drugs and certain other chemicals, including benzene. Benzene is used in many industries to make other products, and is also 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 acute myeloid leukemia (AML) than to acute lymphocytic leukemia.

• 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, Epstein-Barr virus (EBV) most often causes infectious mononucleosis (“mono”). Epstein-Barr virus (EBV) has also been linked with a type of lymphoma that can occur after a stem cell transplant (known as post-transplant lymphoproliferative disorder, or PTLD).

• Smoking – smokers are much more likely to develop acute leukemia than non-smokers, and studies have shown that parents who smoke in the home may increase the risk of leukemia in their children.

• Being very overweight (obese) – some studies have shown that people who are very overweight have a slightly higher risk of developing leukemia than those who are a normal weight.

• Having a weakened immune system – people with lowered immunity (as a result of having HIV or AIDS or taking immunosuppressants) have an increased risk of developing leukemia

• Race/ethnicity: Acute lymphocytic leukemia is more common in whites than in African Americans, but the reasons for this are not clear.

• Gender: Acute lymphocytic leukemia is slightly more common in males than in females. The reason for this is unknown.

• Having an identical twin with acute lymphocytic leukemia: Someone who has an identical twin who develops acute lymphocytic leukemia in the first year of life has an increased risk of getting acute lymphocytic leukemia.

Uncertain, unproven or controversial risk factors

Other factors that have been studied for a possible link to acute lymphocytic leukemia include:

• Exposure to electromagnetic fields (such as living near power lines or using cell phones)
• Workplace exposure to diesel, gasoline, pesticides, and certain other chemicals
• Smoking
• Exposure to hair dyes

So far, none of these factors has been linked conclusively to acute lymphocytic leukemia, but research in these areas continues.

Acute lymphoblastic leukemia prevention

There is no known way to prevent most cases of leukemia at this time. Most people who get acute lymphocytic leukemia have no known risk factors, so there is no way to prevent these leukemias from developing.

Acute lymphocytic leukemia symptoms

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

Acute lymphoblastic leukaemia usually starts slowly before rapidly becoming severe as the number of immature white blood cells in your blood increases.

Most of the symptoms are caused by the lack of healthy blood cells (red cells, white cells and platelets) in your blood supply.

Signs and symptoms of acute lymphocytic leukemia (acute lymphoblastic leukemia) may include:

• Bleeding from the gums
• Bone pain
• Fever
• Frequent infections
• Frequent or severe nosebleeds
• Lumps caused by swollen lymph nodes in and around the neck, armpits, abdomen or groin
• Pale skin
• Shortness of breath
• Weakness, fatigue or a general decrease in energy

Symptoms caused by low numbers of blood cells

Most signs and symptoms of acute lymphocytic leukemia are the result of shortages of normal blood cells (red cells, white cells and platelets), 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
• Pale skin
• Infections that don’t go away or keep coming back
• Bruises (or small red or purple spots) on the skin
• Bleeding, such as frequent or severe nosebleeds, bleeding gums, or heavy menstrual bleeding in women

General symptoms

Patients with acute lymphocytic leukemia also often have several non-specific symptoms. These can include:

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

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

Swelling in the abdomen

Leukemia cells may build up in the liver and spleen, making them larger. 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 the organs are enlarged the doctor can feel them.

Enlarged lymph nodes

Acute lymphocytic leukemia 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, which can lead to bone or joint pain.

Spread to other organs

Less often, acute lymphocytic leukemia spreads to other organs:

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

Symptoms from an enlarged thymus

The T-cell subtype of acute lymphocytic leukemia 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, which can lead to coughing or trouble breathing.

The superior vena cava, 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 superior vena cava, causing the blood to “back up” in the veins. This is known as superior vena cava syndrome. It can cause:

• Swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red color)
• Headaches
• Dizziness
• Change in consciousness if it affects the brain

The superior vena cava syndrome can be life-threatening, and needs to be treated right away.

Acute lymphoblastic leukemia complications

Being immunocompromised (having a weakened immune system) is a possible complication for some people with acute leukemia.

There are two reasons for this:

1. the lack of healthy white blood cells means your immune system is less able to fight infection
2. many of the medicines used to treat acute leukemia can weaken the immune system

This makes you more vulnerable to developing an infection, and any infection you do have is more likely to cause serious complications.

You may be advised to take regular doses of antibiotics to prevent infections occurring. You should report any possible symptoms of an infection immediately to your doctor or care team because prompt treatment may be needed to prevent serious complications.

Symptoms of infection include:

• high temperature (fever) of 101.4 °F (38 °C) or above
• headache
• aching muscles
• diarrhea
• tiredness

Avoid contact with anyone known to have an infection, even if it’s a type of infection that you were previously immune to, such as chickenpox or measles. This is because your previous immunity to these conditions will probably be lower.

It’s important to go outside on a regular basis, both for exercise and for your wellbeing, but you should avoid visiting crowded places and using public transport during rush hour.

Also, make sure all of your vaccinations are up-to-date. Your doctor or care team will be able to advise you about this. You’ll be unable to have any vaccine containing activated particles of viruses or bacteria such as the:

• mumps, measles and rubella (MMR) vaccine
• polio vaccine
• oral typhoid vaccine
• BCG vaccine (used to vaccinate against tuberculosis)
• yellow fever vaccine

Bleeding

If you have acute leukemia, you’ll bleed and bruise more easily because of the low levels of platelets (clot-forming cells) in your blood.

Although major bleeding is uncommon, you need to be aware of the related symptoms that can occur in different parts of the body.

Bleeding can occur:

• inside the skull (intracranial hemorrhage)
• inside the lungs (pulmonary hemorrhage)
• inside the stomach (gastrointestinal hemorrhage)

The symptoms of an intracranial hemorrhage include:

• severe headache
• stiff neck
• vomiting
• change in mental state, such as confusion

The most common symptoms of a pulmonary hemorrhage are:

• coughing up blood from your nose and mouth
• breathing difficulties
• a bluish skin tone (cyanosis)

The two most common symptoms of a gastrointestinal hemorrhage are:

• vomiting blood
• passing stools (feces) that are very dark or tar-like

All three types of hemorrhages should be regarded as medical emergencies. Call your local emergency services number for an ambulance if you suspect that you or your child is experiencing a hemorrhage.

Infertility

Many of the treatments used to treat acute leukemia can cause infertility. Infertility is often temporary, although in some cases it may be permanent.

People who are particularly at risk of becoming infertile are those who’ve received high doses of chemotherapy and radiotherapy in preparation for stem cell and bone marrow transplants.

It may be possible to guard against any risk of infertility before you begin your treatment. For example, men can store sperm samples. Similarly, women can have fertilised embryos stored, which can be put back into their womb following treatment.

Psychological effects of leukemia

Being diagnosed with acute lymphocytic leukemia (acute lymphoblastic leukemia) can be very distressing, particularly if a cure is unlikely. At first, the news may be difficult to take in. It can be particularly difficult if you don’t currently have any leukemia symptoms, but you know that it could present a serious problem later on. Having to wait many years to see how the leukemia develops can be very stressful and can trigger feelings of anxiety and depression.

If you’ve been diagnosed with acute lymphocytic leukemia (acute lymphoblastic leukemia), talking to a counselor or psychiatrist (a doctor who specializes in treating mental health conditions) may help you combat feelings of depression and anxiety. Antidepressants or medicines that help reduce feelings of anxiety may also help you cope better.

You may find it useful to talk to other people living with leukemia. Your doctor or multidisciplinary team may be able to provide you with details of local support groups.

Acute lymphocytic leukemia diagnosis

Certain signs and symptoms can suggest that a person might have acute lymphocytic leukemia (acute lymphoblastic leukemia), but tests are needed to confirm the diagnosis.

Medical history and physical exam

If you have signs and symptoms that suggest you might have leukemia, the doctor will want to get a thorough medical history, including how long you have had symptoms and if you have possibly been exposed to anything considered a risk factor.

During the physical exam, the doctor will probably focus on any enlarged lymph nodes, areas of bleeding or bruising, or possible signs of infection. The eyes, mouth, and skin will be looked at carefully, and a thorough nervous system exam may be done. Your abdomen will be felt for spleen or liver enlargement.

If there is reason to think low levels of blood cells might be causing your symptoms (anemia, infections, bleeding or bruising, etc.), the doctor will most likely order blood tests to check your blood cell counts. You might also be referred to a hematologist, a doctor who specializes in diseases of the blood (including leukemia).

Tests used to diagnose and classify acute lymphocytic leukemia

If your doctor thinks you might have leukemia, he or she will need to check samples of cells from your blood and bone marrow to be sure. Other tissue and cell samples may also be taken to help guide treatment.

Blood tests

Blood samples for acute lymphocytic leukemia tests are generally taken from a vein in the arm.

Complete blood count (CBC) and peripheral blood smear

The complete blood count (CBC) measures the numbers of red blood cells, white blood cells, and platelets. This test is often done along with a differential (or diff) which looks at the numbers of the different types of white blood cells. These tests are often the first ones done on patients with a suspected blood problem.

For the peripheral blood smear (sometimes just called a smear), a drop of blood is smeared across a slide and then looked at under a microscope to see how the cells look. Changes in the numbers and the appearance of the cells often help diagnose leukemia.

Most patients with acute lymphocytic leukemia have too many immature white cells called lymphoblasts (or just blasts) in their blood, and not enough red blood cells or platelets. Lymphoblasts are not normally found in the blood, and they don’t function like normal, mature white blood cells.

Even though these findings may suggest leukemia, the disease usually is not diagnosed without looking at a sample of bone marrow cells.

Blood chemistry tests

Blood chemistry tests measure the amounts of certain chemicals in the blood, but they are not used to diagnose leukemia. In patients already known to have acute lymphocytic leukemia, these tests can help detect liver or kidney problems caused by spreading leukemia cells or the side effects of certain chemotherapy drugs. These tests also help determine if treatment is needed to correct low or high blood levels of certain minerals.

Coagulation tests

Blood coagulation tests may be done to make sure the blood is clotting properly.

Bone marrow tests

Leukemia starts in the bone marrow, so checking the bone marrow for leukemia cells is a key part of testing for it.

Bone marrow aspiration and biopsy

Bone marrow samples are obtained by bone marrow aspiration and biopsy – tests usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases they may be taken from the sternum (breastbone) or other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the skin and the surface of the bone by injecting a local anesthetic, which may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most patients still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed down into the bone. With local anesthetic, most patients just feel some pressure and tugging from the biopsy, but some may feel a brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.

These bone marrow tests are used to help diagnose leukemia. They may also be done again later to tell if the leukemia is responding to treatment.

Lab tests used to diagnose and classify acute lymphocytic leukemia

One or more of the following lab tests may be done on the samples to diagnose acute myeloid leukemia (AML) and/or to determine the specific subtype of acute lymphocytic leukemia.

Routine exams with a microscope

The bone marrow (and sometimes blood) samples are looked at with a microscope by a pathologist (a doctor specializing in lab tests) and may be reviewed by the patient’s hematologist/oncologist (a doctor specializing in cancer and blood diseases).

The doctors will look at the size, shape, and other traits of the white blood cells in the samples to classify them into specific types. A key factor is whether the cells look mature (like normal blood cells), or immature (lacking features of normal blood cells). The most immature cells are called lymphoblasts (or just blasts).

Determining what percentage of cells in the bone marrow are blasts is particularly important. A diagnosis of acute lymphocytic leukemia generally requires that at least 20% of the cells in the bone marrow are blasts. Under normal circumstances, blasts don’t make up more than 5% of bone marrow cells. Sometimes just counting and looking at the cells doesn’t provide a definite diagnosis, and other lab tests are needed.

Cytochemistry

In cytochemistry tests, cells are put on a slide and exposed to chemical stains (dyes) that react only with some types of leukemia cells. These stains cause color changes that can be seen under a microscope, which can help the doctor determine what types of cells are present. For instance, one stain will turn parts of acute myeloid leukemia (AML) cells black, but has no effect on acute lymphocytic leukemia cells.

Flow cytometry and immunohistochemistry

For both flow cytometry and immunohistochemistry, samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For immunohistochemistry, the cells are examined under a microscope to see if the antibodies stuck to them (meaning they have those proteins), while for flow cytometry a special machine is used.

These tests are used for immunophenotyping – classifying leukemia cells according to proteins on or in the cells. This kind of testing is very helpful in determining the exact type of leukemia. For diagnosing leukemia, it is most often done on cells from bone marrow, but it can also be done on cells from the blood, lymph nodes, and other body fluids.

For acute lymphocytic leukemia, these tests are most often used to help determine the exact subtype of in someone already thought to have acute lymphocytic leukemia based on other tests.

Chromosome tests

These tests look at the chromosomes (long strands of DNA) inside the cells. Normal human cells contain 23 pairs of chromosomes (bundles of DNA). In acute lymphocytic leukemia, the cells sometimes have chromosome changes. Recognizing these changes can help identify certain types of acute lymphocytic leukemia, and it can be important in determining a patient’s outlook and likely response to some treatments. For this reason, chromosome testing is a standard part of the work-up for acute lymphocytic leukemia.

The most common chromosome change in acute lymphocytic leukemia is a translocation, in which, 2 chromosomes swap some of their DNA, so that part of one chromosome becomes attached to part of a different chromosome. The most common chromosome change in adult acute lymphocytic leukemia is a translocation that results in a shortened chromosome 22 (called the Philadelphia chromosome). About 1 out of 4 adults with acute lymphocytic leukemia have this abnormality in their leukemia cells. This change is especially important because it can be targeted with certain drugs.

Cytogenetics

For this test, the cells are grown in lab dishes until they start dividing. Then the chromosomes are looked at under a microscope to detect any changes. Because it takes time for the cells to start dividing, cytogenetic testing often takes about 2 to 3 weeks. Not all chromosome changes can be seen under a microscope. Other lab tests can often help find these changes.

Fluorescent in situ hybridization (FISH)

This is another way to look at chromosomes and genes. It uses special fluorescent dyes that only attach to specific genes or parts of particular chromosomes. Fluorescent in situ hybridization (FISH) can find most chromosome changes (such as translocations) that are visible under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.

Fluorescent in situ hybridization (FISH) can be used on regular blood or bone marrow samples. Because the cells don’t have to be able to divide for this test, it can also be used to look at cells from other tissues, like lymph node samples. It is very accurate and can usually provide results within a couple of days. But because fluorescent in situ hybridization (FISH) only tests for certain gene changes (and doesn’t look at the chromosomes overall), it is best for looking for the changes that are important based on the kind of leukemia a person has.

Polymerase chain reaction (PCR)

This is a very sensitive DNA test that can also find certain gene and chromosome changes too small to be seen with a microscope, even if very few leukemia cells are present in a sample. Like fluorescent in situ hybridization (FISH), it is used to find particular gene changes and not to look at the chromosomes overall.

If the leukemia cells have a particular gene (or chromosome) change, polymerase chain reaction (PCR) can be used after treatment to try to find small numbers of leukemia cells that may not be visible with a microscope.

Other molecular and genetic tests

Other, newer types of lab tests can also be done on the samples to look for specific gene or other changes in the leukemia cells.

Lumbar puncture (spinal tap)

Acute lymphocytic leukemia can spread to the area around the brain and spinal cord. To check for this spread, doctors remove a sample of the fluid from that area (cerebrospinal fluid or CSF) for testing. You may lay on your side or sit up for this test. The doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then placed between the bones of the spine and into the area around the spinal cord to collect some fluid.

A lumbar puncture can also be used to put chemotherapy drugs into the CSF to try to prevent or treat the spread of leukemia to the spinal cord and brain.

Lymph node biopsy

A lymph node or part of a lymph node is often removed to help diagnose lymphomas, but this is only rarely needed with leukemia because the diagnosis is usually made looking at blood and bone marrow. In this procedure, a surgeon cuts through the skin to remove all or part of a lymph node. If the node is just under the skin, this is a simple operation that can often be done with local anesthesia, but if the node is inside the chest or abdomen, general anesthesia is used to keep you asleep during the biopsy.

When the entire lymph node is removed, it is called an excisional lymph node biopsy. If only part of the lymph node is removed, it is called an incisional lymph node biopsy.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to create pictures of the inside of the body. Leukemia does not usually form tumors, so imaging tests aren’t as useful as they are for other types of cancer. Imaging tests might be done in people with acute lymphocytic leukemia to help determine the extent of the disease, if it is thought to have spread beyond the bone marrow and blood. They might also be done to look for infections or other problems. .

X-rays

Chest x-rays may be done if the doctor suspects a lung infection. They may also be done to look for enlarged lymph nodes in the chest.

Computed tomography (CT) scan

The CT scan uses x-rays to make detailed, cross-sectional images of your body. The CT scan can show if any lymph nodes or organs in your body are enlarged. It isn’t usually needed to diagnose acute lymphocytic leukemia, but it may be done if your doctor suspects leukemia cells are growing in an organ, like your spleen.

Sometimes a test that combines the CT scan with a PET (positron emission tomography) scan (PET/CT scan) is done. This is not often needed for patients with acute lymphocytic leukemia.

Magnetic resonance imaging (MRI) scan

MRI scans make detailed images of the body using radio waves and strong magnets instead of x-rays. They are very helpful in looking at the brain and spinal cord. This test might be done if a lumbar puncture finds leukemia cells in the cerebrospinal fluid (CSF), or if a person is having symptoms that could mean the acute lymphocytic leukemia has spread to the area around the brain.

Ultrasound

This is an easy test to have, and it uses no radiation. Ultrasound can be used to look at lymph nodes near the surface of the body or to look for enlarged organs inside the abdomen such as the kidneys, liver, and spleen. It can also be used to look at the testicles, if needed.

Acute lymphocytic leukemia subtypes and prognostic factors

For most types of cancer, determining the stage (extent) of the cancer is very important. The stage is based on the size of the tumor and how far the cancer has spread. This can be helpful in predicting a person’s outlook and deciding on treatment.

Acute lymphocytic leukemia (acute lymphoblastic leukemia), on the other hand, does not usually form tumors. It generally affects all of the bone marrow in the body and, in some cases, has already spread to other organs, such as the liver, spleen, and lymph nodes, by the time it is found. Therefore acute lymphoblastic leukemia is not staged like most other cancers. The outlook for a person with acute lymphoblastic leukemia depends on other information, such as the subtype of acute lymphoblastic leukemia (determined by lab tests), the patient’s age, and other lab test results.

Acute lymphocytic leukemia (ALL) is divided into different groups (subtypes). Doctors use two different systems to work out which type a person has. These are the:

• World Health Organisation (WHO) system. Doctors mostly use the World Health Organisation (WHO) system. It’s based on the type of lymphocyte (white blood cell) that has become cancerous and the characteristics the cell has. This system helps your doctors to plan treatment and predict how well the treatment will work. There are 3 different subtypes:
  1. pre (precursor) B cell ALL, this is the most common type in adults
  2. pre (precursor) T cell ALL, this is more likely to affect young adults and is more common in men
  3. mature B cell ALL, this type is identified by particular genetic changes. Mature B cell acute lymphocytic leukemia (acute lymphoblastic leukemia) is sometimes called Burkitt type acute lymphoblastic leukemia because it is similar to another cancer called Burkitt lymphoma.
• French and British (FAB) system. The French American British (FAB) system is an older system that doctors use less often. It divides acute lymphoblastic leukemia into 3 groups (L1, L2 and L3) depending on what the leukaemia cells look like under the microscope.

Ask your doctor which system they are using if you are unsure. The type of acute lymphocytic leukemia (acute lymphoblastic leukemia) you have tells you the type of cell that the cancer started in. Knowing this helps your doctor decide which treatment you need.

In adults, French-American-British (FAB) L1 morphology (more mature-appearing lymphoblasts) is present in fewer than 50% of patients, and L2 morphology (more immature and pleomorphic) predominates ¹⁰. L3 (Burkitt) acute lymphoblastic leukemia (acute lymphoblastic leukemia) is much less common than the other two FAB subtypes. It is characterized by blasts with cytoplasmic vacuolizations and surface expression of immunoglobulin, and the bone marrow often has an appearance described as a starry sky owing to the presence of numerous apoptotic cells. L3 acute lymphoblastic leukemia is associated with a variety of translocations that involve translocation of the c-myc proto-oncogene to the immunoglobulin gene locus t(2;8), t(8;12), and t(8;22).

About 95% of all types of acute lymphoblastic leukemia (except Burkitt, which usually has an L3 morphology by the FAB classification) have elevated terminal deoxynucleotidyl transferase (TdT) expression. This elevation is extremely useful in diagnosis; if concentrations of the enzyme are not elevated, the diagnosis of acute lymphoblastic leukemia is suspect. However, 20% of cases of AML may express TdT; therefore, its usefulness as a lineage marker is limited. Because Burkitt leukemias are managed according to different treatment algorithms, it is important to specifically identify these cases prospectively by their L3 morphology, absence of TdT, and expression of surface immunoglobulin. Patients with Burkitt leukemias will typically have one of the following three chromosomal translocations:

• t(8;14)
• t(2;8)
• t(8;22)

Some patients presenting with acute leukemia may have a cytogenetic abnormality that is morphologically indistinguishable from the Philadelphia chromosome (Ph1) ¹¹. The Ph1 occurs in only 1% to 2% of patients with acute myeloid leukemia (AML), but it occurs in about 20% of adults and a small percentage of children with acute lymphoblastic leukemia ¹². In the majority of children and in more than one-half of adults with Ph1-positive acute lymphoblastic leukemia, the molecular abnormality is different from that in Ph1-positive chronic myelogenous leukemia (CML).

Many patients who have molecular evidence of the BCR-ABL fusion gene, which characterizes the Ph1, have no evidence of the abnormal chromosome by cytogenetics. The BCR-ABL fusion gene may be detectable only by pulsed-field gel electrophoresis or reverse transcription-polymerase chain reaction for the BCR-ABL fusion gene because many patients have a different fusion protein from the one found in CML (p190 vs. p210).

Using heteroantisera and monoclonal antibodies, acute lymphoblastic leukemia cells can be divided into several subtypes (see Table 1).

Table 1. Frequency of Acute Lymphoblastic Leukemia (ALL) Cell Subtypes

Cell Subtype	Approximate Frequency
Early B-cell lineage	80.00%
T cells	10%–15%
B cells with surface immunoglobulins	<5%

[ Source ¹³ ]

Subtypes of acute lymphocytic leukemia (acute lymphoblastic leukemia)

Different systems have been used to classify acute lymphocytic leukemia into subtypes.

In the 1970s, a group of French, American, and British (FAB) leukemia experts divided acute lymphocytic leukemia into 3 subtypes (L1, L2, and L3), based on the way the leukemia cells looked under the microscope after routine staining. This system, known as the FAB classification, has largely been replaced, as newer lab tests now allow doctors to classify acute lymphocytic leukemia more accurately.

Doctors have found that cytogenetic tests, flow cytometry, and other lab tests provide more detailed information about the subtype of acute lymphocytic leukemia and the patient’s prognosis. These tests help divide acute lymphocytic leukemia into groups based on the gene and chromosome changes in the leukemia cells.

The World Health Organization (WHO) system, most recently updated in 2016, includes some of these factors to try to better classify acute lymphocytic leukemia. The WHO system divides acute lymphocytic leukemia into several groups:

B-cell acute lymphocytic leukemia

• B-cell acute lymphocytic leukemia with certain genetic abnormalities (gene or chromosome changes)
  • B-cell acute lymphocytic leukemia with hypodiploidy (the leukemia cells have fewer than 44 chromosomes [normal cells have 46])
  • B-cell acute lymphocytic leukemia with hyperdiploidy (the leukemia cells have more than 50 chromosomes)
  • B-cell acute lymphocytic leukemia with a translocation between chromosomes 9 and 22 [t(9;22)] (the Philadelphia chromosome, which creates the BCR-ABL1 fusion gene)
  • B-cell acute lymphocytic leukemia with a translocation between chromosome 11 and another chromosome
  • B-cell acute lymphocytic leukemia with a translocation between chromosomes 12 and 21 [t(12;21)]
  • B-cell acute lymphocytic leukemia with a translocation between chromosomes 1 and 19 [t(1;19]
  • B-cell acute lymphocytic leukemia with a translocation between chromosomes 5 and 14 [t(5;14)]
  • B-cell acute lymphocytic leukemia with amplification (too many copies) of a portion of chromosome 21 (iAMP21)*
  • B-cell acute lymphocytic leukemia with translocations involving certain tyrosine kinases or cytokine receptors (also known as “BCR-ABL1–like acute lymphocytic leukemia”)*
• B-cell acute lymphocytic leukemia, not otherwise specified

T-cell acute lymphocytic leukemia

• Early T-cell precursor lymphoblastic leukemia.

* It’s not yet clear if there’s enough evidence that it’s a unique group (meaning it is still a “provisional entity”)

Philadelphia positive acute lymphoblastic leukemia (Ph1+ ALL)

In Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1+ ALL) you have a particular change in the chromosomes of the leukemia cells. About 20 to 30 out of every 100 people with acute lymphoblastic leukemia (about 20 to 30%) have this change.

The human body is made up of trillions of cells. Inside each cell is a nucleus and within the nucleus are the cell’s chromosomes. Most cells of your body have 23 pairs of chromosomes. Chromosomes are made up of DNA, which gives the instructions that tell a cell what to do. Sections of DNA are called genes. Genes make proteins which have particular jobs to do in the body. For example some genes control how much a cell grows and divides and when to die. Whilst other genes tell your body what color your hair will be or what color your eyes will be.

When a cell divides to make new cells, the chromosomes normally stay the same. But sometimes mistakes happen.

In Philadelphia chromosome positive acute lymphoblastic leukemia an abnormal change happens to chromosomes 9 and 22. Part of chromosome 9 breaks off where the gene ABL1 is located and part of chromosome 22 breaks off where the BCR gene is located. The broken parts swap places creating a new gene called BCR-ABL1 on chromosome 22, which causes the cell to make too much of a protein called tyrosine kinase. This protein encourages leukaemia cells to grow and multiply. Doctors treat Philadelphia positive acute lymphoblastic leukemia with a targeted cancer drug called imatinib (tyrosine kinase blocker), which blocks this protein. You take them as tablets.

The following tyrosine kinase inhibitors (TKIs) have been approved to treat Philadelphia chromosome-positive ALL (Ph+ ALL):

• Imatinib (Gleevec), taken by mouth, is used to treat:
  • Adult patients with relapsed or refractory Ph+ ALL
  • Pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy
• Dasatinib (Sprycel), taken by mouth, is used to treat:
  • Adults with Ph+ ALL who no longer benefit from or did not tolerate, other treatment
  • Children 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy.
• Ponatinib (Iclusig), taken by mouth, used to treat adults who have:
  • Ph+ ALL who cannot receive any other tyrosine kinase inhibitor (TKI) medicines
  • T315I-positive Ph+ ALL

Common side effects of tyrosine kinase inhibitors (TKIs) include low blood counts, abnormal bleeding and pain, nausea and vomiting, diarrhea, fatigue, rashes, headaches and pain in muscles, bones and joints. They may also cause fluid to collect under the eyes and in the hands, feet or lungs. Uncommon but serious side effects include a change in the rhythm of the heart, blood vessel narrowing or blood clot formation.

Dasatinib may cause fluid to collect around the lungs. Ponatinib side effects may include blood clots, narrowing of blood vessels, heart attack, stroke, liver problems or inflammation of the pancreas.

In addition, another 10 to 30 percent of adults with ALL have a subtype known as Philadelphia chromosome-like ALL (Ph-like ALL). Unlike those with Ph+ ALL, who share a similar genetic mutation, patients with Ph-like ALL have a highly diverse range of genetic mutations that activate tyrosine kinase signaling. Researchers are working to understand better ways to identify these mutations and to determine whether specific tyrosine kinase inhibitors (TKIs) can be effective.

Mixed lineage acute leukemias

A small number of acute leukemias have both lymphocytic and myeloid features. Sometimes the leukemia cells have both myeloid and lymphocytic traits in the same cells. In other cases, a person may have some leukemia cells with myeloid features and others with lymphocytic features. These types of leukemias may be called mixed lineage leukemia, acute undifferentiated leukemia or mixed phenotype acute leukemia (MPAL).

Most studies suggest these leukemias tend to have a poorer outlook than standard subtypes of acute lymphocytic leukemia or acute myeloid leukemia. Not all doctors agree on the best way to treat them. Intensive treatment (such as a stem cell transplant) is often used when possible, as there is a high risk of recurrence after treatment.

Prognostic factors for acute lymphocytic leukemia

As leukemia treatment has improved over the years, research has focused on why some people have a better chance for cure than others. Different factors that affect a person’s prognosis (outlook) are called prognostic factors. They can help doctors decide if people with a certain type of leukemia should get more or less treatment.

Age

Among adults, younger patients tend to have a better prognosis than older patients. There is no set cutoff for this, but generally those younger than 50 do better than those in their 50s, while people in their 50s do better than those in their 60s or older.

Some of this might be because older patients are more likely to have unfavorable chromosome abnormalities (see below). Older patients are also more likely to have other medical conditions that can make it harder to treat them with more intense chemotherapy regimens.

Initial white blood cell count

People with a lower white blood cell count (less than 30,000 for B-cell acute lymphocytic leukemia and less than 100,000 for T-cell acute lymphocytic leukemia) when they are first diagnosed tend to have a better prognosis.

Gene or chromosome abnormalities

Whether the leukemia cells have certain changes in their genes or chromosomes can affect prognosis. For example, patients tend to have a poorer outcome if the leukemia cells have:

• The Philadelphia chromosome (a translocation between chromosomes 9 and 22), although this outlook has improved with modern targeted therapy drugs
• A translocation between chromosomes 4 and 11
• A translocation involving chromosome 14
• Amplification (too many copies) of part of chromosome 21
• Fewer than 44 chromosomes (hypodiploidy)
• 5 or more chromosome changes (complex karyotype)

On the other hand, people tend to have a better outlook if the leukemia cells have:

• A translocation between chromosomes 12 and 21
• More than 50 chromosomes (hyperdiploidy)

Response to chemotherapy

Patients who go into a complete remission (no visible leukemia in the bone marrow – see below) within 4 to 5 weeks of starting treatment tend to have a better prognosis than those for whom this takes longer. Patients who don’t achieve a complete remission at all have a poorer outlook. The presence of minimal residual disease (described below) after initial treatment also seems to affect prognosis, although this is still being studied.

Status of acute lymphocytic leukemia during and after treatment

How well leukemia responds to treatment affects the patient’s long-term chance for recovery.

Remission

A remission (complete remission) is usually defined as having no evidence of leukemia after treatment. This means the bone marrow contains fewer than 5% blast cells, the blood cell counts are within normal limits, and there are no signs or symptoms of the disease. A complete molecular remission means there is no evidence of leukemia cells in the bone marrow, even when using very sensitive lab tests, such as polymerase chain reaction (PCR). Even when leukemia is in remission, this does not always mean that it has been cured.

Minimal residual disease

Minimal residual disease (MRD) is a term used after treatment when leukemia cells can’t be found in the bone marrow using standard lab tests (such as looking at cells under a microscope), but they can still be detected with more sensitive tests (such as flow cytometry or PCR).

Patients with minimal residual disease after treatment are more likely to have the leukemia relapse (come back after treatment) and overall have a poorer outlook than those who achieve a complete remission. Doctors are studying if these patients could benefit from further or more intensive treatment.

Active disease

Active disease means that either there is evidence that the leukemia is still present during treatment or that the disease has relapsed (come back) after treatment. For a patient to be in relapse, more than 5% of the bone marrow must be made up of blast cells.

Acute lymphocytic leukemia survival rate

Survival rates tell you what portion of people with the same type and stage of cancer are still alive a certain length of time (usually 5 years) after they were diagnosed. These numbers can’t tell you how long you will live, but they might help give you a better understanding about how likely it is that your treatment will be successful.

Statistics on the outlook for people with a certain type and stage of cancer are often given as 5-year survival rates, but many people live longer – often much longer – than 5 years. The 5-year survival rate is the percentage of people who live at least 5 years after being diagnosed with cancer. For example, a 5-year survival rate of 90% means that an estimated 90 out of 100 people who have that cancer are still alive 5 years after being diagnosed.

Relative survival rates are often a more accurate way to estimate the effect of cancer on survival. These rates compare people with adrenal cancer to people in the overall population. For example, if the 5-year relative survival rate for a specific type and stage of cancer is 90%, it means that people who have that cancer are, on average, about 90% as likely as people who don’t have that cancer to live for at least 5 years after being diagnosed.

But remember, the 5-year relative survival rates are estimates – your outlook can vary based on a number of factors specific to you.

Cancer survival rates don’t tell the whole story

Survival rates are often based on previous outcomes of large numbers of people who had the disease, but they can’t predict what will happen in any particular person’s case. There are a number of limitations to remember:

• The numbers below are among the most current available. But to get 5-year survival rates, doctors have to look at people who were treated at least 5 years ago. As treatments are improving over time, people who are now being diagnosed with adrenal cancer may have a better outlook than these statistics show.
• These statistics are based on the stage of the cancer when it was first diagnosed. They do not apply to cancers that come back later or spread, for example.
• Besides the cancer stage, many other factors can affect a person’s outlook, such as age and overall health, and how well the cancer responds to treatment.

Your doctor can tell you how these numbers may apply to you, as he or she is familiar with your situation.

Generally for people with acute lymphocytic leukemia:

• around 70 out of 100 people (70%) will survive their leukemia for 5 years or more after they are diagnosed

This is for people of all ages. Younger people tend to do much better than older people:

• in those aged 14 or younger, more than 90 out of 100 (more than 90%) will survive their leukemia for 5 years or more after they are diagnosed
• in those aged between 15 and 24, almost 70 out of 100 (almost 70%) will survive their leukemia for 5 years or more after diagnosis
• in those aged between 25 and 64, almost 40 out of 100 (almost 40%) will survive their leukemia for 5 years or more after they are diagnosed
• in those aged 65 or older, almost 15 out of 100 (almost 15%) will survive their leukemia for 5 years or more after diagnosis

What affects survival?

Your age affects outlook. Younger people have a better prognosis.

Outlook depends on the specific type of white blood cell the acute lymphoblastic leukemia affects. It is also affected by changes in your chromosomes or genes. These are called cytogenetic tests. Some specific genetic abnormalities in your leukemia cells may make the leukemia harder to treat successfully.

Survival is affected by how advanced the acute lymphocytic leukemia is at diagnosis. If you have a high number of white blood cells in the blood at diagnosis, the outlook is poorer. Your outlook is also worse if there are leukemia cells in your brain or spinal fluid when you are diagnosed.

Your outlook is also affected by how well the acute lymphocytic leukemia responds to treatment and how long it takes to get into remission. Remission means the acute lymphocytic leukemia is not active and doctors can’t find any sign of it.

If the acute lymphocytic leukemia comes back (relapses) after treatment, it is sometimes possible to have a second remission with more chemotherapy.

Acute lymphocytic leukemia prognosis

Among children with acute lymphoblastic leukemia, approximately 98% attain remission ¹⁴. Approximately 85% of patients aged 1 to 18 years with newly diagnosed acute lymphoblastic leukemia treated on current regimens are expected to be long-term event-free survivors, with over 90% surviving at 5 years ¹⁵. Between 15 and 20 percent of children who are treated for acute lymphoblastic leukemia and achieve an initial complete remission will have the disease return ¹⁶. The prognosis is much lower for children who have relapsed, compared with newly diagnosed acute lymphoblastic leukemia.

The outlook for adults with acute lymphocytic leukemia is less promising. Around 40% of people aged between 25 and 64 will live for five years or more after receiving their diagnosis. In those aged 65 or over, around 15% will live for five years or more after being diagnosed. Adults with acute lymphoblastic leukemia who relapse have a poor prognosis. Young adults less than 30 years old with a first complete remission of two years or more may have the chance of long-term survival; however, older patients (>30 years) who relapse early do not have realistic survival options with current therapies.

Acute lymphocytic leukemia treatment

In general, treatment for acute lymphocytic leukemia falls into 3 phases:

1. Induction (remission induction) therapy. The purpose of the first phase (induction phase) of treatment is to kill most of the leukemia cells in the blood and bone marrow and to restore normal blood cell production.
2. Consolidation (intensification) therapy. Also called post-remission therapy, this phase of treatment is aimed at destroying any remaining leukemia in the body, such as in the brain or spinal cord.
3. Maintenance therapy. The third phase of treatment prevents leukemia cells from regrowing. The treatments used in this stage are often given at much lower doses over a long period of time, often years.

Depending on your situation, the phases of treatment for acute lymphocytic leukemia can span two to three years, with the maintenance phase taking up most of this time. Treatment may be more or less intense, depending on the subtype of acute lymphoblastic leukemia and other prognostic factors.

Acute lymphoblastic leukemia can spread to the area around the brain and spinal cord (central nervous system or CNS). Sometimes this has already occurred by the time acute lymphoblastic leukemia is first diagnosed. This spread is found when the doctor does a lumbar puncture (spinal tap) and leukemia cells are found in the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord.

Even if leukemia cells aren’t found in the CSF at diagnosis, it’s possible that they might spread there later on. This is why an important part of treatment for acute lymphoblastic leukemia is central nervous system (CNS) prophylaxis – treatment that lowers the risk of the leukemia spreading to the area around the brain or spinal cord.

• Preventive treatment to the spinal cord. During each phase of therapy, people with acute lymphocytic leukemia may receive additional treatment to kill leukemia cells located in the central nervous system. In this type of treatment, chemotherapy drugs are often injected directly into the fluid that covers the spinal cord.

Treatments may include:

• Chemotherapy. Chemotherapy, which uses drugs to kill cancer cells, is typically used as an induction therapy for children and adults with acute lymphocytic leukemia. Chemotherapy drugs can also be used in the consolidation and maintenance phases.
• Targeted therapy. Targeted therapy uses drugs or other substances that target and attack specific cancer cells, but are less likely to harm normal cells. Targeted drugs attack specific abnormalities present in cancer cells that help them grow and thrive. A certain abnormality called the Philadelphia chromosome is found in some people with acute lymphocytic leukemia. For these people, targeted drugs may be used to attack cells that contain that abnormality. Targeted therapy may be used during or after chemotherapy.
• Immunotherapy. Immunotherapy treatments use substances that can stimulate and/or suppress your immune system to help your body fight cancer. There are immunotherapy treatments that target proteins, called cluster of differentiation (CD) antigens, on the surface of leukemia cells. B-cell ALL is typically characterized by the presence of the proteins CD10, CD19, CD20, CD22, CD24 and CD79a. T-cell ALL is typically associated with the presence of CD3.
• Monoclonal antibodies. Monoclonal antibodies are proteins that are made in the laboratory. They can bind to substances in the body, including cancer cells. Most are designed to attach to one specific substance. These drugs can be used alone to destroy cancer cells or to carry drugs, toxins or radioactive substances directly to the cancer cells.
• Radiation therapy. Radiation therapy uses high-powered beams, such as X-rays or protons, to kill cancer cells. If the cancer cells have spread to the central nervous system, your doctor may recommend radiation therapy. You might have radiotherapy as part of your treatment for acute lymphoblastic leukemia (ALL).
• Chimeric Antigen Receptor (CAR) T-Cell Therapy. CAR T-cell therapy is a type of immunotherapy. You might also hear it called a type of adoptive cell transfer. CAR T-cell therapy is a very complex and specialist treatment. With this treatment, a specialist collects and makes a small change to your T cells. After a few weeks, you have a drip containing these cells back into your bloodstream. The CAR T-cells then recognize and attack the cancer cells. 
  
• Bone marrow transplant. A bone marrow transplant, also known as a stem cell transplant, may be used as consolidation therapy in people at high risk of relapse or for treating relapse when it occurs. This procedure allows someone with leukemia to re-establish healthy bone marrow by replacing leukemic bone marrow with leukemia-free marrow from a healthy person. A bone marrow transplant begins with high doses of chemotherapy or radiation to destroy any leukemia-producing bone marrow. The marrow is then replaced by bone marrow from a compatible donor (allogeneic transplant). Stem cell transplantation is a complex treatment. It can cause serious side effects that can be life-threatening, so it may not be a treatment option for every acute lymphoblastic leukemia patient.
• Clinical trials. Clinical trials are experiments to test new cancer treatments and new ways of using existing treatments. While clinical trials give you or your child a chance to try the latest cancer treatment, treatment benefits and risks may be uncertain. Discuss the benefits and risks of clinical trials with your doctor.

Induction therapy

The induction stage of treatment is carried out in hospital or a specialist center. This is because you’ll probably need regular blood transfusions as your blood won’t contain enough healthy blood cells. You’ll also be vulnerable to infection, so it’s important you’re in a sterile environment where your health can be carefully monitored and any infection that develops can be treated quickly. Antibiotics may also be prescribed to help prevent further infection.

Induction chemo usually lasts for a month or so. Different combinations of chemotherapy drugs might be used, but they typically include:

• Vincristine
• Dexamethasone or prednisone
• An anthracycline drug such as doxorubicin (Adriamycin) or daunorubicin

Based on the patient’s prognostic factors, some regimens may also include cyclophosphamide, L-asparaginase (or pegaspargase), and/or high doses of methotrexate or cytarabine (ara-C) as part of the induction phase.

For acute lymphoblastic leukemia patients whose leukemia cells have the Philadelphia chromosome (Ph1+ ALL), a targeted drug such as imatinib (Gleevec) or dasatinib (Sprycel) is often included as well.

For patients who are older (typically over 65) or who have other serious health conditions, many of the same drugs are used for induction, although the doses of the drugs might need to be reduced.

This first month of treatment is intensive and requires frequent visits to the doctor. You may spend some or much of this time in the hospital, because serious infections or other complications can occur. It’s very important to take all medicines as prescribed. Sometimes complications can be serious enough to be life-threatening, but with recent advances in supportive care (nursing care, nutrition, antibiotics, growth factors, red blood cell and platelet transfusions as needed, etc.), these are much less common than in the past.

Most often, leukemia goes into remission with induction chemotherapy. But because leukemia cells may still be hiding somewhere in the body, further treatment is needed.

At the end of induction therapy, doctors will check to see whether the patient has achieved a complete remission. A complete remission is achieved when:

• No more than 5 percent of cells in the bone marrow are blast cells
• Blood cell counts are back to normal
• All signs and symptoms of acute lymphoblastic leukemia are gone.

Sixty percent to 80% of adults with acute lymphoblastic leukemia usually achieve a complete remission status following appropriate induction therapy ¹⁷. Appropriate initial treatment, usually consisting of a regimen that includes the combination of vincristine, prednisone, and an anthracycline, with or without asparaginase, results in a complete response rate of up to 80% ¹⁷. In patients with Ph1-positive acute lymphoblastic leukemia, the remission rate is generally greater than 90% when standard induction regimens are combined with BCR-ABL tyrosine kinase inhibitors. In the largest study published to date of Ph1-positive acute lymphoblastic leukemia patients, overall survival (OS) for 1,913 adult acute lymphoblastic leukemia patients was 39% at 5 years ¹⁸.

Patients who experience a relapse after remission usually die within 1 year, even if a second complete remission is achieved. If there are appropriate available donors and if the patient is younger than 55 years, bone marrow transplantation may be a consideration in the management of this disease ¹⁹. Transplant centers performing five or fewer transplants annually usually have poorer results than larger centers ²⁰. If allogeneic stem cell transplant is considered, a recommendation is that transfusions with blood products from a potential donor be avoided, if possible ²¹..

Chemotherapy

The current standard treatment for acute lymphoblastic leukemia is long-term chemotherapy. Chemotherapy drugs kill fast-growing cells throughout your body, including both cancer cells (leukemia cells) and normal, healthy cells. Chemotherapy for acute lymphoblastic leukemia typically lasts for about 2 to 3 years and it is often intense, especially in the first few months of treatment. The most common treatment regimens use a combination of more than one anticancer drug.

Different types of chemotherapy drugs work in different ways to kill leukemia cells or to stop new leukemia cells from forming. Therefore, more than one chemotherapy drug is frequently used. Chemotherapy is usually given in treatment cycles. Each cycle is made up of a certain number of days of treatment, followed by a certain number of days of rest. The rest days allow the body time to recover before the next treatment cycle begins. Cycles vary in length, depending on which drugs are used.

Although some medications may be given as pills, you’ll need more than 1 medication given as an injection into a vein. During an intravenous (IV) infusion, the drugs are slowly injected into the vein over the course of a few hours or several days in the case of a “continuous infusion.” Often, IV chemotherapy is given through a thin, soft tube called a “central venous line,” a “catheter,” or a “central line” that goes into a vein in your chest. The central line is usually attached to a “port” or other device that is surgically placed under the skin, into the patient’s upper chest, to allow access to the central line.

Some chemotherapy medication may also be directly administered into your cerebrospinal fluid (CSF) to kill any leukemia cells that may have spread to your nervous system and brain.

Chemotherapy damages healthy bone marrow cells as well as the leukaemia cells. So you will generally need to stay in hospital until you have recovered. This is usually about 4 to 6 weeks.

Chemotherapy for acute lymphoblastic leukemia uses a combination of anti-cancer drugs. The most commonly used chemo drugs include:

• Vincristine or liposomal vincristine (Marqibo)
• Daunorubicin (daunomycin) or doxorubicin (Adriamycin)
• Cytarabine (cytosine arabinoside, ara-C)
• L-asparaginase or PEG-L-asparaginase (pegaspargase or Oncaspar)
• 6-mercaptopurine (6-MP)
• Methotrexate
• Cyclophosphamide
• Prednisone
• Dexamethasone
• Nelarabine (Arranon)

People typically get several of these drugs at different times during the course of treatment, but they do not get all of them.

Chemotherapy drugs possible side effects

Chemo drugs can affect some normal cells in the body, which can lead to side effects. The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken. Common side effects can include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Diarrhea or constipation

Chemo drugs also affect the normal cells in bone marrow, which can lower blood cell counts. This can lead to:

• Increased risk of infections (from having too few normal white blood cells)
• Easy bruising or bleeding (from having too few blood platelets)
• Fatigue and shortness of breath (from having too few red blood cells)

Most side effects from chemo go away once treatment is finished. Low blood cell counts can last weeks, but then should return to normal. There are often ways to lessen chemo side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to ask your cancer care team about medicines to help reduce side effects, and let your doctor or nurse know when you do have side effects so they can be managed effectively.

Low white blood cell counts: Some of the most serious side effects of chemo are caused by low white blood cell counts. You may get antibiotics and drugs that help prevent fungal and viral infections before before you have signs of infection or at the earliest sign that an infection may be developing (such as a fever). Drugs known as growth factors, such as filgrastim (Neupogen), pegfilgrastim (Neulasta), and sargramostim (Leukine), are sometimes given to increase the white blood cell counts after chemo, to help lower the chance of infection. However, it’s not clear if they have an effect on treatment success. There are also steps that you can take to lower your risk of infection, such as washing your hands often. These are discussed in Infections in People With Cancer.

Low platelet counts: If your platelet counts are low, you may be given drugs or platelet transfusions to help protect against bleeding.

Low red blood cell counts: Shortness of breath and extreme fatigue caused by low red blood cell counts (anemia) may be treated with drugs or with red blood cell transfusions.

Decisions about when a patient can leave the hospital are often influenced by his or her blood counts. Some people find it helpful to keep track of their blood counts. If you are interested in this, ask your doctor or nurse about your blood cell counts and what these numbers mean.

Side effects of specific chemotherapy drugs

Certain drugs might cause specific side effects. For example:

• Cytarabine (ara-C), especially when used at high doses, can cause dryness in the eyes and can affect certain parts of the brain, which can lead to problems with coordination and balance.
• Vincristine can damage nerves, which can lead to numbness, tingling, or weakness in hands or feet.
• Anthracyclines (such as daunorubicin or doxorubicin) can damage the heart, so the total dose needs to be watched closely, and these drugs might not be used in someone who already has heart problems.

Other organs that could be damaged by certain chemo drugs include the kidneys, liver, testicles, ovaries, and lungs. Doctors and nurses carefully monitor treatment to reduce the risk of these side effects as much as possible. If serious side effects occur, the chemo may have to be reduced or stopped, at least for a time.

Second cancers

One of the most serious side effects of acute lymphoblastic leukemia therapy is an increased risk of getting acute myeloid leukemia (AML) at a later time. This occurs in a small portion of patients after they have received certain chemo drugs. Less often, people cured of leukemia may later develop non-Hodgkin lymphoma or other cancers. Of course, the risk of getting these second cancers must be balanced against the obvious benefit of treating a life-threatening disease such as leukemia with chemotherapy.

Tumor lysis syndrome

This side effect of chemo is most common in patients who have large numbers of leukemia cells in the body, so it is seen most often in the first (induction) phase of treatment. When chemo kills the leukemia cells, they break open and release their contents into the bloodstream. This can overwhelm the kidneys, which aren’t able to get rid of all of these substances at once. Excess amounts of certain minerals can also affect the heart and nervous system. This can often be prevented by giving extra fluids during treatment and by giving certain drugs, such as bicarbonate, allopurinol, and rasburicase, which help the body get rid of these substances.

Steroid therapy

You may also be given corticosteroid injections or tablets to help improve the effectiveness of chemotherapy.

Imatinib

If you have a type of leukemia known as Philadelphia chromosome-positive acute lymphoblastic leukemia, you’ll also be given a medicine called imatinib.

Imatinib is what’s known as a targeted therapy, which works by blocking the signals in the cancerous cells that cause them to grow and reproduce. This kills the cancerous cells. Imatinib is taken orally (as a tablet). The side effects of imatinib are usually mild and should improve over time.

The side effects of imatinib include:

• nausea
• vomiting
• swelling in the face and lower legs
• muscle cramps
• rash
• diarrhea

Depending on how well you respond to treatment, the induction phase can last from 2 weeks to several months.

In some cases, you or your child may be able to leave hospital and receive treatment on an outpatient basis if your symptoms improve.

Central Nervous System (CNS) Prophylaxis and Treatment

It is uncommon for leukemia cells to be present in the cerebrospinal fluid (CSF) at the time of diagnosis, occurring in only 3 to 7 percent of cases. However, without the routine administration of a therapy targeting the central nervous system (referred to as “CNS prophylaxis”), leukemia cells eventually spread to the cerebrospinal fluid in a large percentage of patients (50 percent or more). CNS prophylaxis is administered to prevent leukemia cells from spreading to the area around the brain and the spinal cord. It is typically given to all patients during the induction phase, the consolidation phase and, in some cases, the maintenance phase ²².

Central nervous system-directed therapy may include:

• Intrathecal chemotherapy, in which anticancer drugs are injected into the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. These drugs may include methotrexate, cytarabine and corticosteroids (prednisone, dexamethasone).
• Systemic chemotherapy, in which anticancer drugs are given through a vein to reach any leukemia cells in the central nervous system. These drugs may include high-dose methotrexate, intermediate-/high-dose cytarabine and pegaspargase.
• Cranial irradiation, in which radiation therapy to the brain is used to kill cancer cells.

Assessing treatment response

At the end of induction therapy, blood and bone marrow tests will be done to see how well your treatment is working. Your doctor will check to see whether you have achieved a complete remission.

A complete remission is achieved when:

• No leukemic blast cells are detected in the bone marrow (with a microscope)
• No more than 5 percent of cells in the bone marrow are blast cells
• No blast cells are in the bloodstream
• Blood cell counts are back to normal
• All signs and symptoms of acute lymphoblastic leukemia are gone

If a patient does not achieve remission after the first course of induction chemotherapy, that may indicate the first treatment approach is unlikely to work. In this situation, a “second-line” course of chemotherapy is given, usually using different drugs.

Even when a complete remission is achieved, some leukemia cells that cannot be seen with a microscope may still remain in the bone marrow. The presence of these cells is referred to as minimal/measurable residual disease (MRD). Patients who have achieved remission after initial treatment, but who still have minimal residual disease, are at increased risk of disease relapse. Testing for minimal residual disease can help doctors identify patients who may benefit from further treatment with intensified therapies such as allogeneic stem cell transplantation.

It is important to get tested for minimal residual disease after achieving remission. The tests used most commonly to detect minimal residual disease are flow cytometry, polymerase chain reaction (PCR) and next-generation sequencing. These tests typically use samples of bone marrow cells, but in some cases blood samples can be used. They are much more sensitive than standard tests that examine cell samples with a microscope.

It is often recommended that minimal residual disease testing be done after the completion of induction therapy. Recommendations for additional minimal residual disease testing depend on the treatment regimen that is used. If you are in remission but test positive for minimal residual disease, your doctor may prescribe blinatumomab (Blincyto). Blinatumomab is approved by the US Food and Drug Administration (FDA) to treat adults and children with:

• B-cell acute lymphoblastic leukemia and are in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1 percent
• Relapsed or refractory B-cell acute lymphoblastic leukemia.

For patients who do not achieve remission after the first course of induction chemotherapy, a second course of chemotherapy is given, usually using different chemotherapy drugs.

Postremission therapy

“Postremission therapy” refers to ALL treatments given to patients after their disease is in complete remission. Even when minimal residual disease test results are negative, undetectable residual cancer cells are believed to remain in the body. Because of this, patients with acute lymphoblastic leukemia require additional treatment after they achieve remission. As in the induction phase, individual factors such as the age of the patient, the ability to tolerate intensive treatment, cytogenetic test results, the availability of a matched stem cell donor and other considerations may influence the decision about the best treatment approach. Most of these phases are given in an outpatient setting, while some phases require a brief hospitalization for chemotherapy administration.

Consolidation therapy

The second phase of treatment is called consolidation therapy. This phase can also include phases known as “intensification” therapy. Consolidation therapy begins once acute lymphoblastic leukemia is in remission.

Leukemia can return if just 1 cancerous cell remains in your body. The goal of consolidation treatment is to ensure that any remaining leukemia cells are killed. Consolidation therapy is usually given in cycles over 4 to 6 months.

Treatment involves receiving regular injections of chemotherapy medication. This is usually done on an outpatient basis, which means you won’t have to stay in hospital overnight. But you may need some short stays in hospital if your symptoms suddenly get worse or you develop an infection.

The specific combination of drugs and the duration of therapy for consolidation vary. Depending on the treatment regimen used, consolidation therapy may consist of entirely different drugs than those used during induction, or some of the same drugs that were successful in the induction phase, either at the same or higher doses.

Consolidation therapy protocols may include one or two intensified treatments that are similar to the ones used during the induction phase. These are also known as “delayed intensification” treatments. Generally, several chemotherapy drugs are combined to help prevent the leukemia cells from developing drug resistance.

Some of the drugs used in the consolidation phase may include:

• High-dose methotrexate
• Cytarabine
• Vincristine
• 6-mercaptopurine (6-MP)
• Cyclophosphamide
• Pegaspargase
• Corticosteroids (prednisone, dexamethasone)

In addition, most treatment plans call for the continuation of CNS prophylaxis and treatment.

A targeted drug like imatinib is also continued for patients whose leukemia cells have the Philadelphia chromosome (Ph+ ALL).

Some patients in remission, such as those who have certain subtypes of acute lymphocytic leukemia or other poor prognostic factors, are still at high risk for the leukemia relapsing (coming back). Instead of standard chemo, doctors may suggest an allogeneic stem cell transplant (SCT) at this time, especially for those who have a brother or sister who would be a good donor match. An autologous stem cell transplant (SCT) may be another option. Doctors usually recommend stem cell transplantation for patients whose ALL has high-risk genetic features or for patients who have high rates of minimal residual disease after initial therapy (called “persistent MRD”). However, not everyone can have a stem cell transplant. It is an intense and complex treatment that can cause life-threatening side effects in some patients. Being able to have a transplant also depends on having a matched donor and an adult caregiver. The possible risks and benefits of a stem cell transplant need to be weighed carefully for each patient based on their own case, as it’s not clear that they are helpful for every patient. Patients considering this procedure should think about having it done at a center that has done a lot of stem cell transplants.

Maintenance therapy

The third phase of treatment is called maintenance therapy. The goal of maintenance therapy is to prevent disease relapse after induction therapy and consolidation therapy.

It involves taking regular doses of chemotherapy tablets while having regular check-ups to monitor the effectiveness of your treatment.

Maintenance therapy usually lasts for about 2 years.

Some drugs used in the maintenance phase are given orally and, typically, patients are treated in an outpatient setting. Patients receive lower doses of chemotherapy drugs and, as a result, tend to have less-severe side effects.
Most maintenance therapy regimens include:

• 6-mercaptopurine (administered daily)
• Methotrexate (administered weekly)
• Periodic doses of vincristine and corticosteroids

For patients with Philadelphia chromosome-positive ALL (Ph+ ALL), a Tyrosine Kinase Inhibitor (TKI) is often included during the maintenance phase as well.

The following tyrosine kinase inhibitors (TKIs) have been approved to treat Philadelphia chromosome-positive ALL (Ph+ ALL):

• Imatinib (Gleevec), taken by mouth, is used to treat:
  • Adult patients with relapsed or refractory Ph+ ALL
  • Pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy
• Dasatinib (Sprycel), taken by mouth, is used to treat:
  • Adults with Ph+ ALL who no longer benefit from or did not tolerate, other treatment
  • Children 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy.
• Ponatinib (Iclusig), taken by mouth, used to treat adults who have:
  • Ph+ ALL who cannot receive any other tyrosine kinase inhibitor (TKI) medicines
  • T315I-positive Ph+ ALL

Common side effects of tyrosine kinase inhibitors (TKIs) include low blood counts, abnormal bleeding and pain, nausea and vomiting, diarrhea, fatigue, rashes, headaches and pain in muscles, bones and joints. They may also cause fluid to collect under the eyes and in the hands, feet or lungs. Uncommon but serious side effects include a change in the rhythm of the heart, blood vessel narrowing or blood clot formation.

Dasatinib may cause fluid to collect around the lungs. Ponatinib side effects may include blood clots, narrowing of blood vessels, heart attack, stroke, liver problems or inflammation of the pancreas.

In addition, another 10 to 30 percent of adults with ALL have a subtype known as Philadelphia chromosome-like ALL (Ph-like ALL). Unlike those with Ph+ ALL, who share a similar genetic mutation, patients with Ph-like ALL have a highly diverse range of genetic mutations that activate tyrosine kinase signaling. Researchers are working to understand better ways to identify these mutations and to determine whether specific TKIs can be effective.

If you are taking an oral medication at home, it is important for you to take the medication as prescribed by the doctor. Not taking your mediation as prescribed by the doctor can increase the chance that the cancer will return (relapse).

CNS prophylaxis or treatment is typically continued at this time.

Other treatments

As well as chemotherapy and imatinib, other treatments are used in some circumstances. These are described below.

Targeted therapies

If other treatments don’t work, your cancer comes back or you have a certain type of acute lymphoblastic leukemia, you may be offered another kind of targeted therapy. There are several types of targeted therapy. Your doctors and specialists will talk to you about these if they think they might work for you.

Monoclonal antibodies

Monoclonal antibodies are proteins that are made in the laboratory. They can bind to substances in the body, including cancer cells. Most are designed to attach to one specific substance. These drugs can be used alone to destroy cancer cells or to carry drugs, toxins or radioactive substances directly to the cancer cells.

Blinatumomab (Blincyto)

Blinatumomab (Blincyto) is a bispecific antibody used to treat adults and children with:

• B-cell ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1 percent
• Relapsed or refractory B-cell ALL

Blinatumomab is a liquid that is administered slowly into a vein (by IV) as a continuous infusion over a period of 28 days. Hospitalization of the patient is typically recommended for the first few days of treatment. Side effects of blinatumomab may include:

• Fever
• Headache
• Infection
• Nausea
• Diarrhea
• Swelling
• Neurological complications such as seizures, confusion, disorientation, slurred speech and loss of balance

Inotuzumab ozogamicin (Besponsa)

Inotuzumab ozogamicin (Besponsa) is a monoclonal antibody linked to a chemotherapy drug that is indicated for the treatment of patients with relapsed or refractory B-cell ALL. Inotuzumab ozogamicin targets CD22, a surface protein expressed on the cancer cells of most B-cell ALL patients. When inotuzumab ozogamicin binds to the CD22 antigen on B cells, it enters the cell and then releases the chemotherapy drug, calicheamicin, causing the cell to die.

Inotuzumab ozogamicin is administered by IV infusion and, for appropriate patients, can be given in an outpatient setting. Common side effects include increased risk of infections, bleeding, fatigue, fever, nausea, headache and abdominal pain. Liver injury is also seen and, in rare instances, can be serious and even fatal. Older patients, as well as patients with pre-existing liver disease and those who undergo stem cell transplantation, appear to be at greater risk of serious forms of liver toxicity.

Rituximab (Rituxan)

Rituximab (Rituxan) is a monoclonal antibody that binds to CD20, a protein found on the surface of healthy B cells and on the lymphoblastic B cells of approximately 50 percent of adults with B-cell ALL. When rituximab binds to CD20, it signals the cell to die. Rituximab is not used alone to treat acute lymphocytic leukemia, but instead it is added to a chemotherapy regimen. Some studies have shown that the addition of rituximab to standard chemotherapy improved survival among adults with CD20-positive acute lymphocytic leukemia. Side effects may include allergic reactions, infections, chills, fatigue, body aches and low blood cell counts.

Radiotherapy

Radiotherapy is where high doses of controlled radiation are used to kill cancerous cells.

It’s usually used to treat acute lymphocytic leukemia in the following 2 situations:

• to treat advanced cases of acute lymphoblastic leukemia that have spread to the nervous system or brain
• to prepare the body for a bone marrow transplant

Side effects include:

• hair loss
• nausea
• fatigue

These side effects should pass after your course of radiotherapy has been completed. But your skin may be very sensitive to the effects of light for several months after treatment has finished. If this is the case, avoid sunbathing or exposure to sources of artificial light, such as sunbeds, for several months.

Many younger children treated with radiotherapy will go on to have restricted physical growth during puberty.

A small number of people develop cataracts several years after having radiotherapy. Cataracts are cloudy patches in the transparent structure at the front of the eye (the lens) that can make your vision blurred or misty. They can usually be successfully treated using cataract surgery.

Chimeric Antigen Receptor (CAR) T-Cell Therapy

CAR T-cell therapy is a type of immunotherapy. You might also hear it called a type of adoptive cell transfer. CAR T-cell therapy is a very complex and specialist treatment. With this treatment, a specialist collects and makes a small change to your T cells. After a few weeks, you have a drip containing these cells back into your bloodstream. The CAR T-cells then recognise and attack the cancer cells.

Tisagenlecleucel (Kymriah) is FDA-approved for the treatment of patients up to age 25 years who have B-cell ALL that is refractory or in second or later relapse. This treatment is designed to help your body’s own immune system fight cancer. Each dose is made for a specific patient, using the patient’s own T cells (white blood cells that help the body fight infections and cancer). The T cells are collected from the patient and then genetically modified to add a new gene containing a CAR protein, so that the T cells can identify and kill leukemia cells with CD19 on their surfaces. These modified cells are infused back into the patient’s bloodstream to kill the cancer cells. While this treatment can be very effective, it is also associated with a relatively high rate of serious complications. As a result, it can only be given at specialized cancer centers that have expertise in delivering this form of treatment.

Stem cell and bone marrow transplants

Stem cell transplantation is not used as the first or the primary treatment for acute lymphoblastic leukemia. It may be part of the treatment plan for high-risk acute lymphoblastic leukemia patients, or for patients who do not respond to other treatments. A stem cell and bone marrow transplant is a possible alternative treatment option if you or your child don’t respond to chemotherapy.

The goal of stem cell transplantation is to cure your cancer by destroying cancer cells in your bone marrow with high doses of chemotherapy. Chemotherapy, however, can cause very serious side effects. Although administering higher doses of chemotherapy drugs can kill more leukemia cells, such high doses of chemotherapy can severely damage the stem cells in the bone marrow and may result in anemia, serious infections and uncontrolled bleeding. Stem cell transplantation allows doctors to give higher doses of chemotherapy than can typically be given. After the chemotherapy, the patient receives an infusion of healthy stem cells to replace those that were destroyed by the intensive chemotherapy. The healthy blood stem cells grow and multiply, forming new bone marrow and blood cells.

There are two main types of stem cell transplantation:

• Allogeneic stem cell transplantation: A patient receives stem cells from a matched or a partially matched donor, either related or unrelated to the patient.
• Autologous stem cell transplantation: A patient’s own stem cells are collected before chemotherapy, stored and then given back to the patient after completing chemotherapy.

Stem cell transplantations are more successful if the donor has the same tissue type as you, so the ideal donor is usually your brother or sister. Before transplantation can take place, the person receiving the transplant will need to have aggressive high-dose chemotherapy and radiotherapy to destroy any cancerous cells in their body.

This can put a big strain on the body, so transplantations are usually only successful when they’re carried out in:

• children and young people
• older people in good health
• when there’s a suitable donor, such as a brother or sister

Recent research has shown it’s possible for people over the age of 40 to have a reduced intensity stem cell transplant. This is where lower than normal doses of chemotherapy and radiotherapy are used before the transplant, which places less strain on the body.

The decision to undergo a transplant should be discussed with your doctor. Your doctor will consider many factors, including your age, general health, certain prognostic factors, previous treatments, and if you have a well-matched donor.

Allogeneic Stem Cell Transplantation

Allogeneic Stem Cell Transplantation is the most common type of stem cell transplantation used to treat acute lymphoblastic leukemia. In preparation for the transplant, patients are given high doses of chemotherapy, either with or without radiation therapy, to kill the remaining leukemia cells still present in the body. This part of the treatment, called “myeloablative conditioning,” also kills cells in the bone marrow, including normal blood-forming cells. After the high-dose chemotherapy is completed, patients receive an infusion of the donor stem cells. The donated stem cells restore the bone marrow’s ability to form new blood cells.

An allogeneic stem cell transplantation creates a new immune system for the patient that helps the body fight infections and other diseases. The new immune system also has the potential to recognize and attack any remaining cancer cells in the body. The transplanted immune cells (called the “graft”) identify the leukemia cells as foreign and destroy them. This is called the “graft-versus-leukemia (GVL) effect.”

Allogeneic stem cell transplantation is associated with a higher rate of side effects and mortality than other treatment approaches. However, it may be considered a treatment option for patients with higher-risk acute lymphoblastic leukemia, based on cytogenetic and molecular test results. The decision to perform an allogeneic transplant also depends on the age of the patient and the patient’s understanding of the potential benefits and risks.

Studies show that allogeneic stem cell transplantation may benefit adult acute lymphoblastic leukemia patients in the high-risk and intermediate-risk categories who are younger than 60 years and have a HLA-matched sibling donor. The timing of the allogeneic stem cell transplantation is one of the most important factors influencing transplant outcomes, so it is very important to start a donor search as soon as possible after diagnosis, in order to identify a suitably matched related or unrelated donor.

One possible serious side effect of allogeneic transplantation is graft-versus-host disease (GVHD). This occurs when the transplanted donor immune cells (the graft) identify the cells in the recipient’s body (the host) as foreign and attack them. The parts of the body most commonly damaged by graft-versus-host disease include the skin, liver, stomach, intestines and eyes. Graft-versus-host disease can develop within weeks after transplantation or much later. A doctor can prescribe medications that can help prevent or minimize graft-versus-host disease (GVHD).

Autologous Stem Cell Transplantation

This is a procedure in which stem cells are removed from a cancer patient before the patient undergoes intensive chemotherapy, either with or without radiation therapy. The patient’s removed stem cells are stored and then returned to the patient after the chemotherapy treatment. Autologous stem cell transplantation is not commonly used to treat patients who have acute lymphoblastic leukemia, but it may be a treatment option for acute lymphoblastic leukemia patients participating in a clinical trial.

Reduced-Intensity Allogeneic Stem Cell Transplantation

This type of transplantation may be a treatment option for older patients who cannot tolerate the high doses of chemotherapy used in preparation for a standard allogeneic stem cell transplant. The conditioning therapy in a reduced-intensity transplant uses lower doses of chemotherapy and/or radiation therapy. This therapy reduces the number of cancer cells, but it does not completely destroy the patient’s bone marrow. As in standard allogeneic transplantation, the white blood cells from the donor may recognize any remaining leukemia cells as foreign and destroy them.

As with standard allogeneic stem cell transplantation, the risk of graft-versus-host disease (GVHD) is an important consideration and a potentially disabling side effect.

Clinical trials

In the US, clinical trials are currently being carried out to find the best way of treating acute lymphocytic leukemia. These studies are using innovative new techniques to see how well they work in treating and possibly curing acute lymphocytic leukemia.

It’s important to be aware of new studies so you can choose which treatments to have. But there’s no guarantee the techniques being studied in the clinical trial will be more effective than current treatments.

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, and ask about the pros and cons of enrolling in one of them. See Clinical Trials (https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials.html) to learn more.

Response rates to acute lymphoblastic leukemia treatment

In general, about 80% to 90% of adults will have complete remissions at some point during these treatments. This means leukemia cells can no longer be seen in their bone marrow. Unfortunately, about half of these patients relapse, so the overall cure rate is in the range of 40%. Again, these rates can vary a lot, depending on the subtype of acute lymphoblastic leukemia and other prognostic factors. For example, cure rates tend to be higher in younger patients.

What if the leukemia doesn’t respond or comes back after treatment?

If the leukemia is refractory – that is, if it doesn’t go away with the first treatment (which happens in about 10% to 20% of patients) – then newer or more intensive doses of chemo drugs may be tried, although they are less likely to work. Immunotherapy (monoclonal antibodies or CAR T-cell therapy) may be an option for patients with B-cell acute lymphoblastic leukemia. A stem cell transplant may be tried if the leukemia can be put into at least partial remission. Clinical trials of new treatment approaches may also be considered.

If leukemia goes into remission with the initial treatment but then comes back (relapses or recurs), it will most often do so in the bone marrow and blood. Occasionally, the brain or spinal fluid will be the first place it recurs.

In these cases, it is sometimes possible to put the leukemia into remission again with more chemotherapy (chemo), although this remission is not likely to last. The approach to treatment may depend on how soon the leukemia returns after the first treatment. If the relapse occurs after a long interval, the same or similar treatment may be used to try for a second remission. If the time interval is shorter, more aggressive chemo with other drugs may be needed.

Immunotherapy might be another option for some patients. For example, a monoclonal antibody or CAR T-cell therapy might be an option for some people with B-cell acute lymphoblastic leukemia.

Acute lymphoblastic leukemia patients with the Philadelphia chromosome who were taking a targeted drug like imatinib (Gleevec) are often switched to a different targeted drug.

For patients with T-cell acute lymphoblastic leukemia, the chemo drug nelarabine (Arranon) may be helpful.

If a second remission can be achieved, most doctors will advise some type of stem cell transplant if possible.

If the leukemia doesn’t go away or keeps coming back, eventually treatment with more chemo is unlikely to be helpful. If a stem cell transplant is not an option, a patient may want to consider taking part in a clinical trial of newer treatments.

Acute lymphocytic leukemia in Older Adolescents and Young Adults (AYA)

The term “AYA population” generally refers to patients aged 15 to 39 years. Historically, the Older Adolescents and Young Adults (AYA) population has been treated with either a pediatric acute lymphoblastic leukemia regimen or an adult acute lymphoblastic leukemia regimen, depending on the treatment center’s protocol for this age group. Adult treatment regimens and pediatric treatment regimens differ in the following ways:

1. Pediatric regimens are more intense and complex than those given to older adults.
2. Pediatric regimens tend to use more pegaspargase, vincristine and corticosteroids. By contrast, adult regimens tend to use more cyclophosphamide and anthracyclines, such as doxorubicin and daunorubicin.
3. Pediatric treatments are given for longer periods of time. Central nervous system treatment (CNS prophylaxis) is started earlier and given longer. Some children receive maintenance therapy for up to 3 years, while adults usually receive 2 years of maintenance therapy.

Researchers have found that Older Adolescents and Young Adults (AYA) patients treated with pediatric protocols have improved rates of survival compared with patients of the same age who are treated with adult acute lymphoblastic leukemia protocols. Therefore, clinical trials are looking into the use of a variety of pediatric protocol options for Older Adolescents and Young Adults (AYA) patients.

Acute lymphocytic leukemia in older adults

Older adults, such as those older than 60, tend to experience more complications from acute lymphocytic leukemia treatments. And older adults generally have a worse prognosis than children who are treated for acute lymphocytic leukemia.

Discuss your options with your doctor. Based on your overall health and your goals and preferences, you may decide to undergo treatment for your acute lymphocytic leukemia.

Some people may choose to forgo treatment for the cancer, instead focusing on treatments that improve their symptoms and help them make the most of the time they have remaining.

Alternative medicine

No alternative treatments have been proved to cure acute lymphocytic leukemia. But some alternative therapies may help ease the side effects of cancer treatment and make you or your child more comfortable. Discuss your options with your doctor, as some alternative treatments could interfere with cancer treatments, such as chemotherapy.

Alternative treatments that may ease symptoms include:

• Acupuncture
• Aromatherapy
• Massage
• Meditation
• Relaxation exercises

Coping and support

Although treatment for acute lymphocytic leukemia is typically very successful, it can be a long road. Treatment often lasts two to three years, although the first three to six months are the most intense.

During maintenance phases, children can usually live a relatively normal life and go back to school. And adults may be able to continue working. To help you cope, try to:

• Learn enough about leukemia to feel comfortable making treatment decisions. Ask your doctor to write down as much information about your specific disease as possible. Then narrow your search for information accordingly.
• Write down questions for your doctor before each appointment, and look for information in your local library and on the internet. Good sources include the National Cancer Institute (https://www.cancer.gov), the American Cancer Society (https://www.cancer.org/) and the Leukemia & Lymphoma Society (https://www.lls.org/).
• Lean on your whole health care team. At major medical centers and pediatric cancer centers, your health care team may include psychologists, psychiatrists, recreation therapists, child-life workers, teachers, dietitians, chaplains and social workers. These professionals can help with a whole host of issues, including explaining procedures to children, finding financial assistance and arranging for housing during treatment. Don’t hesitate to rely on their expertise.
• Explore programs for children with cancer. Major medical centers and nonprofit groups offer numerous activities and services specifically for children with cancer and their families. Examples include summer camps, support groups for siblings and wish-granting programs. Ask your health care team about programs in your area.
• Help family and friends understand your situation. Set up a free, personalized webpage at the nonprofit website CaringBridge (https://www.caringbridge.org/). This allows you to tell the whole family about appointments, treatments, setbacks and reasons to celebrate — without the stress of calling everyone every time there’s something new to report.

Late effects of treatment for adult acute lymphoblastic leukemia

Long-term follow-up of 30 patients with acute lymphoblastic leukemia in remission for at least 10 years has demonstrated ten cases of secondary malignancies. Of 31 long-term female survivors of acute lymphoblastic leukemia or AML younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, two congenital problems occurred ²³.

Refractory and Relapsed acute lymphoblastic leukemia

Some patients have residual leukemia cells in their bone marrow even after they receive intensive treatment. In these cases, the disease is referred to as being “refractory” (or “refractory ALL”). Other patients achieve remission but later have decreased numbers of normal blood cells and a return of leukemia cells in their bone marrow. This is referred to as a “relapse” of the disease (or “relapsed ALL”).

Philadelphia-Positive ALL

For patients with relapsed or refractory Ph+ ALL, there are several treatment options.

New mutations in the BCR-ABL1 gene may occur over time. Some mutations can lead to resistance to certain TKIs. Before a patient starts treatment, BCR-ABL1 gene mutation testing should be done to look for new mutations that may cause certain TKIs to stop working. Each TKI works in a slightly different way. Certain TKIs may be able to counteract a mutation that other TKIs cannot. Results of the gene mutation test may explain why a TKI used for a person’s initial treatment stopped working. A patient may then receive a different TKI. Many Ph+ ALL patients receive imatinib (Gleevec®) during induction therapy. In cases of disease relapse, dasatinib (Sprycel®) or ponatinib (Iclusig®) may be treatment options.

The TKI may be given alone or as part of a chemotherapy regimen. In some cases, it may be combined with a corticosteroid. If the TKI is part of a chemotherapy regimen, this regimen will usually be different from the one used during initial therapy. For some older patients who cannot tolerate chemotherapy, using a TKI along with a corticosteroid may be an option. If the disease does not respond to treatment with TKIs, doctors may recommend regimens used for relapsed or refractory cases of Philadelphia-negative ALL. These include:

• Blinatumomab (Blincyto®)
• Inotuzumab ozogamicin (Besponsa®)
• Tisagenlecleucel (Kymirah®)

An allogeneic stem cell transplant is also an option for healthy patients who have an available donor. Some older patients, as well as patients in poor health may not be able to tolerate such an intense treatment.

In refractory cases, different drugs than those used in the first course of treatment may be administered in an effort to induce remission. Stem cell transplantation is a potential option following remission, and it may result in a more durable remission. In relapsed cases, the duration of the remission, the patient’s age and the results of cytogenetic tests may influence the decision about the best treatment approach.

Philadelphia-Negative ALL

For patients with relapsed or refractory Philadelphia-negative ALL, there are several treatment options. One option is to use different drugs than those used during the patient’s induction
regimen. These options, suggested by the National Comprehensive Cancer Network guidelines, may include:

• Blinatumomab (Blincyto®) may be a treatment option for patients with acute lymphocytic leukemia that has not responded to two or more TKIs.
• Inotuzumab ozogamicin (Besponsa®) is a treatment option for adults with either relapsed or refractory B-cell ALL.
• Tisagenlecleucel (Kymriah®) is a treatment option for patients up to 25 years old with relapsed or refractory B-cell ALL.
• Combination regimens that include several chemotherapy drugs, some of which may have been given in the past. Examples of such include:
  • Inotuzumab ozogamicin + mini-hyper CVD (cyclophosphamide, dexamethasone, vincristine, methotrexate, cytarabine) for patients with B-cell ALL
  • Augmented hyper-CVAD: hyperfractionated cyclophosphamide, intensified vincristine, doxorubicin, intensified dexamethasone and pegaspargase, alternating with high-dose methotrexate and cytarabine
  • MOpAD: methotrexate, vincristine, pegaspargase, and dexamethasone with rituximab for CD20-positive disease
• Nelarabine, alone or in combination with other drugs (e.g., nelarabine, etoposide, cyclophosphamide), for patients with T-cell ALL
• Clofarabine, alone or in combination with other drugs (e.g., clofarabine, cyclophosphamide, etoposide)
• Vincristine sulfate liposome (Marqibo®) injection for the treatment of adult patients with Ph-negative ALL in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies
• Fludarabine-based regimens
  • FLAG-IDA: fludarabine, cytarabine, granulocyte colony-stimulating factor ± idarubicin
  • FLAM: fludarabine, cytarabine and mitoxantrone
• Cytarabine-containing regimens (e.g., high-dose cytarabine, idarubicin, intrathecal methotrexate)
• Alkylator combination regimens (e.g., etoposide, ifosfamide, mitoxantrone)

Palliative treatment

At some point, it may become clear that further treatment, even in clinical trials, is extremely unlikely to cure the leukemia. At that time, the focus of treatment may shift to controlling the leukemia and its symptoms for as long as possible, rather than trying to cure it. This may be called palliative treatment or supportive care. For example, the doctor may advise less intensive chemo to try to slow the leukemia growth instead of trying to cure it.

As the leukemia grows in your bone marrow it may cause pain. It’s important that you be as comfortable as possible. Treatments that may be helpful include radiation and appropriate pain-relieving medicines. If medicines such as aspirin and ibuprofen don’t help with the pain, stronger opioid medicines such as morphine are likely to be helpful.

Other common symptoms from leukemia are low blood counts and fatigue. Medicines or blood transfusions may be needed to help correct these problems. Nausea and loss of appetite can be treated with medicines and high-calorie food supplements. Infections that occur may be treated with antibiotics.

References

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