Chemotherapy for Acute Lymphocytic Leukemia

Acute lymphocytic leukemia (ALL) is also called acute lymphoblastic leukemia. “Acute” means that the leukemia can progress quickly and, if not treated, can be fatal within a few months. “Lymphocytic” means it develops from early (immature) forms of lymphocytes, a type of white blood cell.

ALL starts in the bone marrow (the soft inner part of certain bones, where new blood cells are made). Most often, the leukemia cells invade the blood fairly quickly. They can also sometimes spread to other parts of the body, including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles (in males). Some cancers can also start in these organs and then spread to the bone marrow, but these cancers are not leukemia.

Other types of cancer that start in lymphocytes are known as lymphomas (either non-Hodgkin lymphoma or Hodgkin lymphoma). While leukemias like ALL 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.

Understanding acute lymphocytic leukemia

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

Lymphocytes develop from cells called lymphoblasts to become mature, infection-fighting cells. There are 2 main types of lymphocytes:

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

Acute lymphocytic leukemia develops from early forms of lymphocytes. This can start in either early B cells or T cells at different stages of maturity.

The American Cancer Society’s estimates for acute lymphocytic leukemia (ALL) in the United States for 2024 (including both children and adults) are:

  • About 6,550 new cases of ALL (3,590 in males and 2,960 in females)
  • About 1,330 deaths from ALL (640 in males and 690 in females)

The risk for developing  Acute lymphocytic leukemia L 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 ALL are in adults.

Subtypes of Acute Lymphocytic Leukemia (ALL)

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

B-cell Acute Lymphocytic Leukemia 

B-cell ALL with certain genetic abnormalities (gene or chromosome changes)

  • B-cell ALL with hypo-diploidy (the leukemia cells have fewer than 44 chromosomes [normal cells have 46])
  • B-cell ALL with hyperdiploidy (the leukemia cells have more than 50 chromosomes)
  • B-cell ALL with a translocation between chromosomes 9 and 22 [t(9;22)] (the Philadelphia chromosome, which creates the BCR-ABL1 fusion gene)
  • B-cell ALL with a translocation between chromosome 11 and another chromosome
  • B-cell ALL with a translocation between chromosomes 12 and 21 [t(12;21)]
  • B-cell ALL with a translocation between chromosomes 1 and 19 [t (1;19)]
  • B-cell ALL with a translocation between chromosomes 5 and 14 [t(5;14)]
  • B-cell ALL with amplification (too many copies) of a portion of chromosome 21 (iAMP21)
  • B-cell ALL with translocations involving certain tyrosine kinases or cytokine receptors (also known as “BCR-ABL1-like ALL”)

 B-cell ALL, not otherwise specified

T-cell  Acute Lymphocytic Leukemia 

  • Early T-cell precursor lymphoblastic leukemia

 Acute lymphocytic 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 ALL is about 1 in 1,000. The risk is slightly higher in males than in females and higher in white people than in African Americans.

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

  • Feeling tired
  • Feeling weak
  • Feeling dizzy or lightheaded
  • Shortness of breath
  • 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

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

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

General symptoms

Swelling in the abdomen: Leukemia cells may build up in the liver and spleen, making them larger. This might be noticed as fullness, swelling of the belly, or feeling full after eating only a small amount. 

Enlarged lymph nodes: ALL that has spread to lymph nodes close to the surface of the body (such as on the sides of the neck, in the groin, or in underarm areas) might be noticed as lumps under the skin. 

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, ALL 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.
  •  It may spread inside the chest, where it can cause fluid buildup and trouble breathing.
  • Rarely, it  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). 

The superior vena cava (SVC), a large vein that carries blood from the head and arms back to the heart, passes next to the thymus. If the thymus is enlarged, it may press on the SVC, causing the blood to “back up” in the veins. This is known as SVC syndrome. It can be fatal. It can cause:

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


Diagnosing Acute Lymphocytic Leukemia 

There are no special tests recommended to detect acute lymphocytic leukemia (ALL) early. The best way to find leukemia early is to report any possible signs or symptoms of leukemia .  .Some people are known to have a higher risk of acute lymphocytic leukemia (or other leukemias) due to genetic disorders like Down syndrome or because they were previously treated with certain chemotherapy drugs or radiation. Most doctors recommend that these people have careful, regular medical checkups. The risk of leukemia, although greater than in the general population, is still very low for most of these people. 

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

Medical history and physical examination

Tests used to diagnose and classify ALL

  • Blood tests
  • Blood chemistry tests
  • Complete blood count (CBC) and Peripheral blood smear
  • Bone marrow tests
  • Bone marrow aspiration 
  • Bone marrow biopsy 

Lab tests: One or more of the following lab tests may be done on the samples to diagnose AML and/or to determine the specific subtype of ALL.

Routine exams with a microscope

Determining what percentage of cells in the bone marrow are blasts is particularly important. A diagnosis of ALL 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: It entails utilizing a variety of methods to localize the chemical components of cells and cell organelles on thin histological sections.

Flow cytometry and immunohistochemistry: Flow cytometry is a technique that examines individual cells suspended in a solution to determine their dimensions, form, and different surface markers. Conversely, tissue sections can be visualized using immunohistochemistry, a method that identifies specific proteins or antigens.

Chromosome tests: These tests diagnose specific blood and lymphatic system conditions, hereditary diseases, and birth defects.

Cytogenetics: It includes examining the DNA molecule’s structure inside the cell nucleus.

Fluorescent in situ hybridization (FISH): Fluorescent probes that attach to specific regions of a nucleic acid sequence with a high degree of sequence complementarity are used in the molecular cytogenetic technique known as fluorescence in situ hybridization (FISH). 

Polymerase chain reaction (PCR): It enables researchers to sufficiently amplify a very small amount of DNA, or a portion of it, to allow for in-depth analysis. 

Other molecular and genetic tests  They can offer proof of internal illnesses or identify genetic risk factors for specific diseases.

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

Lumbar puncture (spinal tap) : A lumbar puncture, sometimes referred to as a spinal tap, is a medical operation wherein cerebrospinal fluid (CSF) is extracted from the spinal canal using a needle. The clear fluid known as CSF envelops and shields the brain and spinal cord.

Imaging tests

X-rays: X-rays are energetic  and can penetrate most materials, including the body, which makes them valuable for creating images of inside organs and tissues.

Computed tomography (CT) scan: A computed tomography (CT) scan creates cross-sections of the inside of the body, including the bones, blood vessels, and soft tissues, using a succession of x-rays.

Magnetic resonance imaging (MRI) scan: MRIs produce finely detailed images of the body’s organs and tissues by utilizing radio waves and magnetic fields.

Unlike a CT scanner, the MRI machine is narrower and deeper, so you lie on a table that glides into it. The MRI magnets produce a loud tapping or thumping sound.

Ultrasound: High-frequency sound waves are used in ultrasound to create images of the internal organs and structures.


Chemotherapy for Acute Myeloid Leukemia (AML)

Treatment Phases

Treatment of acute myeloid Myeloid Leukemia is usually divided into phases:

  • Induction is the first phase of treatment. It is short and intensive, typically lasting about a week. The goal is to clear the blood of leukemia cells (blasts) and to reduce the number of blasts in the bone marrow to normal.
  • Consolidation is chemo given after the patient has recovered from induction. It is meant to kill the small number of leukemia cells that are still around but can’t be seen because there are so few of them. For consolidation, chemo is given in cycles, with each period of treatment followed by a rest period to allow the body time to recover.
  • In a third phase, called maintenance (or post-consolidation), low doses of chemotherapy (or other treatments) are given for months or years after consolidation is finished. This is often used to treat acute promyelocytic leukemia (APL), and it is sometimes used for other types as well.

Drugs used for Treatment:  The chemo drugs used most often to treat are a combination of: 

  • Cytarabine (cytosine arabinoside or ara-C)
  • An anthracycline drug, such as daunorubicin (daunomycin) or idarubicin

Other chemotherapy drugs that may be used to treat AML include:

  • Cladribine (2-CdA)
  • Fludarabine
  • Mitoxantrone
  • Etoposide (VP-16)
  • 6-thioguanine (6-TG)
  • Hydroxyurea
  • Corticosteroid drugs, such as prednisone or dexamethasone
  • Methotrexate (MTX)
  • 6-mercaptopurine (6-MP)
  • Azacitidine
  • Decitabine

These can affect some normal cells in the body, which can lead to side effects. The side effects of chemotherapy depend on the type and dose of drugs given and how long they are taken. 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)

Side effects of specific drugs: Certain drugs have some specific possible side effects. For example:

  • High doses of cytarabine can cause dryness in the eyes and effects on certain parts of the brain, which can lead to problems with coordination or balance. The drug dose may need to be reduced or stopped altogether if these side effects appear.
  • Anthracyclines (such as daunorubicin or idarubicin) can damage the heart, so they might not be used in someone who already has heart problems.

If serious side effects occur, the chemo may have to be reduced or stopped, at least for a short time. Careful monitoring and adjustment of drug doses are important because some side effects can last a long time.

Tumour lysis syndrome: This side effect of chemo can occur in patients who have large numbers of leukemia cells in the body, mainly during the induction phase of treatment. When chemo kills these 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 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.

Common treatment approaches

Targeted Therapy Drugs for Acute Myeloid Leukemia (AML)

  • FLT3 inhibitors: In some people with AML, the leukemia cells have a change (mutation) in the FLT3 gene. This gene helps the cells make a protein (also called FLT3) that helps the cells grow. Drugs that target the FLT3 protein can help treat some of these leukemias. 
  • Midostaurin (Rydapt) and quizartinib (Vanflyta) are FLT3 inhibitors that can be used along with certain chemotherapy drugs to treat newly diagnosed adults whose leukemia cells have a mutation in the FLT3 gene.
  • Gilteritinib (Xospata) can be used to treat adults whose leukemia cells have a mutation in the FLT3 gene and whose AML has not gotten better on previous treatments or has recurred (come back).

These drugs are consumed orally once or twice a day.

  • IDH inhibitors: In some people with AML, the leukemia cells have a mutation in either the IDH1 or IDH2 gene. These genes help the cells make certain proteins, which are also called IDH1 and IDH2. Mutations in one of these genes can stop blood cells from maturing the way they normally would.
  • Targeted drugs called IDH inhibitors can block these IDH proteins. These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells. Because of this, they are sometimes referred to as differentiation agents.
  • These drugs can be used to treat AML with an IDH1 or IDH2 mutation. Your doctor can test your blood or bone marrow to see if your leukemia cells have one of these mutations.

These drugs are consumed orally once or twice a day. Common side effects can include nausea, vomiting, diarrhea, fatigue, joint pain, shortness of breath, increased levels of bilirubin (a substance found in bile), and loss of appetite. 

  • Gemtuzumab ozogamicin (Mylotarg): This targeted therapy consists of a monoclonal antibody (a lab-made immune protein) linked to a chemotherapy drug. Once inside the body, the antibody attaches to a protein called CD33, which is found on most AML cells. The antibody acts like a homing signal, bringing the chemo drug to the leukemia cells, where it enters the cells and kills them when they try to divide into new cells. Less common but more serious side effects can include:
  • Severe liver damage, including veno-occlusive disease (blockage of veins in the liver),
  • Reactions during the infusion (similar to an allergic reaction). You will likely be given medicines before each infusion to help prevent this.
  • Serious or life-threatening infections, especially in people who have already had a stem cell transplant
  • Changes in the rhythm of the heart
  • BCL-2 inhibitor: Venetoclax (Venclexta) targets BCL-2, a protein in cancer cells that helps them live longer than they should. This drug can be used with chemotherapy in people with newly diagnosed AML who are 75 years of age or older or who are not healthy enough to tolerate strong chemo. It is consumed orally once a day.
  • Side effects can include low levels of certain white blood cells (neutropenia), low red blood cell counts (anemia), diarrhea, nausea, bleeding, low platelet counts (thrombocytopenia), and feeling tired. Less common but more serious side effects can include pneumonia and other serious infections.

Hedgehog pathway inhibitor

 Acute myeloid leukemia  cells can have mutations (changes) in genes that are part of a cell signalling pathway called the hedgehog. The hedgehog pathway is crucial for the development of the embryo and fetus and is important in some adult cells, but it can be overactive in leukemia cells.

Glasdegib (Daurismo) is a drug that targets a protein in this pathway. It can be used with chemotherapy in people with newly diagnosed AML who are 75 years of age or older or who are not healthy enough to tolerate strong chemo. In this group, it has been shown to help people live longer.

It is consumed orally once a day.

Side effects can include muscle and bone pain, fatigue, low white blood cell counts (neutropenia), low red blood cell counts (anemia), bleeding, nausea, low platelet counts (thrombocytopenia), and redness or sores in the mouth. 

Because the hedgehog pathway affects fetal development, these drugs should not be taken by women who are pregnant or could become pregnant. It is not known if they could harm the fetus if taken by a male partner. Anyone taking these drugs should use reliable birth control during and for some time after treatment.


In conclusion, acute lymphocytic leukemia (ALL) progresses rapidly from immature lymphocytes in the bone marrow and can spread to other organs. Chemotherapy is a common treatment for this illness and involves several phases to eradicate leukemia cells, which can lead to side effects affecting normal cells and blood cell counts.

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