Wed. Aug 3rd, 2022
    Childhood leukemia

    What is childhood leukemia?

    Leukemia is cancer of the blood. It originates in the stem cells of the blood. Stem cells are the youngest blood cells that turn into different types of specialized blood cells. Childhood leukemia result from an abnormality in the development of hematopoietic stem cells in the bone marrow (precursor cells of all blood cells: red and white blood cells, platelets).

    In the United States, an arbitrarily adopted standard of ages used is 0 to 14 years inclusive, that is, up to 14 years, 11.9 months. However, the definition of childhood cancer sometimes includes adolescents between the ages of 15 and 19. Pediatric oncology is the branch of medicine dedicated to the diagnosis and treatment of cancer in children.

    These stem cells can evolve into two main types of cells:

    • Lymphoid stem cells, which then turn into lymphocytes (types of white blood cells). Three types of lymphocytes exist: B lymphocytes, T lymphocytes and NK lymphocytes.
    • Myeloid stem cells, which produce red blood cells, other types of white blood cells (granulocytes, monocytes) and platelets.

    As the blood stem cells grow, they produce immature blood cells called blasts, or blast cells. The blasts then become mature blood cells.

    In the case of leukemia, there is an overproduction of blasts. These blasts grow abnormally and do not develop into mature blood cells. Over time, the blasts take the place of normal blood cells, preventing them from doing their jobs.

    There are many different types of leukemia which are first classified according to the type of blood stem cell they look like. Lymphoid leukemia starts in abnormal lymphoid cells. Myeloid leukemia arises from abnormal myeloid stem cells.

    The types of leukemia are then further subdivided based on how quickly the disease grows and progresses. Acute leukemia starts suddenly and develops over a few days or weeks. Chronic leukemia develops slowly over months or even years.

    Read also: Leukemia | Symptoms, Stages, Types, Diagnoses, Chances of Surviving, Treatments

    Acute lymphoblastic leukemia (ALL) is the most common type of leukemia diagnosed in young children. It affects boys more often than girls. Acute myelogenous leukemia (AML) is less common than ALL.

    Rare types of childhood leukemia and leukemia-like disorders may also develop. These include transient abnormal myelopoiesis (MAT), also called transient leukemia, acute promyelocytic leukemia (APL),  juvenile myelomonocytic leukemia (JMML), chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS).

    Common types of childhood leukemia

    One finds mainly acute leukemias, of rapid evolution, as opposed to chronic leukemias more frequent in adults. Depending on the type of white blood cells affected, we are talking about:

    • Acute lymphoid (lymphoblastic) leukemia if lymphocytes (a type of white blood cell) are involved.
    • Acute Lymphoblastic Leukemia (ALL) accounts for 80% of acute leukemia in children.
    • Acute myeloid leukemia (myeloblastic) (AML) if the cells of the myeloid lineage are involved (20%).

    Symptoms

    Acute leukemia comes on suddenly and manifests itself as insufficient bone marrow and the proliferation of abnormal cells, one being the result of the other. Bone marrow failure affects all three types of blood cells. We then observe:

    • tired, pale skin, breathing difficulties (dyspnea), palpitations (tachycardia) and generally feeling unwell, this is a sign of a lack of red blood cells (anemia),
    • recurrent infections such as tonsillitis, bronchitis, gum infections (gingivitis), this is a sign of a lack of normal white blood cells,
    • small bleeding in the thickness of the skin (petechiae), blood loss from the gums, nose, etc., it is a sign of lack of platelets.
    • The signs of cell proliferation are observed in particular by:
      • an increase in the size of the liver, spleen and lymph nodes,
        bone or joint pain, to the point that the child may start to limp (this is due to the proliferation of leukemia
      • cells in the marrow of the affected bones).
        It is rare for a child to have all of these abnormalities. They can often boil down to one or two symptoms.

    Sometimes leukemia spreads to the central nervous system (CNS), which can cause the following symptoms:

    • headache
    • vomiting (especially early in the morning)
    • weakness of the muscles of the face and eyes
    • slightly blurred vision
    • epileptic seizures
    • difficulty keeping balance

    Diagnosis of leukemia in children

    Diagnosis is a process of identifying the cause of a health problem. The diagnostic process for childhood leukemia usually begins with a visit to your family doctor or when the result of a blood test suggests a blood disorder. The doctor will ask you about the symptoms your child is experiencing and do a physical exam. Based on this information, the doctor will refer you to a specialist or order tests for your child to check for leukemia or other health problems.

    The diagnostic process can seem long and overwhelming. It’s okay to worry, but try to remember that other medical conditions can cause leukemia-like symptoms. It is important that the healthcare team rule out any other possible cause of the health problem before making a diagnosis of childhood leukemia.

    The following tests are usually used to rule out or diagnose childhood leukemia. Many tests that can diagnose cancer are also used to find out if leukemia has spread to other parts of the body, such as the brain or testicles. The doctor may also do other tests on your child to check his general health and help plan treatment.

    Health history and physical examination

    Your child’s health history is a history of their symptoms, risks, and any medical events and conditions they may have had in the past. The doctor will ask you questions about his personal or family history of certain genetic disorders, including the following:

    • Down syndrome
    • Bloom syndrome
    • Fanconi anemia
    • ataxia telangiectasia (AT)
    • neurofibromatosis type 1 (von Recklinghausen disease)
    • Wiskott-Aldrich syndrome
    • Klinefelter syndrome
    • Li-Fraumeni syndrome
    • Shwachman-Diamond syndrome

    The physical exam allows the doctor to look for any signs of childhood leukemia. During the physical examination, the doctor may:

    • take vital signs to see if there is a fever, shortness of breath and rapid heartbeat;
    • check the skin for bruises or if it is pale;
    • feel the neck, armpits and groin to see if the lymph nodes are swollen or larger than normal
    • check if the mouth is infected and if the gums are bleeding or swollen;
    • check if the testicles are swollen;
    • feel the abdomen to see if the spleen or liver is larger than normal
    • check if the bones are tender or painful.
    Complete blood count

    The complete blood count (CBC) is used to assess the quantity and quality of white blood cells, red blood cells and platelets. It is used to check how well the bone marrow is functioning and for anemia. Childhood leukemia may be suspected if:

    the number of blood cells does not correspond to normal values;
    there are immature blood cells, or blasts, in the blood (blasts are usually seen only in the bone marrow)
    the number of white blood cells (WBC) is low or high;
    the platelet count is low.

    Determination of bleeding and coagulation (clotting) factors

    Leukemia can cause blood clotting factor levels to be abnormal, which may affect the body’s ability to clot blood. The following tests may be used to measure blood clotting factors:

    • fibrinogen level
    • Prothrombin time (PT) or International Normalized Ratio (INR)
    • partial thromboplastin time (PTT)
    Blood biochemical analyzes

    A blood chemistry test measures the level of chemicals in the blood. It makes it possible to assess the quality of functioning of certain organs and also to detect anomalies. It may be used to establish baseline values ​​before treating leukemia. The following blood chemistry tests can be done when your child’s doctor suspects leukemia.

    Blood urea nitrogen and creatinine can be measured to see how well the kidneys are working.

    Alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (AP) are liver enzymes that are measured to find out how well the liver is working.

    Lacticodehydrogenase (LDH) can be measured to see if cell renewal is more active. It is possible that LDH levels are high because of leukemia or another condition.

    The level of phosphate in the blood can be measured to find out if there is any problem with the kidneys, liver or bones.

    The level of uric acid in the blood may be higher than normal with leukemia or other conditions.

    Electrolytes such as sodium and potassium can be measured as part of routine tests and to check for certain conditions. The level of potassium may be higher than normal in the presence of leukemia.

    Genetic and molecular analyzes

    Several genetic and molecular analyzes can be used.

    Immunophenotyping is the study of proteins expressed by cells. It is used to determine the type or subtype of leukemia. Immunophenotyping is based on a very specific antigen-antibody reaction to identify proteins in tissues or cells. Monoclonal antibodies labeled with a fluorescent substance or a specific enzyme that bind only to specific antigens (proteins) are used. The fluorescent label and the labeling enzyme allow doctors to observe blasts.

    Immunohistochemistry is a process used in immunophenotyping. In the case of immunohistochemistry, a microscope is used to observe fluorescent markers. It also allows doctors to examine cells and their surroundings.

    Flow cytometry is a method used in immunophenotyping. A special device is used to sort and classify cells using fluorescent markers on their surface. It allows doctors to see many antibodies at the same time. The cells are exposed to a laser which causes them to emit light that is measured and analyzed by a computer. It quickly collects data from thousands of cells in a single sample. Flow cytometry helps define the unique characteristics of leukemia cells and distinguish between B-cell ALL, T-cell ALL, and AML. This helps doctors make a diagnosis and make a treatment plan. Flow cytometry can be used to measure response to treatment based on minimal residual disease (MRD). Flow cytometry can detect blasts in the bone marrow with greater sensitivity than microscopy.

    Cytogenetics is the observation of a cell’s chromosomes under a microscope to determine their number, size, shape and arrangement. Cytogenetic techniques reveal chromosomal abnormalities, which helps doctors confirm the diagnosis and establish the type or subtype of leukemia. The results of cytogenetic studies also help doctors plan treatment and predict its effectiveness.

    Fluorescence in situ hybridization (FISH) involves the use of special DNA probes labeled with fluorescent dyes to identify chromosomal abnormalities and other genetic changes in leukemia cells. FISH can diagnose types of leukemia that look similar but have different genetic abnormalities and therefore may need to be treated differently. It is a molecular genetic test that can identify chromosomal abnormalities and other genetic changes in blasts.

    Polymerase chain reaction (PCR) involves making many copies of a particular segment of a gene for testing in the lab. PCR is used to detect mutations, inversions or deletions in DNA that are linked to certain types of leukemia. It can be useful in diagnosing specific types of leukemia and in establishing their prognosis. It can also make it possible to detect MRM for certain types of leukemia with a specific genetic defect which can be monitored during treatment.

    Pulmonary radiography

    In an x-ray, low-dose radiation is used to produce images of parts of the body on film. It is used to check:

    the child’s airways before giving them a sedative for a bone marrow puncture and biopsy;
    the presence of a lung infection;
    if the thymus is larger than normal;
    if the lymph nodes in the chest are larger than normal (mediastinal mass).

    Lumbar puncture

    Lumbar puncture, or rachicentesis, involves removing a small amount of cerebrospinal fluid (CSF) from the spine. CSF is the fluid that surrounds the brain and spinal cord and helps protect them. The CSF taken from the lumbar puncture is examined under a microscope to see if the cancer has spread to the central nervous system (CNS).

    Bone marrow puncture and biopsy

    A bone marrow biopsy and puncture takes cells from the bone marrow for analysis in the laboratory. The results will confirm whether the child has leukemia.

    The samples taken at the puncture can be used for other tests such as flow cytometric immunophenotyping and genetic analyzes of molecules and chromosomes. These tests help doctors determine what type of leukemia the child has and plan the best treatments.

    Risk factors

    • Ionizing radiation ; (subjects treated with radiotherapy for other neoplasms). Also worth mentioning are the cases of leukemia among the survivors of the Hiroshima and Nagasaki explosions and the Chernobyl liquidators.
    • Benzene ; present in oil and gasoline , widely used in the past as a paint solvent and now almost completely banned. The mechanism by which this simple molecule causes leukemia has been extensively studied in experimental animal models. It requires an oxidative conversion into various derivatives (1,4-benzoquinone, 1,2,4-tri-hydroxybenzene, etc.) which then react covalently with the DNA causing interference with the replication and repair processes of the acid. nucleic.
      Some drugs used to treat cancer , especially when combined with radiotherapy, can increase the risk of “secondary” leukemia. Surely the drugs most at risk are the “alkylating” agents (chlorambucil, cyclophosphamide, nitrosoureas).
    • Cigarette smoking (1/4 of all AML occur among smokers; which corresponds to the statistical mean of smokers in Western societies). Benzopyrene, toxic aldehydes, tar and certain heavy metals (such as cadmium and lead) in cigarette smoke are likely to be the most responsible factors.
    • Some diseases such as Down’s syndrome , Fanconi’s anemia , ataxia-telangiectasia and Bloom’s syndrome various types of anemia present in the third stage. In this case, the genetic mutation of some of these pathologies is caused by proteins involved in DNA repair. The risk of developing leukemia in these diseases therefore depends on the organism’s lower efficiency in repairing DNA after certain injuries.
      Human T-lymphotropic virus; the leukemia cells of adult T (ATLL) is a type of leukemia caused by HTLV-1 virus.
      Some types of anemia (hemoglobin deficiency), developed at a very high stage, also lead to leukemia . In addition, anemia can also be caused by leukemia.

    Stages or phases of childhood leukemia

    There is no standard staging system for childhood leukemia, but it can be classified into phases, which are: untreated, in remission, relapsing (relapsing), refractory. Doctors use these and other terms to describe childhood leukemia when discussing treatment and response to treatment.

    Untreated illness

    Untreated childhood leukemia is a disease that has been diagnosed recently and has not yet been treated. In this case, one or more of the following statements apply:

    The number of normal blood cells (red blood cells, white blood cells, platelets) may be low.
    For acute lymphoblastic leukemia (ALL), more than 25% of cells in the bone marrow are usually blasts (immature white blood cells).
    For acute myelogenous leukemia (AML), more than 20% of cells in the bone marrow are usually blasts (immature white blood cells).
    There are signs and symptoms of childhood leukemia.
    Doctors do a complete blood count (CFC) to check the number of different types of blood cells.

    Remission

    Once childhood leukemia has been treated, it can go into remission.

    Complete remission, or complete response, meets all of the following criteria:

    The number of blood cells (red blood cells, white blood cells and platelets) is normal or near normal.
    Less than 5% of the cells in the bone marrow are blasts.
    There are no general signs or symptoms of childhood leukemia, such as fatigue, weight loss, fever, anemia, or bleeding.
    There are no signs or symptoms of childhood leukemia in the brain and spinal cord (central nervous system, or CNS) or elsewhere in the body.
    In partial remission, less than 25% of the cells in the bone marrow are blasts.

    Minimal residual disease (MRD)

    After treatment, there may still be blasts in the bone marrow. Standard laboratory tests, such as microscopy, may not be able to detect these leukemia cells. But more sensitive tests like flow cytometry and polymerase chain reaction (PCR) can. The disease that can only be detected with more sensitive tests is called minimal residual disease, or MRD.

    MRM may be used to assess response to treatment. Even children with a small amount of MRM may be at greater risk of the cancer coming back than children with undetectable MRM.

    Active disease

    A disease is active when more than 5% of the cells in the bone marrow are blasts. This term can be used during or after treatment if the disease has returned.

    Recurrent illness

    Relapsed (relapsed) leukemia is a disease that comes back after going into remission from treatment. A child is considered to have relapsed leukemia when more than 5% of the cells in his bone marrow are blasts. Leukemia can reappear in the blood, bone marrow, or other parts of the body, such as the CNS. It can also do it in the testicles in boys.

    Refractory disease

    Refractory leukemia is cancer that is resistant to treatment or for which treatment has not been effective. A child is considered to have refractory leukemia when the disease does not go into complete remission after treatment.

    Central nervous system involvement

    Central nervous system (CNS) damage occurs when leukemia has spread to the brain or spinal cord. It is the number of white blood cells (WBCs) in the cerebrospinal fluid (CSF).

    In this case, one of the following applies:
    • CNS 1 – no blasts in CSF
    • CNS 2 – WBC count less than 5 / ml with blasts in CSF
    • CNS 3 – WBC count equal to or greater than 5 / ml with blasts in the CSF or signs of leukemia spread to the CNS

    Treatments for child leukemia

    If your child has leukemia, the healthcare team will make a treatment plan just for them. It will be based on your child’s health and specific information about leukemia. When deciding what treatment to offer for childhood leukemia, the healthcare team considers the following:

    • type and subtype of leukemia
    • changes in chromosomes and genes in leukemia cells
    • response to treatment
    • presence of leukemia cells in the brain and spinal cord (central nervous system or CNS)
    • prognostic factors
    • risk category
    • your child’s age
    • your child’s overall health

    Here is some general information on the treatments available for childhood leukemia.

    Chemotherapy

    Chemotherapy is the main treatment for childhood leukemia. It is also used to prevent or treat the spread of disease to the CNS. In chemotherapy, cancer drugs are used to destroy cancer cells.

    Targeted treatment

    Sometimes targeted therapy is given to treat certain subtypes of childhood leukemia or leukemia that don’t respond to other treatments or come back after treatment. Targeted therapy uses drugs to target specific molecules, such as proteins, on the surface or inside of cancer cells to stop the growth and spread of cancer and limit damage to normal cells.

    Immunotherapy

    Sometimes targeted therapy is given to treat certain subtypes of childhood leukemia or leukemia that don’t respond to other treatments or come back after treatment. Immunotherapy helps strengthen or restore the immune system’s ability to fight cancer.

    Radiotherapy

    Radiation therapy is sometimes used to treat childhood leukemia, especially when it has spread to the brain or spinal cord and does not respond to other treatments. Doctors usually give radiation therapy as a treatment for leukemia only when it does not respond to other treatments or is very likely to come back. In radiation therapy, high-energy rays or particles are used to destroy cancer cells.

    Stem cell transplant

    A stem cell transplant may be done to treat certain subtypes of childhood leukemia that are more likely to come back soon after remission. In a stem cell transplant, a large dose of chemotherapy is given to destroy all the cells in the bone marrow. Healthy stem cells are then donated to replace those that have been destroyed in the bone marrow.

    Supportive treatment

    Some children are very sick when they are diagnosed with leukemia. Others get sick during treatment. Leukemia or its treatment can reduce the number of blood cells and cause serious problems, such as infections, bleeding, and even heart failure. Supportive therapy, such as antibiotics, antifungals, blood products (transfusions), growth promoters, or other drugs, may then be given to treat or prevent some of these problems.

    Monitoring

    Post-treatment follow-up is an important part of the management of children with cancer. Your child will need to have regular follow-up visits. These visits allow the healthcare team to monitor his progress and know how he is recovering from the treatment.

    Clinical tests

    Children with cancer can be treated in clinical trials in certain countries. Clinical trials aim to find new methods of preventing, detecting and treating cancer.

    Prognosis and survival for childhood leukemia

    If your child has leukemia, you will have questions about their prognosis. A prognosis is the act by which the doctor best assesses how cancer will affect a child and how he will respond to treatment. The prognosis and survival depend on many factors. Only a doctor who is familiar with your child’s medical history, the type and subtype of leukemia they have, other characteristics of the disease, the treatments chosen and the response to treatment can review all of this together. with survival statistics to arrive at a prognosis.

    A prognostic factor is an aspect of leukemia or a characteristic of the child that the doctor takes into account when making a prognosis. A predictor factor influences how leukemia responds to a certain treatment. We often discuss prognostic and predictive factors together. They both play a role in choosing the treatment plan and in establishing the prognosis.

    Prognostic factors vary depending on the type of leukemia. In childhood leukemia, certain prognostic factors are used to assign the cancer a risk level or risk category. The risk category includes the likelihood that the cancer will not respond to treatment or that it will come back after treatment. Doctors use this information to guide treatment.


    List of all Cancers

    The word “cancer” is a generic term for a large group of diseases that can affect any part of the body. We also speak of malignant tumors or neoplasms. One of the hallmarks of cancer is the rapid multiplication of abnormal growing cells, which can invade nearby parts of the body and then migrate to other organs. This is called metastasis, which is the main cause of death from cancer. Types of cancer (in alphabetical order of the area concerned):

    Types of Cancer | List all of Cancers | Adult, Children, Head and neck, Digestive and Types of Blood Cancer


    Sources: PinterPandai, Cedars-Sinai, The American Childhood Cancer Organization, St. Jude Children’s Research Hospital

    Photo source: Wikimedia Commons

    Photo explanations: pediatric Patients Receiving ChemotherapyDescription Two young girls with acute lymphocytic leukemia (ALL) receiving chemotherapy. They are sitting on a bed and are demonstrating some of the procedures and techniques used with intravenous chemotherapy. The girl on the left has an IV tube in the neck, the other girl’s IV is in her arm, which has an arm board which stabilizes the arm for IV needle insertion.