Cancer Association of South
Africa (CANSA)
Fact Sheet
on
Childhood Acute Myeloid
Leukaemia (AML)
Introduction
Leukaemia is a cancer of the white blood cells. All blood cells are produced in the bone marrow, the spongy substance at the core of some of the bones in the body.
Bone marrow contains:
o red blood cells, which carry oxygen around the body
o platelets, which help the blood to clot and control bleeding
o white blood cells, which help to fight infection.
[Picture Credit: Blood Cell Formation]
There are two different types of white blood cells: lymphocytes and myeloid cells (including neutrophils). These white blood cells work together to fight infection. Normally white blood cells develop, repair and reproduce themselves in an orderly and controlled way. In leukaemia, however, the process gets out of control and
the cells continue to divide in the bone marrow, but do not mature.
These immature dividing cells fill up the bone marrow and stop it from making healthy blood cells. As the leukaemia cells are immature, they cannot work properly. This leads to an increased risk of infection. Because the bone marrow cannot make enough healthy red blood cells and platelets, symptoms such as anaemia and bruising can occur.
There are four main types of leukaemia: acute lymphoblastic (ALL), acute myeloid (AML), chronic lymphocytic (CLL) and chronic myeloid (CML). Chronic leukaemias occur mostly in adults, and are extremely rare in children and young people. Each type of leukaemia has its own characteristics and treatment.
Childhood Acute Myeloid Leukaemia (AML)
Leukaemia is a cancer of the white blood cells. White blood cells help to fight infection. There are two different types of white blood cell – lymphoid cells (also known as lymphocytes) and myeloid cells. Normally these cells repair and reproduce themselves in an orderly and controlled way. In leukaemia, however, the process gets out of control and the cells continue to divide but do not mature.
Acute myeloid leukaemia is an overproduction of immature myeloid cells, called myeloblasts or blast cells.
Immature myeloid cells fill up the bone marrow and stop it making healthy blood cells. As these cells are immature, they cannot work properly. This puts the child at increased risk of infection. Symptoms such as bruising and anaemia are caused by the bone marrow’s inability to make enough healthy red blood cells and platelets.
There are different sub-types of AML. The sub-types of AML are classified according to exactly which type of cell is affected, the stage of development (maturation) the cells are at, and whether the cells are differentiated. Cells that have started to show some of the features of myeloid cells are said to show differentiation. Cells which do not show signs of becoming a particular type of white blood cell are undifferentiated.
Knowing the sub-type of AML is important as it helps doctors to decide on the best treatment.
The most commonly used classification system for AML is the French-American-British (FAB) system:
o M0 Acute myeloid leukaemia with minimal evidence of myeloid differentiation o M1 Acute myeloblastic leukaemia without maturation
o M2 Acute myeloblastic leukaemia with maturation o M3 Acute promyelocytic leukaemia (APL)
o M4 Acute myelomonocytic leukaemia o M5 Acute monocytic/monoblastic leukaemia o M6 Acute erythroleukaemia
o M7 Acute megakaryoblastic leukaemia
Types M4 and M5 are the most frequent; M0 and M6 are both very rare. (Children with Cancer UK).
Incidence of Childhood Acute Myeloid Leukaemia in South Africa
In providing the incidence figures of leukaemia in South Africa, The National Cancer Registry does not make provision for the reporting of the different types of leukaemia – it also does not differentiate between acute and chronic leukaemia.
According to the National Cancer Registry (2009) the following number of leukaemia cases were histologically diagnosed in South Africa during 2009:
Group – Boys 0 to 19 Years 2009 No of Cases All boys 93 Asian boys 2 Black boys 52 Coloured boys 11 White boys 23 Group – Girls 0 to 19 Years 2009 No of Cases All girls 80 Asian girls 2 Black girls 54 Coloured girls 10 White girls 13
The frequency of histologically diagnosed cases of leukaemia in South Africa for 2009 were as follows (National Cancer Registry, 2009):
Group - Boys 2009 0 – 4 Years 5 – 9 Years 10 – 14 Years 15 – 19 Years All boys 36 28 18 11 Asian boys 2 0 0 0 Black boys 17 15 11 9 Coloured boys 4 4 2 1 White boys 11 8 4 0 Group - Girls 2009 0 – 4 Years 5 – 9 Years 10 – 14 Years 15 – 19 Years All girls 25 21 18 16 Asian girls 1 0 1 0 Black girls 13 13 15 13 Coloured girls 5 4 1 0 White girls 6 4 1 2
N.B. In the event that the totals in any of the above tables do not tally, this may be the result of uncertainties as to the age, race or sex of the individual. The totals for ‘all boys’ and ‘all girls’, however, always reflect the correct totals.
Signs and Symptoms of Acute Childhood Myeloid Leukaemia (AML)
Unlike other cancers Acute Childhood Myeloid Leukaemia (AML) does not occur in stages. Instead, it tends to be found spread throughout the bloodstream at the time of diagnosis, and may have invaded an organ. As a result of its ability to affect the whole body at once, it must be treated aggressively as soon as possible. AML’s early symptoms mimic common diseases like the flu, so it can often go undiagnosed.
Signs and symptoms of Childhood Acute Myeloid Leukaemia (AML) can be divided into the following: (1) those caused by a deficiency of normally functioning cells, (2) those due to the proliferation and infiltration of the abnormal leukemic cell population, and (3) constitutional symptoms.
Symptoms due to a deficiency of normally functioning cells include the following:
o Cytopaenias (a reduction in the number of blood cells) - can result from a deficiency of normally functioning cells
o Anaemia - characterised by pallor, fatigue, tachycardia, and headache
o Haemorrhage - most commonly, easy bruising, petechiae, epistaxis (nose bleeds), gingival (gums) bleeding
o Frequent persistent infections o Breathlessness
o Flu-like symptoms
o Fever - should initially always be attributed to infection o Chills
o Malaise (not feeling well) o Joint pains
Symptoms due to the proliferation and infiltration of the abnormal leukemic cell mass and infiltrative disease include the following:
o Extramedullary infiltration - most commonly in the reticuloendothelial system
o Mediastinal mass - may cause symptoms of respiratory insufficiency or superior vena cava syndrome
o Abdominal masses - may cause pain or obstruct the GI or urogenital tracts
o Gingival hyperplasia, CNS infiltration - often associated with monoblastic leukaemia (Children’s Cancer Research Fund; Medscape; Children with Cancer UK).
Diagnosis of Childhood Acute Myeloid Leukaemia (AML)
A number of tests are performed to evaluate a child suspected of having leukaemia. The initial test will be a blood test called a complete blood count (CBC). Your paediatrician or family doctor may order blood tests before referring your child to a specialist. Those tests are often repeated by the oncologist.
Although leukaemia cells may be found in the blood, most commonly the diagnosis and classification of leukaemia is confirmed by looking at a sample of bone marrow under the microscope. This sample is obtained by performing a bone marrow aspirate. A bone marrow aspirate will provide information regarding the subtype of AML.
An additional test that may be performed along with the bone marrow aspirate is the bone marrow biopsy. A bone marrow biopsy may help in making a diagnosis when there are too few cells in the aspirate sample.
A spinal tap (lumbar puncture) is usually performed to look for leukaemia in the central nervous system.
[Picture Credit: Lumbar Puncture]
Following these tests, your doctor will ask the laboratory to perform cytogenetics tests (tests that check the leukaemia’s chromosomes for mistakes, also called mutations). Not all chromosome mutations are easily found and sometimes they can only be seen using
powerful laboratory techniques called molecular analysis (tests that look inside the chromosomes for extremely tiny mistakes). These tiny molecular mutations of the chromosomes may have a powerful impact upon the ability to be cured and have recently become the target of new medical treatments of leukaemia. Based upon the chromosomal findings, your doctor can diagnosis the subtype of AML and can make an initial prognosis (prediction) for the chances of relapse and long-term cure.
(CureSearch for Children’s Cancer).
Treatment of Childhood Acute Myeloid Leukaemia (AML)
The treatment for AML is shorter and more intensive than for Acute Lymphoblastic Leukaemia (ALL). The total duration of treatment for AML is around six months and children will usually be admitted to hospital for the full duration of their treatment. This is because the intensive treatment can make children very unwell and they need a high level of supportive care.
The main treatment is chemotherapy. A combination of chemotherapy drugs and steroid medicines is given according to a treatment plan (also called a protocol or regimen). There are two phases of treatment – remission induction and post-remission treatment.
Remission induction - the initial aim of treatment for AML is to achieve a state called remission where almost all leukaemic cells have been killed, allowing production of normal blood cells to resume.
Remission induction usually includes one or two blocks of a combination of chemotherapy drugs in high doses given over a few days at intervals of one or two weeks. Children with AML are usually given intrathecal chemotherapy after each of the first two blocks of chemotherapy. This involves injecting chemotherapy drugs into the spinal fluid to prevent leukaemic cells from
surviving in the brain and spinal cord. Occasionally radiotherapy to the brain may also be necessary.
Post-remission treatment - post-remission treatment (also known as consolidation or post-induction treatment) aims to destroy any remaining leukaemic cells and to prevent the disease from returning. This phase usually involves two or three more blocks of the same drugs used in
remission induction. [Picture Credit: Intrathecal Therapy]
Sometimes it is necessary to use additional drugs or higher doses of the same drugs; this is known as intensification. Stem cell (bone marrow) transplantation is a special case of intensification. It enables doctors to give higher doses of drugs than would otherwise be possible.
Expert supportive care is therefore necessary and the child will usually need to remain in hospital, even during the gaps between treatment blocks.
All children will continue to be monitored following completion of treatment – for the first year they will be checked every two or three months. Checks will then gradually become less frequent.
The main purposes of follow-up are detection of relapse and detection of treatment complications.
(Children with Cancer UK).
Long-term Effects of Treatment of Childhood Acute Myeloid Leukaemia (AML)
Unfortunately, there are, in some cases, long-term adverse (unwanted or negative) effects from certain aspects of treatment. The long-term effects of chemotherapy depend on the drugs used, the intensity of treatment and on the total amount of the drug received. It is more difficult to establish which drugs are responsible for which long-term effects in situations like childhood AML where high doses of drugs are given over a relatively short period of time. There are known long-term problems which result from the use of certain drugs. Your child’s consultant or specialist nurse will offer you detailed advice before your child begins treatment.
One common concern of parents and of older children is the effect on fertility and you will be given information on this at the time of treatment. The majority of women who were treated in childhood for AML using standard treatments will not have difficulty in becoming pregnant. The minority of girls who receive radiotherapy may have problems in sexual development or in fertility.
Boys who have received radiotherapy may later have difficulty with their fertility. This varies between patients and it is difficult to predict exactly how your child may be affected. Fortunately, most boys will have normal sexual development. It is very important that men who were treated with chemotherapy as children are aware that fertility may return unexpectedly. Because of this, it would be unwise for a sexually active man who has been sterile as a consequence of chemotherapy to assume that this will always continue to be the case.
An important consideration for both boys and girls is whether there is a risk of adverse effects on their own children from treatment they received during childhood. A number of large studies in Britain and abroad have confirmed that there is no increased risk of cancer or of an abnormality in children whose parents received treatment for cancer during childhood.
Your child will have a chance to discuss all of these considerations with the healthcare team as they reach puberty.
(Leukaemia and Lymphoma Research).
Clinical Trials
Clinical trials are research studies that involve people. They are the final step in a long process that begins with research in a lab. Most treatments used today are the results of past clinical trials.
Cancer clinical trials are designed to test new ways to: o Treat cancer
o Find and diagnose cancer o Prevent cancer
o Manage symptoms of cancer or side effects from its treatment
Every trial has a person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the trial, called a protocol. The protocol explains what will be done during the trial. It also contains information that helps the doctor decide if this treatment is right for a particular patient.
The protocol includes information about: o The reason for doing the trial
o Who can join the trial (called “eligibility requirements”) o How many people are needed for the trial
o Any drugs that will be given, how they will be given, the dose, and how often o What medical tests will be done and how often
o What types of information will be collected about the people taking part
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward. Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
(National Cancer Institute).
Medical Disclaimer
This Fact Sheet is intended to provide general information only and, as such, should not be considered as a substitute for advice, medically or otherwise, covering any specific situation. Users should seek appropriate advice before taking or refraining from taking any action in reliance on any information contained in this Fact Sheet. So far as permissible by law, the Cancer Association of South Africa (CANSA) does not accept any liability to any person (or his/her dependants/estate/heirs) relating to the use of any information contained in this Fact Sheet.
Whilst CANSA has taken every precaution in compiling this Fact Sheet, neither it, nor any contributor(s) to this Fact Sheet can be held responsible for any action (or the lack thereof) taken by any person or organisation wherever they shall be based, as a result, direct or otherwise, of information contained in, or accessed through, this Fact Sheet.
Sources and References
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Children with Cancer UK
http://www.childrenwithcancer.org.uk/acute-myeloid-leukaemia Children’s Cancer Research Fund
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