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Leukaemia is a cancer of the white blood cells (leukocytes) and the term leukaemia comes from the Greek words for white and blood. Leukaemia accounts for about 30% to 40% of all childhood cancers in Singapore and throughout the world1. Leukaemia starts in the bone marrow, the spongy internal part of the bones where new blood is made, and the abnormal white blood cells then spread to the blood stream.
When a child has leukaemia, large numbers of abnormal white blood cells called blasts are produced in the bone marrow. These abnormal white blood cells crowd the bone marrow and cause it to be unable to perform its normal function of producing mature red blood cells, white blood cells and platelets.
As the leukaemia progresses, other types of blood cell production such as red blood cells and platelets are affected. The leukaemia cells flood the bloodstream and infiltrate other organs, especially the lymph nodes, liver and spleen. However, they do not protect the body against diseases as normal ones do because they are defective and immature and this may result in an increased risk of infections. As red blood cell and platelet production is also decreased, anaemia and bleeding tendencies may occur.
There are two types of leukaemia, acute (rapidly developing) and chronic (slowly developing). About 5% of leukaemia in children are chronic while 95% are acute2. There are two types of chronic leukaemia - Chronic Myelogenous Leukemia (CML) and Chronic Lymphocytic Leukemia (CLL). CML occurs very rarely in children.
Acute childhood leukaemia is divided into Acute Lymphocytic Leukaemia (ALL) and Acute Myelogenous Leukaemia (AML). This categorisation depends on which cell line (mother cell) the leukaemia starts from. Approximately 80% of children with leukaemia have ALL and about 20% have AML3.
Most ALL cases commonly occur in early childhood, peaking between 2 and 4 years of age. Cases of AML are more spread out across the childhood years but they are slightly more common during the first 2 years of life and during the teenage years.
1National Registry of Diseases Office, 2Korean Journal of Pediatrics, 3Pharmacotherapy Self-Assessment Program
There is currently no known way to prevent childhood leukaemia. The cause of leukaemia is unknown in majority of the cases. Most leukaemia develop from non-inherited mutations (changes) in the genes of growing blood cells. Neither parents nor children have control over the factors that trigger leukaemia.
As white blood cells are defective in children with leukaemia, affected children may experience increased episodes of fever and infections. These children may also be anaemic as leukaemia affects the bone marrow's production of oxygen-carrying red blood cells. The child might appear paler than usual and tire more easily.
In addition, children with leukaemia tend to bruise very easily and may experience frequent nose and gum bleeds. This is due to the decrease in platelet production which affects the blood's ability to clot.
Other symptoms of leukaemia may include:
Leukaemia can spread to the brain and cause headaches, seizures or abnormal vision. It may also present as a stroke if there is a bleed in the brain. If the lymph nodes inside the chest are involved, the enlarged glands can compress the trachea (windpipe) and the surrounding blood vessels. This leads to breathing problems and interference with blood flow to and from the heart.
Prior to examination of the child, a detailed medical history has to be obtained by the doctor which will include the medical history of the child's family members. A physical examination will be performed to look for signs suggestive of leukaemia such as enlarged lymph nodes, liver or spleen. There may also be features of anaemia and thrombocytopenia (low blood platelet count). A neurological examination including examination of the eyes will also be performed and particularly for boys, the genitalia (testes) will be examined for the presence of swelling which is suggestive of leukaemic infiltrates.
Blood is usually taken from the child and sent for basic tests such as a full blood count to measure the number of white blood cells, red blood cells and platelets. It will also reveal the presence of blast cells.
A blood smear is done to look for the presence of leukaemic blasts and may also reveal abnormalities in the red blood cell and platelet population.
From the results of the physical examination and preliminary blood tests, further tests like those below may be needed:
Bone marrow samples are obtained usually from the back of the hip bone to diagnose and further classify the specific type of leukaemia. Various tests will be performed on the bone marrow samples including that of genetic testing as different genetic subtypes would mean different risk groups and hence enable the doctor to better predict the outcome and adjust intensity of treatment accordingly.
A sample of spinal fluid is removed from the lower back and examined for evidence of abnormal cells. This is to determine if the leukaemia has spread to the central nervous system (brain and spinal cord).
All the procedures will be done by our paediatricians specialising in oncology and children will receive anaesthesia or sedatives for any painful procedures.
ALL, AML and chronic leukaemia are all treated with different chemotherapy drugs. The aim is to kill all the leukaemia cells in the body but this usually damages the neighbouring healthy cells. In recent years, new drugs that target specific parts of cancer cells have been developed. These drugs work differently from standard chemotherapy drugs and generally have different and less severe side effects.
9a Viva-University Children's Cancer Centre, we run several clinical trials for treatment of leukaemia, most notably the Malaysia-Singapore ALL study and more recently, Natural Killer Cell (Expanded) Singapore which is more cellular therapy based. Together with our scientists and the support of the clinical and research laboratory, we perform the necessary advanced tests, including analysing the genetic abnormalities in the leukaemia cells, to characterise the leukaemia cells and thus allow us to customise the therapy to suit the individual child. We are also able to modify immune cells to target leukaemia cells such as using expanded natural killer cells to attack cancer cells.
In the next year or 2, we also hope to be able to offer chimeric antigen receptor T-cell (CAR-T) cell therapy to our patients. As shown by the groups in Childrens' Hospital of Philadelphia, CAR-T cell therapy has improved the cure rates of relapsed refractory leukaemia.
We also have a 24-hour helpline that allows children to consult with a member of the oncology team and receive immediate medical attention should the need arise.
Chemotherapeutic drugs can be given orally (taken by mouth), intravenously (given through the blood vessel), intramuscularly (injection into muscle) and also intrathecally (injected into the cerebrospinal fluid through an opening in the spine). The drugs are usually given based on a protocol but adjustments will be made to each individual depending on his or her age, weight, risk factors and response to therapy.
During this period, close monitoring by a paediatrician specialising in oncology is crucial. As treatment progresses, the cancer treatment team will monitor the child closely for side effects, especially looking out for infections as the drugs given will impair the child's immune system and the ability to fight infections. As the bone marrow becomes suppressed, the red blood cells and platelets will decrease and the problems of fatigue, headaches and bleeding may ensue. To decrease the chance of leukaemia invading the central nervous system, children will receive intrathecal chemotherapy, which administers cancer-killing drugs into the cerebrospinal fluid around the brain and spinal cord. Radiation treatments to eradicate leukaemia in the brain may also be used for certain high-risk children.
In some instances, a stem cell transplant may be necessary in addition to chemotherapy, depending on the type of leukaemia a child has. The child will undergo 'conditioning' whereby chemotherapy drugs and sometimes radiotherapy is given to clear the bone marrow of its stem cells to allow a niche for new healthy stem cells to grow and make new healthy cells. These healthy new stem cells are collected from a healthy donor and will be injected into the child's blood.
There have been significant advances in the therapy of childhood leukaemia in Singapore where 60% to 80% of these children are now long-term (at least 10 years and above) survivors. Published in 2009, data from the Singapore Childhood Cancer Survivor Study showed that amongst the childhood cancers, ALL had the highest percentage (80.9%) of surviving patients4.
Published in Journal of Clinical Oncology 2012, the Malaysia-Singapore 2003 study revealed a 6-year overall survival of 88.4% +/-3.1% for children with ALL5.
There are multiple factors that contribute to the high survival rate of leukaemic patients in NUH such as relatively low toxicity of the chemotherapy regimen, good supportive care, use of minimal residual disease monitoring and a centralised risk stratification platform
Information is correct as of October 2017.
Source: 4PubMed, 54Journal of Clinical Oncology
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