Leukaemia is a cancer of the white blood cells (WBCs), which are also known as leukocytes. When a child has leukaemia, large numbers of abnormal white blood cells are produced in the bone marrow. These abnormal white cells crowd the bone marrow and flood the bloodstream, but they do not protect the body against disease as normal ones do because they are defective and immature.

As the leukaemia progresses, other types of blood cell production, including that of red blood cells and platelets are affected. In the long run, this results in a low red blood cell count or anaemia. There is also an increased risk of infection caused by white cell abnormalities.

Leukaemias account for about 40% of all childhood cancers in Singapore and throughout the world. Luckily, there have been significant advances in the therapy of childhood leukaemias in Singapore so much so that 60-80% of these children are now long-term survivors and are probably cured.

Types of Childhood Leukaemia

Leukaemias can be classified into acute (rapidly developing) and chronic (slowly developing) forms. In children, by far the majority (98%) of leukaemias are acute.

Acute childhood leukaemias are also divided into acute lymphocytic leukaemia (ALL) and acute myelogenous leukaemia (AML). This categorization depends on which cell line (mother cell) the leukaemia start from. Approximately 80% of children with leukaemia have ALL, and about 20% have AML.

Risk for Childhood Leukaemia

ALL most commonly afflicts younger children from ages 2 to 8, with a peak incidence at age 4. But it can affect all age groups.

In the majority of cases, the cause of leukaemia is unknown. What is clear is that neither parents nor children have control over the factors that trigger leukaemia. Most leukaemias develop from non-inherited mutations (changes) in the genes of growing blood cells. As errors occur randomly and unpredictably, there is currently no effective way to prevent most types of leukaemia.

Currently in NUH, we are studying the risk profiles of children with leukaemia to hopefully allow us to predict the risk of developing leukaemia, their chances of cure and complications from therapy. This is funded by the National Medical Research Council (NMRC) and A*STAR/ Singapore Cancer Syndicate.

Symptoms of 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 also affects the bone marrow's production of oxygen-carrying red blood cells. This would result in pallor and makes them abnormally tired and short of breath while playing.

Children with leukaemia also tend to bruise very easily and experience frequent nose and gum bleeds. Bleeding, even from minor wounds, might be prolonged as leukaemia destroys the bone marrow's ability to produce clot-forming platelets.

Other symptoms of leukaemia may include:

Pain in the bones or joints, sometimes causing a limp
Swollen lymph nodes in the neck, groin, or elsewhere
Abnormally tired feeling
Poor appetite

In up to 12% of children with AML and 6% with ALL, leukaemia can spread to the brain and cause headaches, seizures, balance problems, or abnormal vision. If ALL spreads to the lymph nodes inside the chest, the enlarged gland can compress on the trachea (windpipe) and the surrounding blood vessels, leading to breathing problems and interference with blood flow to and from the heart.

Diagnosing Leukaemia

A physical examination will be performed to check for signs of infection, anaemia, abnormal bleeding, and swollen lymph nodes. The child's abdomen is also examined to see if there is an enlarged liver or spleen. This can occur with some cancers in children.

In addition medical history of the family will be taken and FBC taken (full blood count) to measure the numbers of white cells, red cells, and platelets in the child's blood. A blood smear will also be taken to check for certain specific types of abnormal blood cells.

From the results of the physical examination and preliminary blood tests, further tests like those below may be needed:

A bone marrow biopsy and aspiration - marrow samples are removed from the body (usually from the back of the hip bone) for testing. In NUH, we have a highly comprehensive panel of routine and investigational tests that can help diagnose, subgroup and prognosticate the type of leukaemia with exceedingly high accuracy.

A lumbar puncture (spinal tap) - where 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).

Bone marrow or lymph node samples will be examined and additional testing will be done to determine the specific type of leukaemia. In addition to these basic laboratory tests, cell evaluations are also generally done, including genetic studies to distinguish between specific types of leukaemia, as well as certain features of the leukaemia cells. Children will receive anaesthesia or sedatives for any painful procedures.

Treating Leukaemia

The goal in the treatment for AML^1-5 and ALL is to attain continuous complete remission of the leukaemia (when there is no more evidence of cancer cells in the body). Types and intensities of treatments are dependent on the patient and the features of his/ her condition. Some of the factors include age and initial white blood cell count. All children with ALL are treated with chemotherapy, but the dosages and drug combinations may differ.

To decrease the chance of leukaemia invading the central nervous system, patients 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 necessary for certain high-risk patients. During this period, close monitoring by a paediatric oncologist is imperative. Intensive leukaemia chemotherapy may incur side effects like hair loss, nausea and vomiting. As treatment progresses, the cancer treatment team will monitor the child closely for these side effects.

In some instances, a bone marrow transplant may be necessary in addition to, or instead of chemotherapy, depending on the type of leukaemia that a child has. Healthy bone marrows are injected into the child's body during the transplant.

Once remission is achieved, maintenance chemotherapy is then used to keep the child in remission. This is given in cycles over a period of 2 to 3 years to keep the cancer from recurring. Leukaemia will almost always relapse (re-occur) if this additional chemotherapy is not given. There are also cases when the cancer returns even though maintenance chemotherapy is given, and other forms of chemotherapy will then be necessary.

With proper treatment, the outlook for children who are diagnosed with leukaemia is excellent. Childhood ALL has >98% remission rate after 1 month of therapy and > 80% are cured with our current research protocols. Recently ~60% of children with AML are curable under our recent research protocol. All children then require regular maintenance chemotherapy and other treatment to continue to be cancer-free. Cure rates will also differ depending on the specific features of a child's disease but most childhood leukaemias have very high remission rates. The majority of these children can achieve permanent remission and be cured of the disease.

In NUH, we have a dedicated multidisciplinary team to manage children with cancer especially those with leukaemia. We are able to provide the complete therapy from diagnosis to chemotherapy, radiation therapy even various types of stem cell transplantation.

Acute Lymphocytic Leukaemia (ALL) Clinical Outcomes

Our research protocols have successfully improved the results of treatment of children with ALL in Singapore since 1988. Our 5-years cure rates have improved from 62% in 1988-1996 to 80% in 1997-2002. It has further improved to 84% from 2003-2008. These rates are comparable with St. Jude Children's Research Hospital, the top cancer hospital for children in the world.⁶ Our multi-centre Malaysia-Singapore (Ma-Spore) trials have allowed highly accurate prediction of outcome and tailoring therapy to maximise the chance of cure and minimising toxicity. This is now expanded into a multi-centre study sponsored by National Medical Research Council (NMRC) and A*STAR/Singapore Cancer Syndicate.

Acute Myelogenous Leukaemia (AML) Clinical Outcomes

NUH started implementing the MRC AML 10 protocol in their treatment of AML patients since Sept 1996. In this new protocol, treatments are of a shorter timeframe (5 months instead of the conventional 2 years).The team has achieved a significantly better 3-year overall (74% vs 35%), event-free (77% vs 20%) and disease-free (83% vs 31%) survival. They were also more likely to achieve a complete remission than non-MRC AML 10 patients. About 60% of these children are expected to be cured. Another new multi-centre study protocol Ma-Spore AML 2006 was implemented in 2005. This is also sponsored by NMRC and A*STAR/Singapore Cancer Syndicate. The 3-year overall survival is 70% and event-free survival rate is 60%. These results are not yet mature, and it is expected to achieve better 5-year survival rates. The international 5-year event-free survival rate is 40-60%.

St Jude-Viva Foundation Programme in NUH

In 2006, the Viva Foundation for Children with Cancer (Singapore) has identified NUH as the Centre for Excellence to develop their "St Jude-Viva Programme" in Singapore. Viva Foundation is a Singapore-based charity foundation which aims to improve the cure of childhood cancer in Singapore and the whole region. St Jude Children's Research Hospital is the top cancer hospital for children in the world and the only NCI (National Cancer Institute) designated Comprehensive Cancer Centre in USA. NUH together with NUS, Viva Foundation and St Jude will work towards improving the cure for children with cancer in Singapore and beyond.

Information is correct as at November 2009

Footnotes

Arceci RJ. Progress and controversies in the treatment of pediatric acute myelogenous leukemia. Curr Opin Hematol 2002;9:353–360.
Loeb DM, Arceci RJ. Treatment of childhood acute myeloid leukemia. In: Pui CH, editor. Treatment of acute leukemias: New directions for clinical research. New Jersey: Humana Press, 2003. pp 255–265.
Creutzig U. Treatment of acute myeloid leukemia in children. In: Pui CH, editor. Treatment of acute leukemias: New directions for clinical research. New Jersey: Humana Press, 2003. pp 237–254.
Langmuir PB, Aplenc R, Lange BJ. Acute myeloid leukaemia in children. Best Pract Res Clin Haematol 2001;14:77–93.
Chessells J. Acute myeloid leukaemia. In: Pinkerton R, Philip T, Fervers B, editors. Evidence-based paediatric oncology. London: BMJ Books, 2002. pp 251–287.
Pui CH, Campana D, Pei D, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. New Eng J Med 2009; 360: 2730-2741

This material does not cover all information and is not intended as a substitute for professional care. Please consult your physician on any matters regarding your health.

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