Childhood Leukaemia

Leukaemia is a type of cancer affecting the white blood cells (leukocytes). The term 'leukaemia' originates from the Greek words for 'white' and 'blood'. It represents 30–40% of all childhood cancers in Singapore and globally1. Leukaemia begins in the bone marrow, the soft part insides the bones where new blood cells are produced. It causes an overproduction of abnormal white blood cells, known as blasts, which then spread to the bloodstream.

In children with leukaemia, these abnormal white blood cells overcrowd the bone marrow, hindering its ability to produce mature red blood cells, white blood cells and platelets. As leukaemia progresses, it disrupts the production of red blood cells and platelets, leading to increased risk of infections, anaemia and bleeding tendencies, since these defective and immature cells cannot protect the body against diseases.

Leukaemia in children can be acute (rapidly developing) and chronic (slowly developing). Chronic leukaemia, comprising Chronic Myelogenous Leukemia (CML) and Chronic Lymphocytic Leukemia (CLL), is rare in children, with only about 5% of cases being chronic2. Acute childhood leukaemia is divided into Acute Lymphocytic Leukaemia (ALL) and Acute Myelogenous Leukaemia (AML), depending on the origin cell line. Approximately 80% of childhood leukaemia cases are ALL and around 20% are AML3. ALL typically peaks between ages two and four, while AML is more  ommon in the first two years and during teenage years.

Source: 1National Registry of Diseases Office, 2Korean Journal of Pediatrics, 3Pharmacotherapy Self-Assessment Program 

There is currently no known prevention for childhood leukaemia. The majority of leukaemia cases arise from non-inherited mutations in the developing of growing blood cells, and these factors are beyond the control of parents and children.

Children with leukaemia often have defective while blood cells, leading to increased episodes of fever and infections. Anaemia is also a common symptom due to the affected bone marrow's reduced production of red blood cells, causing child might appear paler tire easily.

Other symptoms include:

• Easy bruising and frequent nose and gum bleeds, attributable to decreased platelet production affecting blood clotting
• Bone or joint pain, sometimes causing a limp
• Swollen lymph nodes in the neck, groin or elsewhere
• Poor appetite and weight loss

Leukaemia can spread to the brain, resulting in headaches, seizures or vision abnormalities. It might manifest as a stroke due to bleeding in the brain. If lymph nodes inside the chest are affected, enlarged glands can compress the trachea andsurrounding blood vessels, causing breathing difficulties and affecting blood flow to and from the heart.

​Diagnosis

Before assessing a child, clinicians gather a detailed medical history, including that of the child's family. The physical examination may reveal leukaemia indicators such as swollen lymph nodes or an enlarged liver or spleen. Signs of anaemia and thrombocytopenia (low blood platelet count) are also investigated. A neurological examination, including an ocular assessment, is conducted. For boys, an examination of the genitalia is conducted to check for any swelling indicative of leukaemic infiltration.

Laboratory tests typically include a complete blood count to measure the white and red blood cells and platelets, revealing the presence of blast cells. A blood smear is examined for leukaemic blasts and abnormalities in the red blood cells and platelets.

Depending on initial findings, additional tests may include:

• Bone marrow biopsy and aspiration: To diagnose and classify leukaemia, samples are taken from the hip bone. Genetic testing on these samples helps determine different risk groups, aiding in prognosis and treatment planning.
  
  
• Lumbar puncture (spinal tap): Spinal fluid is analysed for abnormal cells to determine if leukaemia has spread to the central nervous system.

These procedures are performed by paediatric oncology specialists, with anaesthesia or sedatives administered for any painful procedures.

Treatment

Different chemotherapy drugs treat ALL, AML and chronic leukaemia. The goal is to eliminate leukaemia cells, which can also affect healthy neighbouring cells. Newer drugs, targeting cancer cells specifically, have been developed with fewer and less severe side effects.

At 9a Viva-University Children's Cancer Centre, clinical trials are conducted, including the Malaysia-Singapore ALL study and Natural Killer Cell (Expanded) Singapore trial, which based on cellular therapy. NUH performs advanced tests to tailor therapy to each child's specific needs, including modifying immune cells to target leukaemia.

In the near future, NUH aims to offer CAR-T cell therapy, which has shown promising results in treating relapsed refractory leukaemia. NUH also has a 24-hour helpline for immediate consultation and medical attention from the hospital's oncology team. 

Chemotherapy

Chemotherapy is administered orally, intravenously, intramuscularly or intrathecally, tailored to each child's age, weight, risk factors and therapy response. Oncology specialists close monitor for side effects, particularly infections, as treatments can weaken the immune system. Suppression of bone marrow may lead to decreased red blood cells and platelets, causing fatigue, headaches and bleeding. Intrathecal chemotherapy and, in high-risk cases, radio therapy are used to prevent leukaemia from spreading to the central nervous system.

Haematopoietic Stem Cell Transplant

For some leukaemia types, a stem cell transplant may complement chemotherapy. This, along with radiotherapy, prepares the bone marrow for new healthy stem cells from a donor, which are then infused into the child's bloodstream.

Therapeutic advancements have markedly improved the prognosis of childhood leukaemia in Singapore, with 60–80% of affected children are achieving long-term survival of a decade or more. The Singapore Childhood Cancer Survivor Study, published in 2009, indicated that ALL had the highest survival rate among childhood cancers, with 80.9% of patients surviving4.

Further, the Malaysia-Singapore 2003 study, published in the Journal of Clinical Oncology in 2012, reported a six-year overall survival of 88.4% +/-3.1% for children with ALL5.

Factors contributing to these high survival rates at NUH include the low toxicity of chemotherapy regimens, comprehensive supportive care, the utilisation of minimal residual disease monitoring and a centralised platform risk stratification.

Information is accurate as of October 2017.

Source: 4PubMed, 54Journal of Clinical Oncology

Continued clinical research is essential for advancing paediatric healthcare. Our doctors are committed to contributing to the future of child health and medicine through both clinical practice and research.

• AEJ Yeoh, H Arrifin, ELL Chai, CSN Kwok, YH Chan, PL Tan, . . . TC Quah (2012). Minimal Residual Disease–Guided Treatment Deintensification for Children With Acute Lymphoblastic Leukemia: Results From the Malaysia-Singapore Acute Lymphoblastic Leukemia 2003 Study. Journal of Clinical Oncology, 30(19):2384-2392. doi: 10.1200/JCO.2011.40.5936
• Aung L, Khyne T, Yeoh AE, Quah TC, Tan AM (2009). A report from the Singapore Childhood Cancer Survivor Study (SG-CCSS): a multi-institutional collaborative study on long-term survivors of childhood cancer, initial analysis reporting for the SG-CCSS. Annals of the Academy of Medicine, Singapore, 38(8):684-9.
• Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Yeoh AE, . . . Mullighan CG (2015). Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. Journal of Clinical Oncology : Official Journey of the American Society of Clinical Oncology, 33(27):2938-48. doi: 10.1200/JCO.2014.59.1636