Leukaemia

Leukaemia (leukemia) is a type of blood cancer that begins in the bone marrow — the tissue inside bones where blood cells are produced. It occurs when abnormal white blood cells grow uncontrollably, crowding out healthy cells (such as red blood cells and platelets) and impairing normal blood function.

White blood cells are a key part of the immune system. In leukaemia, these cells do not mature properly and cannot function as they should. This leads to an increased risk of infections. When red blood cells are reduced in numbers (anaemia), there may be symptoms of anaemia such as fatigue and breathlessness. Reduced platelets counts can lead to bleeding.

Leukaemia is not a single disease but a group of related cancers, with several subtypes based on how quickly the disease progresses and the specific type of blood cell involved.

How prevalent is leukaemia?

Globally, leukaemia is the 13th most frequently diagnosed cancer and the 10th leading cause of cancer death. In Singapore, leukaemia is the most common type of cancer seen in children, accounting for about 35% of diagnoses.

How is leukaemia classified?

Leukaemia is classified by:

1. The speed at which the disease progresses
   • Acute leukaemia develops rapidly and requires immediate medical attention. In this form, the bone marrow produces a large number of immature white blood cells, known as blasts, which accumulate quickly and interfere with the production of healthy blood cells. Symptoms tend to appear suddenly and worsen within a short period of time. It is more common in children.
   • Chronic leukaemia progresses more slowly and may not cause noticeable symptoms in its early stages. In chronic leukaemia, abnormal cells mature do not function effectively. These cells can accumulate gradually over months or years, sometimes being detected incidentally during routine blood tests. It is more common in adults.
2. The type of white blood cell affected
   • Myeloid (myelogenous) leukaemia originates from early myeloid cells, which are precursors to red blood cells, platelets and certain types of white blood cells such as neutrophils. When affected, these cells fail to develop normally, leading to disruptions in oxygen transport, clotting and immune defence.
   • Lymphoid (lymphocytic) leukaemia arises from early lymphoid cells, which develop into lymphocytes. These are a crucial part of the immune system, responsible for producing antibodies and coordinating immune responses. In lymphoid leukaemia, the cancerous cells crowd out healthy lymphocytes, weakening the body’s ability to fight infections.

What are the types of leukaemia?

The four major types of leukaemia are:

• Acute lymphoblastic leukaemia (ALL): Most common in children but can affect adults.
• Acute myeloid leukaemia (AML): More common in adults over 65 but can occur at any age.
• Chronic lymphocytic leukaemia (CLL): [LW2] Typically affects older adults and progresses slowly.
• Chronic myeloid leukaemia (CML): [LW3] Affects mainly adults over 40 and progresses through distinct phases. Rarely occurs in children.

Other rarer types include hairy cell leukaemia (a subtype of CLL) and chronic myelomonocytic leukaemia. 

What are the symptoms of leukaemia?

Leukaemia symptoms can be non-specific and may resemble other common illnesses. They vary depending on the type and progression of the disease. Common symptoms include:

• Persistent fatigue or weakness
• Frequent infections
• Fever or chills
• Easy bruising or bleeding
• Recurrent nosebleeds
• Pale skin (anaemia)
• Unexplained weight loss
• Bone or joint pain
• Swollen lymph nodes, liver or spleen
• Tiny red spots on the skin (petechiae)
• Excessive sweating/night sweats
• Loss of appetite

When should you see a doctor?

You should consult a doctor if you experience persistent or unexplained symptoms such as fatigue, frequent infections, bleeding or prolonged fever. These symptoms may be subtle or mistaken for other conditions.  Early medical evaluation is important, especially for individuals with known risk factors.

Can leukaemia be prevented?

There is no proven way to prevent most forms of leukaemia. However, certain steps may help reduce overall cancer risk:

• Avoid smoking and industrial chemicals like benzene.
• Maintain a healthy lifestyle, including regular exercise and a balanced diet.
• Manage medical conditions and minimise exposure to unnecessary radiation.
• Seek prompt evaluation of unexplained symptoms.

What causes leukaemia?

Leukaemia occurs when genetic changes in the DNA of blood-forming cells cause them to grow and divide uncontrollably. These changes may be influenced by a combination of genetic predisposition and environmental exposures.

While leukaemia is usually not hereditary, certain chromosomal abnormalities, such as the Philadelphia chromosome in CML, have been linked to the disease. These abnormalities interfere with normal cell regulation, leading to uncontrolled cell growth.

However, the exact cause of leukaemia is usually not known.

What are the risk factors for leukaemia?

While anyone can develop leukaemia, several factors may increase the risk:

• Previous cancer treatment: Exposure to chemotherapy or radiation therapy.
• Exposure to high radiation levels: Such as in nuclear accidents or radiation therapy.
• Industrial chemical exposure: Especially to benzene and formaldehyde. Benzene is used to make items such as dyes, pesticides, detergents, plastics and rubbers while formaldehyde is in building materials.
• Smoking or exposure to second-hand smoke: May increases the risk of AML.
• Particular genetic disorders: Including Down syndrome and other rare syndromes.
• Family history: Having a first-degree relative with some types of leukaemia may increase the risk.
• Age and sex: Chronic leukaemias are more common in older adults and males.

How is leukaemia diagnosed?

Leukaemia diagnosis typically begins with a clinical assessment, followed by blood tests. Common diagnostic steps include:

• Physical examination: To check for signs such as pale skin, enlarged liver or spleen or swollen lymph nodes.
• Complete blood count (CBC): May show abnormal levels of white or red blood cells or platelets. People with leukaemia typically have a higher white blood cell count.
• Peripheral blood smear: Blood cells are examined under a microscope for abnormalities.
• Bone marrow biopsy (or aspiration): A sample of bone marrow (usually from the hip) is obtained to confirm the diagnosis and identify the leukaemia subtype.
• Genetic testing: Identifies mutations or chromosomal changes relevant to treatment planning.
• Lumbar puncture: Checks for leukaemia spread to the brain or spinal fluid.
• Imaging tests (CT, MRI or X-rays): Used to detect if leukaemia has affected other parts of the body.

What are the stages of leukaemia?

Unlike many solid tumours, AML and ALL are not staged by tumour size or spread. Instead, disease status is described as untreated, in remission or relapsed.

The staging systems for CLL and CML are detailed below:

CLL

Staged from A to C, this system considers both the white blood cell count and the extent of lymph node involvement.

• Stage A: High white blood cell count with fewer than three areas of lymph node enlargement.
• Stage B: High white blood cell count with three or more enlarged lymph node regions.
• Stage C: High white blood cell count accompanied by low levels of red blood cells and/or platelets, indicating more advanced disease.

CML

Categorised into three progressive phases based on the number of immature white blood cells (blasts) and symptom severity.

• Chronic phase: Few abnormal cells are present, and symptoms may be mild or absent.
• Accelerated phase: Abnormal cells increase, and symptoms such as fatigue or an enlarged spleen may develop.
• Blast phase (blast crisis): A marked increase in blast cells, leading to more severe symptoms and complications similar to those seen in acute leukaemia.

How is leukaemia treated?

Treatment depends on the type of leukaemia, the patient’s age and overall health and how far the disease has progressed, including whether it has reached other parts of the body such as the central nervous system.

Patients may receive care from a multidisciplinary team at public hospitals, including haematologists, oncologists, specialised nurses and allied health professionals.

Common leukaemia treatment options include:

Chemotherapy

This is the primary treatment for most leukaemia cases. Chemotherapy uses drugs to kill leukaemia cells or prevent them from multiplying. Depending on the subtype of leukaemia, patients may receive a single medication or a combination of drugs. These are typically administered as oral tablets or through injections into the vein. Complications of chemotherapy can include infections, bleeding or other side effects related to the drugs given. Treatment is usually given in cycles, spanning several months or longer.

Targeted therapy

These medications work by focusing on specific abnormalities within cancer cells. By blocking certain proteins or genetic mutations that allow leukaemia cells to thrive, targeted therapy can stop their growth or lead to their destruction. Before starting, leukaemia cells will be tested to determine if this therapy is suitable. Tyrosine kinase inhibitors, for example, are commonly used in CML.

Immunotherapy

This approach strengthens the body’s own immune system to detect and attack leukaemia cells. Leukaemia cells sometimes evade immune detection by producing protective proteins. Immunotherapy helps to overcome this barrier. Options include monoclonal antibodies, which attach to specific markers on cancer cells, and immune checkpoint inhibitors, which boost the immune system’s response.

Chimeric antigen receptor (CAR) T-cell therapy

A newer form of immunotherapy, CAR-T cell therapy involves collecting a patient’s own T-cells, re-engineering them in a laboratory to better recognise and attack leukaemia cells and then returning them to the patient’s body. CAR T-cell therapy has shown promise for certain types of relapsed or difficult-to-treat leukaemias.

Radiation therapy

Strong X-rays or energy beams are used to destroy leukaemia cells or stop their growth. Radiation may be directed at specific areas of concern, such as where leukaemia cells have gathered, or used across the entire body in preparation for a stem cell transplant.

Stem cell transplant (or bone marrow transplant)

This procedure replaces diseased bone marrow with healthy blood-forming stem cells. High doses of chemotherapy or radiation are first given to eradicate the leukaemia-producing marrow. The patient then receives an infusion of healthy stem cells, which may come from a donor (allogeneic transplant) or from the patient’s own previously collected cells (autologous transplant). The goal is to restore normal blood cell production.

What are the phases of leukaemia treatment?

Treatment for leukaemia is often delivered in phases:

1. Induction: The first step aims to destroy as many leukaemia cells as possible in the blood and bone marrow to achieve remission. At this stage, blood counts will decline and then return to normal after some time. Induction therapy usually spans several weeks.
2. Consolidation: Also known as intensification therapy, this phase focuses on eliminating any remaining cancer cells that may not have been detected, to reduce the risk of relapse. Consolidation treatment is often given in cycles over several months.
3. Maintenance: Commonly used in ALL, this final phase works to keep the disease in remission by targeting any residual cells. Maintenance therapy can continue for an extended period, sometimes up to two years, to prevent recurrence.

What is the outlook for patients with leukaemia?

Prognosis depends on many factors, including:

• Type of leukaemia
• Patient’s age and general health
• Genetic mutations or chromosomal changes
• Response to treatment
• Disease burden at diagnosis

Is there a cure for leukaemia?

Depending on the type of leukaemia, there may or may not be a cure. However, long-term remission is possible, even in cases that are not considered curable. Advances in treatment, including targeted therapies and transplants, have significantly improved outcomes.

What is the difference between the types of leukaemia?

Leukaemia types differ by the speed of progression (acute vs chronic) and the type of blood cell affected (myeloid vs lymphoid). For example, AML is fast-growing and affects myeloid cells, while CLL is slow-growing and affects lymphoid cells.

Can people with leukaemia live for many years after treatment?

Yes, many individuals diagnosed with leukaemia can achieve long-term remission, where no signs of the disease are present and blood counts return to healthy levels. However, it is difficult to predict the exact duration of remission, as this varies from person to person. There is also a possibility that the cancer may return, which is why regular follow-up care remains important.

Can children get leukaemia?

Yes. Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer. Treatment outcomes in children are generally favourable.

What does leukaemia do to your body?

Leukaemia interferes with the production of normal blood cells, which can lead to anaemia, infection and bleeding. It may also cause enlargement of the liver, spleen or lymph nodes.

Where can I find leukaemia support in Singapore?

Support services are available at major public hospitals and through organisations such as the Singapore Cancer Society and the Children’s Cancer Foundation. These services offer counselling, financial support and survivorship care.

Which type of leukaemia tends to be the most severe?

AML is generally regarded as one of the most aggressive forms of leukaemia. It progresses rapidly and requires prompt treatment soon after diagnosis to control the disease.