Leukemia

Leukaemia is a collective term for a group of blood cancers that originate in the bone marrow and result in the production of large numbers of abnormal, immature blood cells. These precursor cells fail to develop into functional blood components, leading to a reduction in normal red blood cells, white blood cells, and platelets. The resulting deficiencies cause many of the characteristic clinical features of the disease, which affect the blood, bone marrow, and wider haemopoietic and lymphoid systems.

Overview and Characteristics

Leukaemia begins with the malignant transformation of a blood-forming cell in the bone marrow. The abnormal cells proliferate rapidly or accumulate slowly depending on the type. As they grow, they crowd out normal marrow cells, disrupting normal haematopoiesis. This typically leads to symptoms such as fatigue, bruising, bleeding, bone pain, fever, and an increased susceptibility to infections. Diagnosis is usually made through blood tests and bone marrow biopsy.
The precise cause of leukaemia is unknown, but it is thought to arise from a combination of inherited predispositions and environmental influences. Risk factors include exposure to ionising radiation, benzene and other petrochemicals, smoking, certain chemotherapy agents, and genetic conditions such as Down syndrome. A family history of the disease also increases risk.
Leukaemia and lymphomas form part of the wider category of malignancies affecting the haemopoietic and lymphoid tissues. Though the disease may occur at any age, it is the most common cancer in children; however, over 90 per cent of cases occur in adults.

Classification

Leukaemia is first categorised according to its clinical course:

• Acute leukaemias involve a rapid rise in immature blood cells and require immediate treatment. These are the most common leukaemias in childhood.
• Chronic leukaemias progress more slowly and involve an accumulation of more mature but abnormal cells. They commonly affect older adults and may not initially require active treatment.

Leukaemias are further classified according to the blood cell lineage affected:

• Lymphoblastic (or lymphocytic) leukaemias arise from lymphoid progenitor cells, usually involving B lymphocytes.
• Myeloid (or myelogenous) leukaemias arise from myeloid cells that would ordinarily mature into red cells, platelets, or various white cell types.

Combining these categories produces the four major types:

• Acute lymphoblastic leukaemia (ALL)
• Acute myeloid leukaemia (AML)
• Chronic lymphocytic leukaemia (CLL)
• Chronic myeloid leukaemia (CML)

Each main type includes numerous subtypes based on cellular features, cytogenetics, and behaviour. Some rare forms fall outside the standard scheme but remain clinically important.

Specific Types of Leukaemia

Acute Lymphoblastic Leukaemia (ALL): The most common childhood leukaemia, though it also affects older adults. Subtypes include precursor B-cell and precursor T-cell ALL, Burkitt’s leukaemia, and acute biphenotypic leukaemia. Standard treatment involves chemotherapy, often supplemented by radiotherapy. While children often respond well, around 80 per cent of deaths occur in adults.
Chronic Lymphocytic Leukaemia (CLL): Predominantly a disease of adults over 55, with men affected more frequently. It seldom occurs in children. Although incurable, many effective therapies exist, and the five-year survival rate approaches 85 per cent. A notable aggressive subtype is B-cell prolymphocytic leukaemia.
Acute Myeloid Leukaemia (AML): More common in adults than children and more frequent in men. AML is treated primarily with chemotherapy. Prognosis varies by subtype, with an overall five-year survival of around 20 per cent. Subtypes include acute promyelocytic leukaemia, acute myeloblastic leukaemia, and acute megakaryoblastic leukaemia.
Chronic Myeloid Leukaemia (CML): Occurring mainly in adults, CML is strongly associated with the Philadelphia chromosome. Targeted agents such as imatinib (Gleevec/Glivec) have greatly improved outcomes, and the five-year survival rate is about 90 per cent. A related subtype is chronic myelomonocytic leukaemia.
Hairy Cell Leukaemia (HCL): A rare disorder affecting almost exclusively adult men. It is usually indolent and highly treatable, with ten-year survival between 96 and 100 per cent.
T-Prolymphocytic Leukaemia (TPLL): A rare but aggressive mature T-cell leukaemia, more common in men. It is difficult to treat and has a short median survival.
Adult T-Cell Leukaemia/Lymphoma: Caused by human T-lymphotropic virus (HTLV), this disease results from the viral immortalisation of infected T-cells. HTLV is endemic in certain regions worldwide.
Clonal Eosinophilias and Eosinophilic Leukaemias: These conditions involve clonal proliferation of eosinophils. They may be premalignant or malignant and can be associated with myeloid or lymphoid neoplasms, myelofibrosis, or myelodysplastic syndromes.
Transient Leukaemia (Transient Myeloid Leukaemia): A preleukaemic condition that arises almost exclusively in infants with Down syndrome or similar genetic changes. It often resolves spontaneously but evolves into AML in around 10 per cent of cases.
Clonal Haematopoiesis of Indeterminate Potential: An age-related condition involving detectable clones of blood cells with a low risk of progression to myelodysplastic syndrome or leukaemia.

Signs and Symptoms

The most common symptoms stem from bone marrow failure. Crowding of the marrow by malignant cells reduces normal platelet production, leading to easy bruising, bleeding, and poor clotting. A shortage of red blood cells leads to pallor, fatigue, and shortness of breath, while reduced normal white cells increase vulnerability to infections. Bone pain, particularly in children, is also frequent. Enlargement of the spleen or liver may be seen in advanced cases.

Treatment and Prognosis

Treatment varies depending on the specific type of leukaemia and patient factors such as age and general health. Common approaches include:

• Chemotherapy
• Radiation therapy
• Targeted therapy (e.g., imatinib for CML)
• Bone marrow or stem cell transplantation
• Supportive and palliative care

Some chronic types may be managed through watchful waiting until intervention becomes necessary.
Survival outcomes have improved markedly, especially in high-income countries. In the United States, the overall five-year survival rate reached approximately 67 per cent between 2014 and 2020. In children under 15, survival may exceed 90 per cent depending on subtype, whereas infants under one year have poorer outcomes, around 40 per cent. Global data from 2015 estimates that leukaemia affected 2.3 million people and caused over 350,000 deaths.

Epidemiology

Leukaemia shows substantial variation across age groups and regions. It remains the most common paediatric cancer worldwide, with ALL predominating in children. In adults, CLL and AML are the most frequently diagnosed forms. Higher incidence rates are generally observed in developed countries.