Acute Leukaemia

Acute leukaemias are medical emergencies. ALL is the most common malignancy in children (peak age 2-5), while AML is primarily a disease of older adults (median age 65). The proliferation of blast cells Crowds out normal haematopoiesis, resulting in pancytopenia. Presentation is typically acute (days to weeks) with symptoms of anaemia, infection (due to neutropenia), and bleeding/bruising (due to thrombocytopenia). AML is associated with Auer rods and the M3 subtype (Acute Promyelocytic Leukaemia - APML) is notable for its association with DIC. ALL frequently involves the CNS and mediastinum. Diagnosis requires >20% blasts in the bone marrow. Treatment involves intensive chemotherapy, with the goal of achieving complete remission. Supportive care (transfusions and antibiotics) is vital during the induction phase.

Acute leukaemias arise from somatic mutations in haematopoietic stem cells. These mutations lead to a 'maturation arrest'—the cells proliferate but cannot differentiate into functional mature cells. In ALL, the cells are of lymphoid lineage (B-cell or T-cell). In AML, they are myeloid (precursors to granulocytes, monocytes, RBCs, or platelets). A specific translocation in APML, t(15;17), involves the Retinoic Acid Receptor alpha (PML-RARA fusion), and responds to All-Trans Retinoic Acid (ATRA). Risk factors include ionizing radiation, benzene exposure, and previous chemotherapy (alkylating agents). Genetic conditions like Down's Syndrome carry a significantly increased risk of both ALL and AML.

Presenting features: General: Fever, weight loss, night sweats. Marrow Failure: Pallor, lethargy, recurrent/severe infections (sore throat, pneumonia), petechiae, purpura, epistaxis. Infiltration: Bone pain (common in ALL), hepatosplenomegaly, lymphadenopathy, gingival hypertrophy (classic in monocytic AML), and mediastinal mass (T-ALL). CNS involvement (headache, vomiting, nerve palsies) is more common in ALL. APML presents with severe bleeding due to DIC. Laboratory tests typically show a high 'white cell' count (due to blasts), but can be low or normal ('aleukaemic leukaemia').

Bloods: FBC (Anaemia, thrombocytopenia, WBC high/low), Blood film (Blast cells; Auer rods in AML), Clotting screen (checking for DIC), U&Es (Urate, LDH often raised). Gold Standard: Bone marrow aspiration and trephine biopsy (Morphology, Flow cytometry/Immunophenotyping to distinguish AML/ALL, and Cytogenetics/FISH for prognosis). Imaging: CXR (for mediastinal mass). Lumbar puncture: If CNS involvement is suspected (usually in ALL).

Acute Management: Stabilisation, broad-spectrum IV antibiotics for neutropenic sepsis (e.g., Tazocin), and blood/platelet transfusions. APML: Immediate ATRA to prevent fatal DIC. Chemotherapy: 1) Induction: Intensive therapy to achieve remission. 2) Consolidation: To eradicate residual disease. 3) Maintenance: Longer-term, lower-dose therapy (mainly ALL). Supportive: Allopurinol or Rasburicase to prevent Tumor Lysis Syndrome. Bone Marrow Transplant: Considered in high-risk patients or relapse. CNS prophylaxis: Intrathecal methotrexate (mainly ALL).