Leukaemia

Classification

• Acute Leukaemias

  • Acute Myeloid Leukaemia (AML)

    • Median age ~67

    • Subtype M3 (acute promyelocytic leukaemia) associated with Auer rods, responds well to ATRA (all-trans retinoic acid)

    • Other AML subtypes treated with standard induction chemotherapy (e.g. cytarabine + anthracycline) ± haematopoietic stem cell transplant

  • Acute Lymphoblastic Leukaemia (ALL)

    • Median age ~7 (most common paediatric leukaemia)

    • CNS involvement common → prophylactic intrathecal chemotherapy

    • High risk of tumour lysis syndrome (TLS) with intensive chemo → prophylaxis with allopurinol or rasburicase

• Chronic Leukaemias

  • Chronic Myeloid Leukaemia (CML)

    • Median age ~47

    • Philadelphia chromosome (t[9;22], BCR-ABL fusion) → dysregulated tyrosine kinase → proliferation of myeloid line

    • Risk of blast crisis (transforming to acute leukaemia) if untreated

  • Chronic Lymphocytic Leukaemia (CLL)

    • Median age ~87 (often older adults)

    • Often asymptomatic; may find on routine FBC with elevated lymphocyte count

    • Hypogammaglobulinaemia can occur → recurrent infections

    • Treatment deferred unless symptomatic or evidence of progression

Presentation

• Acute Leukaemias (AML, ALL)

  • Rapid onset over weeks to months

  • RBC: Fatigue, pallor, anaemia

  • Platelets: Bleeding tendency (bruising, petechiae, haemorrhage)

  • WBC: Infections due to neutropenia or dysfunctional blasts

  • Bone pain (marrow expansion), fever, night sweats

  • CNS involvement more common in ALL (headache, cranial nerve palsies, ↑ICP)

• Chronic Leukaemias (CML, CLL)

  • Insidious onset over months to years

  • Often asymptomatic or mild symptoms (fatigue, weight loss, low-grade fevers)

  • Hepatosplenomegaly, lymphadenopathy, incidental finding of ↑WBC on routine labs

  • CLL can present with recurrent infections (hypogammaglobulinaemia)

____________________________________

Diagnosis

• Peripheral Blood Film

  • AML/ALL: >20% blasts (myeloblasts or lymphoblasts)

  • CLL: Marked lymphocytosis, often >60% mature lymphocytes

  • CML: Elevated WBC (often >100 × 10^9/L), basophilia, myelocytes in peripheral smear

• Bone Marrow Biopsy

  • Hypercellular marrow, ≥20% blasts for acute leukaemias

  • Assessment of lineage markers (flow cytometry) to distinguish AML vs ALL

• Cytogenetics/Molecular Testing

  • Philadelphia chromosome t(9;22) in CML

  • PML-RARA t(15;17) in APL (M3 AML)

  • Other rearrangements guide prognosis and treatment (e.g. FLT3, NPM1 in AML)

• Additional Labs

  • LDH, uric acid (risk of tumour lysis), LFTs, renal function, coagulation profile

  • Infectious screening (HBV, HCV, HIV) prior to immunosuppressive therapy

____________________________________

Management

• Acute Leukaemias (AML, ALL)

  • Induction Chemotherapy (e.g. cytarabine + anthracycline for AML, hyper-CVAD for ALL) to achieve remission

  • Consolidation ± stem cell transplant depending on risk stratification (cytogenetics, minimal residual disease)

  • Supportive Care

    • RBC and platelet transfusions for cytopenias

    • Infection prophylaxis (antibacterial, antifungal, antiviral) if severe neutropenia

    • Allopurinol/rasburicase for TLS prophylaxis in high tumour burden

    • CNS prophylaxis in ALL (intrathecal methotrexate)

  • APL (Acute Promyelocytic Leukaemia, M3 AML)

    • High risk of DIC, treat with ATRA ± arsenic trioxide, can be highly curable if managed early

• Chronic Myeloid Leukaemia (CML)

  • Tyrosine Kinase Inhibitors (TKIs) (e.g. imatinib, dasatinib, nilotinib) mainstay therapy

  • Monitor BCR-ABL transcript levels for response

  • Allogeneic stem cell transplant considered if TKI resistance or advanced disease (blast crisis)

• Chronic Lymphocytic Leukaemia (CLL)

  • Watchful Waiting if asymptomatic with stable blood counts

  • Active Therapy for progressive disease (lymphadenopathy, B symptoms, cytopenias)

    • Options: chemoimmunotherapy (e.g. FCR - fludarabine, cyclophosphamide, rituximab), novel agents (BTK inhibitors like ibrutinib), anti-CD20 (obinutuzumab)

  • Supportive

    • IVIG replacement in recurrent infections due to hypogammaglobulinaemia

    • Palliative radiotherapy for bulky nodes or splenomegaly

____________________________________

Complications

• Tumour Lysis Syndrome (TLS)

  • Spontaneous or post-therapy (especially ALL, high WBC AML)

  • Hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia

  • Prophylaxis: aggressive hydration, allopurinol or rasburicase

• Infections

  • Severe neutropenia → bacterial/fungal/viral infections

  • Prophylactic antimicrobials for high-risk patients (fluoroquinolones, fluconazole, aciclovir)

• Bleeding

  • Thrombocytopenia, coagulopathy (particularly in APL)

  • Platelet transfusions, cryoprecipitate, FFP as needed

• Organ Infiltration

  • Hepatosplenomegaly, lymphadenopathy, CNS infiltration (ALL)

  • Leukaemic infiltration of gums (monocytic AML)

• Blast Crisis (CML)

  • Transformation to acute leukaemia with poor prognosis

____________________________________

Notes:

• Suspicion: Unexplained fatigue, bruising, infections, high WBC or blasts on FBC → urgent referral to haematology

• Diagnosis: Peripheral smear + bone marrow biopsy ± cytogenetics essential for accurate classification

• Acute: Rapid intervention needed for AML/ALL to prevent life-threatening complications

• Chronic: Monitor stable CLL or manage progressive disease with modern agents (imatinib for CML, BTK inhibitors for CLL)

• Supportive Care: Vigilance for febrile neutropenia (urgent broad-spectrum antibiotics), tumour lysis prophylaxis, transfusion support

• Follow-Up: Long-term monitoring for treatment side effects, secondary malignancies, relapse, and psychosocial support. Coordination with specialists is crucial for optimal outcomes