Acute Leukaemia
An excess of blasts carries the highest chance of turning into acute leukaemia.
Acute leukaemias are aggressive hematologic malignancies characterized by the rapid proliferation of immature white blood cells (blasts) in the bone marrow. This results in the suppression of normal hematopoiesis, leading to life-threatening cytopenias.
Definition and Diagnosis
Diagnosis requires demonstrating a failure of hematopoiesis due to marrow infiltration by malignant precursor cells.
- Full Blood Count: Shows anemia, thrombocytopenia, and variable WBC counts (often leukocytosis).
- Bone Marrow Aspirate: Determines the percentage of blasts and lineage.
- Presence of >20% blasts in bone marrow or peripheral blood.
- Auer rods are pathognomonic for myeloid lineage (AML).
- Morphology, cytochemistry, and flow cytometry are essential for classification.
Classification and Lineage
Acute leukaemia is broadly categorized based on the cell of origin, which dictates the clinical course and management.
- Acute Lymphoblastic Leukaemia (ALL): Primarily affects children; involves B or T-cell precursors.
- Acute Myeloid Leukaemia (AML): Primarily affects adults; involves granulocytic, monocytic, or megakaryocytic precursors.
Etiology and Risk Factors
While most cases are idiopathic, several environmental and genetic triggers are well-documented.
- Genetic: Down Syndrome (Trisomy 21) increases risk significantly.
- Chemical: Prior exposure to benzene or alkylating chemotherapy agents.
- Radiation: Ionizing radiation exposure.
- Hematologic Disorders: Transformation from Myelodysplastic Syndromes (MDS).
Clinical Presentation
Symptoms arise directly from bone marrow failure and the rapid accumulation of malignant cells.
- Anemic syndrome: Fatigue, pallor, and dyspnea.
- Infections: Recurrent fevers due to functional neutropenia.
- Bleeding: Petechiae and mucosal bleeding from thrombocytopenia.
- Organ Infiltration: Bone pain, lymphadenopathy, and hepatosplenomegaly.
Severity and Prognosis
Prognosis is determined by age, cytogenetic abnormalities, and initial response to induction therapy.
- Cytogenetics: Specific translocations (e.g., t(15;17)) carry different prognostic weights.
- WBC Count: Hyperleukocytosis at presentation increases the risk of tumor lysis syndrome and leukostasis.
Red flags and complications
- Hyperleukocytosis and leukostasis leading to respiratory failure, stroke, or vision loss due to thick, sludge-like blood flow.
- Tumor Lysis Syndrome causing renal failure and heart rhythm disturbances from rapid cell breakdown releasing potassium and phosphate.
- Disseminated Intravascular Coagulation (DIC), especially in promyelocytic subtypes, causing uncontrolled bleeding or systemic clotting.
- Neutropenic fever and septic shock due to the lack of mature, functional white blood cells to fight infection.
Management
The strategy focuses on rapidly reducing the blast cell burden while managing systemic imbalances and preventing lethal complications during treatment transitions.
- Induction chemotherapy using Cytarabine and Anthracyclines to destroy the majority of malignant cells and achieve complete remission.
- All-trans retinoic acid (ATRA) for acute promyelocytic leukemia to force immature cells to mature and prevent fatal bleeding.
- Hydration and Allopurinol or Rasburicase to lower uric acid levels and protect the kidneys from tumor lysis syndrome.
- Supportive blood product transfusions including packed red cells for anemia and platelets to prevent spontaneous hemorrhage.
- Prophylactic antibiotics, antifungals, and antivirals to prevent infections while the bone marrow is suppressed.
- Urgent referral to a hematology-oncology specialist center for intensive monitoring and specialized nursing care.
Follow-up and prevention
- Regular bone marrow biopsies and blood counts to monitor for minimal residual disease or early relapse.
- Cardiac monitoring via echocardiograms for patients who received anthracyclines, which can cause long-term heart muscle damage.
- Long-term screening for secondary malignancies and endocrine dysfunction caused by intensive chemotherapy or radiation.
- Psychosocial support and nutritional counseling to improve quality of life and adherence to long-term recovery protocols.
Often confused with
- Leukaemoid reaction: High white cell count due to infection; distinguished by high LAP score and absence of clonal blasts.
- Infectious Mononucleosis: Presents with fever and atypical lymphocytes; diagnosed via Monospot test and lack of significant cytopenias.
- Aplastic Anaemia: Both cause pancytopenia; however, marrow is hypocellular in aplasia while typically hypercellular with blasts in acute leukaemia.
Where results can mislead
- Pseudohyperkalaemia: Extremely high WBC counts can cause potassium leakage from cells in the test tube after blood collection.
- Aleukaemic Leukaemia: Blasts remain in the marrow with a low peripheral white count, potentially masking the diagnosis on a standard CBC.
- Spurious Hypoglycaemia: Large numbers of metabolically active blasts in the sample tube can rapidly consume glucose before the lab processes it.
Questions an examiner may ask
- Differentiate between the morphological features of lymphoblasts and myeloblasts under light microscopy.
- Explain the pathophysiology of Disseminated Intravascular Coagulation (DIC) specifically in Acute Promyelocytic Leukaemia.
- Discuss the prognostic significance of the Philadelphia chromosome in adult Acute Lymphoblastic Leukaemia.
When to seek help
- Unexplained, persistent fever or drenching night sweats
- Easy bruising or spontaneous bleeding from gums or nose
- Severe fatigue with worsening shortness of breath
- Rapidly enlarging, painless lymph nodes or abdominal fullness
Quick questions
What defines the 'blast' threshold for diagnosis?
A diagnosis of acute leukaemia generally requires 20% or more blasts in the bone marrow or peripheral blood, according to WHO criteria.
Why is Auer rod identification clinically significant?
Auer rods are pathognomonic for myeloblasts, confirming Acute Myeloid Leukaemia and excluding Acute Lymphoblastic Leukaemia.
What is the primary cause of death in untreated patients?
Most patients succumb to severe infections due to neutropenia or catastrophic haemorrhage caused by profound thrombocytopenia.
What our notes say
- An excess of blasts carries the highest chance of turning into acute leukaemia. (Internal Medicine (MBIM 4100) special/supplementary exam, Paper Two: 14 August 2)
- Outline 5 clinical features expected in acute leukaemia. (Medical Pathology Final Revision: Chemical, Hema, Systemic)
- Acute leukaemia: normocytic normochromic anaemia; cytopenias from marrow replacement; ALL peaks age 2–5yrs. (Medical Pathology Final Revision: Chemical, Hema, Systemic)
- WHO criterion: ≥20% blasts in bone marrow or peripheral blood confirms acute leukaemia (★) (Acute Leukaemia (AML/ALL) & WBC Disorders: Hematology Guide)