Related Subjects:
| Leukaemias in General
| Acute Promyelocytic Leukaemia
| Acute Myeloblastic Leukaemia (AML)
| Acute Lymphoblastic Leukaemia (ALL)
| Chronic Lymphocytic Leukaemia (CLL)
| Chronic Myeloid Leukaemia (CML)
| Hairy Cell Leukaemia
| Differentiation Syndrome
| Tretinoin (All-trans-retinoic acid (ATRA))
| Haemolytic Anaemia
| Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Acute Myeloid Leukaemia (AML) is an aggressive haematological malignancy ð arising from clonal proliferation of immature myeloid precursors (myeloblasts).
These abnormal cells accumulate in the bone marrow ðĶī, replacing normal haematopoiesis and spilling into blood and tissues.
AML mainly affects older adults ðĩðī, progresses rapidly, and requires urgent treatment. Classic features include anaemia, infections, bleeding, bone pain, and hepatosplenomegaly.
About
- AML is a neoplastic clone of immature myeloid precursors ð§Ž
- Auer rods (needle-like inclusions) are characteristic ðŽ
- Can be primary or secondary (e.g. post-myelodysplasia, post-chemo/radiation) â ïļ
Types
- Primary AML: arises de novo
- Secondary AML: follows MDS, myeloproliferative disease, or cytotoxic therapy ðïļ
Aetiology
- Clonal proliferation with impaired differentiation â marrow packed with blasts ðĻ
- Suppression of normal cells â anaemia ðī, thrombocytopenia ðĐļ, neutropenia ðĪ
- Blast infiltration â gum hypertrophy, skin nodules, CNS infiltration
Genetic Translocations
- t(8;21) â favourable prognosis â
- t(15;17) â Acute Promyelocytic Leukaemia (APL, M3 subtype), high risk of DIC â ïļ but excellent response to ATRA ðŊ
- inv(16) â favourable group ð
Risk Factors
- Age > 60 years (median age ~70) ðĩ
- Genetic predispositions: Down syndrome (esp. M7, 400Ã risk), Fanconi anaemia
- Environmental: benzene âĢïļ, ionising radiation âĒïļ
- Therapy-related AML: post-alkylators, topoisomerase II inhibitors ð
- Pre-existing: MDS, myeloproliferative neoplasms
FAB Classification (M0âM7)
- M0: Minimally differentiated AML, CD13+/CD33+
- M1: Myeloblastic, no maturation
- M2: Myeloblastic with maturation (Auer rods present) ðŽ
- M3: Acute Promyelocytic Leukaemia (APL) â t(15;17), ATRA-sensitive â
- M4: Myelomonocytic â gum infiltration common
- M5: Monocytic â gum/CNS infiltration ð§
- M6: Erythroleukaemia
- M7: Megakaryoblastic AML â associated with Down syndrome
WHO Classification
- AML with recurrent genetic abnormalities (e.g. t(8;21), inv(16), t(15;17))
- AML with multilineage dysplasia (post-MDS)
- Therapy-related AML (poor prognosis) â
- AML not otherwise specified
Clinical Features
- Marrow failure:
- Anaemia â fatigue, pallor ðī
- Thrombocytopenia â bruising, bleeding, petechiae ðĐļ
- Neutropenia â recurrent infections ðĪ
- Infiltration: hepatosplenomegaly, lymphadenopathy, gingival hypertrophy, skin nodules
- Special: DIC risk in APL (M3) âĄ
- Myeloblastomas (chloromas) â extramedullary masses
Investigations
- FBC: Pancytopenia, circulating blasts
- Peripheral smear: Auer rods (needle-like azurophilic inclusions) ðŽ
- Bone marrow biopsy: >20% blasts (WHO criterion)
- Cytogenetics: risk stratification (favourable vs poor)
- Other: U&E, LDH, uric acid (tumour lysis risk â ïļ)
- Coagulation screen: DIC risk in M3
Management
- Supportive: transfusions ðĐļ, antibiotics/antifungals ð, central line, tumour lysis prophylaxis (hydration + allopurinol/rasburicase)
- Induction chemotherapy: â7+3â regimen (cytarabine 7 days + anthracycline 3 days) ð
- Consolidation: high-dose cytarabine or SCT in high-risk patients
- APL (M3): ATRA + arsenic trioxide (or anthracycline). Watch for differentiation syndrome â ïļ
- Targeted agents:
- FLT3 inhibitors (midostaurin) ðŊ
- IDH1/2 inhibitors
- Gemtuzumab ozogamicin (anti-CD33) in certain cases
- Stem cell transplant: for high-risk or relapsed disease ðą
References
ð§ââïļ Case Examples â Acute Myeloblastic Leukaemia (AML)
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Case 1 (Pancytopenia presentation): ðĐļ
A 68-year-old man presents with progressive fatigue, recurrent infections, and easy bruising. Exam shows pallor, petechiae, and mild hepatosplenomegaly. Bloods: Hb 6.8 g/dL, WCC 1.5 Ã 10âđ/L, platelets 30 Ã 10âđ/L. Peripheral smear: blasts with Auer rods.
Analysis: Bone marrow failure due to malignant myeloblast proliferation.
Diagnosis: Acute Myeloblastic Leukaemia.
Management: Bone marrow biopsy confirms AML. Induction chemotherapy (e.g., cytarabine + anthracycline), supportive transfusions, infection prophylaxis. Allogeneic stem cell transplant considered if poor prognosis cytogenetics.
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Case 2 (Hyperleukocytosis + leukostasis): ðŦ
A 45-year-old woman presents with acute dyspnoea, headache, and confusion. Bloods: WCC 120 Ã 10âđ/L, blasts on film. Chest X-ray: diffuse pulmonary infiltrates.
Analysis: Symptomatic hyperleukocytosis â leukostasis (microvascular occlusion). Life-threatening emergency.
Diagnosis: AML with hyperleukocytosis and leukostasis.
Management: ICU admission, urgent cytoreduction (hydroxycarbamide or leukapheresis), followed by induction chemotherapy. Supportive care with fluids and tumour lysis prophylaxis (allopurinol/rasburicase).
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Case 3 (Acute Promyelocytic Leukaemia â APML): â ïļ
A 32-year-old woman presents with mucosal bleeding, bruising, and petechiae. Bloods: Hb 9.2 g/dL, WCC 2.8 Ã 10âđ/L, platelets 20 Ã 10âđ/L, prolonged PT/APTT, low fibrinogen. Blood film: abnormal promyelocytes with Auer rods.
Analysis: APML (AML M3) associated with disseminated intravascular coagulation (DIC). Medical emergency with high early mortality.
Diagnosis: Acute Promyelocytic Leukaemia (t(15;17) translocation, PML-RARA fusion).
Management: Immediate initiation of all-trans retinoic acid (ATRA) + arsenic trioxide, aggressive clotting support, haematology urgent referral. Prognosis excellent if treated early.