Makindo Medical Notes

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 Promyelocytic Leukaemia (APML) is a subtype of Acute Myeloid Leukaemia (AML) 🧬 characterized by the accumulation of abnormal promyelocytes in the bone marrow 🦴 and blood. It is distinct due to the translocation t(15;17), producing the PML-RARα fusion protein, which blocks normal differentiation of myeloid cells. APML carries a particularly high risk of Disseminated Intravascular Coagulation (DIC) ⚠️ but is also one of the most treatable forms of AML when identified promptly and treated with ATRA (all-trans-retinoic acid) and arsenic trioxide. ✨

About

• A rare AML subtype, accounting for ~10–15% of AML cases.
• Notable for its strong association with DIC at presentation and during treatment.
• ATRA therapy directly targets the differentiation block caused by PML-RARα, making APML highly curable compared to other AMLs. 🎯

🧪 Key teaching point: Always suspect APML if a patient presents with cytopenias, abnormal promyelocytes on film, and unexplained bleeding/DIC → start ATRA immediately, even before confirmation.

Aetiology

• Genetic driver: Reciprocal translocation t(15;17).
• PML gene (chr 15) fuses with RARα gene (chr 17) → PML-RARα protein.
• This fusion protein blocks myeloid cell maturation and promotes apoptosis resistance.
• Result: Accumulation of promyelocytes, marrow failure, coagulopathy, and infection risk.

Auer Rods in APML

Auer rods (needle-like azurophilic inclusions) are often multiple and bundled (“faggot cells”) in APML 🔬

Clinical Features

• General AML symptoms: fatigue 😴, weight loss, anorexia.
• Marrow failure → anaemia, infections 🤒, bleeding 🩸.
• Bleeding risk disproportionately severe due to DIC (epistaxis, GI bleeding, intracranial haemorrhage).
• Low or high WCC possible, with abnormal promyelocytes visible on smear.

Investigations

• FBC: Pancytopenia with circulating promyelocytes.
• Coagulation screen: Prolonged PT/aPTT, low fibrinogen, raised D-dimer → DIC ⚠️
• Bone marrow biopsy: Abundant promyelocytes, often with “faggot” Auer rods.
• Cytogenetics: t(15;17) confirming diagnosis.
• Flow cytometry: Myeloid immunophenotype (CD33+, MPO+).

Management

• Urgent ATRA therapy: Vitamin A derivative that releases the differentiation block, allowing promyelocytes → mature neutrophils. ⭐
• Arsenic trioxide: Now standard with ATRA for front-line therapy; excellent remission rates.
• Anthracyclines (e.g. daunorubicin): Sometimes combined in high-risk disease.
• DIC management: Platelet transfusions (maintain >30–50 ×10⁹/L), FFP, cryoprecipitate for fibrinogen support.
• Tumour lysis prophylaxis: Hydration + allopurinol/rasburicase 💧

Differentiation Syndrome (formerly Retinoic Acid Syndrome)

• Occurs in up to 25% of patients within 3 weeks of ATRA initiation.
• Symptoms: Fever 🌡️, weight gain, dyspnoea, pulmonary infiltrates, pleural/pericardial effusions.
• Pathophysiology: Cytokine storm from rapidly differentiating myeloid cells.
• Management: High-dose IV dexamethasone 💊; temporary interruption of ATRA in severe cases.

Prognosis

• APML is now considered the most curable AML subtype 🎉
• Cure rates >85% with ATRA + arsenic-based regimens.
• Biggest danger = early death from haemorrhage (esp. intracranial) → emphasises need for immediate recognition and treatment.

References

• Cancer Research UK
• Leukaemia Care
• NCCN AML Guidelines

🧑‍⚕️ Case Examples — Acute Promyelocytic Leukaemia (APML)

• Case 1 (Bleeding & DIC at presentation): ⚠️ A 29-year-old woman presents with gum bleeding, epistaxis, and widespread petechiae. Bloods: Hb 8.5 g/dL, WCC 3.0 × 10⁹/L, platelets 18 × 10⁹/L. Coagulation: prolonged PT, low fibrinogen, raised D-dimer. Blood film shows abnormal promyelocytes with Auer rods. Diagnosis: APML complicated by disseminated intravascular coagulation (DIC). Management: Start all-trans retinoic acid (ATRA) immediately (before cytogenetic confirmation), aggressive clotting factor replacement (cryoprecipitate, platelets, FFP), and urgent haematology referral.
• Case 2 (Incidental cytopenias): 🩸 A 42-year-old man referred by GP for unexplained bruising and fatigue. FBC shows Hb 9.1 g/dL, WCC 2.5 × 10⁹/L, platelets 30 × 10⁹/L. Coagulation screen shows early derangement. Peripheral smear: promyelocytes with heavy granules. Cytogenetics: t(15;17) translocation (PML-RARA fusion). Diagnosis: Acute Promyelocytic Leukaemia. Management: Immediate ATRA + arsenic trioxide initiated, with supportive transfusion strategy. Patient placed on tumour lysis prophylaxis (rasburicase, IV fluids). Prognosis good with rapid treatment.
• Case 3 (High WCC hyperleukocytosis): 🫁 A 36-year-old woman presents with dyspnoea, headache, and blurred vision. Bloods: WCC 85 × 10⁹/L, blasts with promyelocyte morphology, abnormal coagulation. Diagnosis: APML with hyperleukocytosis and risk of leukostasis. Management: Start ATRA immediately, plus induction chemotherapy (idarubicin + arsenic trioxide). ICU support for TLS risk, hydroxycarbamide to reduce leukocyte count. Close monitoring for differentiation syndrome once therapy initiated (managed with steroids if develops).