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. APML is distinct due to its specific genetic mutation and association with a high risk of bleeding and clotting disorders, particularly Disseminated Intravascular Coagulation (DIC). However, APML is one of the most treatable forms of AML when identified and treated promptly.

About

• A subtype of AML with a predisposition to Disseminated Intravascular Coagulation (DIC).
• Treatment includes all-trans-retinoic acid (ATRA), which promotes the differentiation of promyelocytes.
• APML may cause DIC, which can worsen upon initiating therapy.

Administer all-trans-retinoic acid (ATRA) to stimulate promyelocytes to resume differentiation. It is important to recognize the characteristic translocation t(15;17).

Aetiology

• APML results from the clonal proliferation of myeloid precursors with a reduced capacity to differentiate into mature blood cells.
• The accumulation of malignant promyelocytes leads to systemic symptoms, anaemia, bleeding, and an increased risk of infection.
• Characterized by the specific translocation between chromosomes 15 and 17 [t(15;17)].
• The gene on chromosome 17 codes for the retinoic acid receptor alpha (RARα).
• The gene on chromosome 15 is the promyelocytic leukaemia (PML) gene.
• The PML-RARα fusion protein has reduced sensitivity to retinoic acid, blocking the differentiation of myeloid cells.

Auer Rods in APML

Clinical Features

• Fatigue, weight loss, and anorexia.
• Evidence of infection or haemorrhage.
• Marrow failure presenting with anaemia, low platelets, and abnormal white cell counts (WCC).
• Severe bleeding associated with DIC, which may occur or be precipitated by cytotoxic treatment.

Investigations

• Full Blood Count (FBC): Shows anaemia, thrombocytopenia (low platelets), and leukocytosis or leukopenia with circulating promyelocytes.
• Bone Marrow Biopsy: The definitive test; shows an abundance of promyelocytes with Auer rods.
• Coagulation Tests: Prolonged PT and aPTT, low fibrinogen levels indicating DIC.
• Cytogenetic Analysis: Identifies the t(15;17) translocation.
• Flow Cytometry: Analyzes specific markers on the leukaemia cells to aid in diagnosis.

Management

• APML is considered one of the most curable forms of acute leukaemia. Treatment involves a combination of chemotherapy and ATRA (all-trans-retinoic acid). ATRA, a vitamin A derivative, induces differentiation of promyelocytes into mature neutrophils, leading to clinical remission
• Manage DIC induced coagulopathy with fresh frozen plasma (FFP) and platelet transfusions; aim to maintain platelet counts >30-50 x10⁹/L.
• Monitor and manage DIC aggressively throughout treatment.
• Arsenic is also a new agent being investigated

Differentiation Syndrome (Formerly Retinoic Acid Syndrome)

• Occurs in up to 25% of patients within the first 3 weeks of ATRA treatment.
• Symptoms include fever, weight gain, respiratory distress, pulmonary infiltrates, pleural and pericardial effusions.
• Caused by cytokine release from differentiating myeloid cells.
• Management includes the prompt initiation of high-dose corticosteroids (e.g., dexamethasone) and temporary discontinuation of ATRA if severe.

References

• Cancer Research UK: Acute Promyelocytic Leukaemia
• Leukaemia Care: Acute Promyelocytic Leukaemia
• NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia