Acute Promyelocytic Leukaemia (APML)

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)

Give all-trans-retinoic acid (ATRA), stimulates the cells to resume differentiation. Know Translocation t(15;17)

About

• A form of AML with a predisposition to DIC
• It can be treated with all trans retinoic acid (ATRA)
• ATRA allows the further differentiation of promyelocytes
• APML may cause DIC which can worsen with therapy

Aetiology

• AML is due to the formation of clonal proliferation of myeloid precursors with reduced capacity to differentiate into more mature cellular elements.
• The increased production of malignant cells, along with a reduction in these mature elements, result in a variety of systemic symptoms, anaemia, bleeding, and an increased risk of infection.
• There is a translocation between chromosomes t(15;17) translocation
• The gene on chromosome 17 codes for retinoic acid receptor alpha - RARa
• The gene on chromosome 15 is the promyelocytic gene (PML gene)
• PML-RARa fusion has reduced sensitivity to retinoic acid which blocks differentiation of myeloid cells

Auer rods in APML

Clinical

• Fatigue and weight loss. Anorexia. Evidence of infection or hemorrhage
• Marrow failure with anaemia, low platelets and abnormal WCC
• Severe bleeding, associated with Disseminated Intravascular Coagulation which may occur or be precipitated by cytotoxic treatment

Investigations

• FBC : anaemia, low platelets, high WCC
• Leukaemic forms in the bone marrow, peripheral blood, and other tissues
• Abundance of promyelocytes with Auer rods found
• Marked Low red cells, platelets, WBC (neutrophils) count
• Low fibrinogen, Coagulopathy

Management(See treatment of AML)

• Treat with chemotherapy + ATRA, FFP, Keep platelets > 30-50
• The differentiation can be improved with all trans retinoic acid (ATRA)
• This is a vitamin A derivative that can cause clinical remission.
• The drug allows the neutrophils to continue to develop to maturation.
• Coagulopathy - give platelets, fibrinogen, ATRA

Retinoic acid syndrome.

• Retinoic acid syndrome from ATRA is usually < 3 weeks of treatment.
• Chest pain, fever, and dyspnea. Hypoxia is common
• CXR: diffuse alveolar infiltrates with pleural effusions. Pericardial effusions
• Release of cytokines. Mortality of retinoic acid syndrome is 10%.
• High dose glucocorticoid therapy is usually effective in treatment