Makindo Medical Notes.com

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 Myeloblastic/Myeloid Leukaemia, is a type of cancer that originates in the bone marrow and results in the rapid proliferation of abnormal myeloblasts (immature white blood cells). These abnormal cells accumulate in the bone marrow, interfering with the production of normal blood cells, and can spread to other parts of the body. AML is an aggressive form of leukaemia and requires prompt treatment. Causes fever, weakness, pallor, infections, bleeding, bone pains and splenomegaly.

About

• A neoplastic clone of immature myeloid line precursors particularly in older patients
• May see Auer rods

Aetiology

• AML is due to the formation of clonal proliferation of myeloid precursors with reduced capacity to differentiate into more mature cellular elements.
• The result is an accumulation of leukaemic forms in the bone marrow, peripheral blood, and other tissues causing a marked reduction in red cells, platelets, and neutrophils.
• 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.

Translocation

• t(8;21) occurs in a minority of acute myeloid leukaemia (AML) patients

Risks

• Mostly a malignancy of adults
• Down's syndrome (x 400 M7 type)
• Fanconi anaemia
• Exposure to benzene, Radiation
• De novo or secondary to myelodysplasia and other myeloid malignancies
• Chemotherapy or radiation therapy
• Myelodysplastic Syndromes
• AML is more common in older adults

Classification

• M0:Undifferentiated blasts: CD 13+,CD 33+ and CD 117+ by flow cytometry <3% of cells show MPO/SBB positivity
• M1:lightly granulated blasts
• M2:Granulated blasts often with Auer rods
• M3:Promyelocytic leukaemia: AML M3 is associated with a cytogenetic abnormality namely T(15:17)
• M4:Myelomonocytic leukaemia
• M5:Monocytic leukaemia
• M6:Erythroleukaemia: Auer rods and dysplasia may be seen. PAS positivity is seen in erythroblasts.
• M7:Megakaryocytic leukaemia: Flow cytometry shows positivity for CD 41 and CD 61 which are platelet markers

Acute promyelocytic leukaemia / M3

• Especially memorable for 2 things
• 1. DIC may occur even after treatment has started
• 2. Responds to all trans-retinoic acid (ATRA) a vitamin A derivative

WHO classification

• AML with recurrent genetic disorders e.g. t(8,21), inv16, t(15:17) mostly in young people
• AML with multilineage dysplasia - Evolving from a myelodysplastic disorder
• AML with myelodysplastic syndromes -alkylating agent related, topoisomerase II inhibitor e.g. etoposide related - very poor prognosis
• AML not otherwise categorized - morphology classified as to cell of origin

Clinical

• Presentation is usually with marrow failure
• Anaemia - Weakness, lethargy
• Bleeding, petechiae - low platelets
• Infections - low WCC or increased with Blasts
• DIC seen in any malignancy but associated with M3 type of AML
• Gum and lung infiltration - M4/M5 AML
• Malignant transformation in a patient with myelodysplastic syndrome
• Extramedullary mass (myeloblastoma), skin, bone, paravertebral, intraspinal, jaundice, splenomegaly, CNS signs

Investigations: Important to identify Acute Promyelocytic Leukaemia (APL;M3)

• FBC: Low Hb Low platelets, Low/High WCC
• Electrolytes (elevated K⁺ may be spurious if WBC is high)
• Elevated Uric acid, LDH and Creatinine
• Evidence of DIC: Check coagulation
• Peripheral blood film/bone marrow - Auer rods within blast cells are diagnostic
• Bone marrow biopsy/aspirate - A blast count > 30% is diagnostic
• Flow cytometry and cytogenetics - CD13, CD15, CD33, CD34, CD117
• CXR, lumbar puncture, cardiac scan if prior anthracycline use

Management

• ABC, Manage Sepsis and anaemia. Transfusion, antibiotics for infection
• Central venous catheter for chaemotherapy. Antibiotics. Supportive.
• Induction chaemotherapy: e.g. cytosine arabinoside, daunorubicin leads to severe transient neutropenia and thrombocytopenia. Consolidation chaemotherapy. Prevent tumour lysis syndrome - Hydration, Allopurinol etc.
• APL (M3) All-trans-retinoic acid (ATRA) + anthracycline-based chaemotherapy
• Neutropenia in AML may be prolonged and usually presents with a sore throat and even dysphagia. May be an infection related to break down in bowel mucosa. Risk of fungal (aspergillus and candidal) and bacterial infections. Needs prompt IV antibiotics. Platelet and red cell transfusions.
• Bone marrow transplantation for those with relapse or poor prognosis groups.
• Targeted Therapy:FLT3 inhibitors (e.g., midostaurin) or IDH inhibitors, are used for patients with specific genetic mutations in their leukaemia cells.