AML Flashcards
What is AML and how does it arise?
o Hyper-proliferation of myeloid blasts in the bone marrow. These blasts remain undifferentiated.
o Have different causes/classes: genetic abnormalities, dysplasia, previous chemotherapy or radiotherapy or previous unrelated cancer, underlying genetic conditions, random events, myeloid sarcoma.
o Genetic abnormalities include chromosomal translocations, deletions and inversions. These account or 25% of all AML and can be inherited or acquired due to carcinogen exposure. E.g., t(8,21) = AML1-ETO fusion protein which blocks differentiation of myeloid blasts and increases their proliferation. T(15,17) = PML-RARa fusion protein which is a transcriptional repressor that interferes with gene expression and causes maturation of blasts to arrest beyond the promyelocyte stage.
o Dysplasia is the abnormal development of cells.
o Previous chemotherapy or radiotherapy can cause changes in the cells that leads to AML.
o Down’s Syndrome has genetic abnormalities which increases the risk of developing AML.
o Random events in the cell can occur leading to AML – these are unknown.
o AML can arise in the form of a solid tumour resembling a sarcoma but are made up of myeloid blasts.
What are the symptoms and explanations for them?
o Lethargy and fatigue/anaemia – this is due to the over-proliferation of myeloid blasts overcrowding the bone marrow and negatively impacting erythropoiesis. These blasts also release inhibitory cytokines for erythropoiesis.
o Recurrent infections – this is due to the over-proliferation of immature blasts, meaning there are not enough functioning WBCs, particularly neutrophils, to fight infections. These blasts also overcrowd the bone marrow meaning they negatively impact leucopoiesis.
o Widespread bruising – this is due to the over-proliferation of myeloid blasts overcrowding the bone marrow and negatively impacting thrombopoiesis. This decreases the number of platelets, which means that blood doesn’t clot properly and minor injuries to capillaries do not clot properly so bruise easily instead.
o Swollen gums – this is due to the infiltration of many undifferentiated myeloid blasts into the gums.
What are the laboratory findings?
o Normochromic normocytic anaemia – low RBC count and Hb.
o Thrombocytopenia – low platelets.
o Hyperleukocytosis – increased number of WBCs.
o Neutropenia – decreased number of neutrophils.
o Basophilia – increased number of basophils.
o Eosinophils – increased number of eosinophils.
o Blood film shows a large proportion of the WBCs as blasts >20% blasts, with these blasts having an enlarged nucleus (little cytoplasm) and Auer rods. Normochromic and normocytic RBCs.
What further tests can be done?
o Bone marrow aspirate – hypercellular with a high infiltration of blasts >20%.
o Sudan Black B stain and myeloperoxidase stain positive (stains lipids in primary and secondary myeloid and neutrophilic granules, and primary myeloid granules respectively).
o Bone marrow trephine – same tests as bone marrow aspirate. Allows architecture and structure of cells to be maintained. Not necessary.
o Immunophenotyping – looks for presence of certain markers like CD7 and CD14, and absence of CD3 and CD19.
o Biochemistry tests – LFT, U&E, calcium, LDH.
o Coagulation tests – PT, APTT, TT, fibrinogen and D-dimer, Group and Save (in case of transfusion).
o Cytogenetics – karyotyping of chromosomes assessing genetic abnormalities
o Molecular studies – FISH and PCR to further analyse chromosomal rearrangements or abnormalities.
How is AML treated?
o Chemotherapy using cytosine arabinoside and daunorubicin. 2 stages: induction (2 cycles and aims for complete remission – less than 5% blasts), and consolidation (2 stages but only once complete remission has been achieved). Long term maintenance is not done.
o Allogenic stem cell transplant – once CR has been achieved. Reserved for those with a poor prognosis or those who have relapsed. High risk of morbidity.
o Over 60s or those who cannot take the aggressive treatment: supportive therapy is given. This aims to maintain Hb and platelet levels whilst administering transfusions.
