Acute myeloid Leukemia Flashcards
[Acute leukaemias]
Acute leukaemias are defined by ________________.
- The blasts “crowd out” normal haematopoiesis and patients present with _________________.
- This is a medical emergency as without urgent treatment, the patient could die.
Urgent diagnosis essential:
- Differentiate AML from ALL because the treatment differs
- Treatment more prolonged for ALL (need to treat CNS and testes)
- This is because ALL is able to infiltrate into the CNS and Testes unlike AML
high percentage of blasts (>20%) in the bone marrow or peripheral blood;
bone marrow failure (anaemia, thrombocytopenia, neutropenia)
[Chronic leukaemias]
- Chronic leukaemias are defined as having____________ (or would be acute leukemia).
- Proliferation of _______________
- It is compatible with several years of good quality life without treatment and treatment frequently not urgent
< 20% blasts in the bone marrow
mature lymphocytes/myelocytes.
[ACUTE MYELOID LEUKAEMIA (AML)]
- AML is a clonal disorder of __________ cells that may occur at any age, but becomes increasingly common in older people.
- It is the most common form of acute leukaemia in adults.
- The disorder leads to an infiltration of the bone marrow, with immature cells resulting in impaired production of _______________.
- Blast cells frequently appear in the peripheral blood and may derive from any of the lineages described above.
- The classification of the disorder is based on morphology, cytogenetics, immunophenotyping and clinical behaviour, reminiscent of the classification of lymphoid disorders.
- _____________ is present in AML. Myeloperoxidase is what makes up Auer Rods
FAB Classification of AML
- M1. Undifferentiated blasts
- M2. Lightly granulated blasts
- M3. Granulated blasts often with Auer rods: Contains ↑ Auer Rods
- M4. __________________: Contains ↑↑↑ Auer Rods
- M5. Myelomonocytic leukaemia
- M6. Monocytic leukaemia
- M7. Erythroleukaemia
- M8. Megakaryocytic leukaemia
myeloid progenitor;
neutrophils, platelets and red cells;
Myeloperoxidase
Promyelocytic leukaemia t(15;17)
[ACUTE MYELOID LEUKAEMIA (AML)]
What are the features of bone marrow failure?
Anaemia: breathlessness, pallor, fatigue, claudication, angina
Claudication = cramping pain in the leg
- Neutropenia: Infections, mouth ulcers
Thrombocytopenia: bleeding and bruising, petechiae, gum bleeding
[ACUTE MYELOID LEUKAEMIA (AML)]
What are the features of high WBC count?
Leukostasis: characterized by abnormal intravascular leukocyte aggregation and clumping 🡪 causing microcirculation occlusion 🡪 local hypoxemia and haemorrhage
The brain and lungs are the two most commonly affected organs
Presentation: Headache, blurred vision, TIA, Stroke and dyspnea
[ACUTE MYELOID LEUKAEMIA (AML)]
What are the features of tissue infiltration?
Only AML
- Gum (gum hypertrophy) 🡪 if monocytic variant of AML 🡪 Will look like completely losing all of one’s teeth due to overgrowth of gums
- Skin (violaceous skin deposits: purple discoloration)
Both AML and ALL (however much more common in ALL)
- Lymphadenopathy: only occasional in AML
- Hepatosplenomegaly
- Bone marrow (bone pain)
[ACUTE MYELOID LEUKAEMIA (AML)]
What are the features of substance release?
DIC (bleeding and bruising)
- Due to infection resulting from ↓Mature effective neutrophils
- Due to prothrombotic material (Auer rods) that are released upon blast cell lysis 🡪 most commonly in Acute Promyelocytic Leukemia (M3)
Tumour Lysis Syndrome: due to tumour treatment + spontaneous breakdown of neutrophilic clumps 🡪 causing HyperK, HyperPi, HypoCa, Hyperuricemia, High BUN
[ACUTE MYELOID LEUKAEMIA (AML)]
What are the investigations performed for AML?
Full Blood Count: Anaemia, thrombocytopenia, leukocytosis (blasts in PB)
Bone Marrow Aspirate
- Auer rods (coalesced myeloperoxidase granules) visible in cell cytoplasm
- Upon cell lysis due to treatment 🡪 released Auer
- Presence of Aeur rods helps to differentiate between AML and ALL morphologically otherwise it is difficult to tell them apart!
Special stains: differentiating from ALL (+ve for AML, -ve for ALL)
- Sudan black B
- Myeloperoxidase (Gr)
- Non-specific esterase (Mo)
Immunophenotyping – differentiating from ALL
- ALL/AML: CD34 (representing v early stem cells that have become malignant)
- AML: CD13, CD33, CD117
- Flow cytometry: BM sample analyzed looking for classical Ag (fluorescence detecting)
- Immunohistochemistry: stain tissue with labelled antibody
What is the AML chromosomes associated with good risk?
t(15;17), t(8;21), Inv(16)/t(16;16)
What is the management for AML?
Red blood cell and platelet transfusions
Broad spectrum antibiotics for fever
Leukapheresis: Extreme leukocytosis (WBC > 200): leukapheresis
If Cx by Tumour lysis syndrome
- Hyperuricemia: hydration, allopurinol (if pre-Tx) / Rasburicase (after TLS onset)
- Hyperphosphatemia; aluminum hydroxide, calcium acetate / carbonate
- Hyperkalemia: fluids, diuretics
- Sometimes Haemodialysis if AKI, or severe Electrolyte derangements
If Cx by DIC: FFP, Cryoprecipitate, Plt
Chemotherapy: use combi of agents w/ different MoA, synergy & non-overlapping toxicity.
- Always includes anthracycline eg: daunorubicin & cytosine arabinoside (cytarabine), & consolidation with a minimum of four cycles of treatment given at 3–4-week intervals
All-trans-retinoic acid: for APML
ACUTE PROMYELOCYTIC LEUKAEMIA (APML)
- AML with translocation _________ and particular morphological features.
- It is associated with very good prognosis, and can be treated with Retinoic acid.
- Promyelocytes contain numerous ___________ which is a risk for DIC 🡪 main cause of death
- __________ causes differentiation of promyelocytes and rapid reversal of the bleeding tendency. APML is treated with ATRA combined with several courses of chemotherapy.
- Complete remission occurs in at least 90% of younger adults and at least 70% will expect to be cured.
t(15; 17);
Auer rods
All-trans-retinoic acid (ATRA)
ACUTE MONOCYTIC LEUKAEMIA
Proliferation of monoblast that leads to _________.
________ is not present in acute monocytic leukaemia.
gum infiltration;
MPO
ACUTE MEGAKARYOBLASTIC LEUKAEMIA
- Proliferation of megakaryoblasts.
- Actue megakaryoblastic leukaemia lack MPO and are associated with ___________.
down syndrome before the age of 5
