Acute Myeloid Leukaemia (AML)

Question 1

List some DDx for a presentation of:

• ecchymoses
• menorrhagia
• fatigue
• pallor
• fever
• splenomegaly
• sternal boney tenderness

Answer 1

Neoplastic:
- leukaemia: myeloid, lymphoid
- lymphoma: HL, NHL
- MM
- solid primary w boney mets
- osteosarcoma
Myeloproliferative disorders:
- polycythemia vera
- essential thrombocythemia
- myleofibrosis
- myelodysplasia (20% progress AML)
AI disease: SLE
Bleeding diatheses:
1) Thrombocytopenia- decreased production (e.g. vit B12 or folate deficiency), increased removal (e.g. ITP, Heparin, chronic infection), sequestration (hypersplenism), dilutional (massive transfusion)
2) Platelet dysfunction- Bernard Soulier syndrome, Glanzmann thrombasthenia, Haemolytic-uraemic syndrome (HUS), immune thrombocytopenia (ITP), aspirin
3) Coagulation disorder- haemophilia (A, B, C), vit K deficiency, acquired coag defect (e.g. liver disease, anticoag, DIC, dilutional, drugs- heparin or warfarin)
3) Mixed platelet and coag disorder- Von Wilebrand disease, DIC

Question 2

In the context of AML, explain the syndromes of pallor, ecchymoses, menorrhagia, cachexia, splenomegaly and boney tenderness?

Answer 2

• Anaemia (pallor)- decreased RBCs (BM failure, disrupted haematopoiesis)
• Haemorrhage (ecchymoses, bruising, menorrhagia)- thrombocytopenia (BM failure, disrupted haematopoiesis)
• Cachexia- increased metabolic demand
• Splenomegaly- leukaemic cell infiltration of spleen (increased circulating WBCs/malignant leukocytes)
• Sternal boney tenderness- BM infiltration

Question 3

List the blood tests your would order to investigate AML?

Answer 3

o FBC- WBC (infection, immunity), Hb (anaemia, bleed), platelets (coagulation), pancytopenia (BM infiltration, disrupted haematopoeisis)
o Peripheral blood smear- lymphoblasts or myeloblasts
o ESR/CRP- inflammatory process
o LFTs- liver function, coagulation
o UEC- kidney function, dehydration
o CMP- tumour lysis syndrome (hyperphosphataemia, hypocalcaemia, hyperuricaemia, hyperkalaemia due to cell lysis and high cell turnover)
o Uric acid- elevated due to high cell turnover rate (hyperuricaemia)
o Iron studies- iron deficiency anaemia
o Coagulation studies- DIC
o BSL- DM (hypoglycaemic fatigue)
o TFT- hypothyroidism (fatigue)
o Blood culture- sepsis
o Viral serology (HBV, CHV, HIV, EBV, CMV, VZV)- immunosuppressed

Question 4

What lab investigations would you do for AML? What would you expect to find?

Answer 4

• Bone marrow biopsy (from PSIS)- myeloblasts or lymphoblasts (or respective progenitor cells)
o Blast number- AML requires myeloblasts >20% total cells in BM
o Auer rods- clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of myeloid leukemic blasts (AML)
• Flow cytometry- examines surface and classifies lineage, counts blasts cells -> differentiate AML from ALL
• Cytogenics- chromosome and gene defects -> number of genes involved is prognostic indicator
• Light microscopy- morphology, fast test
• Multiplex PCR- specific DNA

Question 5

What imaging would you do for AML?

Answer 5

Imaging:
o CXR- current LRTI, mets
o CT chest/abdo/pelvis- solid primaries, mets
o Echo- chemo cardiotoxic

Question 6

Describe the FBC findings for myeloblastic leukaemia.

Answer 6

Myeloblastic (AML, CML):
• Myeloid cell line: RBCs, platelets, neutrophils, eosinophils, basophils
Blood film:
• Myeloblasts w immature chromatin, nucleoli in some cells.
• Auer rods (crtyallised myeloid peroxidaseMPI granules ) are a myeloblast hallmark.

• Low RBCs -> normocytic normochromic anaemia
• Low platelets (thrombocytopenia) -> bruising
• High WCC (high replication, poor maturity) -> build up in spleen (splenomegaly)
• Low eosinophils
• Low basophils
• Low neutrophils (neutropenia) -> poor immunity

Question 7

Describe the FBC findings for lymphoblastic leukaemia.

Answer 7

Lymphoblastic (ALL, CLL):
• Lymphoid cell line: B cells, T cells, NK cells
• Blood film: lymphoblasts (normal if confined to BM)
• Low RBC -> normocytic normochromic anaemia (due to disrupted haematopoiesis)
• Low platelets (thrombocytopenia)
• Variable WCC
• Low neutrophils (neutropenia) -> poor immunity

Question 8

Differentiate between acute and chronic leukaemia?

Answer 8

• Acute: >20% blasts on BM, 1 month hx

* Chronic: <20% blasts on BM, hx months-years

Question 9

What are platelets derived from?

Answer 9

• Origin: megakaryocytes in BM -> cytoplasm fragments become platelets
- part of myeloid progenitor line (thus may be reduced in AML)
• Production regulated by thrombopoietin (hormone produced in kidneys, liver) -> acts on myeloid stem cells
• Life span: 8-9 days -> destroyed in spleen and liver (via phagocytosis)

Question 10

Describe the pathogenesis of AML?

Answer 10

• Unregulated growth and differentiation of myeloid stem cells in BM
⇒ Blasts have prolonged generation time -> colonal expansion and accumulation of blasts
⇒ Suppression of normal haemopoiesis -> BM failure

Clinical:
o Anaemia (decreased RBCs)
o Infection risk (decreased mature WBCs, neutropenia)
o Bleeding due to thrombocytopenia (decreased megakaryocytes)

Question 11

What is the goal of AML Rx?

Answer 11

Treatment goal: reduce population of leukaemic clones -> allow recovery of normal stem cells

Question 12

List some risk factors for AML?

Answer 12

• Exposure to radiation (most commonly prostate, NHL, lung and breast ca)
• Exposure to alkylating chemotherapy
• Smoking
• Viruses (e.g. HIV)
• Congenital syndromes (e.g. Downs syndrome, Kleinfelter syndrome, Turner syndrome)
• Haematological disorders
- Pre-leukaemic (e.g. myeloproliferative disorders, AML, MM)
- Benign: aplastic anaemia

Question 13

List some complications of AML?

Answer 13

• Pancyotopenia-related:
o Normocytic normochromic anaemia
o Infection risk (secondary to neutropenia)
o Haemorrhage (secondary to thrombocytopenia)
o DIC
• MSK- bone fractures (lytic lesion), joint involvement (synovial membrane infiltration)
• GIT complications- splenic rupture, portal HTN, portal vein thrombosis (Budd Chiari)
• Metabolic- hypokalaemia (renal loss due to tubular damage from lysozomes), lactic acidosis (due to anaerobic metabolism), hypercalcaemia
• Hyperleukocytosis -> WBC deposit in microvasculature -> resp and neuro distress
• Meningeal syndrome- CNS seeding
• Leukostasis- increased blast number (hyperleykocytosis) increases blood viscosity -> WBC deposit in microvasculature -> respiratory or neurological distress
• Treatment-related (e.g. tumour lysis syndrome, electrolyte disturbance, cardiotoxicity)

Question 14

What are some treatment-related complications of AML?

Answer 14

o GIT- vomiting, diarrhoea
o Tumour lysis syndrome (due to rapid leukaemia cell death following chemo) -> acute pulmonary failure (haemorrhages)
o Hyperuricaemia -> uric acid nephropathy, gout
o Electrolyte disturbance: hyperphosphataemia, hypocalcaemia, hyperkalaemia
o Cardiotoxicity (esp Doxorubicin)
o Graft-vs-host diease (post BM transplant)
o DVT

Question 15

What is the treatment of AML?

Answer 15

Chemo:

• Cytarabine (antimetabolite and nucleoside analog families, MA blocks DNA polymerase function)
• and Daunomycin (blocks topoisomerase II in DNA coiling)

Question 16

Describe AML prognosis?

Answer 16

• With Rx, 5 year survival is 70% 
• Prognostic factors: 
- better if younger (<15yo)
- myelodysplastic syndrome worse
- other comorbidities worse