Acute Myeloid Leukaemia Flashcards
What is acute myeloid leukaemia?
https://www.youtube.com/watch?v=itkRVTqfPsE
Neoplastic proliferation of blast cells derived from marrow myeloid elements.
Who does AML most commonly affect?
Adults - median age at presentation of 65
What can cause AML?
- Long term complication of chemo
- Myelodysplastic disease
- Radiation
- Down’s Syndrome
What are symptoms seen in AML?
Symptoms of marrow failure
- Fatigue
- Dyspnoea
- Symptoms of infection
- Exacerbated angina/claudication
- Bleeding and bruising
Symptoms of infiltration
- Bone pain - less common than ALL
- Headache
What are signs seen in AML?
- Petechiae/Purpura
- Fundal Haemorrhage
- Mucosal bleeding
- Hepatomegaly
- Splenomegaly
- Gum hypertrophy
- Violaceous skin lesions
- Signs of CNS involvement - very rare
How would you distinguish AML from ALL?
Compared to ALL
- Bone and Joint pain less common
- Hepatosplenomegaly less common
- Organ infiltration quite unusual
- Lymphoblasts may/may not be present in blood
- Auer Rods always present
What can occur in acute promyelocytic leukaemia?
DIC - due to thromboplastic release
What is the following?
Gum hypertrophy
How would you investigate suspected AML?
- Bedside - None
- Bloods - FBC, U+Es, LFTs, Blood Film, Coagulation screen, Urate, LDH
- Orifices - none
- X-ray/imaging - CXR
- ECG - no
- Special - Bone marrow Aspirate
What are the following?
Petechiae - Small (1–2 mm) haemorrhages into mucosal or serosal surfaces
What are causes of the following?
- Thrombocytopenia of any cause - autoimmune, heparin-induced, hypersplenism
- Bone marrow failure - malignancy
- Defective platelet function
- DIC
- Infection
- Bone marrow defects
- Factor deficiencies
What is the following?
Purpura - >3 mm haemorrhages, or when ecchymoses and petechiae form in groups
What are causes of the following?
Diseases associated with:
- As with petechiae:
- Trauma
- Vasculitis – particularly palpable purpura
- Amyloidosis
- Over-anticoagulation
- Factor deficiencies
What is the following?
Auer Rods - clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of myeloid leukemic blasts.
THESE ARE PATHOGNOMIC FOR AML
What might you see on FBC in someone with AML?
- Increased WCC, but can be normal/low
- Normocytic, normochromic anaemia
- Thrombocytopenia
What might you see on blood film in someone with AML?
- Blasts cells - not many, less than ALL
- Auer Rods
What might you see on Bone marrow aspirate in someone with AML?
- Increased cellularity, reduced erythropoiesis, reduced megakaryocytes.
- Replacement by blast cells >20%
-
Lineage confirmation by immunophenotyping
- AML – CD33 or CD13
What cytogenetic techniques would you request for testing bone marrow samples in someone with suspected AML?
- Flow cytometry immunophenotyping.
- Fluorescent in-situ hybridisation (FISH) - examines chromosome number and translocations, importantly the Philadelphia chromosome (9;22 translocation present in 90% of CMLs)
- PCR sequencing for DNA mutations - such as JAK-2
How would you manage someone with AML?
- Supportive therapy
- Chemotherapy
- Bone marrow transplant
What supportive therapy would you use in AML?
- Blood/Platelet transfusion
- IV fluids
- Allopurinol
- Hickman/Subcut line - IV access
Why would you give allopurinol to someone as supportive therapy for AML?
To try to prevent tumour lysis syndrome
What chemotherapeutic regimen is often used in AML?
Long periods of marrow suppression, with 5 cycles in 1 week blocks
- Daunorubicin
- Cytarabine
Which mutation can make AML more sensitive to cytarabine?
RAS mutation - present in approx 20% patients
What type of bone marrow transplants are used in AML?
Allogenic from HLA-matched siblings or matched unrelatedd donors
How is a bone marrow transplant performed in AML?
Destroy leukaemia and immune system with cyclophosphamide + total body irradiation. Then repopulate with transplanted marrow
What is used to prevent graft vs host disease?
Ciclosporin +/- methotrexate
What complications can occur in AML?
- Infection - bacterial, fungal or viral
- Increased plasma urate - from chemo
- Leukostasis - Dramatically increased WCC
What is leukostasis?
A medical emergency most commonly seen in patients with acute myeloid leukemia or chronic myeloid leukemia in blast crisis. It is characterized by an extremely elevated blast cell count and symptoms of decreased tissue perfusion.
The pathophysiology of leukostasis is not well understood, but inadequate delivery of oxygen to the body’s cells is the end result. Leukostasis is diagnosed when white cell plugs are seen in the microvasculature
What are symptoms of leukostasis?
Dyspnoea
Neurological symptoms
- Visual changes
- Headache
- Dizziness
- Tinnitus
- Gait instability
- Confusion
- Somnolence
- Coma.
What are signs of leukostasis?
- Hypoxia
- Pulmonary infiltrates
- Reduced GCS
- Retinal vein dilatation
- Papilloedema
- Fundal haemorrhage
What are complications of treatment for AML?
- Graft vs host disease
- Opportunisitc infection
- Relapse of leukaemia
- Infertility
What are characteristics of blast cells?
An immature precursor of myeloid cells or lymphoid cells:
- Bigger than normal counterpart
- Immature nucleus (nucleolus, open chromatin)
- Cytoplasmic appearances often atypical
- Rarely ever seen in serum of normal individuals
If present, are highly suggestive of an acute leukaemia or a chronic disorder that is beginning to transform into an acute disease
How would you treat acute promyelocytic leukaemia??
all-trans retinoic acid (ATRA)
What features assocaited with a picutre of bone marrow failure/an acute leukaemia might point away from AML as a cause and towards ALL as a cause?
Fever and lymphadenopathy are common first signs in ALL, whereas these are rare in AML
