Myeloid Malignancy Flashcards
What is acute myeloid leukaemia?
Haematological malignancy resulting in the overproduction of immature myeloid cells/myeloid progenitors, building up and replacing bone marrow, causing bone marrow failure
What age group is acute myeloud leukemia more common?
Peak age of onset 70 years
How common is AML?
The more common form of acute leukaemia in adults
What is the prognosis of AML?
Long term survival 50%
Give risk factors for AML
Down Syndrome
Radiotherapy
Chemotherapy
Secondary transformation of a myeloproliferative disorder
Associated conditions
- Chronic myeloid leukaemia
- Myelodysplasia
- Myelofibrosis
- Polycythaemia rubra vera
How does AML present?
Anaemia
- Dyspnoea
- Fatigue
- Malaise/weakness
- Pallor
Thrombocytopenic bleeding
- Purpura and muscle membrane bleeding
Infection
- Prolonged neutropenia
Bone pain and tenderness
Gum swelling
Lymphadenopathy
Splenomegaly
When does gum swelling occur in AML?
Only in monocytic variety, due to monocytic infiltration
What is an ecchymosis?
Large bruise
What investigations are used in AML diagnosis?
Bone marrow biopsy
- Auer rods
- High numbers of blast cells
FBC
- Anaemia
- Increased WCC
- Thrombocytopenia
Blood film
- Leukaemic myeloblasts within blood
What biopsy sign is seen in AML?
Blasts >20% of marrow cells
How is AML managed?
Supportive
- Anti-fungal and antibiotic prophylaxis
- Blood transfusions
Chemotherapy
Allogenic stem cell transplantation
What classifications is used for AML?
French-American-British (FAB)
What is acute promyelocytic leukaemia M3?
Type of AML associated with t(15;17) and the fusion of PML and RAR-alpha genes. It presents younger and is associated with
- Auer rods (seen with myeloperoxidase stain)
- DIC or thrombocytopenia at presentation
- Good prognosis
Who is a allogenic stem cell transplant usually from and why?
Usually from a sibling, their immune system recognises the leukemic cells as an antigen
Give complications of AML
Relapse
Severe bleeding and infection
CNS infiltration
DIC
What are the poor prognostic features of AML?
Over 60 years
Over 20% blasts after first course of chemo
Cytogenetics
- Deletions of chromosome 5 or 7
What is chronic myeloid leukaemia?
Malignancy of granulocytes leading to increased production of myeloid precursors, with their differentiation ability still intact
What chromosome is associated with CML?
Philadelphia chromosome
(Philadelphia cheese makes lunch)
What is the Philadelphia chromosome?
Reciprocal translocation of chromosome 9 and 22, causing the BCR/ABL fusion gene
What activity is associated with the Philadelphia chromosome?
Uncontrolled tyrosine kinase activity
What age group is CML more common in?
Occurs in middle aged and elderly
How does CML present?
Anaemia
Massive splenomegaly due to build up of myeloid cells
Weight loss
Gout
Sweating
Bleeding
Bruising
Petechiae
Hyperleukostasis
What is Hyperleukostasis?
Significantly increased blast cells, causing
- Fundal haemorrhage and venous congestion
- Altered consciousness
- Respiratory failure
What investigations are used in CML diagnosis?
Bone marrow biopsy
Philadelphia chromosome
FBC
- Increased WCC
- Low lymphocytes but high neutrophils
- Thrombocytosis
- Anaemia
Blood Film
- Granulocytes at different stages of maturation/myeloblasts and granulocytosis
Decreased leukocyte alkaline phosphatase
How is CML managed?
Supportive
- Blood transfusions
- Antibiotics
Tyrosine Kinase Inhibitors
- Imatinib
Interferon alpha
Allogenic Transplant in TKI failures
Give an example of a tyrosine kinase inhibitor
Imatinib
Name the myeloproliferative disorders
Essential thrombocytosis
Polycythaemia rubra vera
Myelofibrosis
What are the features of essential thrombocytosis?
Platelet count > 600 * 109/l
Both thrombosis (venous or arterial) and haemorrhage can be seen
Characteristic symptom is a burning sensation in the hands
JAK2 mutation is found in around 50% of patients
How is essential thrombocytosis managed?
Hydroxyurea (hydroxycarbamide) to reduce platelet count
interferon alpha is also used in younger patients
Low-dose aspirin may be used to reduce the thrombotic risk
What is polycythaemia vera?
Myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets
What are the features of polycythaemia vera?
Hyperviscosity
Pruritus, typically after a hot bath
Splenomegaly
Haemorrhage/stroke, secondary to abnormal platelet function
Plethoric appearance
HTN
Headaches, dizzy spells and tinnitus
What investigations are used in polycythaemia vera?
FBC
- Increased RBC
- Increased haematocrit
- Normal EPO
Low ESR
JAK2
How is polycythaemia vera managed?
Aspirin
Venesection
hydroxyurea, causes slight increased risk of secondary leukaemia
Phosphorus-32 therapy
What investigations are used in myelofibrosis?
Blood film
- Tear drop poikilocytes
FBC
- Anaemia
- Thrombocytopenia and leucopenia in progressive disease
