Myeloid Malignancy Flashcards
Features of acute myeloid leukaemia
Leukaemic cells do not differentiate
Bone marrow failure
Rapidly fatal if untreated
Potentially curable
Features of chronic myeloid leukaemia
Leukaemic cells retain ability to differentiate
Proliferation without bone marrow failure
Survival for a few years
Long term survival/possible cures increasing with modern therapy
Clinical features of chronic myeloid leukaemia
Anaemia
Splenomegaly, often massive
Weight loss
Hyperleukostasis - fundal haemorrhage and venous congestion, altered consciousness, respiratory failure
Gout
Typical blood count shows no bone marrow failure, just proliferation
Laboratory features of CML
High WCC
High platelets
Anaemia
Blood film shows all stages of white cell differentiation with increased basophils
Bone marrow is hypercellular
Bone marrow and blood cells contain the Philadelphia chromosome
Treatment of CML
Tyrosine Kinase Inhibitors
- imatinib
- dasatinib
- nilotinib
- busitinib
- ponatinib
- direct inhibitors of BCR-ABL, first line in all patients
Allogeneic transplantation - few patients, only in TKI failures
Subgroups of acute myeloid leukaemia
Acute myeloblastic leukaemia
Acute lymphoblastic leukaemia
Clinical features of acute myeloblastic leukaemia
Bone marrow failure
- anaemia
- thrombocytopenic bleeding (purpura and mucosal bleeding)
- infection due to neutropenia (predominantly bacterial and fungal)
Essential investigations of acute myeloblastic leukaemia
Blood count and blood film
Bone marrow aspirate/trephine biopsy
Cytogenetics of leukaemic blasts - carries good prognostic information (more than 20% blasts in bone marrow = acute leukaemia)
CSF examination if symptoms indicate
Molecular genetics for associated acquired gene mutations e.g. FLT3, NPM1, IDH 1 and 2
Treatment of AML
Supportive care
Anti-Leukaemic chemotherapy
- produces complete and absolute neutropenia for 2-3 weeks
- among most intense chemotherapy regimes
- supportive care very important
Stem cell transplantation
- allogeneic
- selective patients
- effect not dependent on chemotherapy
All-Trans Retinoic Acid in APL
What newly developed drugs are used in AML treatment?
Targeted antibodies
- gentuzumab ozogamicin anti-CD33 with calcicheomycin
- midostaurin; TKI, including inhibiting FLT3
Features of myelodysplastic syndromes
Acquired clonal disorders of the bone marrow
Commonly seen in old age
Present as macrocytic anaemia and pancytopenia
Pre-Leukaemia
Fatal as a result of progression to bone marrow failure or AML
Treatment of myelodysplastic syndrome
Supportive
Stem cell transplantation for the few young patients
Presentation of myelodysplastic syndromes
Macrocytic anaemia and pancytopenia
How many people with myelodysplastic syndromes will go on to develop AML?
1/3rd
What are the myeloproliferative disorders?
Polycythaemia vera
Essential thrombocythaemia
Idiopathic myelofibrosis
In what percentage of polycythaemia vera and essential thrombocythaemia is JAK2V617F mutation found?
95% of PV
50% of ET
In what percentage of essential thrombocythaemia is CALR mutation found?
25%
Clinical features of polycythaemia vera
Headache Pruritis Vascular occlusion Thrombosis TIA, stroke Splenomegaly
Laboratory features of PV
Raised haemoglobin concentration and haematocrit
Tendency to also have raised WCC and platelet count
Raised uric acid
True increase in red cell mass when blood volume is measured
Treatment of PV
Venesection to keep haematocrit below 0.45
Aspirin
Hydroxycarbamide
Natural history of PV
Stroke and other arterial or venous thromboses if poorly controlled
Bone marrow failure from the development of secondary myelofibrosis
Transformation to AML
Features of essential thrombocythaemia
Myeloproliferative disease with predominant features of platelet count
Symptoms of arterial and venous thromboses, digital ischaemia and gout
Mild splenomegaly
Treatment of ET
Aspirin
Hydroxyurea
What can ET progress to?
Myelofibrosis or AML
