Myeloid Malignancies Flashcards
What cell causes AML?
Myeloid progenitor
What cells are involved in myeloproliferative disorders?
Neutrophils, eosinophils, basophils, monocytes, platelets and red cells
What are the types of myeloid malignancy?
Acute myeloid leukaemia (AML)
Chronic myeloid leukaemia (CML)
Myelodysplastic syndromes (MDS)
Myeloproliferative neoplasms (MPN)
Describe acute myeloid leukaemia
Leukemic cells do not differentiate
Bone marrow failure
Rapidly fatal if untreated
Potentially curable
Describe chronic myeloid leukaemia
Leukaemia cells retain ability to differentiate
Proliferation without bone marrow failure
Survival for a few years
Long term survival with modern therapy
What are the subgroups of acute leukaemia?
Acute myeloblastic leukaemia (AML)
Acute lymphoblastic leukaemia (ALL)
What are the clinical features of AML?
Anaemia
Thrombocytopenic bleeding - purpura and mucosal membrane bleeding
Infection because of neutropenia - bacterial and fungal
What are essential investigations for AML?
Blood count and blood film
Bone marrow aspirate/ trephine
Cytogenetics
Immunophenotyping
CSF examination if symptoms
Targeted molecular genetics
Extended NGS myeloid gene panels
What is the treatment for AML?
Anti-leukemic chemo. - to achieve and consolidate remission
Allogenic stem cell transplantation
Low risk - all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)
Acute promyelocytic leukaemia
Targeted treatment
What are new developments in AML?
Targeted antibodies
Targeted small molecules
New chemotherapy delivery systems
What are the clinical features of CML?
Anaemia, splenomegaly, weight loss, hyperleukostasis (fundal haemorrhage and venous congestion, altered consciousness and resp. failure) and gout
What are the laboratory features of CML?
High WCC, high platelet count, anaemia, blood film shows all stages of white cell differentiation with increased basophils, bone marrow is hypercellular and bone marrow + blood cells contain Philadelphia chromosome
What is the treatment of CML?
Tyrosine Kinase Inhibitors - Imatinib, Dasatinib, Nilotinib, Busitinib and Ponatinib
First line - direct inhibitors of BCR-ABL
Allogenic transplantation on TKI failures
What are types of myeloproliferative neoplasms?
Polycythaemia Vera (PV)
Essential thrombocythemia (ET)
Idiopathic myelofibrosis
What mutations are seen in myeloproliferative neoplasms?
JAK2 V617F mutation in 95% of PV
50% in ET and myelofibrosis
CALR mutation in 25% of ET
What are the clinical features of polycythaemia vera?
Headaches, itch, vascular occlusion, thrombosis, TIA, stroke and splenomegaly
What are the lab features of PV?
Raised haemoglobin conc. and haematocrit, raised WCC + platelet count, raised uric acid and true increase in red cell mass when blood volume measured
What is the treatment of PRV?
Venesection to keep haematocrit below 0.45 in men and 0.43 in women
Aspirin
Hydroxycarbamide/ alpha interferon
What is the natural history of PRV?
Stroke and other arterial or venous thromboses if poorly controlled
Bone marrow failure from development of secondary myelofibrosis
Transformation to AML
Describe essential thrombocythemia?
Myeloproliferative disease with predominant feature of raised platelet count
Treated with aspirin and hydroxycarbamide or anagrelide
Can progress to myelofibrosis or AML
What are the symptoms of essential thrombocythemia (ET)?
Arterial and venous thromboses, digital ischaemia, gout, headache and mild splenomegaly
