Myeloid Malignancy Flashcards
name the myeloid malignancy disorder s
acute myeloid leukaemia
chronic myeloid leukaemia
myelodysplastic syndromes
myeloproliferative diseases
acute vs chronic myeloid leukemia
Acute Chronic
Leukaemic cells do not differentiate Leukaemic cells retain ability to differentiate
Bone marrow failure Proliferation without bone marrow failure
Rapidly fatal if untreated Survival for a few years
Potentially curable Long term survival/possible cures with modern therapy
clinical features of AML
bone marrow failure
anaemia
thrombocytopenic bleeding
infection as a result of neutropenia
essential investifations in AML
blood count and blood film
bone marrow aspirate
cytogenetics of leukaemic blasts
immunophenotyping of leukaemic blaasts
CSF exam if symptoms
molecular genetics for associated acquired gene mutations
increasing use of NGS myeloid gene panels in AML
describe the blood film in AML
o Might be high normal or low total count
o Neutropenia is definite
o Haemoglobin and platelets may be low
what must the blast count be for a diagnosis of AML to be made?
> 20%
if blast count is less than < 20% when suspecting AML what is it?
myelodysplastic syndrome
what is the purpose of immunophenotyping of leukaemic balsts?
monoclonal antibody stains to distinguish between myeloblasts and lymphoblasts
molecular genetics in AML
Molecular genetics for associated acquired gene mutations
o E.g. FLT3, NPM1, IDH1&2
o Mutations in FLT3 carry adverse prognosis
o NPM1 mutations have a more positive prognosis
o IDH1+2 is an enzyme in the krebs cycle – lead to the production in a leukaemic
substrate
treatment of AML
• Supportive care
• Anti-leukaemic chemotherapy – to achieve and consolidate remission
• Stem cell transplantation – allogenic – to consolidate remission/potential cure
• All trans retinoic acid (ATRA) and arsenic trioxide (ATO) in low risk acute promyelocytic
leukaemia – “chemo free” – high cure rate ~90% in low risk AML
• Targeted treatment
describe the anti-leukaeic chemo used in AML
o Daunorubicin and cytosine arabinoside (DA) – induction
o High dose cytosine arabinoside – consolidation
o Gemtuzamab ozogamicin
o CPX-351
o Aplastic bone marrow for up to 3 weeks – supportive care is crucial for getting through
this
o Remission = blood count returned to normal + <5% lymphoblast
what is the targetted treatment in AML
midostaurin in FLT3 mutated AML
describe the new developments in AML
• Targeted antibodies
o Gemtuzumab, ozogamicin anti CD33 with calicheomycin (mylotarg)
• Targeted small molecules
o Midostaurin, tyrosine kinase inhibitor including inhibiting FLT3
• New delivery systems
o CPX-351
o Old fashioned chemo but in lipid capsule delivering constant dose
clinical features of CML
• Anaemia • Splenomegaly, often massive • Weight loss o Hyper catabolic state – sweat a lot • Hyperleukocytosis o Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure • Gout o Because of high cell turnover
lab features of CML
• High WCC (can be very high) • High platelet count • Anaemia • Blood film shows all stages of white cell differentiation with increased basophils o Blood film looks fairly normal there’s just more of it • Bone marrow is hypercellular • Bone marrow and blood cells contain the Philadelphia chromosome t(9,22) leukocytosis low Hb low MCV thrombocythemia neutrophilia increased monocytes increased eosinophils increased basophils increased lymphoblasts increased promyelocytes, myelocytes, metamyelocytes, reticulocytes
