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
why is there a microcytic anaemia in CML?
iron use to generate new cells
treatment of CML
• Tyrosine Kinase Inhibitors
o Imatinib (Gilvec) (within 3-4 weeks blood count normal), Dasatinib (Sprycel), Nilotinib
(Tasigna), Busitinib, Ponatinib
• Direct inhibitors of BCR-ABL is first line
• Allogenic transplantation (few now) only in TKI failures
what are myelodysplastic syndromes?
acquired clonal disorders of the bone marrow
what do myelodysplastic syndromes present as?
macrocytic anaemia and pancytopenia
why are myelodysplastic syndromes fatal?
progression to bone marrow failure or AML
treatment of myelodysplastic syndromes
supportive
stem cell transplantation for the few young patients
give examples of myeloproliferative neoplasms
polycythaemia vera
essential throbocythemia
idiopathic myelofibrosis
JAK2V617F is found in what percent of PV and ET?
90% PV
50% ET
CALR mutation is found in 25% of what?
ET
clinical features of PV
- Headaches
- Itch
- Vascular occlusion – high numbers of red cells
- Thrombosis
- TIA, stroke
- Splenomegaly
lab features of PV
• A raised haemoglobin concentration and
haematocrit
• A tendency to also have a raised white cell count and platelet count
• A raised uric acid
• A true increase in red cell mass when the blood volume is measured
treatment of PV
- Venesection to keep the haematocrit below 0.45 men and 0.43 women
- Aspirin + venescention
- ? hydroxycarbamide – suppress platelets
- ? rubxolitinib (JAK2 inhibitor) in HC failures with systemic symptoms
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
what is the predominant feature of ET?
raised plateelt count
symptoms of ET
arterial and venous thromboses
digital ischaemia
hout
mild splenomegaly
treatment of ET
aspirin and hydroxycarbamide or anagrelide
what can ET progress to?
myelofibrosis or AML
