Myeloid malignancy Flashcards
What is the difference between acute and chronic malignancy?
○ Acute
- Leukaemic cells do not differentiate
- Bone marrow failure
- Rapidly fatal if untreated
- Potentially curable
○ Chronic
- Leukaemic cells retain ability to differentiate
- Proliferation without bone marrow failure
- Survival for a few years historically
- Long term survival/ possible cures with modern therapy
What are the clinical features of bone marrow failure in acute myeloblastic leukaemia?
- Anaemia
- Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding)
- Infection because of neutropenia (predominantly bacterial and fungal)
What are the essential inestigations in acute myeloblastic leukaemia?
- Blood count and blood film
- Bone marrow aspirate/ trephine
- Cytogenetics (Karyotype) from Leukaemic blasts
- Immunophenotyping of leukaemic blasts
- CSF examination if symptoms
- Targeted molecular genetics for associated acquired gene mutations
□ e.g. FLT3, NPM1, IDH 1 & 2 - Increasing use of NGS myeloid gene panels in AML
What are the treatments of AML?
- Supportive care (very important)
- Anti-leukaemic Chemotherapy: to achieve & consolidate remission
- Allogeneic stem cell transplantation: to consolidate remission/potential cure
- All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)
- Targeted treatment
□ e.g. Midostaurin in FLT3 mutated AML - New developments
□ Targeted antibodies:
® Gemtuzumab Ozogamicin anti-CD33 with Calicheomycin (Mylotarg)
□ Targeted small molecules
® Midostaurin
◊ Tyrosine Kinase Inhibitor including inhibiting FLT3
□ New delivery systems
® CPX -351
Give examples of anti-leukaemic chemotherapy
□ Daunorubicin & cytosine arabinoside (DA) (into)
□ High dose cytosine arabinoside (consolidation)
□ Gemtuzumab Ozogamicin (new, may improve the response)
□ CPX-351 (new may improve the response)
What is All-trans retinoic acid (ATRA) and arsenic trioxide?
□ In low risk Acute Promyelocytic Leukaemia
□ ‘Chemo –free’
□ high cure rate ~ 90%
What are the clinical features of chronic meyeloid leukaemia?
- Anaemia: not just due to marrow failure but also due to chronic disease as there is an increase in cytokines and hepacins
- Splenomegaly, often massive
- Weight loss
- Hyperleukostasis - Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure.
- Gout (because of the huge cell turn over)
What are the labratory 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
- Bone marrow is hypercellular
- Bone marrow and blood cells contain the Philadelphia chromosome - t(9;22)
What is the treatment of CML?
- Direct inhibitors of BCR-ABL: first line in all patients nowadays □ Tyrosine kinase inhibitors (TKIs) ® Imatinib (Glivec) ® Dasatinib (Sprycel) ® Nilotinib (Tasigna) □ Busitinib □ Ponatinib - Allogenic transplantation (few now)- only in TKI failures
What are myelodysplastic syndromes?
○ Acquired clonal disorders of the bone marrow
○ Commonly seen in old age
○ Present as macrocytic anaemia and pancytopenia
○ They are pre-leukaemic
○ They are fatal as a result of progression to bone marrow failure or AML
○ Treatment is supportive or stem cell transplantation for the few young patients
Give examples of myeloproliferative neoplasms
- Polycyhtaemia Vera (PV)
- Essential thrombocythemia (ET)
- Idiopathic myelofibrosis (IM)
What are the clinical features of Polycythaemia Vera?
□ Headache □ Itch □ Vascular occlusion □ Thrombosis □ TIA, stroke □ Splenomegaly
What are the labratory features of Polycythaemia Vera?
□ 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
What is the natural history of polycythaemia Vera?
□ 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 treatment of Polycythaemia Vera?
□ Venesection to keep the haematocrit below 0.45
□ Aspirin
□ Hydroxycarbamide (HC)/ alpha interferon
□ ? Ruxolitinib(JAK2 inhibitor) in HC failures with systemic symptoms
- Good at reducing symptoms
- Doesn’t benifit survival
