Myeloid Malignancies Flashcards
Myeloid malignancies arise from what cells?
- Red cells
- Platelets
- Granulocytes
- Monocytes
Give examples of myeloid malignancies.
- Acute Myeloid Leukaemia (AML)
- Chronic Myeloid Leukaemia (CML)
- Myelodysplastic Syndromes (MDS)
- Myeloproliferative Neoplasms (MPN)
Acute vs chronic myeloid leukaemia
Do leukaemic cells differentiate?
Acute - Do not differentiate
Chronic - Retain ability to differentiate
Acute vs chronic myeloid leukaemia
Bone marrow
Acute - Bone marrow failure
Chronic - Proliferation without bone marrow failure
Acute vs chronic myeloid leukaemia
Survival
Acute - Rapidly fatal if untreated
Chronic - Survival for a few years historically
Acute vs chronic myeloid leukaemia
Treatment
Acute- Potentially curable
Chronic - Long term survival/ possible cures with modern therapy
What are the sub-groups of acute leukaemia?
- Acute Myeloid Leukaemia (AML)
- Acute Lymphoblastic Leukaemia (ALL)
What are the clinical features of AML?
Bone marrow failure
- Anaemia (SOB, angina, fatigued)
- Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding)
- Infection because of neutropenia (predominantly bacterial and fungal)
What are the essential investigations in AML?
- Blood count and blood film (leukaemic blasts)
- Bone marrow aspirate/ trephine (blasts >20% of marrow cells in acute leukaemia)
- 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 (next generation sequencing) myeloid gene panels in AML
How is AML treated?
- Supportive care
- Anti-leukaemic chemotherapy (to achieve and consolidate remission) (remission= blast count less than 5%, bloods normal)
- Allogeneic stem cell transplantation –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%)
- Targeted treatment (e.g Midostaurin in FLT3 mutated AML)
What anti-leukemic chemotherapy is used in treatment of AML?
Daunorubicin & cytosine arabinoside (DA)
What new developments have been made in the treatment of AML?
- Targeted antibodies: (Gemtuzumab Ozogamicin anti-CD33 with Calicheomycin (Mylotarg) )
- Targeted small molecules (Midostaurin, Tyrosine Kinase Inhibitor including inhibiting FLT3)
- New delivery systems (CPX -351)
How does CML present?
- Anaemia
- Splenomegaly, often massive
- Weight loss
- Hyperleukocytosis: Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure
- Gout
What are the laboratory 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 Philadelphia chromosome translocation?
t(9;22)
What is the treatment for CML?
- Tyrosin kinase inhibitors
- Imatinib (Glivec)
- Dasatinib (Sprycel)
- Direct inhibitors of BCR-ABL: first line in all patients nowadays
- Allogenic transplantation (few, only in TKI failure)
What are myelodysplastic syndromes?
- Acquired clonal disorders of the bone marrow that are commonly seen in old age
- They are pre-leukemic
How do myelodysplastic syndromes present?
Macrocytic anaemia and pancytopenia
What is the outcome of myelodysplastic syndromes?
Fatal as a result of progression to bone marrow failure or AML
What is the treatment for myelodysplastic syndromes?
Supportive or a stem cell transplantation for the few young patients
What are the clinical features of Polycythemia vera?
- Headaches
- Itch
- Vascular occlusion
- Thrombosis
- TIA, stroke
- Splenomegaly
What are the laboratory features of Polycythemia 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 a typical blood film of Polycythemia vera ?
Microcytosis with large and abnormal platelets
What is the treatment for Polycythemia vera?
- Venesection to keep the haematocrit below 0.45 - men and 0.43 - women
- Aspirin
- ? Hydroxcarbamide (HC)
- ? Ruxolitinib(JAK2 inhibitor) in HC failures with systemic symptoms
What is the natural history of Polycythemia 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 Essential thrombocythaemia?
A myeloproliferative disease with predominant feature of raised platelet count
How does Essential thrombocythaemia present?
- Symptoms of arterial and venous thrombosis
- Digital ischaemia
- Gout
- Headache
- Mild splenomegaly
How is Essential thrombocythaemia treated?
- Aspirin
- Hydroxycarbamide/ anagrelide
What can Essential thrombocythaemia progress to?
Mylefibrosis or AML
Give examples of myeloproliferative neoplasms
- Polycythemia vera
- Essential thrombocythaemia
- Idiopathic myelofibrosis
What is remission in acute myeloid leukaemia?
remission = blast count less than 5%, bloods normal
