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
Leukaemic cells
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 Myeloblastic Leukaemia (AML)
- Acute Lymphoblastic Leukaemia (ALL)
What are the clinical features of AML?
Bone marrow failure
- Anaemia
- 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
- 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
How is AML treated?
- Supportive care
- Anti-leukaemic chemotherapy (to achieve and consolidate remission)
- 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)
- High dose cytosine arabinoside
- Gemtuzumab Ozogamicin
- CPX-351
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
- Hyperleukostasis : 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)
- Nilotinib (Tasigna)
- Busitinib
- Ponatinib
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?s
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
Give examples of myeloproliferative neoplasms.
- Polycythaemia Vera (PV)
- Essential Thrombocythaemia (ET)
- Idiopathic Myelofibrosis (IM)
What genetic mutations are associated with myeloproliferative neoplasms?
JAK2V617 mutation in
- 95% of PV
- 50% of ET
- 50% of Myelofibrosis
CALR mutation in 25% of ET
What are the clinical features of PV?
- Headaches
- Itch
- Vascular occlusion
- Thrombosis
- TIA, stroke
- Splenomegaly
What are the laboratory 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
What is a typical blood film of PV?
Microcytosis with large and abnormal platelets
What is the treatment for PV?
- 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 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 ET?
A myeloproliferative disease with predominant feature of raised platelet count
What genetic mutations are associated with ET?
- 50% positive for JAK2V617F mutation
- 25% positive for calreticulin (CALR) mutation
How does ET present?
- Symptoms of arterial and venous thrombosis
- Digital ischaemia
- Gout
- Headache
- Mild splenomegaly
How is ET treated?
- Aspirin
- Hydroxycarbamide/ anagrelide
What can ET progress to?
Mylefibrosis or AML
