Myeloid Malignancy Flashcards
In which cells of the bone marrow do myeloid malignancies arise? (4)
- Erythrocytes
- Megakaryocyte = platelets
- Granulocytes = neutrophils, eosinophils and basophils
- Monocytes = macrophages + dendritic cells
In which cells produced by the bone marrow do lymphoid malignancies arise? (2)
- B-cells
- T-cells
Where do almost all the myeloid malignancies originate from?
- The haematopoietic stem cells or the early myeloid progenitor cells
- Different mutations within the H stem cell lead to different phenotypes of disease
What are the main groups of myeloid malignancy? (4)
- Acute myeloid leukaemia (AML)
- Chronic myeloid leukaemia (CML)
- Myelodysplastic Syndromes (MDS) - pre-leukaemic conditions
- Myeloproliferative neoplasma (MPN)
What is the key difference between the development of Acute Myeloid/myeloblastic Leukaemia and Myeloproliferative disorders such as Chronic Myeloid Leukaemia?
Acute myeloid leukaemia = proliferation without any differentiation
Myeloproliferative disorders e.g CML, polycythemia vera etc – proliferation AND differentiation
Characteristics of Acute Myeloid Leukaemia
- Leukaemic cells do not differentiate - they proliferate and are resistant to dying but they do not mature/differentiate
- Bone marrow failure - bone marrow fills up with blast cells so the AML replaces the bone marrow and then it fails
- Rapidly fatal if untreated
- Potentially curable
Characteristics of Chronic Myeloid Leukaemia
- Leukaemic cells retain ability to differentiate
- Proliferation without bone marrow failure
- Long term survival/possible cures with modern therapy
What are 2 important subgroups of Acute Leukaemia?
- Acute Myeloblastic Leukaemia (AML)
- Acute Lymphoblastic Leukaemia (ALL)
What are the key clinical features of Acute myeloid/myeloblastic leukaemia? (3)
Bone marrow failure (Triad) - failure of the 3 lineages (erythrocytes, platelets and granulocytes/monocytes) and as a result you get:
- Anaemia
- Thrombocytopenic bleeding (platelet pattern - purpura, mucosal membrane bleeding etc)
- Infection because of neutropenia (predominantly bacterial and fungal) - lungs (fungal pneumonia), brain abscess etc
Look
- Fungal/bacterial infection is so serious in patients with AML and it is because of this infection risk that you cannot bring flowers or have standing water on these wards.
- Building work also releases spores of aspergillus which can cause death of these patients
What are the essential investigations done for AML?
- Blood count and blood film - thrombocytopenia, neutropenia, leukaemic cells in blood (may not have all of these)
-
Bone marrow aspirate (fluid) or trephine biopsy (tissue)
- Diagnose it when blast cells > 20% of marrow cells in acute leukaemia
- Cytogenetics (Karyotype) from leukaemic blasts - more specific diagnosis - done to find out about growth abnormalities (acquired) in the chromosomes
- Immunophenotyping of leukaemic blasts - identifies whether it is myeloid and lymphoid
- Lumbar puncture - CSF examination if suspected CNS involvement- more common in children
Future = genetics
How is Acute Myeloid Leukaemia treated?
- Supportive care = vital - high quality care with specialised units. Important as you have to get the patient through 5 weeks of absolute bone marrow failure if you use intense therapy
-
Anti-leukaemic chemotherapy - 3 parts to it
- Remission induction - to achieve remission = normal blood counts and less than 5% blasts - daunorubicin
- Consolidation of remission - high dose cytosine arabinoside or some recieve allogenic stem cell transplantation (most successful treatment but complex)
- Maintenance - Midostaurin
Clinical features of Chronic Myeloid Leukaemia
- Anaemia - not due to bone marrow failure as such but more due to chronic disease
- Splenomegaly - often massive due to proliferation within the spleen
- Weight loss - hypercatabolic state
-
Hyperleukostasis - high WCC
- Can cause fundal haemorrhage and venous congestion
- A very high WCC leads to altered consciousness and respiratory failure
- Gout - a lot of uric acid made due to proliferation
Typical CML blood count
- The WCC is very high but notice the different types of white cell count! There are a small number of blasts but lots of other white cells - as we know, the cells in CML differentiate and don’t form blast cells.
- Slightly anaemic
- High platelet count
What is the name of the translocation mutation that is a hallmark of CML?
The philadelphia chromosome Translocation t(9;22)
How is CML treated?
-
Tyrosine Kinase Inhibitors = 1st line - they inibit BCR-ABL (found in almost all CML patients)
- Imatinib
- Dasatinib
- Nioltinib
- Busitinib
- Ponatinib
- Allogenic transplantation - only used if TKI drugs fail
What are some myeloproliferative disorders other than CML?
- Polycythaemia Vera
- Essential thrombocythaemia
- Idiopathic myelofibrosis - General feeling is that this is just a more advanced stage of PV and ET
Which mutation is common in PV, ET and myelofibrosis?
JAK2 mutation
- In 95% of PV
- In 50% of ET and myelofibrosis
What are the clinical features of PV? (6)
- Headaches
- Itch
- Vascular occlusion
- Thrombosis
- TIA, stroke
- Splenomegaly - proliferation
What is a typical blood count in PV?
- Dramatic raise in Hb
- Haematocrit is high
- Platelets are high – stem cell disorder
- Raised uric acid + risk of gout
- A true increase in red cell mass when the blood volume is measured - proliferation
How is PV treated?
KEY THING in treatment of PV is to reduce vascular risk!! Quite like treating hypertension.
- Venesection - take blood away to keep haematocrit below 0.45 in men and 0.43 in women
- Aspirin - reduce risk of thrombosis
- Cytoreduction with chemotherapy like drug - reduce/supress WBC count or platelet levels
What is the natural history of PV like?
- Stroke and other arterial or venous thromboses if poorly controlled
- Bone marrow failure from the development of secondary myelofibrosis
- Transformation to AML
Essential thrombocythaemia - discuss
Myeloproliferative disease with predominant feature of raised platelet count
- 50% positive for JAK2V617F mutation
- 20% CARL mutation
- Symptoms of arterial and venous thromboses, digital ischaemia, gout or headache
- Mild splenomegaly
- Can progress to myelofibrosis or AML
What is Polycythaemia vera and essential thrombocythaemia?
Polycythaemia vera = proliferation of eryhtroid cell line
Essential thrombocythaemia = proliferation of megakaryocytic cell line (cells that become platelets)
