Myeloid malignancy Flashcards
What are the categories of myeloid malignancy?
- Acute myeloid leukaemia
- Chronic myeloid leukaemia
- Myelodysplastic syndromes (MDS)
- Myeloproliferative neoplasms (MPN)
What are the differences between acute and chronic leukaemia?
Acute
- Leukaemia cells do not differentiate
- Bone marrow failure
- Rapidly fatal if untreated
- Potentially curable
Chronic
- Leakaemia cells retain ability to differentiate
- Proliferation without bone marrow failure
- Survival for a few years historically
- Long term survival possible
What are the two subgroups of acute leukaemia?
- Acute myeloblastic leukaemia (AML)
- Acute lymphoblastic leukaemia (ALL)
- predominates in childhood
How does acute myeloid leukaemia come about?
- LSC - leukaemic stem cell
- These early myeloid progenitor cells do lose the self renewal, however mutational events re confer the re-emergence of self renewal – LSC malignant but retains a version of normal physiology.
- Self renewal + proliferation allows the growth of the cancer cells, pushing out the normal haemotopoitic cells.
- Treatments have to target the leukaemic stem cells
Clinical features of AML
What is the triad of bone marrow failure?
- Anaemia
- Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding)
- Infection because of neutropenia (predominantly bacterial and sometimes fungal)
On image shown bone marrow has been replaced by monotonous pop. of blast cells. Bulk AML population
Investigations for AML?
- Blood count and blood film – routine haem lab
- Bone marrow aspirate/ trephine
- Cytogenetics (Karyotype) from leukaemic blasts
- Immunophenotyping of leukaemic blasts – panel of monoclonal antibodies and look at pattern of stain, distinguish myeloblast from lymphoblast
- CSF examination if symptoms
On blood tests what is diagnostic for AML?
- Diagnosis is made if blast count is more than 20%
What is the management of AML?
- Supportive care – impacts outcome other than any development
- Anti-leukaemic Chemotherapy –to achieve & consolidate remission
- Daunorubicin & cytosine arabinoside (DA) – induction therapy
- High dose cytosine arabinoside – consolidation therapy
- Gemtuzumab Ozogamicin
- CPX-351
- Allogeneic stem cell transplantation –to consolidate remission/potential cure, giving a new immune system…!
There are some new druggos - he was super keen about them - they are more targeted and chemo free, see in lecture if wanna be a keen been
What are some of the new developments in AML treatment?
- Targeted antibodies:
- Targeted small molecules
What is the survival in UK of AML?
What is CML?
How do patients present with CML?
Chronic myeloid leukaemia
- Anaemia
- Splenomegaly, often massive
- Weight loss – sweat a lot
- Hyperleukostasis - Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure.
- Gout due to high cell turnover
- Do NOT transfuse blood – anaemia is providing protection, causes the blood to be hyperviscous
What are common features of CML on blood results?
Key diagnostic lab feature for CML?
- 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)
How would CML present on a blood film?
- lots of neutrophils, eosinophils etc
- More differentiated cells and more than usual
What are the treatments for CML?
Tyrosine Kinase inhibitors
- Imatinib
- Dasatinib
- Nilotinib
- Direct inhibitors of BCR-ABL : First line in all patients nowadays
What are myelodysplastic syndromes?
- Acquired clonal disorders of the bone marrow
- Rare and occur in old age
- 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
