Flashcards in Myeloid Malignancies Deck (23)
What are the 4 major myeloid malignancies?
How does AML work?
A mutation in a stem cell --> Leukaemic stem cell
Allows self-renewal of progenitor cells, proliferation & blocking of differentiation
Leads to a mass of blast cells pushing out the healthy stem cells --> Bone marrow failure
Clinically how would you encounter a case of AML?
Bone Marrow Failure:
- Thrombocytopenic bleeds (Purpura/petechiae & mucosal bleeds)
- Neutropenic infections (bacterial/fungal)
How would you approach an AML patient?
FBC & blood film
Bone Marrow Aspirate (confirms)
Once you have a diagnosis of leukaemia what further testing is done?
Cytogenetics & immunophenotyping of blasts (allows determining myeloblasts vs lymphoblasts as well as subclasses)
CSF exam if they have CNS symptoms
Targeted molecular genetics - Assesses ass mutations that tell us about prognosis and treatment e.g. FLT3
How do we manage someone with AML?
- Supportive Care
- Anti-leukemic Chemo
- Allogenic Stem Cell Transplant
Targeted Treatment e.g. Midostaurin in FLT3 AML
How can you treat Low risk Acute Promyelocytic Leukaemia?
Can do it "chemo-free" with:
ATRA (all-trans retinoic acid) & ATO (Arsenic Trioxide)
How would a patient with CML present?
What are the presentations of hyperleukostasis?
How do we test for CML?
FBC & Blood Film (High WCC, platelets, myeloid cells & anaemia)
Bone Marrow Aspirate - Hypercellular
Philadelphia Chromosome t(9;22) found in bone marrow & blood cells
How can you treat CML?
- Tyrosine Kinase inhibitors e.g. Imatinib (Glivec)
- Allogenic Stem Cell Transplants (If TKI fails)
What are myelodysplastic syndromes?
Acquired clonal disorders of the bone marrow that mostly affect elderly people
How do myelodysplastic syndromes present?
With macrocytic anaemia & pancytopenia
It can progress to bone marrow failure & AML
How do you treat Myelodysplastic syndromes?
Treatment is supportive
Some young patients can get stem cell transplant
What are the major types of myeloproliferative neoplasms?
Polycythaemic Vera (PV)
Essential Thrombocythaemia (ET)
Idiopathic Myelofibrosis (IM)
What mutations are associated with Myeloproliferative neoplasms?
JAK2V617F - 95% of PV & 50% of ET
CALR - 25% of ET
What happens in PV?
Excess of myeloid cells (predominantly RCs) -->
Vascular occlusion & thrombosis
What test results would you expect in PV?
- Raised Hb & haematocrit
- Raised WCC & platelets
- Raised URic Acid
- Increased RC mass
How do you treat a case of PV?
Venesection (lowers haematocrit)
Hydroxycarbamide --> IF fails use Ruxolitinib (JAK2 inhibitor)
When would we use Hydroxycarbamide in PV cases?
Only if they have additional vascular risk factors e.g. HTN or DM
OR if they're >60
What is Essential Thrombocythaemia?
A myeloproliferative neoplasm, predominantly affecting platelets
- Digital Ischaemia
How do we treat ET?
Hydroxycarbamide or Anagrelide