Myeloid malignancies Flashcards
What is included in myeloid malignancies?
AML
CML
Myelodysplastic syndromes (MDS)
Myeloproliferative neoplasms (MPN)
What are clinical features of AML?
Bone marrow failure:
- Anaemia
- Thrombocytopenia bleeding (purport and mucosal membrane bleeding)
- Infection due to neutropenia
What are investigations for AML?
Blood count and blood film Bone marrow aspirate - blasts >20% marrow cell in AML Cytogenetics from leukaemia blasts Immunophenotyping of leukaemia blasts CSF exam Targeted molecular genetics - gene mutations
What is the treatment for AML?
Supportive Anti-Leukaemia chemotherapy - daunorubicin & cytosine arabinoside (DA) - high dose cytosine arabinoside - Gemtuzumab Ozogamicin - CPX-351 Allogeneic stem cell transplantation All-trans retinoid acid (ATRA) and arsenic trioxide (ATO) Targeted treatment
What are clinical features of CML?
Anaemia Splenomegaly, often massive Weight loss Hyperleukostasis Gout
How can hyperleukostasis present in CML?
Fundal haemorrhage
Venous congestion
Altered consciousness
Resp failure
What does a CML blood count look like
High platelets
Slight anaemia
High WBC
High neutrophils
High monos, eos, baso
Presence: blasts, promyelocytes, myelocytes, metamyelocytes
Bone marrow and blood cells contain the Philadelphia chromosome t(9;22)
What is a highly sensitive genetic test for CML?
Philadelphia chromosome
What is the Philedelphia chromosome?
A specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells)
What is the treatment for CML?
Tyrosine Kinase Inhibitors (TKIs) Allogeneic Transplantation (TKI failures)
What is the mode of action of TKIs?
Blocks phosphorylation of tyrosine, pathway of CML blocked off
What is a TKI for CML?
Imatinib
What are examples of myeloproliferative neoplasms (MPN)?
Polycythaemia Vera (PV) Essential Thrombocythaemia (ET) Idiopathic Myelofibrosis
In myeloproliferative neoplasms, where does the proliferation concentrate?
RBCs and platelets
What is polycythaemia vera?
Blood cancer
Bone marrow makes too many RBCs
High hemotocrit
What is the most common gene mutation that causes polycythaemia vera?
JAK2
What are complications of polycythaemia vera?
Enlarged spleen
Blood clots
Inflammation
Peptic ulcers
What are the clinical features of polycythaemia vera?
Headaches Itch Vascular occlusion Thrombosis TIA/stroke Splenomegaly Bad circulation Red face/plethoric
What are lab features of PV?
Raised haemoglobin concentration and haematocrit
Raised WCC and platelet count
Raised uric acid
True increase in red cell mass when blood volume measured
What is there a risk of if raised uric acid in PV?
Gout
What is a normal hematocrit?
45-50%
What is the haematocrit?
Ratio of the volume of red blood cells to the total volume of blood.
What is the treatment of PV?
Venesection (bloodletting)
Aspirin
Hydroxcarbamide (HC)/Alpha interferon
What is the main aim of PV treatment?
Reduce risk of stroke
What is natural history of PV?
Stroke - poorly controlled
Bone marrow failure from development secondary myelofibrosis
Transformation to AML
What is essential thrombocythaemia (ET)?
Myeloproliferative disease with raised platelet count
What gene mutations can cause ET?
JAK2
CALR
What are the symptoms of ET?
Arterial and venous thromboses Digital ischaemia Gout Headache Mild splenomegaly
What is the treatment for ET?
Aspirin
Hydroxycarbamide/anagrelide
What can ET progress to?
Myelofibrosis
AML
What is pancytopenia?
Deficiency of all three cellular components of the blood (red cells, white cells, and platelets)
