Myeloid malignancy

Question 1

What are investigations for myeloid malignancies?

Answer 1

• blood count + blood film
• bone marrow aspirate/trephine
• cytogenetics (karyotype) from leukamic blasts
• immunophenotyping of leukaemic blasts
• CSF examination if symptoms
• targeted molecular genetics for associated aquired gene mutations
• e.g. FLT, NPM1, IDH 1 + 2
• inc. use of NGS myeloid gene panels in AML

Question 2

What is the treatment for acute myeloid leukaemia?

Answer 2

• supportive care
• anti-leukaemic chemotherapy
• daunorubicin + cytosine arabinoside (DA)
• high dose cytosine arabinoside
• gemtuzumab ozogamicin
• CPX-351
• allogeneic stem cell transplant
• all-tran retinoic acid (ATRA) and arsenic trioxide (ATO) (in low risk acute promyelocytic leukaemia)
• targeted treatments
• e.g. midostaurin in FLT2 mutated AML

Question 3

What is the mechanism of action of calicheomycin (mylotarg)- targeted antibody?

Answer 3

1. CD33 expresion level
2. CD33 saturation
3. internalisation
4. activation of calicheamicin
5. new expression of CD33
6. binding of GO
7. efflux of calicheomycin
8. induction of DNA breaks

Question 4

What are features of chronic myeloid leukaemia (CML)?

Answer 4

• anaemia
• splenomegaly (often massive)
• weight loss
• hyperleukostasis
• fundal haemorrage, venous congestion, altered conciousness, respiratory failure
• gout

Question 5

What are labratory features of chronic myeloid leukamia (CML)?

Answer 5

• (very) high WCC
• high platelet count
• anaemia
• blood film
• all stages of white cell differentiation
• inc. basophil
• bine marrow hypercellular
• bone marrow + blood cells, contain Philadelphia chromosome t(9;22)

Question 6

What is the treatment for chronic myleoid leukaemia (CML)?

Answer 6

• tyrosine kinase inhibitors (TKIs)
• imatinab (Glivec)
• dasatinib (Sprycel)
• Nilotinib (Tasigna)
• busitinib
• ponatinib
  (direct inhibitors of BCR-ABL)
• allogenic transplantation
  -only if TKI fails

Question 7

What are features and treatment for myelodysplastic syndromes?

Answer 7

• aquired clonal disorder of bone marrow
• commonly old age
• pre-leukaemic
• macrocytic anaemia, pancytopenia
• fatal- progression to bone marrow failure or AML
• supportive treatment
• stem cell transplantation (young)

Question 8

What are different types of myeloproliferative neoplasms (MPN)?

Answer 8

• polycythaemia vera (PC)
• JAK2V617F mutation- 95%
• essential thrombocythaemia (ET)
• JAK2V617F mutation- 50%
• CALR mutation- 25%
• idiopathic myelofibrosis (IM)
• JAK2V617F mutation- 50%

Question 9

What are features of polycythaemia vera (PV)?

Answer 9

• headaches
• itch
• vascular occlusion
• thrombosis
• TIA, stroke
• splenomegaly
• bone marrow failure- from secondary myelofibrosis
• transformation to AML

Question 10

What are labratory features of polycythaemia vera (PV)?

Answer 10

• inc. haemoglobin concentration + haematocrit
• inc. WCC + platelets
• inc. uric acid
• true inc. red cell mass when blood volume is measured
• blood film
• large + abnormal platelets

Question 11

What is the treatment for polycythaemia vera (PV)?

Answer 11

• venesection
• keep haematocrit < 0.45 (men)/< 0.43 (women)
• aspirin
• hydroxycarbamide (HC)
• ruxolitinib (JAK2 inhibitor)
• if HC failure + systemic symptoms

Question 12

What are features and treatment for essential thrombocythaemia (ET)?

Answer 12

• inc. platelet count
• arterial + venous thromboses, digital ischaemia, gout, headache
• mild splenomegaly
• progress to myelofibrosis, AML
• aspirin + hydroxycarbamide
• anagelide