Myeloid malignancies

Question 1

WHO deifintion of AML

Answer 1

more than 20% blasts in the bone marrow aspirate

Question 2

causes of AML

Answer 2

de novo, CML, paroxysmalnocturnal haemoglobuinuria, Polycythemia ruba vera (PRV), previous exposure to radiation, previous chemotherapy.

Question 3

clinical features of AML

Answer 3

BONE MARROW FAILURE TRIAD = Anaemia, thrombocytopenic bleeding (purpura and mucosal bleeding), infection because of neutropenia (bacterial and fungal e.g.aspergillus fumigata), Bone pain, splenomegaly,
eccymosis, haematoma, are examples of thrombocytonpenic bleeding.

Question 4

Ix AML

Answer 4

blood count and film - INCREASED WCC, Anaemia and LOW PLATELETS
BM aspirate >20%
cytogenics from leukaemic hosts (C5 OR 7) and immunophenotyping of leukaemic blasts, CSF examination if symptoms.

Question 5

Mx AML

Answer 5

supportive care, allogeneic astem cell transplantaiton, anti-leukaemic chemotherapy (Daunorubicin and cytosine arabinoside), aTrans-Retinoic acid.
Targeted antibodies (gentuzumab), Mylotarg

Question 6

Clinical features of CML

Answer 6

Anaemia
 Splenomegaly, often massive
 Weight loss
 Hyperleukostasis - Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure.
Gout

Question 7

Laboratory features of CML

Answer 7

High WCC ( can be very high )
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)

Question 8

Philadelphia chromosome - whhat is it?

Answer 8

a specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). Reciprocal translocation: t(9;22), Formation of BCR-ABL fusion gene, Constitutive tyrosine kinase activity, Present in >80% of CML, Discovered by Nowell and Hungerford in 1960

Question 9

what is Philadelphia chromosome diagnosis confirmed by?

Answer 9

BCR-ABL

Question 10

Tx CML

Answer 10

Imatinib: tyrosine kinase inhibitor (Or: Dasatinib (Sprycel), Nilotinib (Tasigna), Busitinib, Ponatinib) - direct inhibitors of BCR-ABL OR USE ALLOGENIC TRANSPLANTATION

Question 11

Myeloproliferative Neoplasms (MPN) EXMAPLES

Answer 11

Polycythaemia Ruba Vera (PV/ PRV)
Essential Thrombocythaemia (ET)
Idiopathic Myelofibrosis

Question 12

PRV clinical features

Answer 12

headaches, itch, vascular occlusion, thrombosis, TIA, stroke, splenomegaly

Question 13

PRV lab features

Answer 13

raised Hb, platelets, WCC and uric acid

Question 14

Tx PRV

Answer 14

Venesection to keep the haematocrit below 0.45 - men and 0.43 - women.
Aspirin,
Hydroxcarbamide (HC)/Alpha Interferon,
Ruxolitinib(JAK2 inhibitor) in HC failures with systemic symptoms.