Chronic Myeloproliferative Disorders and Chronic Myeloid Leukaemia

Question 1

Clonal proliferation of bone marrow stem cells usually leading to excess production of one or more haemopoietic lineage

Answer 1

Chronic myeloproliferative disorders

Question 2

3 types of chronic myeloproliferative disorders

Answer 2

Polycythaemic vera- RBCs
Esstential thrombocytosis- platelets
Idiopathic myelofibrosis-reactive fibrosis of bone marrow and extramedullary haemopoeisis in the liver and spleen

Question 3

What percentage of chronic myeloproliferative disorders transform to acute leukaemia

Answer 3

10%

Question 4

Immature RBCs released into the blood following a bleed

Answer 4

Reticulocytes

Question 5

Symptoms of polycythaemia vera

Answer 5

Stroke, MI, splenomegaly, gangrene, gout (everytime you breakdown cells, uric acid released into the blood), plethoric face

Question 6

Lab findings of polycythaemic vera

Answer 6

increased haematocrit

Question 7

Haematocrit

Answer 7

RBCs relative to plasma

Question 8

3 types of polycythaemia vera

Answer 8

Primary e.g. PV
Relative e.g. not enough plasma- alcoholics, D&V
Secondary e.g. COPD, altitude, EPO production tumours, renal disease

Question 9

What is the distinguishing features between primary and secondary polycythaemia

Answer 9

If EPO is high, likely to be secondary

JAK2 mutation, likely to be primary

Question 10

What is the result of the JAK2 mutation

Answer 10

Erythrocyte replication cycle constantly on

Question 11

Persistent elevation of peripheral blood platelet count as a result of increased marrow platelet production in the absense of a systemic cause

Answer 11

Thrombocytosis

Question 12

Clinical features of thrombocytosis

Answer 12

Thrombosis (gangrene, cerebral, coronary arteries)
DVT
Superficial thrombophlebitis
Headaches, visual disturbance
Splenomegaly (50%)

Question 13

Lab findings for essential thrombocytosis

Answer 13

Platelet count >405x109/L
JAK2 mutation in 50%
Hypercellular bone marrow and increased numbers of megakaryocytes
CALR mutation in 45%

Question 14

What is the effect of the CALR mutation

Answer 14

Cell signalling protein found in myeloid progenitors- may activate cell signal pathways

Question 15

Treatment for thrombocytosis

Answer 15

Antiplatelet treatment
Interferon- inhibitor of megakaryocytes
Hydroxycarbaminde- decreased DNA synthesis

Question 16

Prognosis for idiopathic myelofibrosis

Answer 16

5 years- much worse than the others

Question 17

What are the 3 main characteristics of idiopathic myelofibrosis

Answer 17

Splenomegaly
Extramedullary haematopoiesis
Replacement of bone marrow with fibrosis

Question 18

Clinical features of idiopathic myelofibrosis

Answer 18

Massive splenomegaly- left hypochondrial pain
Fever, weight loss, pruritis, hepatomegaly and night sweats
Abdominal swelling caused by portal hypertension

Question 19

CML is characterised by excess production of what cells?

Answer 19

Myeloid cells- neutrophils and granulocytes

Question 20

Describe the genetic mutation in CML

Answer 20

Leukaemic cells have t(9;22) translocation known as the philadelphia chromosome (BCR-ABL gene fusion forms TK gene that tells cells to proliferate)

Question 21

Clinical features of CML

Answer 21

Occurs at all ages

Weight loss, night sweats, itching, left hypochondrial pain, gout, splenomegaly

Question 22

Lab features of CML

Answer 22

Leucocytosis

Question 23

Treatment for CML

Answer 23

Imatinib (Gleevec) inhibits TK encoded by BCR-ABL gene

Question 24

B cell clonal lymphoproliferative disease- lymphocytes accumulated in the blood, bone marrow, lymph nodes and spleen

Answer 24

Chronic lymphocytic leukaemia

Question 25

What age does CLL typically present?

Answer 25

Over 72 yrs

Question 26

Clinical features of CLL

Answer 26

Lymphadenopathy, night sweats, weight loss due to bone marrow failure, splenomegaly
Hypogammaglobulinaemia-predisposed to infection
Autoimmune haemolytic anaemia

Question 27

Lab findings of CLL

Answer 27

Increased peripheral blood lymphocytes. Weak expression of IgM

Question 28

Peripheral blood cytopenias, mostly frequently affecting more than 1 lineage, usually in association with a hypercellular marrow indicating ineffective haemopoiesis

Answer 28

Myelodysplasia

Question 29

Lab findings for myelodysplasia

Answer 29

Macrocytic anaemia
Neutropenia
Hypercellular bone marrow