Myeloproliferative Disorders and CLL

Question 1

What translocation drives CML?

Answer 1

Philadelphia chromosome +ve, (9;22)

Question 2

What does the BCR-ABL gene cause?

Answer 2

Increased tyrosine kinase activity- which is why treatment is imatinib (BCR-ABL tyrosine kinase inhibitor)

Question 3

What is CML?

Answer 3

A myeloproliferative disorder.
Neoplastic proliferation of myeloid cells, especially granulocytes and their precursors; basophils are characteristically increased.

Question 4

Age group typically affected by CML?

Answer 4

MIDDLE AGED 40-60

Question 5

Common feature of CML?

Answer 5

SPLENOMEGALY

Question 6

When is imatinib treatment for CML most effective?

Answer 6

Chronic phase

Question 7

Blood results for CML?

Answer 7

Neutrophilia

Raised WCC

Question 8

Blood film of CML?

Answer 8

LEFT SHIFT- high number of young immature white blood cells
Leukocytosis
Eosiniophilia
Basophilia

Hypoblated megakaryocytes in bone marrow

Question 9

Diagnosis of CML?

Answer 9

Use FISH currently, PCR for BCR-ABL1 fusion gene resulting form t(9;22), forming philadelphia chromosome.

Question 10

Phases of CML and features?

Answer 10

Chronic- responsive to therapy <5% blasts
Accelerated- >10% blasts, less responsive to therapy, increasing manifestations such as splenomegaly
Blast phase: >20% blasts behaves like Acute leukaemia, treatment similar to AML possibly with allogeneic SCT for young people.

Question 11

Bone marrow of CML?

Answer 11

HYPERCELLULAR BM with spectrum of immature (myelocytes) and mature granulocytic cells in the blood.

Question 12

Blood film of CLL?

Answer 12

SMEAR CELLS/SMUDGE CELLS
Remember SMEAR CLLs
High WBC with lymphocytosis

Question 13

Difference between CLL and small lymphocytic leukaemia (SLL)?

Answer 13

Essentially the SAME disease process but CLL primarily seen in the bone marrow
SLL in the LYMPH NODES (generalised lymphadenopathy)

Question 14

Age range affected by CLL and gender more commonly affected?

Answer 14

Elderly >50

Twice as common in MALES

Question 15

What is CLL associated with?

Answer 15

Autoimmune haemolytic anaemia and ITP

Question 16

Staging of CLL?

Answer 16

Binet staging A, B &C
A: High WBC, <3 groups of enlarged lymph nodes
Usually no treatment needed
B: >3 groups of enlarged lymph nodes (consider treating)
C: Anaemia or thrombocytopenia (treat)

Question 17

What is richter syndrome?

Answer 17

Transformation of CLL to aggressive disease- diffuse large B cell lymphoma

Question 18

What is CLL?

Answer 18

A lymphoproliferative disease, neoplastic proliferation of naive B cells.

Question 19

Philadelphia chromosome negative myeloproliferative disorders?

Answer 19

Polycythemia vera
Myelofibrosis
Essential thrombocytosis

Question 20

What is essential thrombocythaemia?

Answer 20

A myeloproliferative disorderw here megakaryocytes dominate the bone marrow.

Question 21

Gene mutation associated with essential thrombocythaemia?

Answer 21

JAK2 mutation in 50%

Question 22

Clinical features of essential thrombocythaemia?

Answer 22

Venous and arterial thrombnosis & haemorrhage

Either platelets over functioning or not functioning.

Question 23

Blood film and bone marrow of myelofibrosis?

Answer 23

TEAR DROP POIKILOCYTES (DACROCYTE), LEUKOERYTHROBLASTIC SMEAR (tear drop RBCs, nucleated RBCs, immature granulocytes)
BM0 fibrosis, ‘dry tap’

Question 24

What is myelofibrosis?

Answer 24

A myeloproliferative disorder with fibrosis of bone marrow, reduced production of all cell lineages, pancytopenia.

Question 25

Mutation in myelofibrosis?

Answer 25

JAK2 present in 50%

Question 26

Clinical features of myelofibrosis?

Answer 26

Extramedullary haematopoieosis: MASSIVE SPLENOMEGALY, hepatomegaly, weight loss, fever

Question 27

Mutation in polycythaemia vera?

Answer 27

JAK2 MUTATION IN 95%!!!

Question 28

A secondary cause of polycythaemia?

Answer 28

Raised EPO- so disease state such as RENAL CELL CARCINOMA GET ECTOPIC EPO
High altitude, chronic hypoxia e.g. COPD

Question 29

Clinical features of polycythaemia rubra vera?

Answer 29

Blurred vision, headache
Thrombosis
Histamine release>aquagenic pruritis (itching after bathing)
Most common cause of Budd-chiari

Question 30

Investigation results for Polycythaemia vera?

Answer 30

Raised Hb

Raised haematocrit

Question 31

Treatment for polycythaemia rubra vera?

Answer 31

Venesection (reduces RBC mass)

Hydroxycarbamide to lower count

Question 32

Which Haem disorders present with MASSIVE splenomegaly?

Answer 32

CML and myelofibrosis

Both myeloproliferative disorders!

Question 33

What is tumour lysis syndrome?

Answer 33

Combination of metabolic and electrolyte abnormalities that occur in patients with cancer after initiation of cytotoxic treatment but also spontaneously. Characterised by excessive cell lysis resulting in HYPERURICAEMIA, HYPERPHOSPHATAEMIA, HYPERKALAEMIA and HYPOCALCAEMIA. Most common with LYMPHOMAS and LEUKAEMIAS, in particular BURKITT’s LYMPHOMA and ALL.