Myleoproliferative neoplasms

Question 1

What are leukaemias?

Answer 1

Malignant diseases arising from bone marrow stem cells

Question 2

What are the risk factors for leukaemias?

Answer 2

Chromosomal abnormalities e.g. downs syndrome
Smoking
Ionising radiation
Chemicals
Preexisting myeloproliferative disorders

Question 3

What are the common leukaemias in the ages ranges <14, 40 to 60 and >60

Answer 3

<14 ALL
40-60 AML
>60 CLL

Question 4

What are the different blocks that occur in acute and chronic leukaemias?

Answer 4

In acute leukaemia the block is at an early stage in stem cell development
In chronic leukaemia the block is at a later stage in stem cell development

Question 5

What are the clinical findings in acute and chronic leukaemias?

Answer 5

Acute:
-Fever is common - indicates infection
-Bleeding from thrombocytopenia
-anaemia
-hepatosplenomegaly and painless lymphadenopathy (indicate metastasis)
-bone pain and tenderness from bone marrow expansion
Chronic:
-Insidious onset of signs and symptoms
-Hepatosplenamegaly
-Painless lymphadonopathy

Question 6

What are the labratory findings in acute and chronic leukaemias?

Answer 6

Acute:
-Raised white cell count
-Blast cells usually present
-Normocytic to macrocytic anaemia
-Thrombocytopenia
-Bone marrow shows hypercellular with blast cells
Chronic:
-Also raised cell count but cells show evidence of maturation
-Normocytic to macrocytic anaemia
-Thrombocytopenia - not as common in CML
-Bone marrow is hypercellular with less than 10% blast cell

Question 7

What are the four main types of chronic myeloproliferative disorder?

Answer 7

Polycythemia vera - RBC
Chronic myelogeneous leukaemia -WBC
Myelofibrosis with myeloid metaplasia - Fibroblasts
Essential thrombocytopenia - Platelets

Question 8

What are the general characteristics of myeloproliferative disorders?

Answer 8

Splenomegaly
Propensity for reactive bone marrow fibrosis
Propensity for transformation to acute leukaemia

Question 9

What are the two types of polycythemia?

Answer 9

Relative polycythemia - drop in blood volume means there is a greater concentration of RBCs, there is no increase in RBC production
Absolute polycythemia - increased production of RBCs from the bone marrow (usually from hypoxic stimulus)

Question 10

What is the pathogenesis of polycythemia vera?

Answer 10

Clonal expansion of myeloid stem cells due to JAK 2 mutation
This plays a role in haematopoesis signalling
This causes increased red cells, granulocytes, mast cells and platelets

Question 11

What are the clinical findings in polycythemia vera?

Answer 11

Hepatosplenomegaly
Ruddy face from congested vessels
Thrombotic events from hyperviscoity
Can get signs of impaired CNS circulation e.g. headaches
Gout - increased cell breakdown and purines
Signs of histamine release (pruritus after bathing)

Question 12

What are the lab findings and treatment of polycythemia vera?

Answer 12

Lab:
-Increased RBC
-Decreased EPO
-Hypercelllar bone marrow with fibrosis at later stages
Treatment:
-phlebotomy to reduce hyperviscocity
-hydroxyurea - prevents DNA replication and reduces cell division
-Interferon alpha 2b -stimulates bodys immune system against cancer

Question 13

What is the pathogenesis of chronic myelogeneous leukaemia?

Answer 13

Translocation of the ABL protooncogene to the BCR section on chromosome 22 causes clonal expansion of pluripotent stem cells

Question 14

What are the clinical and lab findings in chronic myelogeneous leukaemia?

Answer 14

Clinical:
-Generalised fatigue and weight loss
-Splenomegaly
-Painless lymphadenopathy
Lab:
-Increased WBC count with cells at all stages of maturation
-Normocytic to macrocytic anaemia
-Thrombocytosis
-Bone marrow hypercellular
-Philadelpha chromosome present in 95% of cases

Question 15

What are the treatments for chronic myelogeneous leukaemia?

Answer 15

Imatinib - oral tyrosine kinase inhibitor

Stem cell transplant only curative treatment

Question 16

What is the pathogenesis of myelofibrosis with myeloid metaplasia?

Answer 16

Mutation in the JAk2 gene leads to clonal myeloproliferation
Causes early onset marrow fibrosis
Haematopoesis moves to the spleen and liver

Question 17

What are the clinical findings and lab findings in mylefibrosis with myeloid metaplasia?

Answer 17

Clinical:
-Massive splenomegaly
-Splenic infarcts and pleural effusions
Lab:
-Bone marrow fibrosis
-Peripheral raised WBC
-normocytic anaemia - teardrop shaped RBCs

Question 18

What is the treatment for myelofibrosis with myeloid metaplasia?

Answer 18

Hydroxyurea

Interferon alpha

Question 19

What is Ruxolitinib?

Answer 19

An oral JAk inhibitor that can be used

Question 20

What is the pathogenesis and clinical findings in essential thrombocythenia?

Answer 20

Path:
-JAK2 mutation causes excess formation of dysfunctional platelets
Clinical:
-Bleeding most common finding
-thrombosis can also occur
-Splenomegaly

Question 21

What are the lab findings and treatment for essential thrombocythenia?

Answer 21

Lab:
-Thrombocytosis- platelet morphology is abnormal
-Bone marrow hypercellular with many megakaryocyte
Treatment:
-Hydroxyurea

Question 22

What is myeodysplasia?

Answer 22

Usually occurs in older people and causes bone marrow failure
Lab findings show a severe pancytopenia
Bone marrow shows finged sideroblasts