Chronic Myeloproliferative Disorders (MPD)

Question 1

definition of Myeloproliferative disorder?

Answer 1

the name for a group of conditions that cause platelets, granulocytes, and red blood cells, to grow or multiply by rapidly producing new tissue, parts, cells or offspring

they are clonal haemopoietic stem cell disorder with inc production of one or new types of haemopoitic cells

Question 2

difference between MPD and AL?

Answer 2

maturation is preserved in MPD

Question 3

subtypes of MPD

• what gene is not found in other MPD but found in CML?
• give the 3 subtypes of MPD which do not have the gene present in CML?

Answer 3

-BCR-ABL1 positive

-Idiopathic myelofibrosis(fibrosis and scarring in BM)
Polycthaemia Rubra Vera (overproduction of RBCs)
Essential Thrombocythaemia (overproduction of platelets)
CML

Question 4

When should MPD be considered clinically? (6)

Answer 4

High granulocyte count +/-
High RBC/Hb count +/-
High platelet count +/-
Eosinophilia/basophilia
Splenomegaly
Thrombosis in an unusual place 
ONLY IF NO REACTIVE EXPLANATION

Question 5

Chronic Myeloid Leukaemia

• what is it?
• describe the disease progression? (2)
• clinical features?
• changes seen on FBC?
• treatment
• what chromosome is seen, how does it occur? what gene is formed? what is the product of this gene and how can it be managed?

Answer 5

-proliferation of Myeloid cells
(granulocytes and precursors and other lineages (platelets)

-Chronic phase- with intact maturation for 3-5 years
Blast crisis- reminiscent of acute leukaemia with maturation defect

-Asymptomatic
Splenomegaly 
Hyper metabolic symptoms
Gout
hyperleukocytosis problems, Priapism (erect penis does not return to normal state)

-Hb Normal/dec
Leucocytosis 
neutrophilia 
myeloid precursors (myelocytes) 
Eosinophilia 
Basophilia 
Thrombocytosis 

-fatal without a BM tranplant in chronic phase

-Philadelphia chromosome
reciprocal translocation from chromosome 9 to 22
forms the BCR-ABL1 gene
gene product is tyrosine Kinase causing abnormal phosphorylation and changes seen in CML
use tyrosine kinase inhibitors e.g. Imatinib to manage

Question 6

give the 5 features common to MPD?

Answer 6

Asymptomatic

increased cellular turnover (gout, fatigue, weight loss, sweats)

Symptoms/signs due to splenomegaly

Marrow failure (fibrosis or leukaemia transformation: lower with PRV and ET)

Thrombosis (TIA, MI, abdo vessel thrombosis, claudication, erythromelalgia)

Question 7

Polycythaemia rubra vera (PRV)

• What is it?
• what must it be distinguished from? (2)
• clinical features? (3)
• investigations? (4)
• what mutation is commonly found in PRV
• treatment? (3)

Answer 7

-high Hb/haematocrit accompanied by erythrocytosis i.e. true increased RBC mass
can have excess production of other lineages

-Secondary Polycythaemia
(chronic hypoxia, smoking, EPO tumour)
Pseudopolycythaemia
(dehydration, diuretic therapy, obesity)

-features of MPD
Headache, fatigue
Itch- aquagenic pruritus

-Hx
Examination- splenomegaly 
FBC, Film
JAK2 mutation status  
rarely EPO levels and BM

-JAK2, a kinase
causes loss of auto-inhibition and activation of erythropoiesis in the absence of ligand

-Vensect to haematocrit <0.45 (be aware of splenomegaly risk)
Aspirin
cytotoxic oral chemo e.g. hydroxycarbamide

Question 8

Essential thrombocythaemia (ET)

• What is it?
• clinical features?
• diagnosis-what must be excluded?
• investigations? (3)
• treatment? (2)

Answer 8

-uncontrolled production of abnormal platelets

-MPD features (esp vasoocclusive complications)
abnormal platelet function characterised by thrombosis and bleeding due to acquired Von Willebrand disease

-exclude reactive
thromobocytosis (due to blood loss, inflammation, malignancy & iron deficiency), CML

-JAK2 mutation and MPL mutation
characteristic BM appearance- megakaryocyte hyperplasia

-Anti platelet agents (Aspirin)
Cytoreductive therapy to control proliferation (hydroxycarbamide, anagrelide, interferon alpha)

Question 9

Myelofibrosis

• name the 2 types
• name the 5 cardinal features of MF?
• describe the clinical features (3)
• investigations & Dx? (4)
• treatment? (4)

Answer 9

-Idiopathic
Post-polycythaemia or essential thrombocythaemia

-Marrow failure
BM fibrosis
extra medullary haematopoiesis (liver & spleen)
Leukoerythroblastic film appearance
Teardrop shaped RBCs in peripheral blood

-marrow failure 
(anaemia, bleeding, infection)
Splenomegaly 
(LUG abdo pain, early satiety, portal hypertension)
hypercatabolism 

-blood film- typical leucoerythroblastic appearance and tear shaped RBCs
BM- dry aspirate needed due to fibrosis, fibrosis on trephine biopsy
Genetic screen- JAK2 or CALR mutation in a proportion
FBC- high platelet count + anaemia

-supportive care 
(blood transfusion, platelets, antibiotics)
Allogenic stem cell transplantation 
(if under 50 & fit)
Splenectomy 
??
JAK2 inhibitors e.g. ruxolitinib
(improve spleen size)

Question 10

causes of a leucoerythroblastic blood film? (3)

Answer 10

reactive in sepsis

Marrow infiltration

Myelofibrosis

Question 11

Give the reactive causes of raised counts of the following cells:

• Granulocytes
• Platelets
• Red cells

Answer 11

-infection e.g. pyogenic bacteria causing nuetrophilia
physiological e.g. post op/ steroids

-infection
Fe def
Malignancy
Blood loss

-Dehydration (diuretics): pseudopolycythaemia
Secondary polycythaemia e.g. hypoxia induced