Chronic Myeloproliferative Disorders

Question 1

Describe the Pathogenesis of Chronic myelogenous leukemia… (Age, chromosome)

Answer 1

Age: 20-50 yrs
Marked neutrophil leukocytosis
90-95% Ph chromosome (forms BCR-ABL hybrid gene)
Inc tyrosine kinase activity (prevents apoptosis)

Question 2

Describe the clinical features/symptoms of CML

Answer 2

Can be asymptomatic 
Fatigue
Weight loss
Low grade fever
Normocytic/normochromic
Night sweats
Splenomegaly 
3 phases: chronic, accelerated, blast/acute

Question 3

What is needed to be diagnosed as having CML?

Answer 3

Severe leukocytosis
Inc eosinophils & basophils
Bone marrow hyperplasia, can be fibrotic
M:E ratio: 25:1

Question 4

What are the treatments for CML?

Answer 4

Myelosuppresive therapy
Leukopheresis
Allogenic bone marrow transplant

Question 5

Describe the pathogenesis of PV?

Answer 5

Age: 60-70
Hyper cellular bone marrow w/ hyperplasia
Overproduction of nature RBCS WBCS & PLTS
Inc Hgb, HCT & RBC Mass (inc blood viscosity)
90% have JAK2 mutation

Question 6

Describe the clinical features of PV

Answer 6

(Most things that inc red cell mass)
Hypertension, hyperviscosity, vascular abnormalities
Headache, blurred vision, fatigue, plethora
Thrombosis
Abnormal platelet function
Inc Blood cell turnover (hyperuricemia, gout, stomach ulcers)
Hepatomegaly & splenomegaly

Question 7

What is the diagnosis criteria for PV?

Answer 7

Inc in all 3 cell lines
Retic count slightly inc 
Inc RDW
neutrophilia & basophilia
Elevated LAP score
Microcytes, elliptocytes, TDS

Question 8

What is the pathogenesis of IMF?

Answer 8

Bone marrow fibrosis, proliferation of megakaryocytic & granulocytic cells & extramedullary hematopoiesis
Absence of Ph chromosome

Question 9

What are the symptoms of IMF

Answer 9

Splenomegaly
Marrow fibrosis
Pancytopenia
Osteosclerosis

Question 10

What is the criteria for having IMF

Answer 10

Inc platelet count, WBC inc then dec
Inc bone marrow cellularity, 50% dry tap
TDS

Question 11

What is the treatment for IMF

Answer 11

No treatments to reverse process
Hydroxyurea
Splenectomy
Allogenic peripheral stem cell or bone marrow transplant
IMF had worst prognosis (3-5 yr survival)

Question 12

What is the pathogenesis of ET

Answer 12

Clonal disorder of multi potential stem cells
Main inc in megakaryocytes
Inc in PLT production due to hypersensitivity of megakaryocytes to cytokines & thrombopoietin

Question 13

What is the criteria for ET

Answer 13

Unexplained elevated PLT count
Megakaryocytic hyperplasia
Absence of Ph chromosome