Chronic myeloproliferative disorders (CML) General Info

Question 1

What cells are proliferating in chronic myeloproliferative disorders?

Answer 1

myeloid cells - NOT blasts, but maturing cells

Question 2

Who do chronic myeloproliferative disorders occur in?

Answer 2

only adults

Question 3

Do the chronic myeloproliferative disorders tend to have a long or short course?

Answer 3

long course

Question 4

What are the four chronic myeloproliferative disorders?

Answer 4

chronic myeloid leukemia
polycythemia vera
essential thromobocythemia
myelofibrosis

Question 5

What cell proliferates the most im CML?

Answer 5

neutrophils - with left shift

Question 6

What cells proliferate the most in polycythemia vera?

Answer 6

red cells

Question 7

What cells proliferate the most in essential thrombocythemia?

Answer 7

platelets in blood and megakaryocytes in bone marrow

Question 8

What cells proliferate the most in myelofibrosis?

Answer 8

trick question - they all proliferate. the key symptoms is that the bone marrow becomes fibrosis

Question 9

What’s the general underlying defect in all the chronic myeloproliferative disorders?

Answer 9

something goes wrong in a stem cell early in the pathway and it presents along the myeloid arm - so you get an increased WBC with left shift in all of them

Question 10

WHat type of protein is mutated in the chronic myeloproliferative disorders?

Answer 10

tyrosine kinases

Question 11

What organ typically is enlarged in the chronic myeloproliferative disorders?

Answer 11

the spleen

Question 12

CML presents with neutrophilia and an increase in what other blood cell?

Answer 12

basophilia (it’s baically the only thing that will cause this)

Question 13

What’s the chromosome in CML/

Answer 13

philadelphia chromosome

Question 14

Will hemoglobin be up or down in CML?

Answer 14

down

Question 15

What will platelet count do in CML?

Answer 15

go up initially, but as disease progresses it will decrease

Question 16

What is LAP? Is it up or down in CML and why?

Answer 16

It’s leukocyte alkaline phosphatase - expressed in healthy neutorphils, but not in malignant neutrophils

So you get a decrease in LAP in CML - it’s a way to differentiate the neutrophilia from CML and just a really bad infection with left shift

Question 17

What’s the best test for CML?

Answer 17

PCR for the philadelphia chromosome

Question 18

What are the symptoms of CML?

Answer 18

slow onset (often asymptomatic) fever, fatigue, night sweats, abdominal fullness

Question 19

What are the three phases of CML?

Answer 19

1. chronic phase
2. accelerated phase
3. blast crisis

Question 20

What are the characteristics of the chromic phase?

Answer 20

stable blood counts
easily controllable
usually 3-4 years if untreated

Question 21

What happens in the accelerated phase?

Answer 21

counts become rapidly unstable and you’re in blast crisis within 6-12 months

Question 22

What is blast crisis?

Answer 22

basically it switched to acute leukemia - super high mortality

Question 23

Why can people with CML in the blast phase develop and acute LYMPHOCYTIC leukemia?

Answer 23

because remember the defect is in a stem cell - the disease just seems to present in the myeloid arm until this stage

Question 24

What are the 3 levels of remission in CML?

Answer 24

hematologic remission (WBC less than 10,000, normal morphology, normal Hb, normal platelets, no splenomegaly)
Cytogenetic remission (no metaphases with T9:22)
Molecular remission (no BCR/ABL by PCR - this is the one you want)

Question 25

What are the major emergencies that can occur with polycythemia vera?

Answer 25

thrombosis and hemorrhage

Question 26

What's mutated in almost all cases of PV?

Answer 26

Jak-2

Question 27

WHat's the difference between a primary and secondary polycthemia vera?

Answer 27

primary - an intrinsic myeloid cell problem | secondary - due to increased erythropoietin due to some sort of O2 lack

Question 28

WHat are the diagnostic criteria for A (maor) PV?

Answer 28

increased red cell mass normal O2 saturation splenomegaly

Question 29

What are the B (minor) criteria for PV?

Answer 29

1. thrombocyosis 2. increased WBC without infection 3. increased LAP (unlike CML) 4. Increased B12 (we don't know why)

Question 30

What are the clinical symptoms and signs for PV?

Answer 30

headache, pruritis, dizziness, thrombosis, infarction, splenomegaly, hepatomegaly, plethora (the blood pools in the face and you look red)

Question 31

Is Jak-2 activity increased or decreased in PV?

Answer 31

increased - so the RBCs can proliferate on their own

Question 32

What are the main treatment goals for PV?

Answer 32

phlebotomy - you gotta get the bloo dout because it's so sludgy they'll die form thrombosis maybe myelosuppressive drugs

Question 33

What's the prognosis for PV?

Answer 33

9-14 years, death from thrombosis or hemorrhage

Question 34

What's high in essential thrombocythemia?

Answer 34

platelets in the blood, megakaryocytes in the bone marrow

Question 35

Who gets essential thrombocythemia?

Answer 35

yunng women can get it

Question 36

What are the diagnostic criteria for thrombocythemia (remember it's a diagnosis of exclusion)?

Answer 36

``` plateelet count over 600,000 Hb less than 13 or RBC mass normal no philadelphia chromosome no marrow fibrosis no othe rreason for thrombocytosis (because this is a super rare disorder) ```

Question 37

What are the clinical symptoms and signs of essential thrombocythemia?

Answer 37

bleeding (because the platelets don't work properly), thrombosis, purpura, bruising, pallor, tacchycardia, and enlarged spleen

Question 38

What's the treatment for essential thrombocythemia?

Answer 38

platelet pheresis and maybe myelosuppressive drugs | aspirin to avoid clotting

Question 39

What's the median survival of ET and what's the usual cause of death?

Answer 39

5-8 years - thrombosis or hemorrhage

Question 40

What's the main clinical feature of chronic myelofibrosis?

Answer 40

Panmyelosis (everything proliferates) and then the marrow becomes fibrotic

Question 41

What are the clinical signs and symptoms of chronic myelofibriosis?

Answer 41

left upper quadrant fullness | weakness, fatigue, palpitations, huge spleen (biggest of all these disorders), pallor, tachycardia

Question 42

What odd shape of RBCs can be seen in chronic myelofibrosis?

Answer 42

teardrop RBCs - because they have to pull their way out of the fibrotic bone marrow

Question 43

What's the teratment for chronic myelofibrosis?

Answer 43

supportive basically- maybe myelosuppressive drugs early on

Question 44

What's the prognosis in MF? cause of death?

Answer 44

3-5 years from marrow failure