Chronic myeloproliferative disorders (CML) General Info Flashcards
What cells are proliferating in chronic myeloproliferative disorders?
myeloid cells - NOT blasts, but maturing cells
Who do chronic myeloproliferative disorders occur in?
only adults
Do the chronic myeloproliferative disorders tend to have a long or short course?
long course
What are the four chronic myeloproliferative disorders?
chronic myeloid leukemia
polycythemia vera
essential thromobocythemia
myelofibrosis
What cell proliferates the most im CML?
neutrophils - with left shift
What cells proliferate the most in polycythemia vera?
red cells
What cells proliferate the most in essential thrombocythemia?
platelets in blood and megakaryocytes in bone marrow
What cells proliferate the most in myelofibrosis?
trick question - they all proliferate. the key symptoms is that the bone marrow becomes fibrosis
What’s the general underlying defect in all the chronic myeloproliferative disorders?
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
WHat type of protein is mutated in the chronic myeloproliferative disorders?
tyrosine kinases
What organ typically is enlarged in the chronic myeloproliferative disorders?
the spleen
CML presents with neutrophilia and an increase in what other blood cell?
basophilia (it’s baically the only thing that will cause this)
What’s the chromosome in CML/
philadelphia chromosome
Will hemoglobin be up or down in CML?
down
What will platelet count do in CML?
go up initially, but as disease progresses it will decrease
What is LAP? Is it up or down in CML and why?
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
What’s the best test for CML?
PCR for the philadelphia chromosome
What are the symptoms of CML?
slow onset (often asymptomatic) fever, fatigue, night sweats, abdominal fullness
What are the three phases of CML?
- chronic phase
- accelerated phase
- blast crisis
What are the characteristics of the chromic phase?
stable blood counts
easily controllable
usually 3-4 years if untreated
What happens in the accelerated phase?
counts become rapidly unstable and you’re in blast crisis within 6-12 months
What is blast crisis?
basically it switched to acute leukemia - super high mortality
Why can people with CML in the blast phase develop and acute LYMPHOCYTIC leukemia?
because remember the defect is in a stem cell - the disease just seems to present in the myeloid arm until this stage
What are the 3 levels of remission in CML?
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)
What are the major emergencies that can occur with polycythemia vera?
thrombosis and hemorrhage
What’s mutated in almost all cases of PV?
Jak-2
WHat’s the difference between a primary and secondary polycthemia vera?
primary - an intrinsic myeloid cell problem
secondary - due to increased erythropoietin due to some sort of O2 lack
WHat are the diagnostic criteria for A (maor) PV?
increased red cell mass
normal O2 saturation
splenomegaly
What are the B (minor) criteria for PV?
- thrombocyosis
- increased WBC without infection
- increased LAP (unlike CML)
- Increased B12 (we don’t know why)
What are the clinical symptoms and signs for PV?
headache, pruritis, dizziness, thrombosis, infarction, splenomegaly, hepatomegaly, plethora (the blood pools in the face and you look red)
Is Jak-2 activity increased or decreased in PV?
increased - so the RBCs can proliferate on their own
What are the main treatment goals for PV?
phlebotomy - you gotta get the bloo dout because it’s so sludgy they’ll die form thrombosis
maybe myelosuppressive drugs
What’s the prognosis for PV?
9-14 years, death from thrombosis or hemorrhage
What’s high in essential thrombocythemia?
platelets in the blood, megakaryocytes in the bone marrow
Who gets essential thrombocythemia?
yunng women can get it
What are the diagnostic criteria for thrombocythemia (remember it’s a diagnosis of exclusion)?
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)
What are the clinical symptoms and signs of essential thrombocythemia?
bleeding (because the platelets don’t work properly), thrombosis, purpura, bruising, pallor, tacchycardia, and enlarged spleen
What’s the treatment for essential thrombocythemia?
platelet pheresis and maybe myelosuppressive drugs
aspirin to avoid clotting
What’s the median survival of ET and what’s the usual cause of death?
5-8 years - thrombosis or hemorrhage
What’s the main clinical feature of chronic myelofibrosis?
Panmyelosis (everything proliferates) and then the marrow becomes fibrotic
What are the clinical signs and symptoms of chronic myelofibriosis?
left upper quadrant fullness
weakness, fatigue, palpitations, huge spleen (biggest of all these disorders), pallor, tachycardia
What odd shape of RBCs can be seen in chronic myelofibrosis?
teardrop RBCs - because they have to pull their way out of the fibrotic bone marrow
What’s the teratment for chronic myelofibrosis?
supportive basically- maybe myelosuppressive drugs early on
What’s the prognosis in MF? cause of death?
3-5 years from marrow failure
