CML Module 5/15/14 Flashcards
What sort of cells would you find in CML
Mature cells + left shift in neutrophil series but not a whole lot of blasts.
CML disorder of stem cells. Stem cell before myeloid/lymphoid progenitors even.
Chronic Myeloproliferative Disorders things you must know
- Malignant proliferation of myeloid cells (not blasts, but maturing cells) in blood, bone marrow
- Four disorders: CML, PV, ET, MF
- Occur only in adults***
- Long course
What is proliferating the most?
CML–neutrophils
PV–red cells
ET–platelets
MF–everything
Features common to all 4 disorders
- Occur only in adults***
- Long clinical course
- Increased WBC with left shift (not a huge left shift where you only see blasts. May see a couple.)
- Hypercellular marrow
- Big spleen (extra medullary hematopeoisis)
- May evolve into acute leukemia (can acquire additional genetic abnormalities)(when happens usually a terminal event)
- Mutated tyrosine kinases
CML things you must know
- Neutrophilic leukocytosis
- Basophilia
- Philadelphia chromosome
- Three phases
Laboratory findings in CML
- Dramatically increased WBC
- Neutrophilia with left shift
- Basophilia
- Decreased hemoglobin
- Increased platelet count (at first)
- Decreased LAP (neutrophil/leukocyte alkaline phosphatase)(enzyme present in neutrophils)(in CML malignant neutrophils they don’t make LAP).
CML genetics
t(9:22)
9 doesn’t really do mud.
New chromosome 22 you end up w/ hybrid gene that makes nasty/super active tyrosine kinase.
Clinical findings in CML
Symptoms
- slow onset
- fever, fatigue, night sweats
- abdominal fullness (dragging sensation d/t huge spleen)
Signs
- huge spleen
- big liver
- maybe some lymphadenopathy
Phases of CML
Chronic phase
- stable counts
- easily controlled
- 3-4 years (untreated)
Accelerated phase (50%)
- unstable counts
- blast crisis within 6-12 months
Blast crisis (50%)
- acute leukemia (ironically many get acute lymphoblastic leukemia because the initial pathogenetic problem happens in stem cell that hasn’t even decided myel v. lym progenitor series)
- high mortality
Remission
Hematologic remission
- no splenomegaly
- WBC <10,000, normal morphology
- normal HgB, platelet count
Cytogenetic remission
-no metaphases w/ t(9;22)
Molecular remission (most sensitive) -No BCR/ABL transcripts by PCR
Polycythemia Vera things you must know
High RBC (makes blood sludgy)
Different from secondary polycythemia
Thrombosis and hemorrhage
Jak-2 mutation
Polycythemia Vera general info
“Polycythemia”=increased red cell mass (other reasons exist for increased red cell besides PV such as living at high altitude etc)
Primary (intrinsic myeloid cell problem)
Secondary (d/t increased erythropoietin)
Diagnostic criteria for PV
A (major criteria) (A1 and A2 required but mixture of others)
A1 increased red cell mass
A2 normal O2 saturation
A3 splenogmegaly
B (minor) criteria
B1 thrombocytosis
B2 increased WBC w/o infection
B3 increased LAP (not a typo even though not the case in CML)
B4 increaed B12
Clinical findings in PV
Signs
- HA, pruritis (possibly d/t basophils), dizziness
- thrombosis (so many red cells around), infarction
Sx
- big spleen, liver
- plethora (red face)
JAK-2 in PV
Normal JAK-STAT pathway (don’t need second messenger)
- cell signaling pathway
- important in many different cell types
JAK-STAT in PV
- Mutated JAK-2: activity increased in PV (inhibited inhibitor)
- Cells grow on their own
-Important for diagnosis and drug therapy
Tx and prognosis of PV
Tx
- Phlebotomy
- Maybe myelosuppressive drugs
Prognosis
- Median survival: 9-14 years
- Death from thrombosis or hemorrhage
- Leukemic transformation in some patients
Essential Thrombocytopenia things you must know
Very high platelet count
Can occur in young women (30’s but still not in kids)***
Diagnosis of exclusion
Thrombosis and hemorrhage
Diagnostic criteria for ET
platelet count >600,000 (normal up to 450,000)
HgB <13 (not high) or RBC mass normal (these criteria needed to rule of PV)
No Philadelphia chromosome (rule out CML)
No marrow fibrosis (rule out chronic myelofibrosis)
No other reason for thrombocytosis
Clinical features of ET
Sx
- bleeding (platelets aren’t working correct or sometimes get a secondary bleeding disorder)
- thrombosis (makes sense w/ high platelet count)
Signs
- purpura, bruising
- pallor, tachycardia
- biggish spleen
Treatment and prognosis of ET
Tx
- platelet pheresis
- maybe myelosuppressive drugs
- aspirin
Prognosis
- median survival: 5-8 years
- death from thrombosis or hemorrhage
- leukemic transformation in some patients
Chronic Myelofibrosis
Panmyelosis…
…then marrow fibrosis (probably megakaryocytic releasing fiber type stuff)
extramedullary hematopoiesis (can have large spleen)
teardrop red cells (typical but not exclusive to MF)
Clinical findings in MF
Sx
- left upper quadrant fullness
- weakness, fatigue, palpitations
Signs
- huge spleen (would have biggest spleen out of the four diseases)
- pallor, tachycardia
Treatment and prognosis of MF
Tx
- supportive
- maybe myelosuppressive drugs (early on)
Prognosis
- median survival: 3-5 years
- death from marrow failure
- leukemic transformation in some patients
Summary
In a patient with a high WBC with a left shift, a
hypercellular marrow, and splenomegaly:
- Is it CML? (Ph’)
- Is it PV? (criteria)
- Is it MF? (fibrosis)
- Is it ET? (thrombocytosis)
- If not, “MPD not otherwise specified”
