CML Module - Krafts Flashcards
Chronic leukemias involve:
More mature lymphocytes
What things must you know about chronic myeloproliferative disorders?
- Malignant proliferation of myeloid cells (not blasts, but maturing cells) in blood, bone marrow [not blocked at a certain stage]
- Four disorders: CML, PV, ET, MF
- Occur only in adults
- Long course (could live a few years without treatment)
What are the names of the two chronic leukemias?
These are not benign, they’re leukemias!!
- Chronic myeloproliferative disorders (four)
- Chronic lymphoproliferative disorders
What are the four chronic myeloproliferative disorders?
- Chronic myeloid leukemia (neutrophils predominating)
- Polycythemia vera (red cells predominating)
- Essential thrombocytopenia (not throbocytosis! - megakaryocytic/platelet predominating)
- Myelofibrosis (everything proliferating same amount, then it becomes fibrinoid)
What is unique about chronic myeloproliferative disorders?
-They include mostly mature cells, but can also include some of the lesser developed upper cells in the myeloid lineage
What is proliferating most in the myeloproliferative disorders?
- CML - neutrophils
- PV - red cells
- ET - platelets
- MF - everything!
What features are common to all four myeloproliferative disorders?
- Occur only in adults
- Long clinical course
- Inc. WBC with left shift (usually seen in routine CBC)
- Hypercellular marrow
- Big spleen
- May evolve into acute leukemia (almost all of these - as an end stage event, process changes from chronic to acute)
- Mutated tyrosine kinases (CML and other myeloproliferative disorders - mutated thing telling itself to grow all the time)
What MUST you know about Chronic Myeloid Leukemia? (EXAM!!)
- Neutrophilic leukocytosis
- Basophilia
- Philadelphia chromosome (EXAM!!)
- Three phases
What do you see in slides of CML?
- Abundant mature neutrophils
- Some myelocytes, promyelocytes, blasts
- BASOPHILIA - multiple basophils in a field
- Hypercellular
What are the laboratory findings in CML?
- VERY HIGH WBC count (from malignant cells)
- Neutrophilia with left shift (more malignant early cells)
- Basophilia
- Low hemoglobin
- High platelet count (at first) (malignant platelets, normal platelets are decreased in number)
- Dec. LAP (leukocyte alkaloid phosphatase - enzyme present in neutrophils - if bening, LAP should be increased)
What chromosomal abnromalities are found in CML?
- Translocation between chromosome 9 and 22
- Chromosome 22 - Philidelphia chromosome - where the action happens
- BCR-ABL hybrid gene –> tyrosine kinase
What are the clinical findings (symptoms & signs) in CML?
Symptoms (release of enzymes makes patients sick: fever, night sweats from too many cytokines!): -Slow onset -Fever, fatigue, night sweats -Abdominal fullness Signs: -Big spleen -Big liver
What is the chronic phase of CML like?
Most patients present with this, but how they pass through the phases is random in timeline and length
- Stable counts
- Marrow full of cells
- Neutrophil series
- Hemoglobin decreased, platelets up
- Easily controlled (with drugs)
- 3-4 years (untreated)
What is the accelerated phase of CML?
50% of chronic phase patients go onto accelerated phase.
- Unstable counts
- Blast crisis within 6-12 months
- Things are changing quickly
- Not much you can do for patient
- Patients usually die in this phase or when they go into blast crisis
What is the blast crisis phase of CML?
50% of chronic phase patients do onto blast phase. It is extremely difficult to treat and patient likely dies in a month or so.
- Acute leukemia
- More than 20% blasts in blood
- Blasts can be either myeloid or lymphoid!
- High mortality
What is CML remission like?
Hematologic Remission
- No splenomegaly
- WBC extremely sensitive
What MUST you know about Polycythemia Vera?
- High RBC (makes blood sludgy)
- Different from secondary polycythemia
- Thrombosis and hemorrhage
- Jak-2 mutation
What are the types of Polycythemia Vera? (EXAM!?)
“Polycytemia” = Inc. red cell mass
- Primary (intrinsic myeloid cell problem - low erythropoietin)
- Secondary (due to increased erythropoietin)
What are the clinical findings in PV?
Symptoms -Headache, pruritis, dizziness -Thrombosis, infarction (clotting and bleeding tendency - something wrong with platelets and the way they interact) Signs -Big spleen, liver -Plethora (flushing of face and neck)
What does Polycythemia Vera look like on a slide?
- Red cells are right next to each other/on top of each other
- Bone marrow is hyper cellular
- Erythroid series is predominant
What is different about the JAK-2 in PV?
Normal JAK-STAT pathway --Cell signaling pathway --Important in many different cell types JAK-STAT in PV --Mutated JAK-2; activity increased in PV (JAK activating STAT all the time) --Cells grow on their own -Important for diagnosis and drug therapy -95% of PV have this mutation
What is the treatment for PV?
- Phlebotomy
- Maybe myelosuppressive drugs
What is the prognosis for PV?
- Median survival: 9-14 years
- Death from thrombosis or hemorrhage
- Leukemic transformation in some patients
What things MUST you know about essential thrombocythemia?
- Very high platelet count in blood
- Can occur in young women (still adults) - many other diseases peak in 50s or 60s
- Diagnosis of exclusion
- Thrombosis and hemorrhage
What is the diagnostic criteria for ET?
- Need to make sure platelet count is REALLY HIGH
- Platelet count >600,000
- Hgb
What are the clinical features of ET?
Symptoms: -Bleeding -Thrombosis Signs -Purpura, bruising -Pallor, tachycardia -Biggish spleen
What do you see in the slide (blood) and bone marrow of essential thrombocythemia?
- Lots of platelets here
- Hypercellular bone marrow
What is the treatment of ET?
- Platelet pheresis
- Maybe myelosuppressive drugs
- Aspirin
What is the prognosis of ET?
- Median survivial: 5-8 years
- Death from thrombosis or hemorrhage
- Leukemic transformation in some patients
What things MUST you know about Chronic Myelofibrosis?
- Panmyelosis. . . (all myeloid lines are proliferating at once)
- . . .then marrow fibrosis
- Extramedullary hematopoiesis (VERY MASSIVE FOR CM)
- Teardrop red cells
What are the clinical findings in MF?
Symptoms: -Left upper quadrant fullness -Weakness, fatigue, palpitations Signs: -Huge spleen -Pallor, tachycardia
What do you see in bone marrow of Chronic myelofibrosis?
Hypercellular, swooshy, compact
-LOTS OF RETICULAR FIBERS
What does chronic myelofibrosis look like in the blood?
Teardrop shaped red cells!
-Cells become transformed when moving through blood stream
What is the treatment for MF?
- Supportive
- Maybe myelosuppressive drugs (early on)
What is the prognosis for MF?
- Median survival: 3-5 years
- Death from marrow failure
- Leukemic transformation in some patients
In a patient with high WBC with a left shift, hyper cellular marrow, and splenomegaly:
- Is it CML? (Ph’)
- Is it PV? (criteria - headaches, flushing, dizziness, clotting & bleeding, etc.)
- Is it MF? (fibrosis - in bone marrow)
- Is it ET? (thromobcytosis)
- If not, it’s “MPD not otherwise specified”
