CML Module - Krafts Flashcards

1
Q

Chronic leukemias involve:

A

More mature lymphocytes

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2
Q

What things must you know about chronic myeloproliferative disorders?

A
  • 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)
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3
Q

What are the names of the two chronic leukemias?

A

These are not benign, they’re leukemias!!

  1. Chronic myeloproliferative disorders (four)
  2. Chronic lymphoproliferative disorders
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4
Q

What are the four chronic myeloproliferative disorders?

A
  1. Chronic myeloid leukemia (neutrophils predominating)
  2. Polycythemia vera (red cells predominating)
  3. Essential thrombocytopenia (not throbocytosis! - megakaryocytic/platelet predominating)
  4. Myelofibrosis (everything proliferating same amount, then it becomes fibrinoid)
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5
Q

What is unique about chronic myeloproliferative disorders?

A

-They include mostly mature cells, but can also include some of the lesser developed upper cells in the myeloid lineage

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6
Q

What is proliferating most in the myeloproliferative disorders?

A
  • CML - neutrophils
  • PV - red cells
  • ET - platelets
  • MF - everything!
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7
Q

What features are common to all four myeloproliferative disorders?

A
  • 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)
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8
Q

What MUST you know about Chronic Myeloid Leukemia? (EXAM!!)

A
  • Neutrophilic leukocytosis
  • Basophilia
  • Philadelphia chromosome (EXAM!!)
  • Three phases
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9
Q

What do you see in slides of CML?

A
  • Abundant mature neutrophils
  • Some myelocytes, promyelocytes, blasts
  • BASOPHILIA - multiple basophils in a field
  • Hypercellular
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10
Q

What are the laboratory findings in CML?

A
  • 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)
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11
Q

What chromosomal abnromalities are found in CML?

A
  • Translocation between chromosome 9 and 22
  • Chromosome 22 - Philidelphia chromosome - where the action happens
  • BCR-ABL hybrid gene –> tyrosine kinase
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12
Q

What are the clinical findings (symptoms & signs) in CML?

A
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
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13
Q

What is the chronic phase of CML like?

A

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)
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14
Q

What is the accelerated phase of CML?

A

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
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15
Q

What is the blast crisis phase of CML?

A

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
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16
Q

What is CML remission like?

A

Hematologic Remission

  • No splenomegaly
  • WBC extremely sensitive
17
Q

What MUST you know about Polycythemia Vera?

A
  • High RBC (makes blood sludgy)
  • Different from secondary polycythemia
  • Thrombosis and hemorrhage
  • Jak-2 mutation
18
Q

What are the types of Polycythemia Vera? (EXAM!?)

A

“Polycytemia” = Inc. red cell mass

  • Primary (intrinsic myeloid cell problem - low erythropoietin)
  • Secondary (due to increased erythropoietin)
19
Q

What are the clinical findings in PV?

A
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)
20
Q

What does Polycythemia Vera look like on a slide?

A
  • Red cells are right next to each other/on top of each other
  • Bone marrow is hyper cellular
  • Erythroid series is predominant
21
Q

What is different about the JAK-2 in PV?

A
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
22
Q

What is the treatment for PV?

A
  • Phlebotomy

- Maybe myelosuppressive drugs

23
Q

What is the prognosis for PV?

A
  • Median survival: 9-14 years
  • Death from thrombosis or hemorrhage
  • Leukemic transformation in some patients
24
Q

What things MUST you know about essential thrombocythemia?

A
  • 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
25
What is the diagnostic criteria for ET?
- Need to make sure platelet count is REALLY HIGH - Platelet count >600,000 - Hgb
26
What are the clinical features of ET?
``` Symptoms: -Bleeding -Thrombosis Signs -Purpura, bruising -Pallor, tachycardia -Biggish spleen ```
27
What do you see in the slide (blood) and bone marrow of essential thrombocythemia?
- Lots of platelets here | - Hypercellular bone marrow
28
What is the treatment of ET?
- Platelet pheresis - Maybe myelosuppressive drugs - Aspirin
29
What is the prognosis of ET?
- Median survivial: 5-8 years - Death from thrombosis or hemorrhage - Leukemic transformation in some patients
30
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
31
What are the clinical findings in MF?
``` Symptoms: -Left upper quadrant fullness -Weakness, fatigue, palpitations Signs: -Huge spleen -Pallor, tachycardia ```
32
What do you see in bone marrow of Chronic myelofibrosis?
Hypercellular, swooshy, compact | -LOTS OF RETICULAR FIBERS
33
What does chronic myelofibrosis look like in the blood?
Teardrop shaped red cells! | -Cells become transformed when moving through blood stream
34
What is the treatment for MF?
- Supportive | - Maybe myelosuppressive drugs (early on)
35
What is the prognosis for MF?
- Median survival: 3-5 years - Death from marrow failure - Leukemic transformation in some patients
36
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"