Hematology Week 3: Chronic Myeloid Leukemia Flashcards
Case 1
- not acutely ill but borderline sick
- dx is often incidental, patients might not be that sick but can be an incidental finding
- Fatigue is a very common presentation
- Weight loss = splenomegaly pushing on the belly
- so early Satiety
Chronic Myeloid Leukemia
CML Blood Smear
3 listed
- WBC extremely high
- Abs Basophil count is very high
- very significant left shift
If only myeloblasts are proliferating?
Acute Myeloid Leukemia (AML)
If all myeloid lineages are proliferating?
Chronic Myeloid Leukemia (CML)
Immature Myeloid
Acute Myeloid Leukemia (AML)
Immature Lymphoid AKA
Acute Lymphoblastic Leukemia (ALL)
Mature Myeloid AKA
Chronic Myeloid Leukemia (CML)
Mature Lymphoid AKA
Chronic Lymphocytic Leukemia (CLL)
CML Phases
3 listed
- Chronic Phase
- Accelerated Phase
- Blast Phase
CML Accelerated Phase Diagnostic Criteria
7 listed
- 10-19% blasts in periphery or BM
- OR >20% basophils in periphery
- OR persistent thrombocytopenia (not treatment-related)
- OR Persistent thrombocytosis
- OR increasing WBC
- OR increasing splenomegaly
- OR all responsive to therapy
CML Blast Phase Diagnostic Criteria
3 Listed
- >20% blasts in the periphery or BM
- Clusters of blasts in BM
- Extramedullary blasts
CML Chronic Phase Diagnostic Criteria
2 listed
- <10% blasts in the periphery or BM
- often dx is incidental
Most CML is diagnosed in which phase?
chronic phase of CML
Without treatment chronic phase CML will progress to _____ in _____ years and transform into?
- Accelerated phase/Blast Phase in 3-5 years
- AML or ALL
Benign Leukemoid reaction blood smear shows
4 listed
- Increased WBC count <50x109
- mild left shift
- No basophilia
- Toxic changes are present (indicating response to infectious or inflammatory process)
% of cells in blood
- Leukemoid reaction - still neutrophil and band predominance, some metamyelocytes, few myelocytes and blasts are rare
- CML - the predominance of bands and neutrophils but there are more immature forms and a myelocyte bulge (have over predominance of myelocytes)
LAP Score
3 listed
- Historical test for boards
- Leukocyte alkaline phosphatase (LAP) Activity can be visualized in granulocytes by a special stain
- Indicates activation of neutrophils to fight off infection or inflammatory process
High overall LAP Score indicates?
activated neutrophils as seen in reactive neutrophilia
Low overall LAP Score indicates?
non-activated neutrophils more typical of CML
CML Vs Leukemoid Reaction
6 listed
- Leukemoid reaction has toxic changes seen by LAP score
- CML shows basophilia
- CML shows Myelocyte bulge pattern
- Leukemoid reaction shows clinical evidence of infection
- CML shows very high WBC count
- CML shows low LAP score
Key Genetic Finding in CML
3 listed
The Philadelphia Chromosome
t(9;22)(q34;q11.2)
BCR-ABL1 gene fusion
Philadelphia chromosome is tested for with?
FISH Test
The most common mutation associated with Myeloproliferative Neoplasms
Tyrosine Kinase Mutations
Abnormal BCR-ABL1 fusion protein
Overactive tyrosine kinase
Imatinib (Gleevec) MOA
- Block Overactive Tyrosine Kinase
- inhibits BCR-ABL1 protein and block activity
CML Treatment Prior to Imatinib
interferon/HSCT - high toxicity morbidity/mortality
Examples of other Tyrosine Kinase Inhibitors
5 listed
Other TKIs
- Dasatinib
- Nilotinib
- Bosutinib
- Ponatinib
- Imatinib
Imatinib Toxicities
3 listed
- Fluid retention
- Muscle pain/cramps
- GI disturbance
Dasatinib Toxicities
2 listed
- 20-25% pleural effusions
- rare pulmonary arterial hypertension
Nilotinib Toxicities
5 listed
- Vascular events
- peripheral arterial occlusive disease
- CAD
- Hyperglycemia
- hypercholesterolemia
Imatinib Complete Hematologic Response
5 listed
- normalizes CBC
- WBC <10
- Plts < 450
- no left shift
- disappearance of splenomegaly
Imatinib Cytogenetic Response
2 listed
- No Ph+ metaphases
- when karyotype is done t(9;22) won’t be found
Imatinib Molecular Response
2 listed
- complete - no detectable BCR-ABL mRNA by PCR
- Major -> 3 log reduction in BCR-ABL mRNA from baseline
Imatinib Relapse
- any loss of hematologic or cytogenetic response
- First check compliance
What to do if Imatinib relapse?
First check for compliance
1 reason for relapse of CML
Medication non-compliance
PCR detection of BCR-ABL1 fusion detection
Tests for BCR-ABL1
3 listed
- Karyotype to visualize translocation
- FISH
- PCR for BCR-ABL1
PCR BCR-ABL1 Transcripts
1000x Reduction in BCR-ABL1
Major molecular response
3 log Reduction in BCR-ABL1
Major Molecular Response
Question 1
D. It is associated with CML and CML is associated with basophilia
Leukemoid reaction is not associated with basophilia
Question 2
B No
- CML cannot be cured as of yet but BCR-ABL1 can be inhibited by Imatinib
- the cancerous cells aren’t eradicated but are prevented from proliferating
Question 3
- check for compliance
- however additional mutations can occur and TKI wont be able to inhibit now
- solution is switch to a different TKI
Nomenclature
- overlap in naming CML
- can be named a myeloproliferative neoplasm and a big 4 leukemia
Key Questions to answer
