Chronic Myeloid Leukemia Flashcards
What is chronic myeloid leukemia
stem cell disease characterized by excessive accumulation of clonal myeloid (precursor) cells in hematopoietic tissues
What is the cause of CML
Translocation between chromosme 9 and 12 causing a fusion of BCR-ABL
What are the 3 phases of leukemia
Chronic or indolent phase, advanced phase, blastic phase
What percentage of people with CML are asymptomatic
40%
What are specific organ changes that may indicate CML
Increased size of spleen and liver
What are the three types of response to theapy for CML
Hematologic, cytogenetic, and molecular
What occurs in a hematologic response in CML
Normalization of peripheral blood counts (WBC less than 10k, platelets less than 450k, non-palpable spleen)
What occurs in a cytogenetic response in CML
Percentage of cells positive for the Philadelphia chromosome in a bone marrow biopsy (elimination of ph-positive cells)
What occurs in molecular response in CML
negative PCR result for BCR-ABL mRNA
What is the only performed cure of CML, when is it done
Allogenic bone marrow transplantation or stem cell transplantation/ Chronic stage (best in young patients)
What is the first drug to be used to treat CML
Imatinib
What are the 2nd generation TKIs for CML
Dasatinib, Nilotinib, Bosutinib
What is the 3rd generation TKI for CML
Ponatinib
What is the MOA of imatinib
Blocks ATP from binding BCR-ABL
What are the side effects of imatinib
Myelosuppression, diarrhea, musculoskeletal pain, rash, edema
What are the enzyme that most if not all TKIs must be aware of
CYP3A4 and 2C9
What are the 2nd generation TKIs that are known to cause QT prolongation
Dasatinib and Nilotinib
What are the adverse effects of using dasatinib, avoided
pleural effusions, myelosuppresion, pulmonary hypertension/ history of lung disease
What patients should avoid nilotinib
vaso-occlusive vascular disease, ischemic heart disease, peripheral artery occlusive disease, diabetes, pancreatitis
What are the side effects of nilotinib
myelosupppresion, qt pronlongation and pancreatitis
What are the side effects of using bosutinib
diarrhea, nausea, abdominal pain, vomitting
Why would a patient be given ponatinib
Overcome resistance to other TKIs due to BCR-ABLs mutations (T315I)
Which TKIs need to be taken with food
Imatinib and Bosutinib
Which TKIs can be taken with or without food
Dasatinib and Ponatinib
Which TKI should be taken on an empty stomach
Nilotinib
What are the TKIs that are most effected by PPIs antacids and H2RAs due to lessened exposure, only affected by PPIs
Bosutinib, Dasatinib, Nilotinib/ Ponatinib
Which TKI should not be used in patients with cardiovascular problems because QT prolongation arrhythmia risk, contraindicated with flouroquinolones
Nilotinib
What can be given for a pleural effusion
Steroids
If a patient has a low risk score chronic CML what are the primary treatment options
All of the 1st and 2nd generation TKIs
If a patient has a intermediate or high risk score for chronic CML what are the primary treatment options
All of the 2nd generation TKIs (Bosutinib, Dasatinib, Nilotinib)
T/F: If a patient has less than 1% BCR-ABL cells they have TKI sensitive disease no matter the time frame
True
If a patient has between 1 to 10% BCR-ABL cells at what time is there disease still considered TKI sensitive, possibly TKI resistant, TKI resistant
3 to 6 months, 12 months, greater than 15 months
If a patient has greater than 10% BCR-ABL cells when would it be consider that there possibly has TKI resistant, TKI resistant
3 months, 6 months and after
What are the options if a patient possibly has TKI Resistance/ has TKI resistance
Switch to alternate TKI OR continue same TKI (as long as its not imatinib) OR dose escalation (imatinib:800 mg) AND consider evaluation for allogenic HCT/ switch to alternate TKI AND evaluate for allogenic HCT
If a patient has advanced ACCELERATED phase CML what is the preferred treatment
All 2nd and 3rd generation TKIs
T/F: If a patient is in advanced BLAST phase CML it should be treated as acute leukemia
True
