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27 Cards in this Set
- Front
- Back
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What chromosome is diagnostic of CML?
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Philadelphia chromosome t (9,22)
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Philadelphia chromosome t (9,22) is diagnostic of what cancer?
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CML
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CML is associated with genetics
(true/false) |
False - no hereditary component
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CML is associated with chemical exposure
(true/false) |
False - no chemical exposure identified
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CML is associated with ionizing radiation
(true/false) |
True - higher incidences in locations that have suffered atomic disasters
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What are three (3) major signs/symptoms of CML?
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Thrombocytopenia
Splenomegaly Leukocytosis with a myeloid shift |
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The pathophysiology of CML is that it is proliferation of ______________________________________________________
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normal myeloid cells to blast crisis
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What are the phases of CML?
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Chronic phase
Accelerated phase (advanced) Blast crisis (advanced) |
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What white count would be considered blast crisis?
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200,000
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In blast crisis, where are more than 20% of blasts found?
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Peripheral blood
Bone marrow |
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What are the five (5) treatments for CML in the chronic phase?
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Oral TKIs
Busulfan Hydroxyurea Interferon-alpha HSCT |
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What is the mechanism of action of Imatinib (Gleevec)?
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TKI that binds the ABL tyrosine kinase in CML and inhibits it
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What are some toxicities associated with Imatinib (Gleevec?)
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Fluid retention
Myelosuppression (anemia, thrombocytopenia, neutropenia) Minor toxicities (nausea, muscle cramps, weight gain, rash, hepatic) |
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What are the drug interactions with Imatinib (Gleevec)?
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3A4 interactions
Acetaminophen CBZ Macrolides Dexamethasone Ketoconazole/itraconazole Phenytoin Warfarin |
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What are the two (2) second-generation TKIs?
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Dasatinib (Sprycel)
Nilotinib (Tasigna) |
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To what conformations of the ABL-kinase does dasatinib bind?
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Active and inactive conformations
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To what conformations of the ABL-kinase does nilotinib bind?
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Inactive form
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To what conformations of the ABL-kinase does imatinib bind?
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Active form
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Rank the potency of the TKIs used in CML
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Dasatinib > Nilotinib > Imatinib
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What mutation in the tyrosine kinase can prevent the TKIs from binding and working effectively?
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Threonine-315-isoleucine mutation
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What are the toxicities associated with dasatinib?
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Pleural effusions*
Superficial edema* Neutropenia, thrombocytopenia, anemia |
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What are some drug interactions associated with dasatinib?
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3A4 inhibitors*
Other interactions similar to imatinib |
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What are some drug interactions associated with nilotinib?
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3A4 inhibitors*
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Nilotinib interacts with what P450s?
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2C8, 2C9, and 2D6 inhibitor
(warfarin) |
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What are the four (4) special considerations with nilotinib?
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QT prolongation
Use in caution with hepatic impairment Elevations in lipase and amylase can occur (pancreatitis) Bilirubin and LFT elevations |
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What is the goal of treatment in advanced phase for CML?
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Return to chronic phase and reduce tumor burden prior to HSCT
(get white count down, stabilize disease) |
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Rank the TKIs in order of ascending cost
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Imatinib < Dasatinib < Nilotinib
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