Chapter 101 CML Flashcards
CML chimeric gene product
BCR-ABL1
Philadelphia chromosome
t(9;22)(q34.1;q11.2)
Phases of CML when untreated
Biphasic/triphasic
Early indolent or chronic phase
Accelerated phase
Terminal blastic phase
First BCR-ABL1 TKI approved in 2000
Imatinib mesylate
Criteria of accelerated-phase CML
Median survival <1.5 years
Presence of 15% or more peripheral blasts
30% or more peripheral blasts plus promyelocytes
20% or more peripheral basophils
Cytogenetic clonal evolution (presence if chromosomal abnormalities in addition to Ph)
Thrombocytopenia <100 x 10^9/L
Blastic-phase CML definition
Presence of 30% or more peripheral or marrow blasts or the presence of sheets of blasts in extramedullary disease
Commonly myeloid (60%)
Lymphoid markers of lymphoblasts in lymphoid blastic phase CML
CD10
CD19
CD20
CD22
Importance of identifying lymphoid blastic-phase CML
Quite responsive to anti-ALL-type chemotherapy (e.g. hyper-CVAD + TKIs)
6 agents approved by the US FDA for the treatment of CML
Imatinib Nilotinib Dasatinib Bosutinib Ponatinib
Omacetaxine
The only TKI active against T315I, a gatekeeper mutation resistant to the other oral TKIs
Ponatinib
Acceptable frontline therapies in CML
Imatinib
Nilotinib
Dasatinib
Approved for the treatment of chronic and accelerated phase CML after failure of two or more TKIs
Omacetaxine
Second generation TKIs
Dasatinib
Nilotinib
Bosutinib
Third generation TKI
Ponatinib
Imatinib dose
Imatinib 400mg daily
