CML TREATMENTS Flashcards
alkylating agents
nitrogen mustard
busulfan
Increasing the frequency of long-term patient survival, especially when combined with cytarabine.
Interferon-a
inducing the suppression of the Ph chromosome
Reducing the rate of cellular progression to blast cells
Interferon-a
Interferon-a can be combined with
Cytarabine
(autologous or allogeneic HSCs) were the best hope of cure, especially in patients younger than age 55.
Bone marrow transplantation
BM transplant
Optimal survival occured when the patient was treated during the chronic phase within 1 year of diagnosis and was younger than age_______
50
- bind the abnormal BCR::ABL1 protein
- Blocking the constitutive tyrosine kinase activity and reducing signal transduction activation.
TKI
- Current first-line therapy
TKI
- first synthetic TKI designed to selectively bind the ATP binding site and thus inhibit the tyrosine kinase activity of the BCR::ABL1 fusion protein.
Imatinib mesylate
• Goals of therapy includes:
complete hematologic, cytogenetic, and molecular remission
normalized CBC and differential
absence of Ph chromosome by karyotype analysis
absence of measurable BCR::ABL1 transcripts.
IMATINIB
Goals of imatinib
complete hematologic, cytogenetic, and molecular remission
normalized CBC and differential
absence of Ph chromosome by karyotype analysis
absence of measurable BCR::ABL1 transcripts.
is reactivation of apoptotic pathways
Complete remission
-measure of the effectiveness: the number of log reductions of BCR::ABL1 transcripts by
RT-PCR.
IMATINIB
Limitation: development of RESISTANCE resulting in relapse.
______.- Inability to reach the remission milestones (most treatment failures)
______- loss of a previous response
Primary
Secondary
> It is effective against all imatinib-resistant mutants (except the T315| mutation):
first-line therapy imatinib therapy unless the T315l mutation has been identified
• DASATINIB
> binds the ABL1 portion of the BCRABL1 protein with an affnity similar to imatinib
> also inhibits SRC family kinases (SFK), c-kit, PDGFR, and ephrin A receptor kinase
DASATINIB
Similar to dasatinib - rescue patients with imatinib resistance against all mutants currently identified (except the 315l mutation)
NILOTINIB
a derivative of imatinib and binds more speciffcally than imatinib to ABL1, stabilizing the ABL1 protein.
NILOTINIB
> binds to the ATP binding site of the ABL1 protein in the inactive conformation with 30x greater potency than imatinib
NILOTINIB
It inhibits ABL1 and SRC kinases, FGFR, and MAPK
does not signiffcantly inhibit PDGFR or c-kit.
BOSUTINIB
> binds both the active and the inactive conformations of ABL1 and is 10 times more potent than imatinib.
BOSUTINIB
rescue about 70% of patients who developed the T3151 mutation in response to first- and second-generation TKI therapy.
PONATINIB
• rescue therapy for patients resistant to imatinib, dasatinib, and nilotinib
PONATINIB
> a plant alkaloid that induces apoptosis, inhibits protein synthesis, and upregulates BAX and PARP
HOMOHARRINGTONE
