Lecture 10 Flashcards
Leukemia
Chronic Myeloid Leukemia has a mutation in ? (* based on the lineage)
Hemapoietic progenitor cells
Early in the lineage
Where exactly is the mutation for CML from ?
Inversion between chromosome 9 and 22
resulting in BCR-ABL and phildelphia chromosome
What is the Philadelphia chromosome ?
chnaged chromosome 22+
What is the consequences of mutations causing CML ?
abnormal tyrosine Kinase
proliferate and avoid apoptosis
What are the signs and symptoms for CML ?
most people are asymptomatic
Splenomegaly ( spleen stores WBCs) –> weight loss, anorexia, early satiety
Leukocytosis ( WBC>25)
Leukostatis ( WBC >100) infiltrates the organs and compromising their function
Compromises hematopoiesis ( anemia, bone pain)
Fever, nigh sweats
What are the different phases of CML ?
Chronic, accelerated and blast
What is the characterisitcs for chronic CML ?
COMMON
<10% of immature cells ( blast) are in the peripheral or bone marrow
What is the characteristics of accelerated CML ?
10-19% blasts in the periphery and bone marrow
What do we treat leukostasis with ?
Hydroxyurea ( cell breakdown + allopurinol
What is the indicaton and MOA of hydroxyurea and allopurinol ?
ONLY for symptoms management of leukostasis
urea –> stops RNA reductase and cause major cell apoptosis
Allopurinol –> prevent tumour lysis breakdown from urea
What are the TX for CML ?
TKinhibitors –> small molecules
1st : imaticinb
2nd: Dasatinib and nilotinib
I Don’t kNow
What is the goal of care for chronic phase ?
maintain and induce remission
prevent worsening
minimize txicity
What are the SE of BCR-ABL TKi ?
myelosuppression
N/V ( mild)
Fluid retention ( manage with diuretics)
Rash
Hepatotoxicity ( limit tylenol) - Imatinib)
QTc ( higher with nilotinib)
Vascular
Diarrhea ( loperamide)
Which of the BCR- ABL TKI needs to be with food ?
Ima and Dasa
Which of the BCR- ABL TKI increase tylenol exposure ? Hepatoxicity
Imatinib
Which BCR-ABL TKi is affected by GI acid ?
Dasa and nilo ( 2nd gen)
What are the causes of CML TX failure ?
compliance
DDI
resistance
What are the symptoms of ALL ?
Acute lymphoblactis leukemia
B symptoms : fever, night sweats, weight loss
Cytopenias
Bone pain
CNS if it leaks there
Who is highly affected by ALL ?
Acute Lymphoblastic Leukemia
When is a bad diagnosis of ALL ?
blasts found in the peripheral blood
What is the goals for ALL ?
Cure/ prevent relapses ( CNS or testes) / minimise and manage Tx
Can we use nilotinib in ALL ?
nilotinib is a BCR-ABL TKi
depends if pts has BCR-ABL positive
What are the sancturary sites for ALL?
CNS and testes
What are the TX for ALL initially ?
Anthracycline
Vincristine
CS
Asparaginase
CNS prophylaxis ( mtx)
After remission, pts are on this for maintenanace ALL ?
Oral CS , methotrexate
What is the MOA of asparginase ?
deplete cancer cells from asparaginase ( they can’t make their own like normal cells)
What are the SE of asparaginase ?
Severe hypersensitivity
Liver, pancreas toxicity
VTE
High TG , BG
What are we monitoring pts of MTX for ALL ?
high doses ( can cross BB)
eliminated in the kidney ( best in alkaline urine –> give sodium bicarbonate)
Organ toxicity: liver, pancreas, neuro,
TDM
How do we rescue pts on MTX ?
provide leucovorin
TDM
Which medications have potential DDI with MTX ?
PPI –> clearance
NSAIDs –> kidneys
penicillins
What are the consequences of tumour lysis syndrome ?
Massive cell breakdown
AKI, seizures
edema,
ECG changes
