Exam 2 - HM 2 Leukemias Grove Flashcards
what genetic abnormality is associated with CML (~95% of pts)? How does it work?
Philadelphia chromosome (chromosome 22; BCR-ABL fusion gene causes constitutively active TK -> uncontrolled WBC growth)
what presentation of CML can be a medical emergency?
leukocytosis (very high WBC count) can lead to leukostasis (includes organ dysfunction)
T or F: PCR or FISH can be used to see if something is causing dysregulation of WBCs
T
CML 3 phases
chronic phase (CP) - 90% of pts at diagnosis
accelerated phase (AP)
blast crisis (BC)
what is the only way to cure CML?
allogenic hematopoietic stem cell transplant (HSCT)
which of the following drugs are approved first line for CML?
a. imatinib
b. dasatinib
c. nilotinib
d. bosutinib
e. all of the above
e. all of the above
(imatinib prob most used, then others could be 2nd line as well)
TKI SE: nausea
a. imatinib
b. dasatinib
c. nilotinib
d. bosutinib
e. ponatinib
a. imatinib
TKI SE: fluid retention (pleural effusion)
a. imatinib
b. dasatinib
c. nilotinib
d. bosutinib
e. ponatinib
b. dasatinib
TKI SE:
-QTc prolongation
-metabolic syndrome
a. imatinib
b. dasatinib
c. nilotinib
d. bosutinib
e. ponatinib
c. nilotinib
TKI SE: diarrhea
a. imatinib
b. dasatinib
c. nilotinib
d. bosutinib
e. ponatinib
d. bosutinib
TKI SE:
-ischemic rxn
-vascular occlusion
-HTN
a. imatinib
b. dasatinib
c. nilotinib
d. bosutinib
e. ponatinib
e. ponatinib
with which TKI for CML should we avoid acid reducers?
a. imatinib
b. dasatinib
c. nilotinib
d. bosutinib
e. ponatinib
b. dasatinib
which CML drugs work in T315l mutations? SELECT ALL THAT APPLY
a. imatinib
b. bosutinib
c. asciminib
d. omacetaxine
e. dasatinib
f. ponatinib
c, d, e
what is the “deep molecular response” for CML?
BCR-ABL of 0.01% or less; means reduction in leukemia cells and pt might be able to discontinue
how long must a pt be on a TKI for CML?
3 years
CLL is a cancer of which cells?
B lymphocytes (B cells)
constitutional sx of CLL (5 of them; slide 38)
-lymphadenopathy
-hepatosplenomegaly
-peripheral lymphocyte doubling time < 6 months
-anemia (Hgb < 10)
-thrombocytopenia (plt < 100,000)
is CLL a slow or fast progressing disease?
slow (indolent)
two CLL cytogenetics (slide 39)
Del(11q), Del(17p)
which chromosomal deletion in CLL is associated with extensive lymphadenopathy, disease progression, and shorter median survival time?
a. del(11q)
b. del(17p)
a. del(11q)
which chromosomal deletion in CLL is associated with the loss of the TP53 gene and a poorer response to chemotherapy?
a. del(11q)
b. del(17p)
b. del(17p)
CLL diagnosis criteria needs monoclonal B lymphocytes > what value?
5 x 10^9 in peripheral blood
first line oral drugs for CLL (4 of them)
-ibrutinib
-zanabrutinib
-acalabrutinib
-venetoclax
what is the preferred tx for the following CLL pt?
-no deletions
-IGVH-mutated disease
a. BTK inhibitor
b. venetoclax
c. venetoclax + obinutuzumab
d. chemo-immunotherapy
d. chemo-immunotherapy
look at venetoclax drug interactions (slide 52)
sure
which CLL drug has the highest risk of A fib and bleeding?
a. acalabrutinib
b. ibrutinib
c. zanubrutinib
d. venetoclax
b. ibrutinib
which CLL drug can cause tumor lysis syndrome?
a. acalabrutinib
b. ibrutinib
c. zanubrutinib
d. venetoclax
d. venetoclax
(use a ramp-up dosing schedule to lower risk)
what is transient lymphocytosis? what drug class can cause this?
Transient inc in lymphocyte count. Caused by TKI inhibitors for CLL (peaks early in tx and resolves by week 12)
AML is due to defect in the pluripotent stem cell or a myeloid _______ stem cell
precursor
AML presentation (3 things; slide 62)
-signs of pancytopenia (anemia, neutropenia, thrombocytopenia)
-bone pain
-gum hypertrophy
what is used for AML diagnosis?
bone marrow biopsy: greater than 20% blasts
mutation important for AML
a. T315l
b. BRAFV790E
c. FLT3
d. del(17q)
c. FLT3
two steps of AML tx
-induction (goal: remission)
-consolidation (goal: prevent relapse)
intensive induction tx for AML (2 drugs)
cytarabine + anthracyline (7+3 regimen)
consolidation therapy for AML (3 options)
-3-4 cycles of high dose cytarabine
-venetoclax + azacitidine
-allogenic stem cell transplant
important SE of high dose cytarabine
cerebellar SE
drug added to induction chemo on day 8 in newly diagnosed FLT3+ AML pt
a. acalabrutinib
b. midostaurin
c. imatinib
d. carboplatin
b. midostaurin
2nd line therapy for AML FLT3+ disease
a. ibrutinib
b. venetoclax
c. imatinib
d. gilteritinib
d. gilteritinib
subclass of AML to know
APL (acute promyelocytic leukemia) ~10% of AML
APL genetic abnormality
t(15;17) = PML:RARA
transolocation between chromosome 15 and 17, leads to PML-RARA fusion gene, which produces abnormal protein that leads to accum of promyelocytes
APL tx (2 drugs)
ATRA (all trans retinoic acid)
ATO (arsenic)
ATRA side effect
a. differentiation syndrome
b. QT prolongation
a. differentiation syndrome
differentiation syndrome: what drugs can be used for prophylaxis? what drug is used for tx?
prophylaxis -> steroids
tx -> hydroxyurea
T or F: ALL is most common in pts 65+
F (median age at diagnosis is 17)
ALL is caused by a defect in the lymphopoietic stem cell or an early _______ precursor
lymphoid
what drug class can we add-on to multi-agent chemo in pts with Philadelphia Positive ALL?
tyrosine kinase inhibitor (TKI)
which disease presentation includes painless testicular enlargement, lymphadenopathy, gum hypertrophy, and bone pain?
a. CML
b. CLL
c. AML
d. ALL
d. ALL
-ALL can hide in sanctuary sites such as the _____ and _____
-all pt should receive ____ prophylaxis or tx
-most protocols include __________ __________
brain, testes
CNS
intrathecal chemotherapy
ALL Ph+ maintenance tx (3 drugs)
TKI + vincristine + prednisone
ALL Ph- maintenance tx (3 drugs)
methotrexate + 6MP + vincristine
what are the two parts of the HyperCVAD regimen for ALL?
Hyper-fractionated Cyclophosphamide
Vincristine
Doxorubycin (Adriamycin)
Dexamethasone
Methotrexate + cytarabine + methylprednisolone
what is pegasparagase?
drug used for ALL; breaks down asparagine, which cancer cells cannot make their own so they undergo cell death
which of the following is FALSE about blinatumomab?
a. binds CD19 and CD3
b. first FDA approved T-cell engager
c. CRS and ICANS toxicities
d. used for CML refractory/relapsed disease
d. used for CML refractory/relapsed disease
(used for ALL)
2 frequently used protocols for ALL
HyperCVAD or ECOG1910
