Lab Dx of Cancer, Intro to Hematologic Malignancies, Acute Leukemias Flashcards
PSA
early detection/screening
men over 50, poor specificity for cancer
alpha-fetoprotein
diagnostic, assess for presence of testicular cancer
ER
HER2
KRAS
Predictive: Effective drug therapy
CEA
carcinoembryonic antigen
Post-Therapeutic Monitor: Detect tumor recurrence
colorectal cancer
BRAC1
Risk Stratification: Chance of getting cancer
k-ras mutation
Predicts lack of therapeutic response to a specifc drug
Testing should be done in all pts w/ metastatic colorectal cancer
Absence of MLH-1
raises possibility of inherited tumor susceptibility in the family
CA-125
ovarian cancer screening
can also be elevated in normal post-menopausal women
genetic diseases inc risk of hematologic malignancy
Down syndrome Klinefelter syndrome
Wiskott-Aldrich syndrome
Bloom syndrome Fanconi anemia neuroqbromatosis ataxia telangiectasia
viral infections inc risk of hematologic malignancy
EBV
HTLV
HHV-8
HIV
bacterial infections inc risk of hematologic malignancy
H. pylori
–> gastric MALT lymphoma
most significant tumor suppressor gene
p53
fluorescence in situ hybridization
each normal chromosome produces 2 dots
monosomy –> 1dot
trisomy –> 2dots
flow cytometry
uses Abs labeled to recognize cell surface antigens
most common childhood cancer
ALL
genetic disorders that are risk fx for acute leukemia
Down Klinefelter Turner Neurofibromatosis Fanconi anemia
leukostasis
stasis of blood in cerebral/pulm circulation
blast >50,000
HA, visual change, confusion, stroke, coma (cerebral)
dyspnea, tachypnea, hypoxia
AML>ALL
ALL extra-medullary manifestations
lymphadenopathy
splenomegaly
mediastinal mass
leukemic meningitis rare at dx, CNS = common site of relapse
testes
AML extra-medullary manifestations
leukemic cutis
gingival hypertrophy
chloromas (green tumor of blasts)
ALL metabolic abnormalities
tumor lysis syndrome
AML metabolic abnormalities
hypOkalemia (via renal tubular damage by enzyme released from myeloblasts)
hypOglycemia (artificial finding due to metabolic activity of blasts in blood tube after draw)
WHO dx of AML
> 20% blasts in bone marrow
+ cytogenetic findings
Auer rods
linear aggregates of primary granules seen only in myeloblasts
myeloblast nucleoli
single-multiple
lymphoblast nuclei
less conspicuous nucleoli
AML stains
lysozyme
myeloperoxidase
non-specific esterase
ALL stains
terminal deoxynucleotidyl transferase (TdT)
AML cell surface antigens
CD13
CD33
CD117
ALL cell surface antigens
precursor B cell
CD10
CD19
CD20
ALL cell surface antigens
precursor T cell
CD2 CD3 CD4 CD5 CD7 CD8
acute leukemia transfusion support
required for effective support
platelets (count of 10,000 is threshold)
leukocyte depleted
irradiated
leukostasis
IV fluids
leukapheresis
hydroxyurea to reduce leukemic burden
steroids helpful if ALL
avoid rbc transfusion (inc viscosity)
DIC tx during acute leukemia
replace clotting fx w/ FFP
replace fibrinogen w/ cyroprecipitate
platelet transfusion
tumor lysis syndrome tx during acute leukemia
IV hydration for rapid saline diuresis
allopurinol to prevent accumulation of uric acid
RASBURICASE
hemodialysis if renal failure
rasburicase
catalyzes oxidation of uric acid to soluble allantoin
AML poor prognosis factors
older age
11q23 (MLL)
deletions of 5/7 (alkylating agents)
multiple cryogenic abnormalities
hx of BM disorder
AML favorable risk cytogenetics
t(15;17)
core binding factors
AML intermediate risk cytogenetics
normal karyotype
AML therapy-related AML from chemo
alkylating agents (4-6 yr post exposure)
topoisomerase II inhibitors (1-3 yr post exposure)
poor prognosis, unfavorable risk
AML curative therapy
induction (quickly restore normal hematopoiesis)
post-remission (consolidation, eradicate residual leukemia cells)
most common AML induction regimen
cytarabine + anthracyline
daunorubicin, idarubicin
AML complete remission
<5% blasts in BM w/ recovery of normal hematopoiesis and resolution of all extra medullary infiltrates
acute promyelocytic leukemia
t(15;17)
or detection of PML/RAR
younger pts
leukopenia
often DIC at dx
APL tx
ATRA (all trans-retinoid acid), vitamin A analogue
ligand for RAR receptor, binds PML-RAR fusion protein
restores transcription of genes allowing differentiation
NO lysis of blasts/marrow aplasia
APL differentiation syndrome
leukocytosis
fever
pulm infiltrates
fatal if not recognized and tx w. steroids
arsenic trioxide (ATO)
induces apoptosis in APL cells and targets PML/RAR fusion protein –> differentiation
standard tx for APL
ATRA
anthracycline for induction
maintenance tx for ATRA and oral anti-metabolite
long-term remission in 70%
ATO w/ ARTA
tx for what?
acute promyelocytic leukemia
ALL poor prognosis
infants/adults
t(9;22) Philadelphia
translocations (MLL, on 11)
hypOploidy
T cell
boys
ALL good prognosis
1-9 y/o
t(12;21)
hypERploidy
normal cytogenetics
B cell immunophenotype
girls
minimal residual disease at end of induction tx
ALL induction therapy
multi-agent chemo
anthracycline vincristine glucocorticoid L-asparaginase cytarabine cyclophosphamide methotrexate
tyrosine kinase inhibitors in Ph+
_____ is a sanctuary site for leukemic blasts
CSF
to prevent relapse, CNS prophylaxis in ALL includes
intrathecal chemo with or without craniospiral irradiation
ALL maintenance therapy
prolonged chemo (shown to extend survival/improve cure rates)