AL 2 Flashcards
fatigue & short breath
low amt Hb, not enough O2
arm bruising, purple spots on legs
low platelet count
AL & wbc
low neutrophils, lymphocytes, >20% blasts
what are blasts?
immature wbc
AL diagnosis!
clin presentation, morphology, immunophenotype, cytogenetics, molecular studies
clin info in AL
~lacking but critical. history of prior BM disorder (MDS). prior cytotoxic therapy. down syndrome
MDS
myelodysplastic syndrom
1st indication of AL
morphology, guides approp ancillary tests & indicates
blast count for morphology
> 20% blasts in PB or BM
morphology can indicate subtype, genetic changes. example?
auer rods only in ML
needles
illinois BM aspirate needle & jamshidi BM biopsy needle
BM biopsy MI
morphology, immunohistochem
BM aspirate MFCCFM
morph features, flow cytometric, cytgenetic FISH, molecular analysis
what is performed in all suspected AL cases
flow cytometry
immunophenotype is needed for
diagnosis, classification.
phenotypes can be
AML, ALL, or mixed
immunophenotyping may ID aberrant antigen exp corresponding to what
specific genetic changes
hard to morphologically tell AML from ALL using what?
morphology (rely on immunophenotype)
flow cytometry involves
laser, electronics, fluidic & optic system… flor labelled cell parts, light scattered when hit cell
CD45 is example of
leukocyte antigen. expressed on all hematopoietic cells
cells express myeloperoxidase MPO only in
ML. see brown stain (instead of blue)
all new cases should include
karyotyping (key for classification)
molecular methods may be better than cytogenetics for some
abnormalities (translocations, duplication, deletion)
FISH
fluorescent in situ hybridization.
confirm translocation w FISH
add probes, red binds gene on xsome 17, green for 15. in normal cell, 2R & 2G. in leukemia, see yellow (fusion signal)
molecular studies in AL
PCR based assays & NGS
PCR
detect new fusion proteins in AML w recurrent translocations
what mutations are tested w PCR in all new AML cases
FLT3 & NPM1
NGS
perform routinely in clinic for all new AL cases
acute promyelocytic leukemia
w PML-RARA
mutation w too many b-lymphocytes
CLL chronic lymphocytic leukemia
myeloproliferative neoplasms w too many
neutrophils - CML myelogenous
platelets - ET essential thrombocythemia
rbc - polycythemia vera
too many blasts
ALL or AML
AML, ALL common in what age
AML - elderly
ALL - kids
underlying disorder
marrow infiltration w blasts
BM fail
neutropenia, anemia, thrombocytopenia
lab features
BM fail, circulating blasts, intravascular coagulation
circulating blasts
wbc ~ incr but not always
intravasc coag
coagulopathy, hemolysis w rbc frags, thrombocytopenia (low platelet)
BM fail leads to
infection, fatigue, bleeding
circulating blasts leads to
leukostasis (pulm, CNS) & tissue infiltration (lymphadenopathy, splenomegaly, CNS, skin)
intravasc coag leads to
bleeding
lab & clin presentations ~acute/subacute
days to wks
AL classification
FAB - morphology, cytochem only, limited immunophenotyping
2017 WHO - morph, immunophenotype, cytogenetics, molecular, prior disease & therapy history
AL treatment depends on
type (ALL/AML), age of patient (ped vs adult vs old), curative vs palliative intent
combination chemotherapy (2)
induction - for full remission. consolidation - prevent relapse
supportive care TANPS
transfusions, antibiotics, nutrition, psychosocial support
standard 3 + 7 AML treatment (chemo)
daunorubicin + cytarabine. no particular targets, just kill dividing cells
daunorubicin interact w dna how
intercalation, inhibition of macromolecular biosynth. also inhib topoisomerase 2 (relax dna supercoils for transcrip)
admin daunorubicin & cytarabine. how?
both IV. daunorubicin - 3 days, cytarabine 7 days
cytrarabine similar to what human compound (but still diff enough to kill)
cytosine deoxyribose (deoxycytidine) which is incorporated into dna
new targeted therapies for APL
retinoic acid, arsenic trioxide
BM transplant for who
younger patients (relapsed/high risk AL)
BM transplant HSC from who
matched: sibling or unrelated donor
BM transplant is toxic therapy
yes, many side effects as new immune system attacks own organs (take immunosuppresants) but potential for cure
graft vs leukemia effect
transplant new cells, kill out residual leukemia :) thx to immune response to tumor
prognosis wrt age
survival % higher in young ppl (ALL better than AML), ~none for 75+
treatment is long
at least 1 month, but some improvement in outcomes (targeted approaches)
