Acute Leukemia Flashcards
high proliferation rate, high blast count (immture) and happens rapidly
acute leukemia
an emergency!
malignancy of immature white cells called blasts
acute leukemia
- uncontrolled proliferation of immature cells in BM which manifests in the PB
- cytopenias + increased blast %
- acute is aggressive =emergency!
genetically damaged hematopoietic stem cell
malignant transformation - probable mechanisms: > increased + unregulated proliferation > impaired maturation/differentiation > blockage in apoptosis
T or F. Children are more at risk for acute myeloblastic leukemia
F! lymphoblastic (adults more at risk for myeloblastic)
incidence = first peak in children <5 y/o then another peak in old age
risk factors for acute leukemia (or bad luck cancer)
- increasing age (genetic mutations accumulate)
- acquired marrow disorders (myelodysplasia, myeloproliferative neoplasms, aplastic anemia)
- mutagen exposure (toxic chemicals, chemotherapy, radiation)
- inherited chromosomal disorders that can affect BM (Down’s, Fanconi’s)
clinical features of acute leukemia
cytopenias from BM failiure organ infiltration (leukostasis, bone pain, hepato- & splenomegaly, extramedullary infiltration)
Acute Leukemia treatment
- intensive multi-agent chemotherapy (very toxic side effects)
primary classification of acute leukemia is based on…
lineage
the fundamental basis of diagnosis
- morphology
- diagnosis requires >20% of WBCs to be blasts (either in PB or BM diffs)
- several exceptions*
How to know if a blast is myeloid or lymphoid
very variable!! morphology is not infallible
- only Auer rods are definitive (myeloid)
- it is important to recognize when blasts are present in general
after lineage, the next most important factor for classification of acute leukemia is
cytogenetics
90% of adult leukemias; 15% of childhood leukemias
acute myeloid leukemia
T or F. overall survival in adults for AML remains great
F, it’s poor
most effective acute leukemia treatment
hematopoietic stem cell/BM transplant
- most effective bt associated with significant morbidity and mortality
immunophenotyping for acute leukemia
- specific patterns of molecules associated with different cell lineages
- used with morphology
- tool = flow cytometry
used to detect specific gene fusion transcripts that arise from certain mutations or translocations
PCR (molecular pathology)
- NPM1, FLT3, t(9;22), etc.
- next gen sequencing
- risk stratification and prognosis
90% of adult leukemias
AML
- mostly in elderly but can occur at any age (prolonged exposure to environmental carcinogens)
- 15% of childhood leukemias
most common risk factors for AML
- radiation, toxins, chemicals, chemo
- arising from another myeloid neoplasm (MDS, MPN, MDS/MPN)
- from non-neoplastic marrow disorders = aplastic anemia, inherited bone marrow failure syndrome (Fanconi, Shwachmann-Diamond, etc.)
AML with recurrent genetic abnormalities (3)
- t(15;17)
- t(8;21)
- t(16;16) or inv(16)
<20% lasts; oligoblastic; good prognosis leukemias
CBFB-MYH11
inv(16) or t(16;16)
- good prognosis AML
- core-binding factor B
- affects proper myeloid maturation
- less common in older
- frequently accompanies with or a relapse if myeloid sarcomas = tumour-like collection of blasts
AML with inv(16) morphology
- myelomonocytic = blasts show granulocytic and monocytic differentiation
- increase eos in BM
- abnormal marrow eos
> “amphophilic”
> both pink AND purple-violet baso granules
> granules large and chunky
explain FISH
- red and green fluorescent probes target and flank both sides of a known chromosome break point
- yellow fluorescence = probes are together (chromosome is intact)
- separate red and green = chromosome has broken
APL with t(15;17)
- very unique
- acute promyelocytic leukemia
- PML-RARA
- middle-age adults
- pancytopenia and bleeding
> DIC
> dysregulated hemostasis and coagulation
this is treated differently than other AMLs
APL t(15;17)
- specific chemotherapy plus ATRA (all-trans retinoic acid)
> high dose vit A!
> cell maturation = leukemic blasts grow up into neuts and die
- very good prognosis; best of all AMLs