B3.038 Big Case Acute Leukemia Flashcards
which cells live longer: lymphoid or myeloid?
lymphoid
what are the 3 major subcategories of myeloid neoplasms?
myeloproliferative neoplasms
acute myeloid leukemia
myelodysplastic syndromes
when do these myeloid neoplasms arise?
prior to the -blast stage, when cells are rapidly proliferating
what are the 4 major subcategories of lymphoid neoplasms?
precursor B/T lymphoblastic leukemia/lymphoma
mature B cell neoplasms
mature T cell neoplasms
Hodgkin lymphoma
what is different between neoplasmic origins in lymphoid vs myeloid cells?
lymphoid cells have the ability/potential for cell division throughout their entire life span, so mature cells may acquire mutations
myeloid cell neoplasm occur earlier in differentiation because after the blast stage they are incapable of division
define acute leukemia
neoplasm derived from precursor hematopoietic cells with proliferation and accumulation of immature (blast) cells
-proliferation without maturation
increased blasts (>20%) in bone marrow
what is the difference between acute and chronic leukemia?
acute: primarily immature cells (blasts), when untreated, rapidly progressive and fatal in weeks to months
chronic: primarily mature or maturing cells, when untreated, slowly progressive and fatal in months to years
differentiate between the terms leukemia and lymphoma
leukemia: primary presentation in BM and blood
can be derived from myeloid cells or lymphoid cells
lymphoma: primary presentation in lymph nodes or other lymphoid tissues
derived from lymphoid cells only
***some lymphoid neoplasms can present as either a leukemia or as a lymphoma and are referred to as leukemia/lymphoma
what are 2 major subcategories of acute leukemia?
acute myeloid leukemia (AML)
acute lymphoblastic leukemia/lymphoma (ALL/LBL)
what are 2 types of ALL?
B-lymphoblastic leukemia/lymphoma
T-lymphoblastic leukemia/lymphoma
epidemiology of AML
incidence increases steadily through adult life
typically >20-30 onset
epidemiology of ALL
most common malignancy of childhood/ early adolescence
85% B-ALL, 15% T-ALL (worse prognosis)
second peak after 50
what are some etiological associations with acute leukemia?
ionizing radiation
trisomy 21 (increase in both types)
chromosomal instability syndromes (DNA repair issues)
immunodeficiency states (mainly ALL)
chemo drugs (mainly AML)
other stem cell hematologic disorders like aplastic anemia, myelodysplastic syndromes, paroxysmal nocturnal hemoglobinuria, or myeloproliferative neoplasms (mainly AML)
clinical findings associated with acute leukemia
bone marrow insufficiency due to replacement by blasts
-anemia, thrombocytopenia, neutropenia
-not usually lymphocytopenia bc they last longer
bone pain (mainly ALL) due to bone expansion from inside where nerves are located
hepatosplenomegaly
lymphadenopathy (ALL only bc AML cells don’t go through lymph nodes)
pathologic findings in blood due to acute leukemia
anemia
neutropenia
thrombocytopenia
circulating blasts
pathologic findings in bone marrow due to acute leukemia
increased cellularity
increased blasts
histological appearance of blast cells
primitive, immature
continuous division, thus open chromatin within nuclei
nucleus»_space;> cytoplasm bc cytoplasm doesn’t have much of a function when cell is so rapidly proliferating
sometimes confused with lymphocytes
components of acute leukemia diagnosis
> 20% blasts in the bone marrow
lineage determination - immunophenotype (flow cytometry)
auer rods - if present, confirm AML
AML immunophenotype markers
myeloperoxidase+ TdT- CD34+ CD13+ CD117+
B-ALL immunophenotype markers
TdT+
myeloperoxidase-
CD10+
CD19+
T-ALL immunophenotype markers
TdT+ myeloperoxidase- CD2+ CD3+ CD5+ may co express CD4 and CD8
auer rods appearance on histology
needle like structures in cytoplasm
confirms AML lineage, but not all AMLs have them present
general principles of acute leukemia prognosis and treatment
induction therapy (usually multi agent chemo) - goal is to produce complete remission (kill all leukemia blasts, multiple cycles) post-induction therapy - goal is long term disease survival (keep blasts away) supportive care
what are targeted therapies?
increasing in use based on genetic and other determinants
monoclonal Ab
small molecule inhibitors
favorable features for AML prognosis
t(15:17) - acute promyelocytic leukemia
t(8;21), inv(16) - certain other molecular markers
unfavorable features for AML prognosis
age >60 WBC >100000 prior myelodysplastic syndrome (probs more genetically fucked) therapy related AML certain genetic and molecular markers
describe acute promyelocyctic leukemia
characterized by a t(15;17) translocation
- disrupts retinoic acid receptor (RAR-a) gene
- abnormal promyelocyte-like cells with multiple Auer rods
- frequent association with DIC due to release of granules
- all trans retinoic acid (ATRA) used for treatment
- favorable to intermediate prognosis
how does ATRA therapy work against acute promyelocytic leukemia?
ATRA fits into a binding site on the RAR-a that is not accessible to RA due to a mutation
ATRA activates receptor
activation of gene transcription follows
allows malignant cells to mature into short lived PMNs which will eventually self destruct
favorable ALL prognosis
precursor B-ALL 4-10 years old <10000 WBC no organomegaly hyperdiploidy t(12;21)
unfavorable ALL prognosis
precursor T-ALL <2 or >10 years old >100000 WBC extensive organomegaly t(4;11) t(9;22) poor response to initial therapy = worse outcome
childhood ALL outcomes
95% remission
75-85% cure rate if favorable prognostic features
adult ALL outcomes
prognosis is poorer than childhood due to multiple disease and host factors
AML outcomes
60% remission rate and 15-30% 5 year survival
better outcomes for favorable subtypes
