B3.038 Big Case Acute Leukemia

Question 1

which cells live longer: lymphoid or myeloid?

Answer 1

lymphoid

Question 2

what are the 3 major subcategories of myeloid neoplasms?

Answer 2

myeloproliferative neoplasms
acute myeloid leukemia
myelodysplastic syndromes

Question 3

when do these myeloid neoplasms arise?

Answer 3

prior to the -blast stage, when cells are rapidly proliferating

Question 4

what are the 4 major subcategories of lymphoid neoplasms?

Answer 4

precursor B/T lymphoblastic leukemia/lymphoma
mature B cell neoplasms
mature T cell neoplasms
Hodgkin lymphoma

Question 5

what is different between neoplasmic origins in lymphoid vs myeloid cells?

Answer 5

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

Question 6

define acute leukemia

Answer 6

neoplasm derived from precursor hematopoietic cells with proliferation and accumulation of immature (blast) cells
-proliferation without maturation
increased blasts (>20%) in bone marrow

Question 7

what is the difference between acute and chronic leukemia?

Answer 7

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

Question 8

differentiate between the terms leukemia and lymphoma

Answer 8

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

Question 9

what are 2 major subcategories of acute leukemia?

Answer 9

acute myeloid leukemia (AML)

acute lymphoblastic leukemia/lymphoma (ALL/LBL)

Question 10

what are 2 types of ALL?

Answer 10

B-lymphoblastic leukemia/lymphoma

T-lymphoblastic leukemia/lymphoma

Question 11

epidemiology of AML

Answer 11

incidence increases steadily through adult life

typically >20-30 onset

Question 12

epidemiology of ALL

Answer 12

most common malignancy of childhood/ early adolescence
85% B-ALL, 15% T-ALL (worse prognosis)
second peak after 50

Question 13

what are some etiological associations with acute leukemia?

Answer 13

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)

Question 14

clinical findings associated with acute leukemia

Answer 14

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)

Question 15

pathologic findings in blood due to acute leukemia

Answer 15

anemia
neutropenia
thrombocytopenia
circulating blasts

Question 16

pathologic findings in bone marrow due to acute leukemia

Answer 16

increased cellularity

increased blasts

Question 17

histological appearance of blast cells

Answer 17

primitive, immature
continuous division, thus open chromatin within nuclei
nucleus&raquo_space;> cytoplasm bc cytoplasm doesn’t have much of a function when cell is so rapidly proliferating
sometimes confused with lymphocytes

Question 18

components of acute leukemia diagnosis

Answer 18

> 20% blasts in the bone marrow
lineage determination - immunophenotype (flow cytometry)
auer rods - if present, confirm AML

Question 19

AML immunophenotype markers

Answer 19

myeloperoxidase+
TdT-
CD34+
CD13+
CD117+

Question 20

B-ALL immunophenotype markers

Answer 20

TdT+
myeloperoxidase-
CD10+
CD19+

Question 21

T-ALL immunophenotype markers

Answer 21

TdT+
myeloperoxidase-
CD2+
CD3+
CD5+
may co express CD4 and CD8

Question 22

auer rods appearance on histology

Answer 22

needle like structures in cytoplasm

confirms AML lineage, but not all AMLs have them present

Question 23

general principles of acute leukemia prognosis and treatment

Answer 23

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

Question 24

what are targeted therapies?

Answer 24

increasing in use based on genetic and other determinants
monoclonal Ab
small molecule inhibitors

Question 25

favorable features for AML prognosis

Answer 25

t(15:17) - acute promyelocytic leukemia

t(8;21), inv(16) - certain other molecular markers

Question 26

unfavorable features for AML prognosis

Answer 26

age >60
WBC >100000
prior myelodysplastic syndrome (probs more genetically fucked)
therapy related AML
certain genetic and molecular markers

Question 27

describe acute promyelocyctic leukemia

Answer 27

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

Question 28

how does ATRA therapy work against acute promyelocytic leukemia?

Answer 28

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

Question 29

favorable ALL prognosis

Answer 29

precursor B-ALL
4-10 years old
<10000 WBC
no organomegaly
hyperdiploidy
t(12;21)

Question 30

unfavorable ALL prognosis

Answer 30

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

Question 31

childhood ALL outcomes

Answer 31

95% remission

75-85% cure rate if favorable prognostic features

Question 32

adult ALL outcomes

Answer 32

prognosis is poorer than childhood due to multiple disease and host factors

Question 33

AML outcomes

Answer 33

60% remission rate and 15-30% 5 year survival

better outcomes for favorable subtypes