Flashcards in Acute Leukemia (Goorha) Deck (59):
What are the two divisions of acute leukemia?
acute myeloid and acute lymphoblastic leukemia
What cellular feature is characteristic of leukemia?
accumulation of malignant WBCs in BM and blood
What causes the morbidity and mortality associated with leukemia?
1. BM failure
(anemia, neutropenia, thrombocytopenia)
2. Infiltration of organs
(such as liver, spleen, lymph nodes, meninges, brain, skin, testes)
FAB classification of acute myeloid leukemia:
FAB classification of acute lymphoblastic leukemia:
Most common form of leukemia in children
Acute leukemia that occurs in all age groups:
Highest in kids ages 3-7
Increasingly common with advanced age
What is the difference between primary and secondary AML?
primary AML = de novo
secondary AML develops from myelodysplastic syndrome or other hematatological malignancies
Which is more difficult to treat: primary or secondary AML?
Acute leukemia that shows a notable rise in patients around 40 years old:
Three treatment phases of ALL:
1. remission induction
2. consolidation (intensification)
Why is allopurinol administered to ALL patients receiving treatment?
it counters hyperuricemia resulting from tumor cell breakdown
Do adults or children with ALL have better cure rate? Why?
Children; this is possibly due to worse genetic features in adults
Disorders associated with causing acute leukemia (etiology):
1. Myelodysplastic syndromes
2. Myeloproliferative diseases
3. Down’s syndrome
4. Fragile chromosome syndromes (Fanconi’s anemia)
5. Aplastic anemia + Paroxysmal Nocturnal Hemoglobinuria
Etiologies of acute leukemia related to exposure:
1. Idiopathic (vast majority)
2. Prior chemotherapy
3. Prior radiotherapy
4. Chemical exposure (benzene)
Where does malignant transformation occur in acute leukemia?
hematopoetic stem cells or early progenitors
What does genetic damage lead to, in acute leukemia?
(1) increased rate of proliferation
(2) reduced apoptosis
(3) block in cellular differentiation
Collectively, what is the result of genetic damage associated with acute leukemia?
accumulation of blast cells (early BM hematopoietic cells)
Acute leukemia is defined as:
1. > 20% blasts in blood or BM
2. cytogenetic or molecular genetic abnormalities (even if blasts are <20%)
T/F: Acute leukemias are aggressive diseases.
T: no treatment = death
What is immunotyping (in terms of AML/ALL)?
analysis of the pattern of antigen expression on surface of blast cells
What is FAB AML classification M0?
What are FAB AML classification M1 and M2?
M1: no maturation
M2: granulocytic maturation
What is FAB AML classification M3?
What is FAB AML classification M4?
granulocytic and monocytic maturation
What is FAB AML classification M5?
monoblastic or monocytic
What are FAB AML classification M6 and M7?
What is FAB ALL classification L1?
small, uniform blast cells with a high nucleus:cyto ratio
What is FAB ALL classification L2?
larger, heterogenous blast cells with a lower nucleus:cyto ratio
What is FAB ALL classification L3?
blasts with vacuoles and basophilic cytoplasm
What morphologic structure is diagnostic of AML?
What tests may be useful when trying to differentiate between ALL and AML?
Immunological markers (flow cytometry)
4 myeloid antigens:
4 lymphoid antigens:
What is an example of a genetic translocation linked to acute promyelocytic leukemia?
How do ATRA and arsenic counter an oncoprotein (or fusion oncoprotein)?
--Oncoprotein (gene product) binds to DNA and activates self-renewal of leukemic stem cells
--ATRA/arsenic releases the co-repressors bound to the DNA ("deprogramming" leukemia self-renewal)
--Normal transcription can now occur, allowing cell to differentiate into a normal cell
What's the diagnosis?
elevated WBC and smear showing auer rods
How does determining the specific genetic defect associated with an acute leukemia improve patient's outcome?
useful in determining pronosis/treatment
What is remission induction therapy (AML)?
1 to 2 courses of intensive therapy to achieve a complete response (no detectable leukemia cells)
What is post-remission therapy (AML)?
"consolidation therapy", in which 3 to 4 courses of intensive short-course therapy are used to further reduce the subclinical effects of a tumor
What often follows post-remission therapy (AML)?
1. maintenance therapy: months to years of less intensive therapy (further prevents recurrence)
2. allogeneic bone marrow transplantation
T/F: AML treatment is more favorable for older patients.
F: younger patients (perhaps because they tolerate chemo better)
What are 4 treatment strategies for older adults with AML?
1. Supportive care
2. Standard intensive chemotherapy, not clear that any consolidation is beneficial
3. New agents (noncytotoxic agents)
4. Reduced-intensity conditioning HSCT (has shown a more favorable response than traditional high-intensity treatment)
What genetic abnormalities are associated with poor outcomes in adults and children will ALL?
MLL-AF4 and BCR-ABL translocations
What genetic abnormalities in childhood ALL (rare in adults) are associated with a good outcome?
E2A-PBX and TEL-AML
("abnormalities of hyperdiploidy")
What is the prophylactic CNS treatment in ALL?
intrathecal methotrexate or ARA-C
What are maintenance therapy drugs used in ALL?
6-MP, methotrexate, prednisone
What are induction therapy drug options for ALL?
4. PRED +/- Daunorubicin
What are consolidation therapy drug options for ALL?
2. HD Ara-C
5. thioguanine or 6-mercaptopurine
**do we need to know this??
In acute leukemia, therapy is tailored to:
specific genetic abnormalities
What are 4 ways to improve outcomes, in terms of treatment?
Treatment at specialized centres
Stem Cell Transplantation
Molecular abnormality associated with poor prognosis in AML:
Molecular abnormality associated with intermediate prognosis in AML (in addition to cytogenetic abnormalities):
3 cytogenetic abnormalities associated with good risk in AML:
3. t(15;17) **ATRA
What would you use to treat APML (M3), according to the lecture?
What would you use to treat inv(16) or t(8;21), according to the lecture (in addition to standard induction)?
high dose ARA-C