Term
| What are the major risk factors associated with AML? |
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Definition
1) Heredity
- DNA repair (Fanconi anemia, Bloom syndrome, Ataxia telangiectasia)
2) Radiation
- Atomic bond
- Therapeutic levels if combined with alkylating agents
3) Occupational-Benzene
- Plastics, rubber
4) Therapy-associated
- Alkylating agents (4-6 years later with chromosome 5 & 7 alterations)
- Topo-II inhibitors (1-3 years with 11q23) |
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Term
Which of the following is NOT associated with the development of AML?
1. Therapeutic radiation with cyclophosphamide treatment
2. Bloom syndrome
3. Working in a rubber factory
4. Prophylactic use of Cipro during SCT |
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Definition
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Term
What chromosomal abnormalities are associated with the following morphological features of AML?
1. APL
2. AML with abnormal marrow eosinophils |
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Definition
1. t(15:17)(q22;q12)
2. inv(16)(p13q22) |
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Term
| Describe a typical clinical presentation of AML |
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Definition
1) patient complains of fatigue or weakness (often weight loss)
**sometimes fever (10%) or abnormal hemostasis (5%) is initial symptoms
2) Rarely, Granulocytic sarcoma or "chloroma" (mass soft tissue lesion)
3) Usually see anemia (normocytic, normochromic) with reduced reticulocyte count, leukopenia and thrombocytopenia. |
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Term
| What are the most important prognostic indicators in AML? |
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Definition
1) Age at diagnosis
- therapeutic initiation and different biology (elderly patient cells express MDR1 and CD34)
2) Chromosomal findings
- t(15:17) is good
- complex karyotypes are poor
3) H/x of myelodysplastic syndrome or hematological disease is associated with lower cure rate and survival time |
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Term
| What treatment options are available for AML? |
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Definition
1) Induction
- intensive chemo if <60 (Cytarabine and anthracyclines)
- controversial in elderly
2) Post-remission management
- High-dose Cytarabine is effective
- If relapse occurs, only cure is SCT
- |
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Term
| What is Acute promyelocytic leukemia (APL) and how does it differ from other forms of AML? |
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Definition
10-15% of cases, and 80-85% long-term cure with chemo + ATRA
1) APL characterized by "maturational blockade"
- enzyme-filled primary granules can initiate DIC and cause bleeding.
2) See "Aur rod-laden" pro-myelocytes, with no HLA-DR and characteristic t(15:17) translocation
3) Treatment is unique
- t(15:17) encodes chimeric protein (PML/RA receptor alpha), which is a nuclear hormone receptor transcription factor
- Give all-trans-retinoic acid (ATRA), a RAR-alpha ligand, to relieve block on differentiation. |
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Term
| How does Acute Lymphocytic Leukemia differ from AML? |
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Definition
Less common (most common childhood variant is B cell ALL), but may present similarly.
- Most commonly pre-B cell origin
- Involves lymph nodes and commonly extra-nodal sites |
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Term
Alkylating agents associated AML occurs after:
1. 2 years
2. 10 years
3. 5 years
4. 8 years |
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Definition
3
Treatment related acute leukemias and treatment related myelodysplastic syndromes are diseases which are difficult to treat and have an extremely poor prognosis. Those caused by alkylating agents tend to occur about 4-6 years from the beginning of treatment and involve aberrations in chromosomes 5 and 7. Patients who receiving topoisomerase I inhibitors often develop treatment related MDS earlier (1-3 years) and have more complex chromosomal abnormalities (11q23). |
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Term
Chromosomal abnormality associated with acute promyelocytic leukemia is:
1) T(9,11) (p22;q23)
2) T(8,21) (q22;q22)
3) Inv (16)(p13q22)
4) 11q23
5) T(15,17) (q22;q12) |
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Definition
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Term
Favourable Prognostic factors associated with AML include all of the following EXCEPT:
1) T(15,17)
2) Monosomy -5
3) Inv (16)
4) T (8;21) |
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Definition
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Term
Treatment of leukemia involves an induction phase followed by a consolidation phase with cytarabine based chemotherapy.
True or False |
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Definition
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Term
In APL – pathophysiology involves formation of a fusion protein PML-RARA which enhances gene transcription and promotes differentiation of cells.
True or false |
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Definition
False
The PML-RARA fusion protein suppresses gene transcription and blocks cell differentiation. This fusion protein is a consequence of the characteristic t(15;17). Of therapeutic importance, is that all-trans-retinoic acid (ATRA) relieves the blockade and promotes differentiation. |
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Term
Acute Lymphocytic Leukemia is more common in adults. Treatment involves non-cell cycle dependent agents like steroids and asparaginase.
True or false |
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Definition
False
More common in kids and 90% cure rate (decreases with age)
Treatment does include non-cell cycle dependent agents like steroids and asparaginase as well as prophylaxis for CNS involvement (craniospinal) |
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