Hematology Week 2: Acute Myeloid Leukemia Flashcards
(63 cards)
1
Q
Myeloid vs Lymphoid lineages
A
2
Q
AML cell
A
myeloblast
blast of the myeloid lineage
3
Q
Myeloblast threshold for AML
A
>or=20% of the total nucleated cells in the blood or BM
4
Q
AML Smear
A
Can see Auer rod which tells us myeloid lineage and are neoplastic
5
Q
AML Key Diagnostic Findings
4 listed
A
- Auer rod
- MPO+
- CD33+
- CD34+
- Blasts >=20%
6
Q
AML BM Aspirate Morphology
A
Hypocellular BM taken over by sheets of blasts
7
Q
Typical CBC findings and Differential in AML
A
Decreased Reflecting reduced BM production
- RBCs
- Platelets
- Neutrophils
Can have high/low WBC counts
- key is that blasts are >20%
8
Q
Most Common Leukemia in Adults
A
AML
9
Q
AML Survival Curve
A
10
Q
Subtypes of AML
3 listed
A
Need BM biopsy to determine subtype
- Low risk
- Intermediate risk
- High Risk
11
Q
AML Risk Assesment tool
A
12
Q
Low-Risk AML Genetic Findings
3 listed
A
- t(15;17) PML-RARA fusion
- t(8;21) RUNX1-RUNX1T1 fusion
- t(16;16) or inv(16) CBFB-MYH11 fusion
13
Q
Intermediate Risk AML Genetic Findings
A
Normal Karyotype
14
Q
High-Risk AML Genetic Findings
3 listed
A
- Complex Karyotype (>=3 abnormalities)
- Monosomy for chromosome 7
or
- 7q deletion
15
Q
Treatment of AML
A
- Induction Chemotherapy = 7+3
- Consolidation Chemotherapy
16
Q
AML left untreated is?
A
Universally fatal
17
Q
7+3 Induction Chemotherapy
6 listed
A
- 7 days Cytarabine + 3 days Anthracycline
- Extremely toxic therapy
- 7 days of chemo resulting in severe bone marrow suppression that may last several weeks
- Called induction chemotherapy to try to induce remission
- High risk of infection and bleeding during this time
- May not be tolerated by elderly or patients with comorbidity
18
Q
Consolidation Chemotherapy
2 listed
A
- High Dose Cytarabine
- Given 3-4 times after remission is achieved to consolidate that remission
19
Q
Anthracycline key Toxicity
A
Cardiac Failure
20
Q
Cytarabine Key Toxicities
A
Cerebellar Toxicity
21
Q
Anything that ends in Rubicin is an?
A
Anthracycline
22
Q
Doxorubicin AKA
A
Adriamycin
23
Q
Doxorubicin MOA & Metabolism & Elimination
3 listed
A
- Binds directly to DNA and intercalates interfering with DNA repair, transcription and replication which induces apoptosis
- Widely distributed except in CNS
- Metabolized in the liver and eliminated in the bile
24
Q
Doxorubicin Classic Toxicity
A
- Cardiotoxicity
- (Tachycardia, arrhythmia, refractory CHF)
- results from free-radical damage due to the low levels of free radical buffers in cardiac tissue
25
HSCT for AML?
2 listed
* For high-Risk Subgroups in first remission or any patient in relapse
* patient must have minimal or no disease before transplant
26
Treatment for patients \>60 in AML
\>60 unfit for high-dose therapy
so
use low-intensity therapy
* 5-Azacytidine or decitabine (**hypomethylating agents**)
* May require 3-4 cycles to see the response
* may increase survival - effective but less toxic
Best supportive care
* Transfusions
* Antibiotics
27
AMl and genetic components
Genetic mutations or translocations that increase cellular proliferation
+
Genetic mutations or translocations that blocks myeloid differentiation or maturation
=
AML
Both of these are needed for AML
28
AML Class I Mutation description
A mutation that increases cellular proliferation
29
AML Class I Mutation examples
FLT3 Mutation
30
FLT3 Mutation Class?
Class I Mutation
31
AML Class II Mutation Description
Alterations that impair cellular differentiation (often involve transcription factors)
32
AML Class II Mutation Examples
3 listed
* t(15;17) PML RARA
* t(8;21) RUNX1-RUNX1T1
* t(16;16) or inv(16) CBFB-MYH11
33
t(15;17) PML RARA Mutation class?
Class II
34
t(8;21) RUNX1-RUNX1T1 Mutation Class
Class II
35
t(16;16) or inv(16) CBFB-MYH11 Mutation class
Class II
36
AML Class III Mutation
Epigenetic Changes (affecting gene methylation)
37
t(16;16) or inv(16) CBFB-MYH11 MOA
MYH11 protein binds onto CBFß-RUNX1 becomes a gene repressor
38
t(8;21) RUNX1-RUNX1T1 MOA
RUNX1T1 binds to CBFß and RUNX1 to make it a repressor of genes necessary for genes of cellular differentiation
39
Paths to AML
4 listed
* Mutations over a lifetime
* Genotoxic therapy
* disease progression from myeloid neoplasm (e.g. MDS, MPN)
* Inherited predisposition (e.g down syndrome)
40
Midostaurin MOA
* First in class multi-targeted kinase inhibitor
* activity in FLT-3 mutated AML with significantly increased overall and event-free survival
* Used in conjunction with standard induction chemotherapy
* Significantly increases survival
41
Pathway to AML matters
42
* Immature cells with many granules
* multiple Auer Rods
* Disseminated intravascular Coagulation
* Schistocytes
*
43
M3 AKA
APL
44
Histological findings in APL
* Immature cells with many granules and multiple Auer rods
* schistocytes on peripheral smear
* can be in DIC
* APL or M3 is same thing
45
APL is a medical?
EMERGENCY typically because of the DIC
46
What cell type is proliferating?
AML
47
What cell type is proliferating?
CML
48
APL
49
APL AKA
Acute Promyelocytic Leukemia
50
APL Genetics
t(15;17) fusion of PML-RARA
51
APL Genetics testing
Karyotype or FISH
52
APL MOA and ATRA therapy
kicks repressor off and overcomes blockade that was causing cells to be arrested in their development
53
ATRA AKA
All-Trans-Retinoic-Acid
54
APL Overview
55
APL Treatment?
Highly curable with ATRA or arsenic trioxide and chemotherapy
56
ATRA overcomes?
the differentiation blockade caused by (15;17)
57
APL Histological features
BM packed with abnormal promyelocytes often with multiple Auer Rods
These are considered blast equivalents
58
APL unique risk
Unique risk of fatal hemorrhage due to disseminated intravascular coagultion (DIC)
59
Clinical aspects of APL
60
Differentiation Syndrome?
61
Keep in mind with APL
62
AML Key Points
5 listed
63
ATRA Toxicity
Differentiation Syndrome
