6. Acute Leukemias - Aml

Front 1

What is the definition of Acute Leukemia?

Back 1

A Neoplastic proliferation of immature cells recapitulating the progenitor cells of the hematopoietic system.

Front 2

What are the 2 main categories of acute leukemia?

Back 2

1. Myeloblastic
2. Lymphoblastic

Front 3

How does Acute leukemia differ from Chronic leukemia?
-Cell types
-Duration of untreated Natural history

Back 3

Chronic = Immature cells, with weeks-months duration
Acute = Mature cells, with duration of months-years

Front 4

What are 2 ways in which the blasts in acute leukemia are immature?

Back 4

-Genetically
-Immunophenotypically

Front 5

What are the 2 types of acute leukemia?

Back 5

AML
ALL

Front 6

What is the predominant age of patients with AML?

Back 6

Around 60 yrs old

Front 7

What is the predominant age of patients with ALL?

Back 7

Under 18 yrs old

Front 8

What is the prevalence per 100,000/year population of
-AML
-ALL

Back 8

AML = 3

ALL = 1.4

Front 9

What is the M:F ratio of
-AML
-ALL

Back 9

AML = 1:1
ALL = 1.4:1

Front 10

Why is it important to differentiate ALL and AML?

Back 10

Because the therapeutic regimens differ drastically!

Front 11

What are the 4 bases for differentiating ALL and AML?

Back 11

1. Morphology
2. Cytochemistry
3. Immunophenotyping
4. Genetics

Front 12

What is a hallmork morphologic finding in AML?

Back 12

Auer rods

Front 13

What 2 things are found in AML that are not found in ALL?

Back 13

-Auer rods
-Myelodysplasia

Front 14

What type of blast size is seen in
-AML
-ALL

Back 14

AML = large and uniform

ALL = small and variable

Front 15

How are the different blasts distinguished?

Back 15

-Cytochemical stains
-Immunophenotyping

Front 16

What are the 2 most useful cytochemical stains for blasts?

Back 16

-Myeloperoxidase
-NSE

Front 17

What is myeloperoxidase specific for?

Back 17

Myeloblasts

Front 18

What is Nonspecific esterase (NSE) specific for?

Back 18

Monocytic blasts

Front 19

What has largely replaced cytochemical staining?

Back 19

Immunophenotyping

Front 20

What are the 2 types of immunophenotyping done?

Back 20

-Immunohistochemistry of tissues in situ
-Immunocytochemistry

Front 21

What is the type of instrument that immunocytochemistry is done on?

Back 21

Flow cytometry

Front 22

What lymphoid antigens are specific for Tcells?

Back 22

CD1a, 2, 3, 4, 5, 7, 8

Front 23

What are the 3 B-lineage antigens?

Back 23

CD19
CD20
CD22

Front 24

What are the generic myeloid antigens?

Back 24

CD13
CD15
CD33
CD117
Myeloperoxidase

Front 25

What are the megakaryocyte myeloid antigens?

Back 25

CD41
CD61

Front 26

What is CD14?

Back 26

Monocytes

Front 27

What is CD34?

Back 27

The marker for BLAST - in either AML or ALL

Front 28

What is TdT

Back 28

A marker for ALL (lymphos)

Front 29

What is CD117?

Back 29

A marker for AML

Front 30

So the single digit CDs are:

Back 30

Mostly T-cell antigens (think ALL)

Front 31

Numbers around the 20s are:

Back 31

Bcell antigens (ALL again)

Front 32

Mid-teen CDs are:

Back 32

Myeloid

Front 33

Except for CD14 which is:

Back 33

Monocyte

Front 34

What is Acute Myeloid Leukemia?

Back 34

A heterogenous set of systemic neoplasms of myeloid progenitor cells

Front 35

What is generally the outcome of AML? (overall long-term survival)

Back 35

Poor
-Long term survival is only 25%

Front 36

What are the primary sites of AML?

Back 36

-Primarily in Blood/bone marrow
-May be extramedullary

Front 37

What are the 4 most common clinical features seen in AML, and what are they related to?

Back 37

-Weakness
-Fatigue
-Petechiae
-Infections
Related to cytopenias

Front 38

What are 3 less common findings in AML?

Back 38

-Organomegaly
-Lymphadenopathy
-Infiltration of other extramedullary tissues

Front 39

What clinical feature of CML is seen in specific variants?

Back 39

Coagulopathy

Front 40

What is the diagnostic criterion for calling AML?

Back 40

Greater than 20% blasts of Myeloid origin in the bone marrow or blood

Front 41

What is the marrow like in AML generally?

Back 41

Hypercellular

Front 42

Are the blasts in AML able to mature?

Back 42

To a variable and limited degree

Front 43

What is the limited and variable maturation of myeloid blasts in AML often like?

Back 43

Dysplastic

Front 44

To what myeloid lineage will the blasts in AML mature?

Back 44

ANY, sometimes more than one

Front 45

What are the 4 maturation lineages that are myeloid?

Back 45

-Granulocytic
-Monocytic
-Megakaryocytic
-Erythroid

Front 46

What is the diagnosis if the myeloid blasts are present but less than 20%?

Back 46

MDS or MPD

Front 47

What are the 4 WHO classifications of AML?

Back 47

-AML with recurrent cytogenetic abnormalities
-AML with multilineage dysplasia
-AML and MDS related to therapy
-AML NOS

Front 48

Which is the type of AML to get, if you're going to get it?

Back 48

AML with recurrent cytogenetic abnormalities

Front 49

What are the chromosome changes in
-AML w/ recurrent cytogenetic abnormalities
-AML with multilineage dysplasia

Back 49

AML w/ RCA - reciprocal translocations
AML w/ MD - Loss of whole chromosomes or parts of them

Front 50

What is the age variation seen in
-AML w/ RCA
-AML w/ MD

Back 50

Flat age variation in AML-RCA
Increases w/ age in AML-MD

Front 51

Which type of MDL is likely preceded by MDS?

Back 51

AML-Multilineage dysplasia

Front 52

Which type of MDL has generally better prognosis? Poor?

Back 52

AML-RCA - good prognosis
AML-MD - poor prognosis

Front 53

What are the 4 variants of AML w/ RCA (recurrent cytogenetic abnormalities)? Which are favorable or not?

Back 53

t8;21 - AML1/ETO (fav)
inv(16) - CBFb/MYH11 (fav)
t(15;17) - PML/RARa (fav)

11q23 (MLL) rearrngmts (bad)

Front 54

What is the name for AML with an 8:21 translocation?

Back 54

AML1/ETO

Front 55

What does ETO stand for?

Back 55

eight twenty one

Front 56

What are the 2 main morphologic features of AML w/ t8;21?

Back 56

-Prominent granulocytic maturation
-Prominent auer rods

Front 57

What is the most common of the AMLs with RCA?

Back 57

AML w/ inv (16)

Front 58

What are 2 other names for AML w/ inv (16)

Back 58

-CBFbeta/MYH11
Used to be called M4-Eo

Front 59

What morphologic features distinguish AML w/ inv(16)?

Back 59

-Myelomonocytic variation
-See eos in the bone marrow

Front 60

What is the most important AML w/ RCA to know and why?

Back 60

AML w/ t(15;17) - because it responds to the drug ATRA!!

Front 61

What is ATRA?

Back 61

All trans retinoic acid

Front 62

What is the other name for AML w/ t(15;17)?

Back 62

Acute Promyelocytic Leukemia (M3)

Front 63

What are the 4 common morphologic features of Acute Promyelocytic leukemia?

Back 63

-Hypergranular
-Reniform nuclei
-Faggot cells
-Leukopenic

Front 64

What variant of AML w/ t(15;17) has HYPOgranular cells and a leukocytosis?

Back 64

Microgranular variant

Front 65

What condition is often seen at diagnosis of AML w/ t(15;17) and what is the implication of it?

Back 65

-DIC
-Result is early morbidity and mortality

Front 66

What is the gene product of the t(15;17) chromosome abnormality?

Back 66

PML-RAR-alpha

Front 67

Why is the PML-RAR-alpha fusion gene bad?

Back 67

Because it disrupts the Retinoic acid receptor which is essential for normal myeloid maturation.

Front 68

What happens as a result of disrupting the RAR?

Back 68

Maturation is arrested at the Promyelocytic stage

Front 69

What overcomes the block and allows for myeloid cells to mature in promyelocytic leukemia?

Back 69

ATRA - it also quickly corrects the coagulopathy.

Front 70

What is the downside of ATRA treatment for AML w/ t(15;17)?

Back 70

Relapse is inevitable if ATRA is given alone and not along with conventional AML agents.

Front 71

In what age group is AML w/ 11q23(MLL) prevalent?

Back 71

Infants

Front 72

What is the general morphology seen in MLL?

Back 72

Monocytic with hyperleukocytosis

Front 73

How does the pronosis of AML w/ 11q23 (MLL) contrast to all the other AMLs w/ RCA?

Back 73

It has an intermediate to poor prognosis instead of favorable.

Front 74

What prompts a diagnosis of AML with Multilineage Dysplasia?

Back 74

Observing dysplasia in >50% of two or more lineages of cells

Front 75

What does AML w/ MD often follow?

Back 75

Myelodysplastic syndrome - but it doesn't necessarily always.

Front 76

In what age of patients is AML with MD predominantly seen?

Back 76

Older

Front 77

What are 3 forms of unfavorable cytogenetics in AML w/ MD?

Back 77

-7q deletion
-5q deletion
-Complex karyotypes

Front 78

What is the prognosis of AML with MD like in general?

Back 78

Unfavorable

Front 79

What is Therapy-related AML caused by?

Back 79

Previous chemotherapy and/or radiotherapy

Front 80

What are 2 types of therapy related to causing AML?

Back 80

-Alkylating agents
-Topoisomerase II inhibitors

Front 81

What is the timeframe for development of
-Alkylating agent-related AML/MDS?
-TopoII inhibitor related AML/MDS?

Back 81

Alkylating related = 5 yrs post treatment

TopoII Inhib related = 2.5-3 yrs

Front 82

What is the risk of developing AA-related AML/MDS related to?

Back 82

-Total dose
-Patient age

Front 83

What type of morphology is often seen in Alkylating agent related AML/MDS?

Back 83

Multilineage dysplasia

Front 84

What type of morphology is most often seen in TopoII inhibitor related AML/MDS? What is NOT often seen?

Back 84

OFten seen:
-Monocytic differentiation
-Myelomonocytic differentiation

Not often seen: MDS

Front 85

So of the drug-related AML/MDS cases, which is more likely to show MDS?

Back 85

Alkylating agent related

Front 86

What cytogenetic abnormalities are common in Alkylating agent related AML/MDS? How often?

Back 86

5q deletions
7q deletions
Complex karyotypes
Present in 100%

Front 87

What is the prognosis for therapy related AML and MDS?

Back 87

Poor

Front 88

What is the most common cytogenetic abnormality in Topoisomerase II Inhibitor related AML/MDS?

Back 88

11q23(MLL) translocation

Front 89

So the TopoII inhibitor-related AML/MDS closely resembles what other AML?

Back 89

The poor prognosis variant of AML with RCA (infantile de novo)

Front 90

What are cases of AML that do not fulfill the criteria for the other 3 groups (AML with RCA, AML w/ MD, or therapy related) get labelled as?

Back 90

AML not otherwise categorized

Front 91

How is AML not otherwise categorized, categorized?

Back 91

Based on morphology

Front 92

What are the classifications of AML NOC?

Back 92

FAB M0,1,2,4,5,6,and 7

Front 93

What are the first 3 classes, MO, M1, AND M2 based on?

Back 93

Degree of maturation
-0=minimally differentiated
-1=without maturation
-2=with maturation

Front 94

What are the last 4 classes, M4, M5, M6, and M7 based on?

Back 94

Lineage of differentiation
4=myelomonocytic
5=monoblastic/cytic
6=erythroid
7=megakaryoblastic

Front 95

What is the exception to the rule that most of the acute myeloid leukemias are restricted to the bone marrow and blood?

Back 95

Myeloid sarcoma

Front 96

What IS myeloid sarcoma?

Back 96

An extramedullary tumor of immature myeloid cells

Front 97

How can Myeloid sarcoma develop?

Back 97

Before, during, or after an additional AML diagnosis

Front 98

What are the 2 new latest and greatest prognostic markers in AML?

Back 98

-FLT3
-Nucleophosmin

Front 99

What is Flt3?

Back 99

A receptor tyrosine kinase that activates hematopoietic precursor survival and proliferation

Front 100

What types of AML can FLT3 be found in?

Back 100

A variety

Front 101

What is Nucleophosmin? (NPM)

Back 101

A nucleocytoplasmic shuffling protein

Front 102

When is NPM seen in AML?

Back 102

When the karyotype is NORMAL, in 50-60% of cases of AML

Front 103

What type of prognosis is assoc
-with FLT3
-with Nucleophosmin

Back 103

Flt3: poor prognosis

NPM: good prognosis, as long as there is no FLT3 present