12-1: 1/11 - Acute Leukemias And Myelodysplastic Syndrome

Front 1

Risk factors for AML:
General
Drugs
Diseases

Back 1

Genetics: three-fold increase if sibling has AML

Inc'd maternal Age

DOWN'S SYNDROME--500-fold increase!

Exposure to alkylating agents (used for Hodgkin's disease, BrCa, non-malignant dz); latent period of 5-10 years!!

Exposure to topoisomerase II inhibitors (etoposide, topotecan); latency period of 1-3 years

Previous myelodysplastic syndrome

Dz:
PVera
Essential Thrombocytopenia
Myelofibrosis

Front 2

AML:
Clinical Presentation

Back 2

Acute!
Anemia (fatigue, pallor)
Thrombocytopenia (petechiae)
Lack of normal immune system and inc'd risk of infections
Gingival Hyperplasia

Note: despite increased blast

Front 3

What is leukostasis?
Risks?
When is the risk greater?

Back 3

Too many blasts in blood; blast cells have high adherence to one another and cause conglomeration of cells in bv's

Can lead to strokes (CVA), pulmonary embolism

Risk escalates with blast count > 50,000

Front 4

What is the most important prognostic factor of AML?

Back 4

Cytogenetics

Front 5

What is flow cytometry?

Back 5

Tool that evaluates markers on cell surfaces to better define disease etiology.

Front 6

How is AML definitively diagnosed?

Back 6

BM biopsy and aspirate

Can't dx based on smear and counts alone

Front 7

In BM aspirate, what defines AML?

Back 7

BM blast percentage >20% that are myeloblasts

Front 8

What are the good prognostic cytogenetic findings for AML?

Back 8

Inversion 16: t(16;16)

t(8;21); ETO translocation (eight-twenty-one)

t(15;17): fusion between PML (pro-myelocytic) and Retinoic Acid Receptor genes alpha (PML-RAR alpha)

ANYTHING ELSE IS BAD

Front 9

What are the intermediate prognostic cytogenetic findings for AML?

Back 9

Normal cytogenetics (XY, XX)

EVERYTHING ELSE (other than good prognostic factors) HAS POOR PROGNOSIS

Front 10

In patients with normal cytogenetics, what abnormal gene finding indicates a poor prognosis?

Back 10

FLT3 ("flit 3")

Front 11

What flow cytometry results are indicative of AML?

Back 11

CD33+
CD13+
Tdt -

Front 12

What is M3?

What are its histologic features?

Back 12

Acute Promyelocytic Leukemia (hypergranular)

Promyeloblasts show up in blood stream. May have Auer rods.

Present with low PLT and often in DIC/fibrinolysis (high risk for clot).

Front 13

M3 - APML:
Translocation
Treatment

Back 13

Translocation: t(15;17)

Treatment: All-Trans-Retinoic-Acid (ATRA) in combn with chemotx

Front 14

ATRA Syndrome:
General
Presentation
Treatment

Back 14

Capillary leak syndrome after initiation of ATRA

Present with fevers, weight gain, resp distress, pneumonias, hypotn, rengal failure, pleural/pericardial effusions

Tx with high dose steroids EARLY

Front 15

What are the two phases of treatment of AML? (General)

Back 15

1) Induction: intitial treatment to put someone in complete remission
2) Consolidation: multiple repeat treatments to maintain remission and aim for cure.

Front 16

AML:
Treatment

Back 16

1) Induction:
7+3:
Day 1-7: Ara-C
Days 1-3: Anthracycline

Follow labs closely to prevent tumor lysis syndrome. Goal is to have day 14 marrow be disease free (aplastic)

2) Consolidation:
Good risk cytogenetics (inversion 16; ETO): 3-4 cycles Ara-C (chemotx)
Intermediate risk: Autologous or Allogeneic transplant

If high risk: Allogeneic transplant

Front 17

What is elderly AML and why is it so difficult to treat?

Back 17

Elderly = Age>55-60
Poor response bc likely have multi-drug resistance resistance gene

Can't tolerate chemo due to other co-morbidities

Front 18

Elderly AML:
Treatment

Back 18

5-azacitadine
Decitabine
(hypomethylating agent)

Front 19

When is leukophoresis indicated?

Back 19

Inc'd WBC; blast count>50K

Front 20

ALL:
RIsk Factors

Back 20

Down's
Klinefelter's
Fanconi's

Survivors of atomic bomb

Rarely related to chemo or chemicals

CML can transform into ALL!!

Front 21

What are the different type of B-cell and T-cell ALLs?

Which is most common?

Back 21

B-Cell:
Early Pre-B-Cell
Common ALL
Pre-B-Cell (MOST COMMON)
Mature B-Cell

T-Cell:
Pre-T-cell
Mature T-cell

Front 22

L1 vs L2 vs L3:
Cell Type
Disease association

Back 22

These are blast types:

L1: Small cells, usually pediatric
L2: large cell, usually adult ALL
L3: Burkitts Lymphoma

Front 23

Diagnose:
Tdt+
CD19+

Back 23

Pro-B

Front 24

Diagnose:
Tdt+
CD19+
CD10+

Back 24

Pre-Pre-B
OR
Pre-B

Front 25

Diagnose:
Tdt+
CD19+
CD10+
CD20+

Back 25

Pre-B

Front 26

Diagnose:
Tdt-
CD19+
CD10+
CD20+

Back 26

Early B Burkitts

Front 27

T-cell ALL will exhibit which cell markers?

Back 27

Tdt
CD7, CD2, CD5

Front 28

What translocation is associated with a good prognosis in ALL?

Back 28

t(12;21)

Front 29

ALL:
Clinical Presentation

Back 29

ACUTE dev't of pallor, weakness, fatigue, petechiae (due to BM failure)

**PAINLESS LAD**

Hepatosplenomegaly

Front 30

ALL:
Extramedullary Sites
What does this mean for prophylactic treatment?

Back 30

ANYWHERE;
**Must do lumbar puncture and prophylactic CNS tx (intrathecal chemotx)**

Testicle = major site of recurrence in children

Front 31

Patients with ____ do not require leukophoresis. Why?

Back 31

Pts with ALL don't require leukophoresis bc blasts don't cause leukostasis

Front 32

ALL:
Lab Findings

Back 32

Elevated LDH
Hypercalcemia (paraneoplastic)
Tumor Lysis Syndrome (Hyperkalemia, elevated uric acid, hyperphosphatemia, hypocalcemia)

Front 33

ALL:
Poor prognostic factors

Back 33

High WBC count
Inc'd age
Cytogenetic abnlts
Mediastinal Mass
MALES
AA or HISPANIC origin

Front 34

ALL:
Treatment

Back 34

1) initial:
-High volume fluids to prevent TLS
-Allopurinol
-Hydrea to bring down WBC
-ABx prophylaxs (fluoroquinolones)
-Transfusions PRN
-DON'T NEED LEUKOPHORESIS

2) Multiple drug tx intrathecal chemotx for 2 years

3) BM TRANSPLANT FOR ALL--must do early on

Front 35

How does ALL differ from AML?

Back 35

-Usually older population
-Presentation is LAD, effects from cytopenia rather than infection
-Large undiff'd cells without granules or auer rods
-No risk of leukostasis

Front 36

80% of patients with this disorder are over the age of 60.

Back 36

Myelodysplastic syndrome

Front 37

What is myelodysplastic syndrome?

Back 37

Ineffective hematopoiesis:

Cells made are defective

Cells unable to leave marrow space, which is why marrow hypercellular

Fnal capacity of cells is diminished, particularly nphils

Front 38

Myelodysplastic Syndrome (MDS):
Clinical presentation

Back 38

Chronic development, not acute

Infection (inc'd risk due to npenia and granulocyte dysfn)

Fatigue, weakenss due to anemia

Easy bleeding/bruising due to thrombocytopenia

RARE: LAD, SPLENOMEGALY

Front 39

MDS:
Lab findings

Back 39

Low WBCs
Macrocytic Anemia
PLTs usually low

Front 40

Good prognostic factors for MDS.

Back 40

Normal cytogenetics
Lack Y chromosome
5q deletion

Front 41

Poor prognostic factors for MDS.

Back 41

Multiple chrom abnlts; esp, chrom 7

Front 42

% blasts affects the prognosis of this disorder.

What is the prognosis?

Back 42

In MDS:
<5% blasts (good prognosis)
more than 5%--poor prognosis

Front 43

IPSS: Scale/point system for scoring for MDS based on blasts.

Back 43

Blasts <5% = 0
11-20% blast = 1.5 points
20% blast puts you in AML

High risk category: sig thrombocytopenias (PLT<100), ANC<1.5, excess blasts-->poor prognosis

IPSS Scores:
Low: 0
Int-1: 0.5-1
Int-2: 1.5-2
High: 2.5-3.5

Front 44

MDS:
Treatment

Back 44

<55:
Low: WW or SCT
Int: Transplant

55-75:
Low: Supportive care
High, good perf: Clinical Trials
High, poor health performance: Supportive Care

Front 45

What constitutes supportive care?

Back 45

GF Support:
EPO
G-CSF with npenia or active infections
Transfusions PRN

Front 46

Azacitine:
Drug Class
Use

Back 46

DNA demethylating agens

Use in MDS to delay onset of leukemia (by 8 mos)

Front 47

Decitabine:
Drug Class
Use

Back 47

DNA Demethylating agent

Use in MDS (to delay onset of leukemia?)

Front 48

Lenolidamine:
Use

Back 48

MDS with 5q- patients (present with higher PLT count), makes patients transfusion independent.

Lenolidamide blocks angiogenesis (growth of BVs)

Front 49

This disorder presents with morphologic changes in all three cell lines.

Back 49

MDS