Acute Myeloid Leukemia & Myelodysplastic Syndrome -Krafts

Question 1

Myelodysplastic Syndrome (MDS)

Answer 1

• Problem: Abnormal stem cells
• Dysmyelopoiesis
• Maybe increase in blasts
• May evolve into acute leukemia

Question 2

What does dysplasia of MDS look like?

RBC:
Neutrophils:
Megakaryocytes:

Answer 2

Red cells: megaloblastic nuclei, fragmentation

Neutrophils: hypogranulation, hyposegmentation

Megakaryocytes: small, non-lobulated cells

Question 3

Clinical/Lab findings in MDS

Answer 3

• older patients (>50)
• Asymptomatic, or BM failure (fills up with abnormal cells and they fail to get out)
• Macrocytic anemia

Question 4

MDS: Tx and prognosis

Answer 4

Low grade: support and follow

High grade: be aggressive. be be aggressive.

Question 5

Acute Leukemia

Answer 5

• sudden onset
• Adults or children
• Rapidly fatal w/out treatment
• composed of IMMATURE cells (blasts

Question 6

Chronic Leukemia

Answer 6

• slow onset
• Adults only (>40)
• longer course
• Composed of MATURE cells

Question 7

How does Acute Leukemia occur?

Answer 7

Sporadic.

Cause:

1. clonal expansion
2. maturation failure

Badness:

• crowd out normal cells (worst thing)
• inhibit normal cell function
• infiltrate other organs

Question 8

Acute Leukemia=

Answer 8

Malignant proliferation of immature myeloid or lymphoid cells in the BM

Question 9

Clinical finding in Acute Leukemia:

Answer 9

Symptoms of BM failure:

• fatigue
• infections
• bleeding

Bone pain (expanding marrow)
Organ infiltration 

*sudden onset

Question 10

Lab findings in acute leukemia:

Answer 10

marked leukocytosis

• blasts/immature cells
• anemia
• thrombocytopenia

Question 11

Acute Myeloid Leukemia:

Things you much know

Answer 11

• Malignant proliferation of myeloid blasts in blood, bone marrow
• *20% cutoff for diagnosis
• Many subtypes
• BAD prognosis

Question 12

M0, M1, M2, M3

Answer 12

Involve neutrophilic series

myeloblasts, promyelocytes…

Question 13

M4 and M5

Answer 13

Involve monocytic series

M4: acute MYLEOmonocytic leukemia

M5: acute monocytic leukemia

Question 14

M6

Answer 14

acute ERYTHROBLASTIC leukemia

Question 15

M7

Answer 15

acute MEGAKARYOBLASTIC leukemia

Question 16

M0

Answer 16

acute myeloblastic leukemia, minimally differentiated

Question 17

M1

M2

Answer 17

M1: acute myeloblastic leukemia -without maturation

M2: acute myeloblastic leukemia WITH maturation

Question 18

M3

Answer 18

acute PROmyleocytic leukemia

Question 19

Need 20% blasts?

Answer 19

Count everything with nucleus (not mature RBCs)

if 20% are myleoblasts ===then you can diagnose acute myeloid leukemia

Question 20

How do you know if leukemia is myeloid?

Answer 20

1. Dysgranulopoiesis: funny looking neutrophils
2. Auer rods: only in malignant myeloblasts
3. Cytochemistry:
   
   • Nonspecific esterase (NSE) stain will show monocytic cells
   • Myleoperoxidase stain stains neutrophils
4. Immunophenotyping
5. Cytogenetics

Question 21

AML New Classification

Answer 21

AML with genetic abnormalities
AML with FLT-3 mutation
AML with multilineage dysplasia
AML, therapy-related
AML, not otherwise classified

Question 22

AML-M0

Things you must know

Answer 22

• increased myeloblasts (lots & tons)
• bland (can’t really tell they’ve decided to go myeloid instead of lymphoid)
• MPO negative
• Need markers

Question 23

AML -M1

Things you must know

Answer 23

• Lots and lots of myeloblasts
• ***No maturation **
• Can tell they decided to be myeloblasts
• Auer rods
• MPO positive

Question 24

AML-M2

Things you must know

Answer 24

• Increased myeloblasts
• maturing neutorphils
• T(8;21) in some cases ==better prognosis

Question 25

AML- M3

Things you must know

Answer 25

• lots and lots of PROmyelocytes (at least 20%)
• Faggot cells- lots of Auer rods
• DIC=disseminated intravascular coagulation (b/c cells have pro-coagulates in them)
• ***t(15;17) in ALL cases

**BEST prognosis of all AMLs

Question 26

AML-M4

Things you must know

Answer 26

• Increased myeloblasts
• increased MONOCYTIC cells
• Extramedullary tumor masses –like to go into CNS put chemo in CSF
• inv(16) in some cases

Question 27

AML-M5

Things you must know

Answer 27

Increased monocytic cells

NSE positive (stain for monocytes)
M5A and M5B (two types) 
Extramedullary tumor masses

Question 28

AML-M6

Things you must know

Answer 28

Increased ERYTHROBLASTS
increased myeloblasts
Dyserythropoiesis (cells not growing properly)

Question 29

AML-M7

Things you mustttt know

Answer 29

increased MEGAKARYOBLASTS

• bland blasts
• MPO negative (stain for neutrophils)
• Need markers

Question 30

AML with genetic abnormalities

Answer 30

t(8;21) some cases of AML-M2
inv(16) some cases of AML-M4
t(15;17)*** ALL cases of AML-3
11q23 –>bad prognosis (more common in monocytic AMLs)

Top 3 have good prognosis

Question 31

AML with FLT-3 mutation

Answer 31

• FLT-3 is a tyrosine kinase
  Mutation allows:
  1. white cell count to get really high
  2. cells to divide really quickly
• present in 1/3 of cases of AML
• Monocytic cells usually
• POOR prognosis

Question 32

AML with multilineage dysplasia

Answer 32

funny looking cells in more than one lineage
≥ 20% blasts + dysplasia in ≥ 2 cell lines

Elderly
Severe pancytopenia (all cell counts are low, even malignant cells) 

PORR prognosis

Question 33

AML therapy related

Answer 33

Previous chemotherapy
Alkylating agents (Busulfan) or topoisomerase II inhibitors (Etoposide)
2-5 years to onset

Chromosomal abnormalities sometimes (5, 7, 11q23)
Very hard to treat

Question 34

AML Tx and prognosis

Answer 34

Tx: chemo or BM transplant

Prognosis:

• dismal
• t(8;21), inv(16), t(15;17) better
• FLT-3, therapy-related is worse