Krafts- Acute myeloid leukemias and myelodysplastic syndromes

Question 1

What are the differences between acute and chronic leukemia?

Answer 1

sudden onset vs. slow onset
occur in adults or children vs. adults only
rapidly fatal w/out tx vs. longer course
composed of immature cells vs composed of mature cells

Question 2

What are lymphoid leukemias?

Answer 2

ALL

CLL

Question 3

What are myeloid leukemias?

Answer 3

AML

CML

Question 4

What causes acute leukemia and what does it lead to?

Answer 4

Clonal expansion
Maturation failure

Leads to….
Crowding out of normal cells
Inhibit normal cell function
Infiltrate to other organs

Question 5

What are the clinical findings of acute leukemia?

Answer 5

Sudden onset (days)
Bone marrow failure–> fatigue (anemia), infections (WBC), bleeding (throbocytopenia)
Bone pain
Organ infiltration (liver, spleen adn brain)

Question 6

What are the characteristic lab findings of acute leukemia?

Answer 6

Blasts/immature cells in blood
Leukocytosis
Anemia
Thrombocytopenia

Question 7

How do you treat acute leukemia?

Answer 7

Chemo

bone marrow transplant

Question 8

What is the prognosis for acute leukemia?

Answer 8

DISMAL

Question 9

What translocations make the prognosis for acute leukemia better and what makes it worse?

Answer 9

t (8:21)
inv (16)
t (15;17)

**FLT-3, therapy-related worse

Question 10

What are the characteristics of acute myeloid leukemia?

Answer 10

Malignant proliferation of myeloid blasts in blood, bone marrow

20% cutoff–20% of nucleated cells must be malignant

Many subtypes

Bad prognosis

Question 11

What do you use to diagnose Acute myeloid leukemia?

Answer 11

Cytochemistry
Immunochemistry
Cytogenetics (Flow cytometry)

Question 12

What morphology is common to AML?

Answer 12

Dysngranulopoesis–Granulocytes that “look funny”
Auer Rods
Blast cells from the monocytic series

Question 13

What to AML’s only have increased myeloblasts, and what are the differences between these two?

Answer 13

M0- AML minimally differentiated
bland myeloblasts, MPO negative

M1- AML without maturation
auer rods, MPO positive

Question 14

Which AML is associated with maturing neutrophils?

Answer 14

M2- acute myeloblastic leukemia w/ maturation

Myeloblats and some maturing neutrophils

Question 15

What translocatin is associated w/ M2?

Answer 15

t (8;21)

Question 16

What AML is associated with Faggot cells and DIC?

Answer 16

M3- acute promyelolytic leukemia
Increased numbers of promyelocytes
Faggot cells- tons of auer rods
Contains DIC granules that are pro-coagnulant

Question 17

What is a complication often caused by DIC?

Answer 17

If these cells break granules are released that are pro-coagulant–> clotting–> clotting factors are used up–> bleeding

Question 18

What translocation is associated w/ M3?

Answer 18

t (15,17)

Question 19

What is the treatment for M3 and what does it do?

Answer 19

All-trans retinoic acid

Removes block on pro-myelocyte maturation

Question 20

What AMLs effect the neutrophillic series?

Answer 20

MO-M3

MO-M1 = blasts
M2= blasts + maturing neutrophils
M3= pro-myelocytes

Question 21

What AMLs effect the monocytic series?

Answer 21

M4

M5

Question 22

What AMLS effect the erythroid series?

Answer 22

M6

Question 23

What AMLs effect the megakaryocyte series?

Answer 23

M7

Question 24

What is the difference between M4 and M5?

Answer 24

M4- acute MYELOmonocytic leukemia (increased myelo and mono cells)

M5- acute MONOcytic leukemia
Increased mono cells

Question 25

What types of tumors are often seen with M4 and where are they seen?

Answer 25

Extramedullary tumor masses CNS, gums, testes

Question 26

What inv is associated with M4 and what is it indicative of?

Answer 26

Inv 16 Better prognosis

Question 27

What stain can be used to diagnose M5 that is specific to monocytes?

Answer 27

NSE (non-specific esterase)

Question 28

What types of tumor masses are seen with M5?

Answer 28

Extramedullary tumor masses

Question 29

M6 is associated with....

Answer 29

Increased erythroblasts and myeloblasts

Question 30

What is a common feature of M6?

Answer 30

Dyserythropoiesis--funny looking RBCs, bubbly vaculization

Question 31

M7 is associated w/

Answer 31

acute megakaryoblastic leukemia Increased megakaryocytes bland blates

Question 32

Is M7 positive or negative for MPO?

Answer 32

negative---need markers

Question 33

AML w/ FLT-3 mutations is associated w/ what enzyme? Is present in how many cases? Effects what cells? Prognosis?

Answer 33

Tyrosine kinase 1/3 of all cases Monocytic cells Poor prognosis d/t faster cell growth and more relapse

Question 34

What is AML w/ multilineage dysplasia?

Answer 34

More than one cell line (multi-lineage) has abnormal cell changes (dysplasia) ``` >20% blasts + dysplasia in >2 cell lines Severe pancytopenia (all cells lack) ```

Question 35

Multilineage dysplasia is often seen in what population? What chromosomal abnormalities is it associated with? Prognosis?

Answer 35

Elderly 5,7 Poor prognosis

Question 36

Therapy related AML is often associated with what two chemo drugs?

Answer 36

Busulfan- alkylating agent Etoposide- Topo II inhibitor

Question 37

What chromosomal abnormalities are associated with drug related AML? Is it hard to treat? When does it occur?

Answer 37

5, 7, 11q 23 VERY Hard to treat Usually occurs 2-5 years after chemo

Question 38

t(8;21) AML? Prognosis?

Answer 38

M2 Maturing neutrophils better prognosis

Question 39

inv(16) AML? Prognosis?

Answer 39

M4 monocytes better prognosis

Question 40

t (15;17) AML? Prognosis?

Answer 40

M3 promyelocytes (faggot, DIC) Better prognosis

Question 41

11q23 AML? Prognosis?

Answer 41

Usually seen in AMLs w/ monocytic component | 1/3 of all AML cases

Question 42

FLT-3 AML? Prognosis?

Answer 42

Worse prognosis often seen w/ monocytes

Question 43

What is MDS?

Answer 43

Myelodysplastic syndrome is a problem with myeloid stem cells --> dysmyelopoiesis--> increased blasts--> can evolve to acute leukemia

Question 44

Clinically, MDS is observed in what pt population and what are the common sxs?

Answer 44

Elderly | Asymptomatic or bone marrow failure

Question 45

What type of anemia is associated MDS and what are the common dysplasias?

Answer 45

Macrocytic anemia Dysplasia: RBC- megaloblastic neuclei, fragmentation Neutrophils- hypogranulation, hyposegmentaiton Megakaryocytes- small, non-lobulated cells

Question 46

What is the tx for low/high grade MDS?

Answer 46

low- support, follow | high- aggressive