M. Acute Leukemia (L15)

Question 1

What percentage of bone marrow cells are blasts normally? What percentage is seen in Acute Leukemia?

Answer 1

• < 3%

* >20%

Question 2

What is the general pathophysiology of Acute Leukemia?

Answer 2

• Disruption of hematopoiesis –> inability for cells to mature –> buildup of myloid or lymphoid blasts/stem cells
• Proliferative cells crowd out normal cells in bone marrow –> acute presentation of anemia, thrombocytopenia & neutropenia
• Blasts enter blood –> increased (lymphocytic or myelocytic) WBC in peripheral blood (large immature cells with little cytoplasm and nucleolus)

Question 3

What “step” in hematopoiesis are acute leukemias “stuck” in?

Answer 3

• Transition from HSC to lymphoblast and myloblast but then get stuck

Question 4

What are the 2 main types of Acute Leukemia & what type of proliferative cell type is present? Which is most common? Mnemonic?

Answer 4

• Acute Myloid Leukemia (AML) = myloblasts
• Acute Lymphoid Leukemia (ALL) = Lymphoblasts
• AML is most common
M for More (L for little)

Question 5

How does Acute Leukemia present on Bone Marrow Biopsy?

Answer 5

• 100% cellularity (no fat cells)

Question 6

What is the “rule of thumb” to estimate what percentage of bone marrow should normally be cellular?

Answer 6

100 – age

Question 7

What age groups are AML & ALL found in? Mnemonic?

Answer 7

• ALL = children (Think L for little)

* AML = adults (M = more for more common)

Question 8

Time wise, what is the onset of Acute Leukemia?

Answer 8

• Presents with severe symptoms within a few weeks

* Can rapidly become fatal if not treated

Question 9

What is the clinical presentation for Acute Leukemia?

Answer 9

• Crowding in BM by proliferative cells –> Pancytopenia –> below symptoms:
• Anemia –> fatigue & pallor
• Thrombocytopenia –> bleeds/bruising
• Decrease in functional WBCs –> infection & fever
• Leukocytosis as proliferative WBCs spill into circulation
• Hepatosplenomegaly
• Skin and gum WBC infiltration
• CNS involvement

Question 10

What is the leading cause of non-traumatic death in children?

Answer 10

ALL

Question 11

What ethnic group and sex is ALL most common in?

Answer 11

White boys

Question 12

What increases the likelihood of ALL?

Answer 12

• Down syndrome
• Radiation
• Genetic syndromes

Question 13

What are the 2 main types of ALL? Which is more common? Which is more aggressive?

Answer 13

• Pre-T Cell ALL
• Pre-B Cell ALL
• B is more common (85%)
• T is more aggressive

Question 14

Where do Pre-T ALL masses present most often?

Answer 14

• Superior Mediastinum (where thymus is)

* Cause SOB as compress structures

Question 15

What is the key finding for the L3 FAB classification on bone marow aspirate smear? What disease is it related with?

Answer 15

• Vacuoles

* Burkitts

Question 16

What are characteristics that lead to a good prognosis for ALL? Bad?

Answer 16

• 50k bad)
• 1-10 yo (10 bad)
• Lack of CNS involvement (CNS involvement bad)

Question 17

What is the overall prognosis of ALL?

Answer 17

• Good, 98% go into remission

* 2/3 have long term remission while 1/3 relapse

Question 18

What age group is de novo AL seen in? What are the cytogenetic characteristics? Better or worse prognosis?

Answer 18

• Younger age children
• Less complex cytogenetics
• Better prognosis

Question 19

What causes secondary Leukemia?

Answer 19

• Prior diagnosis of myeloproliferative disorder or myelodysplastic disorder
• Toxins (occupational, chemo, accidental)

Question 20

What are Auer Rods diagnostic of?

Answer 20

AML

Question 21

What is the overall prognosis of AML?

Answer 21

• 60% remission

* 80% of remission has reoccurrence

Question 22

What is butterfly shaped nuclei diagnostic of?

Answer 22

• APL, a type of AML

Question 23

How is the prognosis of ALL & AML changed if t(9:22) translocation is present?

Answer 23

Worse Prognosis

Question 24

What mutation causes Acute Promyelocyte Leukemia (APL)?

Answer 24

• T(15:17) PML:RARalpha
• Fuses anti-apoptotic factor & retinoic acid receptor –> blocks myeloid proliferation
DIC PRONE

Question 25

DIC is seen in what type of Acute Leukemia?

Answer 25

APL

Question 26

What type of Acute Leukemia is one of the first examples of targeted gene therapy?

Answer 26

APL (AML)

Question 27

What type of AL stains with myeloperoxidase (MPO)? Color of MPO?

Answer 27

AML | Dark blue

Question 28

What is the main morphological feature of lymphoblasts and myloblasts?

Answer 28

• Large size which is mostly made up of nucleus

Question 29

None specific esterase stains what cell type? Color of stain?

Answer 29

Megaloblasts | Greenish red color

Question 30

What is a neoplastic buildup of lymphocytes called? How about mylocytes?

Answer 30

ALL | AML

Question 31

How does incidence for AML & ALL change in relationship to age?

Answer 31

``` ALL = bimodal but much higher in kids than in elderly AML = risk increases with age ```

Question 32

What does M3 in the FAB classification system signify?

Answer 32

APL

Question 33

Does acute leukemia present with peripheral leukocytosis or leukopenia?

Answer 33

Either | There is a decrease in functional WBCs, but the proliferative WBCs may or may not spill into the circulation

Question 34

Is extramedullary involvement more often seen in AML or ALL?

Answer 34

ALL

Question 35

What condition can be a precursor to ALL?

Answer 35

Initially present as nodal or skin disorder --> progress to bone marrow

Question 36

Most common cancer in newborn to 15yo? 15-40? 40-60? >60?

Answer 36

ALL AML AML (60%) or CML (40%) CLL

Question 37

4 types of AML based on lineage?

Answer 37

Acute Monocytic Leukemia Acute Erythroid Leukemia Acute Megacaryocytic Leukemia Acute Promyelocytic Leukemia (APL)

Question 38

What type of acute leukemia is associated with DIC?

Answer 38

APL (type of AML)

Question 39

Patients with what type of AML are prone to bleeding?

Answer 39

APL because of the associated DIC

Question 40

For what type of Acute Leukemia is all trans retinoic acid (Vit A) a treatment?

Answer 40

APL

Question 41

What cytogenetic conditions are associated with a better ALL prognosis?

Answer 41

t(12:21) | Hyperploidy (Trisomy 4 & 10)

Question 42

What cytogenetic conditions are associated with a worse ALL prognosis?

Answer 42

t(9:22) t(1:19) MLL gene

Question 43

What is the L1 category of ALL?

Answer 43

Lymphoblasts with very little cytoplasm (very high N/c ratio)

Question 44

What types of extramedullary involvement is seen in pre-T & pre-B ALL?

Answer 44

Both = CNS, Skin, Liver Spleen | B only = Gonads, Lymph nodes

Question 45

Are neoplasms of precursors more common in children or adults? What about effector cell neoplasms?

Answer 45

Neoplasms of precursor cells tend to be more common in children, while those of antigen-dependent effector and memory cells tend to be more common in adults.

Question 46

Where do different types of neoplastic cells go?

Answer 46

–neoplasms of bone marrow precursor cells are often acute leukemias; –those of germinal center cells occur in follicular areas of lymph nodes and other tissues, –those of memory B-cells are often found in sites of antigenic stimulation, such as the gastrointestinal tract.

Question 47

What type of cells are building up in chronic leukemia?

Answer 47

Abnormal but relatively mature cells

Question 48

How urgently must treatment be started for acute leukemias? Chronic?

Answer 48

``` Acute = begin immediately Chronic = sometimes observe for a while before begin ```

Question 49

What is taken into account for FAB & WHO classifications?

Answer 49

``` FAB = morphology and cytochemistry WHO = morphology, cytochemistry & clinical presentation ```

Question 50

What are Auer rods made of?

Answer 50

Fusion of primary granules