Acute Myeloid Leukemia & Myelodysplastic Syndrome - Krafts

Question 1

What is the official definition of leukemia?

Answer 1

malignant proliferation of immature myeloid or lymphoid cells in the bone marrow

Question 2

What are the two types of acute leukemia?

Answer 2

1. Acute myeloid leukemia
2. Acute lymphoblastic leukemia

Question 3

What is the etiology behind leukemia?

Answer 3

• most are sporadic (spontaneous)
• toxins (benzene)
• genetic conditions increase chance
  
  • e.g. Down’s syndrome

Question 4

What is the cause of acute leukemia?

Answer 4

• clonal expansion
• maturation failure (arrest)
  
  • get stuck somewhere in myelopoiesis

Question 5

What is so bad about acute leukemia?

Answer 5

• Crowd out normal cells
  
  • fill up marrow space
  • no room for RBCs
• Inhibit normal cell function
• Infiltrate other organs (worst)
  
  • especially bad if enter the brain

Question 6

What are most morphologic cell types in acute leukemia?

Answer 6

Immature cells

(most blast cells)

Question 7

What are the clinical findings in acute leukemia?

Answer 7

• sudden onset (days)
• Symptoms of bone marrow failure
  
  • fatigue (not enough red cells)
  • infections (not enough white cells)
  • bleeding (can’t make platelets)
• Bone pain (due to expanding marrow)
• Organ infiltration (liver, spleen, brain)
  
  • leave bone marrow and enter organ

Question 8

What are the laboratory findings in acute leukemia?

Answer 8

• Marked leukocytosis (really high white count)
  
  • Blasts/immature cells in blood
• Anemia
• Thrombocytopenia

Question 9

What is the “Old” Classification system of AML based on?

Answer 9

only morphology

Question 10

What percent blast cells do you need to diagnose Acute Myeloid Leukemia?

Answer 10

Neet at least 20%

Question 11

What charactizes a blast cell in Acute Myeloid Leukemia?

Answer 11

• Immature white cells:
• Large nucleus
• Small amount of cytoplasm
• Fine chromatin (see through it)

Question 12

How do you know when a leukemia is myeloid?

Answer 12

• Dysgranulopoiesis
  
  • nucleus is not segmenting properly (one big lobe)
  • cytoplasm does not have any specific granulation (or unable to detect it at all)
• Auer rods
  
  • long needle-like structures in cytoplasm
  • only occur in malignant myeloid cells (usually only blast cells)
  • not all cases have them
• Cytochemistry
  
  • non-specific esterase stain - stains monocytes
  • myeloperoxidase - stains neutrophils
• Immunophenotyping
• Cytogenetics

Question 13

How is the “New” classification of AML different from the “old”?

Answer 13

• more characteristics than just morphology
• identifies cytogenetic abnormality
• has therapy-related category (developed after chemo)
• gives better idea of prognosis

Question 14

What classifies AML as “M0”?

Answer 14

• least mature (so immature)
  
  • barely differentiated into myeloid
• significantly increased myeloblast count
• bland cells
  
  • no auer rods
  • no granules
  • can’t tell what they are
• MPO (myeloperoxidase) negative
• Need markers (on cell surface)
  
  • flow cytometry detects these

Question 15

What classifies AML as “M1”?

Answer 15

• <90% myeloblasts
• No maturation (all blasts, none beyond this stage)
• Auer rods present
• MPO (myeloperoxidase) positive

Question 16

What classifies AML as “M2”?

Answer 16

• increased myeloblasts
• maturing neutrophils
• t(8;21) in some cases
  
  • special translocation
  • better prognosis

Question 17

What classifies AML as “M3”?

Answer 17

• increased promyelocytes (at least 20%)
  
  • not a lot of blast cells present
• Faggot cells (“bundle of sticks”)
  
  • has a ton of auer rods
• DIC (disseminated intravascular coagulation)
  
  • cells bust open and lead to clots
  • granules stimulate coagulation
  • use up all coag factors and then start bleeding
• t(15;17) in ALL cases
  
  • particular translocation that gives the patient a better prognosis (best for AML)
  • involves retinoic acid receptor - drug is Tretinoin (ATRA)
    
    • allows immature cells to mature

Question 18

What classifies AML as “M4”?

Answer 18

• Increased myeloblasts (at least 20% present)
• Increased monocytic cells
• Extramedullary tumor masses
  
  • tumor leaves bone marrow and goes into tissues (esp. CNS, gums)
• inv(16) in some cases
  
  • well-known translocation that gives patient a better prognosis

Question 19

What classifies AML as “M5”?

Answer 19

• Increased monocytic cells
  
  • promonocyte (overlapping, folds in nucleus)
• NSE (non-specific esterase) positive
• M5A (monoblasts) and M5B (promonocytes)
• Extramedullary tumor masses

Question 20

What classifies AML as “M6”?

Answer 20

• increased erythroblasts
• increased myeloblasts
• dyserythropoiesis
  
  • red cells are not growing properly
  • look abnormal

Question 21

What classifies AML as “M7”?

Answer 21

• Increased megakaryoblasts
• Bland blasts
• MPO (myeloperoxidase) negative
• Need markers
  
  • identified by flow cytometry

Question 22

What are the four specific types of AML with genetic abnormalities?

Answer 22

• t(8;21)
  
  • AML-M2
• inv(16)
  
  • AML-4
  • neutrophilic and monocytic
  • super dark granules
• *t(15;17)
  
  • in ALL cases of AML-3
  • treat with ATRA to let cells mature
• 11q23
  
  • not associated with any one leukemia
  • monocytic AML
  • bad prognosis

Question 23

What is the significant about AML with FLT-3 mutation?

Answer 23

• Mutation of FLT-3 (a tyrosine kinase)
  
  • allows white cell count to get REALLY high
  • increased proliferation rate of WBCs
• Present in 1/3 of cases of AML!
• Monocytic cells
• Poor prognosis

Question 24

What is significant about AML with multilineage dysplasia?

Answer 24

• Not very common
• Type of acute myeloid leukemia that has dysplasia (funny looking cells) in more than one myeloid lineage
  
  • at least 20% blasts + dysplasia in at least 2 cell lines
• More common in Elderly
• Severe pancytopenia
  
  • all cell counts are DOWN
• Chromosome abnormalities (5, 7)
• Poor prognosis

Question 25

What is significant about therapy-related AML?

Answer 25

* Previous chemotherapy treatment * alkylating agents (Busulfan) or topoisomerase II inhibitors (Etoposide) * 2-5 years to onset * Chromosomal abnormalities sometimes (5, 7, 11q23) * **VERY HARD TO TREAT!!!!**

Question 26

How do you treat AML?

Answer 26

* Know type of AML * specific treatments for some (ATRA) * Chemotherapy * get rid of bulk of tumor * Bone marrow transplant * if patient can tolerate it * do not need for AML-M3 * only hope for permanent cure

Question 27

What is the prognosis of AML?

Answer 27

* Dismal, bad * better prognosis in kids * t(8;21), inv(16), t(15;17) have better prognosis * FLT-3, therapy-related have worse prognosis

Question 28

What classifies Myelodysplastic Syndrome (MDS)?

Answer 28

* Problem: abnormal stem cells * Dysmyelopoiesis * May have increased blasts * May evolve into acute leukemia * Varied types & features

Question 29

What does dysplasia look like in red cells?

Answer 29

Megaloblastic nuclei Fragmentation

Question 30

What does dysplasia look like in neutrophils?

Answer 30

hypogranulation hyposegmentation

Question 31

What does dysplasia look like in megakaryocytes?

Answer 31

small, non-lobulated cells | (actually get smaller)

Question 32

What are the clinical/lab findings in Myelodysplastic Syndrome?

Answer 32

* Older patients * Asymptomatic OR bone marrow failure symptoms * fatigue * infection * bleeding * Macrocytic anemia

Question 33

What is the treatment for Myelodysplastic Syndrome?

Answer 33

* Low-grade * support * follow * High-grade * be aggressive * could turn into leukemia