Acute Leukemia - Nikcevich

Question 1

Define Acute Myelogenous Leukemia

Answer 1

Uncontrolled clonal proliferation and accumulation of neoplastic hematopoietic precursor cells of myeloid lineage

Question 2

What are the key characteristics of AML?

Answer 2

Inhibition of normal hematopoiesis
Defective maturation (young cells)
Dissemination to blood
20% myeloblasts in Bone Marrow
Median age diagnosis: 63

Question 3

What risk factors increase your risk of developing AML?

Answer 3

Down Syndrome, Li Fraumeni Syndrome, Ataxia telangiectasia, Fanconi Anemia, Wiskott-Aldrich, Familial leukemia, Myelodysplasia, PNHH

Question 4

What causes secondary AML?

Answer 4

Prior chemotherapy
Radiation exposure
Benzene

Question 5

What is the key prognostic feature of AML?

Answer 5

Cytogenetics

Question 6

What other prognostic factors contribute to AML?

Answer 6

Under 55 years old
Absence of infection or myelodysplastic syndrome
Low WBC
t(8;21), inv(16), t(15;17)
Normal Karyotype with FLT-3 negative, NPM1 positive
Presence of Auer rods

Question 7

What is an allogeneic transplantation?

Answer 7

Stem Cell Transplant from a donor

Question 8

What is the #1 prognostic feature in leukemia that drives the treatment and prognosis?

Answer 8

Cytogenetics

Question 9

What cytogenetic abnormality has an unfavorable risk in acute leukemia and is associated with previous chemotherapy treatment?

Answer 9

11q23

Question 10

What is the difference between the FAB and WHO classification of acute leukemia?

Answer 10

FAB: > 30% BM myeloblasts, old, not used much anymore
M0 (undifferentiated myeloid)
M1 (acute myeloid without maturation)
M2 (acute myeloid with maturation)
M3 (acute promyelocytic leukemia)
M4 (acute myelomonocytic leukemia)
M5 (acute monocytic leukemia)
M6 (acute erythroleukemia)
M7 (acute megakaryocytic leukemia)
WHO: >20% BM myeloblasts, new, used more
AML with recurrent cytogenetic abnormalities – t(8;21), t(15;17), t(inv16), 11q23
AML with multilineage dysplasia
AML and MDS, therapy-related
AML not otherwise categorized – similar to FAB list
Acute biphenotypic leukemia

Question 11

When is extramedullary disease present?

Answer 11

Cell maturation outside of bone marrow
Most common in monocytic leukemias
hypertrophic gums
can occur in skin, CNS, orbits, bone, lung, kidney, spleen, liver, ovaries

Question 12

What is consolidation therapy?

Answer 12

Treatment after remission
killing any remaining cancer cells
“mop up” with more chemotherapy

Question 13

What is allogeneic stem cell transplantation?

Answer 13

treatment for first or second relapse
transplant stem cells from another person
donor sources include siblings, children, parents, umbilical cord blood, or matched unrelated donor

Question 14

When is transplant preferred over consolidation chemotherapy?

Answer 14

Poor risk cytogenetics
Intermediate-risk cytogenetics with matched sibling donor
Extramedullary disease (chloroma)
1st or 2nd relapse

Question 15

What cytogenetics are common with Acute promyelocytic leukemia (M3)?

Answer 15

Most with t(15;17)
creates fusion gene, PML/RAR-alpha
Poor risk disease with t(11;17)

Question 16

If a patient is diagnosed with Acute promyelocytic leukemia (M3) and DIC, what is the goal for treatment?

Answer 16

Don't let the sun set on M3!
Start ATRA (all-trans retinoic acid) in

Question 17

What is the common presentation of DIC in the setting of Acute promyelocytic leukemia (M3)?

Answer 17

Coagulopathy
Depressed fibrinogen
Thrombocytopenia
Fatal hemorrhage

Question 18

What could cause fatigue, headache, and blurred vision in a patient with AML-M4? Tx?

Answer 18

Hyperleukocytosis
Hyperviscosity
sludging in vasculature with ischemia and/or infarct
Tx: leukophoresis to reduce WBC to

Question 19

What should you do if you see a patient for fatigue and fevers that turns out to have a low hemoglobin, normal platelet count, and normal WBC with automated differential reporting monocytosis?

Answer 19

When see monocytosis on differential → don’t be fooled
Automated differential reports monocytosis BUT automatic cell counters can confuse blast cells and monocytes
So… look under microscope – bone marrow biopsy shows M4 AML leukemia

Question 20

What new treatment paradigms will we see for Acute Myelogenous Leukemia in the future?

Answer 20

Targeted therapies
Flt-3 receptor tyrosine kinase inhibitors
Quizartinib
Effective (47% response rate) in relapsed AML
May be effective “bridge to transplant” strategy
CBF (core binding factor)
Dasatinib
C-kit overexpression in CBF + AML