Acute Leukemia Case Dr. Nikcevich 5/14/14

Question 1

Increased risk of acute leukemia with?

Answer 1

Down syndrome, ataxia telangiectasia, Fanconi anemia, Li Fraumeni syndrome, Wiskott-Aldrich, familial leukemia, myelodysplasia, PNH

Secondary AML from prior chemotherapy, radiation exposure, benzene

Question 2

Clinical features of AML

Answer 2

• Pancytopenia
• B symptoms such as fever, night sweats, chills, malaise, weight loss
• Extramedullary disease
• Hyperleukocytosis
• Coagulation abnormalities (DIC w/ AML-3)

Question 3

Favorable features in AML

Answer 3

• Age<55
• Absence of infection/sepsis/antecedent MDS
• Low WBC
• Good cytogenetics: t(8;21), t(16:16); t(15;17)
• Normal karyotype w/ NPM1+, Flt3- (most favorable)
• Presence of Auer rods

Question 4

Unfavorable features in AML

Answer 4

• Poor risk cytogenetics
• Age >60
• Presence of infection or sepsis
• Poor performance status
• Presence of prior MDS
• Secondary AML
• Extreme Leukocytosis
• Extramedullary disease

Question 5

Treatment age 60 or younger

Answer 5

• Induction chemotherapy w/ anthracycline plus cytosine arabinoside 7 + 3 regimen
• If remission (14 days after starting therapy if bone marrow empty or blasts <5%) then consolidation chemotherapy (mop up whats left) or transplantation
• If no remission induced w/ alternative regimen, then consider allogeneic transplantation. No remission is a poor prognostic sign.

Question 6

Consolidation therapy

Answer 6

High-dose cytosine arabinoside x 4 cycles. Can result in cerebral toxicity. Before each dose have them sign name and if can’t sign on line then have it. Also could use tests such as rapid alternating, finger nose, and heels up shin.

Question 7

Transplant

Answer 7

• Allogenic stem cell transplantation for poor risk cytogenetics, intermediate-risk cytogenetics w/ matched sibling donor, extra medullary disease, first or second relapse.
• Autologous stem cell transplantation has no proven benefit.

Question 8

Treatment > 60 yo

Answer 8

• Induction chemotherapy w/ anthracycline plus cytosine arabinoside 7 + 3 regimen
• If remission then consolidation therapy w/ reduced intensity cytosine arabinoside
• Probably no role for allogeneic transplant
• Consider observation and supportive care in lieu on induction therapy

Question 9

Acute promyelocytic leukemia (M3)

Answer 9

• Most w/ t(15;17) which creates fusion gene, PML/RAR-alpha
• Poor risk disease w/ t(11;17)
• Induction therapy w/ ATRA plus anthracycline-based chemotherapy
• 2 years maintenance therapy w/ ATRA, 6-MP, and methotrexate
• Relapse use arsenic trioxide
• DIC a common presentation
• -coagulopathy
• -depressed fibrinogen
• -thrombocytopenia
• -fatal hemorrhage

Question 10

AML-M4

Answer 10

• Hyperleukocytosis
• -Hyperviscosity
• -Sludging in vasculature

-Leukopheresis to reduce WBC to <100K

Question 11

Flt-3 receptor tyrosine kinase inhibitors

Answer 11

Quizartinib

• may be effective bridge to transplant
• QTc prolongation