Acute Leukemia Cases - Nikcevich

Question 1

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

Answer 1

Cytogenetics

Question 2

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

Answer 2

11q23

Question 3

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

Answer 3

• 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 4

When is extramedullary disease present?

Answer 4

• 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 5

What is consolidation therapy?

Answer 5

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

Question 6

What is allogeneic stem cell transplantation?

Answer 6

• 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 7

When is transplant preferred over consolidation chemotherapy?

Answer 7

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

Question 8

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

Answer 8

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

Question 9

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

Answer 9

• Don’t let the sun set on M3!
• Start ATRA (all-trans retinoic acid) in <6 hours!

Question 10

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

Answer 10

• Coagulopathy
• Depressed fibrinogen
• Thrombocytopenia
• Fatal hemorrhage

Question 11

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

Answer 11

• Hyperleukocytosis
  
  • Hyperviscosity
  • sludging in vasculature with ischemia and/or infarct
• Tx: leukophoresis to reduce WBC to <100K

Question 12

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 12

• 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 13

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

Answer 13

• 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