Acute Leukemia: Clinical Cases and Correlates Flashcards Preview

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Flashcards in Acute Leukemia: Clinical Cases and Correlates Deck (51)
1

What is AML?

-Uncontrolled clonal proliferation and accumulation of neoplastic hematopoietic precursor cells of myeloid lineage
---Inhibition of normal hematopoiesis
---Defective maturation
---Dissemination into blood and other tissues
---20% myeloblasts in BM (WHO) or 30% myeloblasts in BM (FAB)

2

What is the #1 thing to think about with leukemia? (EXAM)

What are the cytogenetics? This drives prognosis and treatment

3

What are you thinking if you see a patient with fever, chills and swollen glands under neck?

Viral illness

4

What are you thinking if you see fever, chills, and diffuse adenopathy (all over body)?

HIV, AML (leukemia) (BAD STUFF)

5

Who is at increased risk for acute myelogenous leukemia? (EXAM)

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

6

What can cause secondary AML (acute myelogenous leukemia)?

Prior chemotherapy, radiation exposure, benzene

7

What is the median age of diagnosis for AML? How many cases in the US?

-Median age: 63 (80% > 15) - mostly adults
-7,400 deaths in US in 2002
-10,600 new cases in US in 2002

8

What can AML do the the mouth? (EXAM)

Can cause gums to hypertrophy

9

What are the clinical features associated with AML?

-Pancytopenia (red cells, white cells & platelets reduced)
---Anemia (often asymtomatic in elderly)
---Neutropenia
---Thrombocytopenia
-B symptoms: fever, night sweats, chills, malaise, weight loss
-Extremedullary disease - outside of the blood & bone marrow!
---Monocytic leukemias are most common (infiltration of leukemia in the gums)
---Skin, CNS, orbits, bone, lung, kidney, spleen, liver, ovary
-Hyperleukocytosis
--->100,000 blast count/ml
---APML, moncytic AML, inv(16), 11q23

10

How should you treat AML?

Promptly with hydroxyurea, leukopheresis, chemotherapy

11

What are the two methods of classification of AML?

FAB
WHO

12

What does AML look like on a blood film?

-Monocytic blast
-Cleft in the nucleus of monocytes
-You'll also see an auer rod

13

What is the FAB classification?

- >30% BM myeloblasts
-M0 (undifferentiated myeloid leukemia)
-M1 (acute myeloid leukemia without maturation)
-M2 (acute myeloid leukemia with maturation)
-M3 (acute promyelocytic leukemia)
-M4 (acute myelomonocytic leukemia)
-M5 (acute monocytic leukemia)
-M6 (acute erythroleukemia)
-M7 (acute megakaryocytic leukemia)

14

What is the WHO classification of AML?

- >20% BM myeloblasts
-AML with recurrent cytogenetic abnormalities
---ex: 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

15

What is the MAJOR PROGNOSTIC FACTOR for AML?

CYTOGENETICS - major and most important thing in terms of prognosis and treatment

16

What are favorable features of the AML? (good prognostic indicators)

-Age

17

What are unfavorable features of AML? (poor prognostic indicators)

-Poor risk cytogenetics
-Age >60
-Presence of infection or sepsis
-Poor performance status
-Presence of prior MDS
-Secondary AML
-Extreme leukocytosis
-Extramedullary disease (enlarged lymph nodes all over - adenopathy all over)

18

WHAT IS THE SINGLE MOST IMPORTANT PROGNOSTIC FACTOR FOR AML?

CYTOGENETICS

19

What cytogenetic outcomes have a favorable risk?

t(8;21) (best), t(16;16), t(15;17)

20

What cytogenetic outcomes have an intermediate risk?

(Normal karyotype)
-NPM1+/Flt3- genotype most favorable

21

What cytogenetic outcomes have an unfavorable risk?

del 5, del 7, trisomy 8, 11q23, other complex karyotypes

22

How do you do cytogenetics?

-Undergo tissue assay
-Prepare 20 cells in metaphase
-Pathologist looks at cells under microscope and tells you what's going on

23

How are most AML cases treated if 60 years or younger?

-Induction chemotherapy with anthracycline (daunorubicin, mitoxantrone, idarubicin) plus cytosine arabinoside. "7 + 3" regimen.
-If remission obtained (60-70% remission rate), then consolidation chemotherapy or transplantation
-If no remission, then especially poor prognostic sign
---If remission induced with alternative regimen, then consider allergenic transplantation

24

What is the "7 + 3" regimen?

-7 days of cytosine arabinoside (continuous infusion)
-3 days of 3 (idarubicin, mitoxantrone, daunorubicin)
-They're in the hospital for 3 weeks

25

Who should receive consolidation chemotherapy and what is it?

-High-dose cytosine arabinoside x 4 cycles
-Good risk cytogenetics (8;21, inv16, 15;17)
-Normal karyotype with NPM1+, Flt3-
-Intermediate risk cytogenetics w/o matched sibling donor or unwilling/unable to have transplant in 1st CR

26

What determines your eligibility for a stem cell transplant?

Poor risk cytogenetics

27

Why is cord blood so good?

-It is so simple and easy to do
-But it's not good because you have such a limited supply (baby is not identified)

28

When should you do allogenic stem cell transplantation?

-Poor risk cytogenetics
-Intermediate-risk cytogenetics with matched sibling donor
-Extramedullary disease (chloroma)
-1st or 2nd relapse
-Donor sources include siblings, children, parents, MUD-matched unknown donor, umbilical cord blood

29

What is autologous stem cell transplantation used for?

-No proven benefit over consolidation chemotherapy in 1st CR
-Consider for patients w/o an allogenic donor

30

What type of transplant is better?

Allogenic

31

How are AML cases treated if older than 60 years?

-USUALLY DON'T DO ALLOGENIC TRANSPLANTS
-Induction chemotherapy with anthracycline (daunorubicin, mitoxantrone, idarubicin) plus cytosine arabinoside. "7+3" regimen.
-If remission obtained (60% remission rate), then consolidation chemotherapy with reduced intensity cytosine arabinoside
-Mylotarg (anti-CD33 moAb) coupled to calicheamicin) for relapsed disease
-Consider observation and supportive care in lieu of induction chemotherapy

32

Is GVHD (graft vs. host disease) curable?

NO!

33

What are you thinking if patient has fatigue, malaise, fevers?

-Infection, Lyme's, Tick-borne illness

34

What are you thinking if patient has fatigue, malaise, fevers and nosebleed (epistaxis)?

-Thrombocytopenia, problem with coagulation system (less common)
-Tick borne illness can also present with thrombocytopenia

35

What is normal range for WBC count?

In single digits

36

What are normal platelets?

150-200 K

37

If fibrinogen is under 100?

Patient is consuming their factors or they don't have good liver function

38

What is a common drug that can elevate WBCs?

Steroids - cause demargination of neutrophils from the vascular system!

39

What can cause fever, fatigue, malaise and nosebleed? What does it look like on a blood smear?

M3 AML - acute promyelocytic leukemia
-You'll see heavily granulated promyelocytes!
-Stack of AUER RODS seen in cells
-Much mononuclear infiltrate is evident in slides!

40

What should you remember about acute promyelocytic leukemia (M3)? (EXAM)

-t(15;17) translocation
-If they relapse, they get arsenic trioxide

41

What should you know about acute promyelocytic leukemia (M3)?

-Most with t(15;17). Creates fusion gene, PML/RAR-alpha
-Poor risk disease with t(11;17)
-Induction therapy with ATRA plus anthracycline-based chemotherapy
-Consolidation with 2 courses anthracycline-based chemotherapy
-2 years maintenance chemotherapy with ATRA, 6-MP, and methotrexate
-Relapse
---Arsenic trioxide

42

What commonly happens with APML - M3?

-Auer rods
-DIC a common presentation
---Coagulopathy
---Depressed fibrinogen
---Thrombocytopenia
---Fatal hemorrhage

43

If a patient has M3 and DIC. . .

. . .start ATRA (all-trans retinoic acid) in

44

What can you not 'let the sun set on' or miss?

AML M3

45

What do you think when you hear 50 f, fatigue, headache, blurred vision?

-Electrolyte balance
-Dehydration
-Needs glasses

46

What does 1 gram of hemoglobin equal?

1 unit of blood

47

What is seen in the blood smear of someone with M4 AML?

Hyperleukocytosis
-Too big monocytes with cleft in nucleus
-Lymphocytes are too large (much larger than red cells)
---Indicates = bone marrow failure

48

What causes fatigue, headache and blurred vision in a patient with M4 AML?

Hyperleukocytosis
--Hyperviscosity
--Sludging in vasculature with ischemia and/or infarct
Leukopheresis to reduce WBC

49

What happens with automated blood counters?

-Can misdiagnose monocytosis - could actually be leukemia
-Cell counters can confuse blasts and monocytes

50

What can happen with a blood transfusion?

-Patient can have new blood type, the HLA of the donor
-This is called 100% donor chimerism - their cells even use the DNA of the donor

51

What are two new treatment paradigms in AML?

1. Flt-3 receptor tyrosine kinase inhibitors
-Quizartinib
-Effective (47% response rate ) in relapsed AML
-May be effective "bridge to transplant" strategy
-Studies underway to combine with conventional induction therapy
-Notable side-effects include QTc prolongation
2. CBF (core binding factor)
-Dasatinib
-C-kit overexertion in CBF+ AML