Wake Chronic Leukemias

Front 1

To which types of leukemia cells are steroids cytotoxic?

Back 1

Lymphocytic
Not myeloid

Front 2

Chronic myelogenous leukemia

Back 2

- MALIGNANT cell is relatively IMMATURE stem cell
- Result is EXCESS production of MATURE cells of multiple lineages

Front 3

What does CBC show in CML?

Back 3

- Elevated total white cell count
- Differential reveals elevated numbers of neutrophils, bands, myelocytes, metamyelocytes, eosinophils, basophils, platelets
- Normal levels of lyphocytic cells, but there percentages appear low

Front 4

Which cell is effected in CML?

Back 4

Myeloid stem cell

Front 5

What are the risk factors for CML?

Back 5

NONE

Front 6

How do we diagnose CML?

Back 6

Karyotype, FISH, PCR
- find the Philidelphia chromosome
- t(9;22) bcr-abl
9 is now longer
mutation is on short 22

Front 7

What is on Chromosome 9?

Back 7

abl gene (Abelson leukemia virus)

Front 8

What is on Chromosome 22?

Back 8

bcr gene (breakpoint cluster region)

Front 9

In terms of cellular activity, what does t(9;22) mean?

Back 9

- the tyrosine kinase is always phosphorylated (ie always “on”)
- provides a constant signal to certain pathways that result in cell growth that exceeds apoptosis

Front 10

abl protein

Back 10

a tyrosine kinase, which is an enzyme involved in signal transduction

Front 11

Where does chromosome 22 break?

Back 11

- it can break in different regions within the bcr gene, resulting in different sizes of bcr-abl protein products:
p190 (190 kDa protein): seen in ALL
p210 (210 kDa protein): seen in CML

Front 12

What are the different phases of CML?

Back 12

Chronic phase:
<5% blasts in the marrow
Accelerated phase:
Many different criteria
5-20% blasts in the marrow
Blast crisis:
>20% blasts in the marrow
Tx like any other acute leukemia 7+3+3
Can be myeloid or lymphoid (flow cytometry)

Front 13

How do we treat CML?

Back 13

1. Gleevec
OR
2. High dose interferon
not well tolerated: toxic: fever, fatigue, flu-like sxs
3. Allogenic stem cell transplant
very high associated morbidity and mortality
involves high levels of chemo and radiation

Front 14

Gleevec
(imatinib mesylate)

Back 14

- TKI (tyrosine kinase inhibitor)
- STI (signal transduction inhibitor)
- Small molecule inhibitor
- No real long term follow up
- Pill taken once a day

Front 15

Gleevec
Side effects

Back 15

- Mild nausea and vomiting
- Periorbital edema
- Pleural effusions

Front 16

Gleevec
non-CML treatments

Back 16

GI stromal tumors
binds to c-kit
Chronic eosinophilic leukemia
binds to platelet derived growth factor receptor (PDGFR alpha)
seen in hypereosinophilic syndrome

Front 17

Gleevec resistance

Back 17

T315I mutations
... this mutation is also resistant to 2nd generation tyrosine kinase inhibitors

Front 18

Name the second generation tyrosine kinase inhibitors:

Back 18

Dasatinib
Nilotinib

Front 19

Treatment of Myeloid blast crisis?

Back 19

“7+3”
cytarabine x 7 days with daunorubicin x 3 days

Front 20

Treatment of Lymphoid blast crisis?

Back 20

Complex multi-agent chemotherapy regimen
Exactly what we would use for de novo ALL

Front 21

Treatment of accelerated phase?

Back 21

higher doses of Gleevec

Front 22

Chronic Lymphocytic Leukemia

Back 22

- Malignant cell is more differentiated than CML
- Results in excess numbers of mature-appearing lymphocytes
- Continuum with SLL (small lymphocytic lymphoma) that has no circulating neoplastic cells and resides in lymph nodes

Front 23

Lymphomas

Back 23

cancerous cells that hang out in lymph nodes

Front 24

Leukemias

Back 24

cancerous cells that hang out in bm and blood

Front 25

What will the CBC look like in a CLL patient?

Back 25

- Elevated total white cell count
- Differential is primarily lymphocytic
- Hemoglobin and platelets are normal
Except in advanced stages of disease when Hb and platelets can be low

Front 26

How do we diagnose CLL?

Back 26

Use flow cytometry of peripheral blood sample to find B cells with T cell clusters of differentiation

Front 27

What will be on the surface of CLL cells?

Back 27

CD5 (T cell CD)
CD19
CD23
CD20 (weak expression)
surface immunoglobulin

Front 28

Why are chromosomal studies important in CLL?

Back 28

Prognosis

Front 29

Which light chains are present in CLL?

Back 29

there is light chain restriction:
- only kappa or lamba, not both

Front 30

CLL Stage 0
Risk?
Location?
Median Overall Survival?

Back 30

Risk: Low
Location: Lymphocytosis only
Median Overall Survival: >10 years

Front 31

CLL Stage 1
Risk?
Location?
Median Overall Survival?

Back 31

Risk: Intermediate
Location: Lymphocytosis. Lymphadenopathy
Median Overall Survival: >8 years

Front 32

CLL Stage 2
Risk?
Location?
Median Overall Survival?

Back 32

Risk: Intermediate
Location: Lymphocytosis, Splenomegaly
Median Overall Survival: ~5 years

Front 33

CLL Stage 3
Risk?
Location?
Median Overall Survival?

Back 33

Risk: HIGH
Location: Lymphocytosis,
Hb < 11.0 due to progression of CLL in the marrow (anemia)
Median Overall Survival: 8-12 months

Front 34

CLL Stage 4
Risk?
Location?
Median Overall Survival?

Back 34

Risk: HIGH
Location: Lymphocytosis, Plts < 100K due to progression of CLL in the marrow (thrombocytopenia)
Median Overall Survival: 8-12 months

Front 35

When do you start CLL treatment?

Back 35

When symptomatic (you can go years without treatment)
- Symptomatic lymphadenopathy (if hinders your life)
- Symptomatic splenomegaly (persistent RUQ pain, large spleen effects stomach and food intake)
- “Symtomatic” counts (Anemia or thrombocytopenia as a result of progression of CLL in the marrow)

Front 36

Is the absolute white cell count an indication of CLL treatment?

Back 36

NO

Front 37

What are some systemic effects of CLL?

Back 37

1. Insufficient immune system
2. Overactive immune system
3. Inappropriate destruction of “self” cells

Front 38

Insufficient immune system in CLL

Back 38

>Difficult to fight infection
- Often need prolonged courses of antibiotics
>Hypogammaglobulinemic
- Quantitative immunoglobulins often reveal patients to be pan-hypoglobulinemic
- If persistent infections or infections severe enough to require hospitalization, treat with IVIG (to boost immune system)

Front 39

Inappropriate destruction of “self” cells in CLL

Back 39

- Autoimmune hemolytic anemia
- Immune thrombocytopenic purpura

Front 40

Lab results for autoimmune hemolytic anemia

Back 40

- Elevated LDH, bilirubin
- Low Hb, haptoglobin
- Can be Coombs positive
- do NOT need bone marrow for dx

Front 41

Treatment of autoimmune hemolytic anemia

Back 41

Steroids (suppress immune system)

Front 42

How can we tell if a CLL patient’s thrombocytopenia is from ITP or stage IV disease?

Back 42

Do a bone marrow
- Stage 4 CLL = no megakaryocytes .: chemotherapy
- CLL with ITP = megakaryocytes in marrow .: steroid treatment

Front 43

DLBCL Treatment

Back 43

R-CHOP
CLL chemo is ineffective against DLBCL and pts will still have CLL after treatment completed

Front 44

Richter’s transformation

Back 44

- Development of diffuse large B cell lymphoma arising from one CLL clone
- May have B symptoms, one area of lymphadenopathy out of proportion to others

Front 45

How do you determine that pt has Richter's transformation

Back 45

PET scan will show transformed sites:
- CLL not PET avid
- DLBCL is very PET avid
- Must document with biopsy to prove transformed disease

Front 46

CLL transformation to Prolymphocytic Leukemia

Back 46

>55% prolymphocytes
- Treatment is different from standard CLL treatment
- Less mature, more aggressive
Histologically: More cytoplasm, single nucleolus

Front 47

CLL treatment

Back 47

Chemotherapy
Purine analog based
- Fludarabine based
- Pentostatin based

Front 48

What should we do while treating CLL?

Back 48

- Patients are at significant risk for tumor lysis syndrome with the first cycle of treatment ... BE CAREFUL
- Hydration and frequent lab monitoring is important

Front 49

Hairy Cell Leukemia Treatment

Back 49

Cladribine (purine analogs)
- CA is so slow growing that one round of treatment does not eliminate CA but eliminates it's problems

Front 50

Hairy Cell Leukemia
Bone Marrow Histology

Back 50

- Cytoplasmic projections
- cells look like fried eggs
- Marrow also has lots of fibrosis

Front 51

Hairy Cell Leukemia

Back 51

- B cell malignancy (CD19, 20, 22)
- Comprises 2% of all leukemias
- Very slow-growing
- Clinically, notable for very large spleens, and dry taps on bone marrows

Front 52

Hairy Cell Leukemia Dx

Back 52

- Flow cytometry to show CD103
- Or with TRAP-positive (only stains hairy cell leukemia)

Front 53

CD103

Back 53

T cell marker found on cell surface in hairy cell leukemia

Front 54

tartrate-resistant acid phosphatase

Back 54

- a stain that only labels hairy cell leukemia
(>: it is TRAP-positive)