12-1: 1/12 - Chronic Lymphocytic Leukemias

Front 1

Chronic Lymphoid Leukemia is a __-cell malignancy.

Back 1

B-cell

Front 2

Characteristics of CLL cells.

Back 2

Mature appearing, functionally incompetent lymphocytes in BM, blood, organs.

Front 3

What is the most common form of leukemia in adults in western countries?

Back 3

CLL

EXTREMELY RARE IN CHILDREN, median age 72

Front 4

CLL:
Clinical Presentation

Back 4

>50% asyx
If do have syx, they're non-specific: fatigue, weight loss, anorexia

Front 5

What's a normal WBC?
WBC in CLL?

Back 5

Normal WBC: 5-10K
CLL WBC: 300K!!

Front 6

Hallmark of CLL.

Back 6

Marked lymphocytosis (~300K in blood)

Front 7

What is a smudge cell and what is it indicative of?

Back 7

Smudge cell = cell that ruptured when performing peripheral smear.

Patients with CLL have more fragile cells and are more likely to have smudge cells on smears.

Front 8

CLL:
Chains expressed in flow cytometry
CD Markers

Back 8

Express either kappa or lambda light chains

CD Markers:
CD19+
CD23+
CD5+ *** (normally a T cell marker, but expressed in small subset of B cells)

(some CD20+ too)
High numbers = B Cell

Front 9

CD5+ is associated with ______.

Back 9

CLL or Mantle Cell Lymphoma

Front 10

What disease does CLL overlap with? Describe the overlap.

Back 10

CLL: older pts w/tons of WBCs in blood/organs, LAD
SLL: same presentation but with more nodal distribution

Front 11

Does CLL result in LAD and hepatosplenomegaly?

Why or why not?

Back 11

Yes, with disease progression, small WBCs accumulate in BM, spleen, LNs, and liver; thus, resulting in generalized LAD and hepatosplenomegaly.

Front 12

Clinical consequences of CLL:
Immune System
Bone Marrow

Back 12

1) immune fn disrupted:
-hypogammaglobulinemia (inc'd risk infection-->death)

-autoab's developed against RBC/platelets-->autoimmune hemolytic anemia or thrombocytopenia

2) BM replaced by malignant lymphocytes-->anemia & thrombocytopenia

Front 13

List findings associated with CLL that are associated with decreased median survival (in order of severity).

Back 13

Lymphocytosis in blood and BM (12.5 years)
Lymphocytosis and LAD (8.4 years)
Lymphocytosis + splenomeg/hepatomeg (5.9 years)
Lymphocytosis and anemia (1.6 years)
Lymphocytosis and thrombocytopenia (1.6 years)

Front 14

CLL has tendency to transform into ________. Provide 2 examples.

Back 14

CLL has tendency to transform into more aggressive lymphoid neoplasms.

Ex: Prolymphocytic transformation (nastier than CLL)
Richter's Syndrome (Diffuse Large Cell Lymphoma)--aggressive

Front 15

CLL:
Median Age of Survival
Prognostic Factors

Back 15

Median survival >20 years; tx: WW

But 50% of early stage CLL pts exhibit rapidly progressive dz

Prog Factors: Cytogenetics!
Ex: 17p deletion (p53)--5 year survival

Front 16

Sequencing of Ig Heavy Chain Variable Region reveals what about CLL prognosis?

Back 16

Mutated IgVH (cells have passed through germinal center)-->good prognosis (25 year median survival)

Unmutated IgVH: more aggressive form of CLL (9.75 years median survival)

Front 17

How is ZAP-70 useful in determining CLL prognosis?

Back 17

ZAP-70 = key signal transduction molecule for molecules, but for some reason is expressed in CLL cells with UNmutated IgVH genes (poor prognosis).

Thus, people with LOW ZAP (LOW CD38) do really well (correlated with mutated IgVH).

Front 18

How is CD38 useful in determining CLL prognosis?

Back 18

CLL = ZAP

Low CD38-->Low ZAP-->good prognosis

High CD38-->High ZAP-->poor prognosis

Front 19

CLL:
Treatment

Back 19

Asyx: WW

Syx:
Alkylating agents:
-Chloambucil (oral single agent)
-Cyclophosphamide
-Benadmustine

Steroids

Nucleoside analogues:
-Fludarabine (can use alone or with other agents)

Monoclonal Abs: Rituximab (anti-CD20)--not very good by itself bc only small populn of CLL is CD20+

Mnemonic: use FCR (fludarabine, cyclophosphamide, rituximab)***

Front 20

CLL vs CML:
Median Age
Symptoms
Defects
Treatment

Back 20

CLL:
Median age 70s
Largely Asyx
Defect in mature B cell

CML:
Median age 50s
Often syx w/fatigue, weight loss
t(9,22) defect; pluripotential HSC
Imatinib = tx

Front 21

Hairy Cell Leukemia:
What category of leukemia is it?Typical clinical presentation
Diagnostics
Treatment

Back 21

Hairy Cell Leukemia = Rare, low-grade, chronic B cell leukemia

Classic presentation: Middle aged white man with pancytopenia, splenomegaly, no LAD.

Diagnostics: TRAP test!

If positive, treat with Cladribine--purine analogue (very responsive to this drug; normal age-matched life expectancy)

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