Chronic Lymphocytic Leukemia - Nikcevich

Question 1

What is the most common leukemia in adults?

Answer 1

Chronic Lymphocytic Leukemia

Question 2

What is the median age diagnosis for CLL? Median survival?

Answer 2

Median age Dx = 65 yoa

Median survival = 9 years

Question 3

Which type of Ig VH genes have a better prognosis – mutated/unmutated?

Answer 3

Mutated Ig VH genes have better prognosis!

unmutated = negative prognosis

Question 4

What CD markers do you look for on flow cytometry in the diagnosis of CLL?

Answer 4

CD5+
CD19+
CD20+
CD23+

Question 5

What CD markers are unique to Mantle cell lymphoma?

don’t want to miss!

Answer 5

CD5+
CD23-
cyclinD1+

Question 6

What is the difference between Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL)?

Answer 6

the tissue phase of CLL is different

Question 7

What are four autoimmune complications of CLL?

Answer 7

Autoimmune hemolytic anemia
Coombs' positive
reticulocytes present
Pure red cell aplasia
bone marrow is not making red cells at all
no reticulocytes present
parvovirus may cause this
Immune-Related Thrombocytopenia (ITP)
Neutropenia

Question 8

Why is Rai staging important in CLL?

Answer 8

Can assign survival based on stage.

Question 9

What are five CLL-cytogenetic abnormalities from BEST to WORST?

Answer 9

Best: 13q-
Normal karyotype
Trisomy 12
11q-
Worst: 17q-

Question 10

What kind of study should ALWAYS be done with CLL?

Answer 10

FISH studies

Question 11

What do you do if the lab at your facility is unable to perform Ig gene mutation studies?

Answer 11

CD38 may be a surrogate marker for Ig gene mutations – detect via flow cytometry (easily)
CD38+ = unmutated Ig genes = poorer prognosis (9 year median survival)
CD38- = mutated Ig genes = better prognosis (>20 years median survival)

Question 12

What is ZAP-70 expression?

Answer 12

Correlates with Ig VH gene mutations
Correlates with CD38+ expression
poorer prognosis

Question 13

When should you treat a patient with CLL?

Answer 13

Constitutional symptoms
Progressive lymphocytosis
Progressive lymphadenopathy
Progressive splenomegaly
Progressive bone marrow failure
Autoimmune complications
Richter’s transformation or secondary PLL
Your patient is uncomfortable with observation

Question 14

What are the potential therapeutic options for treatment of CLL?

Answer 14

Corticosteroids
Alkylating agents: Chlorambucil, Cyclophosphamide, Bendamustine, Ibrutinib
Nucleoside analogs: Fludarabine, Pentostatin → selective depletion of CD4+ T cells (like HIV) → risk of infections!

Question 15

What type of unique cells on a blood smear are good prognostic evidence in CLL?

Answer 15

Smudge cells

fragile cytoskeletons

Question 16

What is the BEST way to treat patients with CLL?

Answer 16

Indication to treat; prognostic factors (stage, CD38 expression, ZAP-70, etc.)
Younger, good PS patients: clinical trial; PCR or FCR; bendamustine plus rituximab; ibrutinib
Older, more frail patients: chlorambucil (+/- prednisone); bendamustine plus rituximab; ibrutinib
Allogeneic transplant the only curative modality for CLL – need matched-sib donor
Substantial morbidity/mortality → the price of curing CLL is GVHD

Question 17

What drug does Dr. Nikcevich this is a “game changing drug” that will most likely become a first line therapy for CLL? Why?

Answer 17

IMBRUVICA (ibrutinib)

extremely effective to treat CLL + autoimmune complications

Question 18

What is the therapeutic target of Ibrutinib?

Answer 18

BCR signaling pathway

BTK inhibitor