Chronic Lymphocytic Leukemia Cases - Daniel 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 V_H genes have a better prognosis – mutated/unmutated?

Answer 3

Mutated Ig V_H 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 V_H 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!
  
  • <200 WBC just like AIDS – prophylactic antimicrobial therapy to prevent PJP (Bactrim, Dapsone)
  • Also on acyclovir to prevent against hepatic infection
  • Can also put on antifungals
• Monoclonal antibodies: Rituximab (anti-CD20), Ofatumumab (anti-CD20)
• Combination chemo: PCR, FCR
• Allogeneic stem cell transplantation

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 think 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