Chronic Lymphocytic Leukemia

Question 1

How is LPL level detected and what does it mean?

Answer 1

RNA expression.

Its function in CLL is unknown
But high levels correlates to Unmutated IGHV genes

Question 2

What are the 1st-line treatment options for CLL in those

Answer 2

Chemo-immunotherapy with options of:

• FCR
• FR
• PCR (Pentostatin, Cyclophosphamide, Rituximab)
• Bendamustine +/- Rituximab

Question 3

What is detected at high levels in a poor-prognostic CLL?

Answer 3

Higher levels of:

• LPL
• CLLU1
• ZAP70
• CD38

Question 4

What is the COMPLEMENT 1 Trial?

Answer 4

Chlorambucil+Ofatumumab > Chlorambucil

Question 5

Tell me about the Binet staging

Answer 5

Stage A

- Hb 10g/dL or more + Platelets 100k or more +

Question 6

What is CLL8

Answer 6

FCR>FC

Question 7

What do you need to worry about with Alemtuzumab?

Answer 7

High risk of CMV re-activation

Question 8

What does CLL10 study tell us?

Answer 8

This study confirms the superiority of FCR over BR in younger patients.

> 65yo, outcome similar or both regimens, but less toxic for BR.

Question 9

What is a tumor flare reaction?

Answer 9

Painful LN Enlargement or N enlargement with evidence of local inflammation occurring with treatment initiation

May also be a/w speed enlargement, low-grade fever and/or rash

Question 10

What is considered a complex karyotype?

Answer 10

3 or more unrelated chromosome abnormalities in more than 1 cell on karyotype.

Question 11

How is CD38 level detected and what does a high level mean?

Answer 11

Detected by flow cytometry
High expression –> enhanced cell-cell interaction and/or enzyme activity
- high levels correlated to unmutated IGHV genes (which is a poor prognosticator)

Question 12

What combination gives the highest:

1) CR
2) ORR
3) Med PFS

Answer 12

1) CR = FCR
40-50%
Supported by CLL8, CLL10

2) ORR = FCR = BR
- 98%
- CLL10

3) med PFS = FCR > BR > FC > Obinutuzumab/Chlorambucil
- 60m vs 45m vs 30m vs 27m
- CLL8, CLL10, CLL11

Question 13

What are the specific Genomic alterations in CLL

Answer 13

Del 17p13

• > 80% with TP53 mutations
• ultra-high to high risk
• Deregulation of TP53 pathway and loss of cell-cycle regulation

Del 11q

• intermediate to high risk
• Deregulation of ATM, BIRC3 and/or other candidate genes

Trisomy 12

• 19-20%
• intermediate prognosis

Del 13q

• ~55%
• low risk
• Deregulation of miR15a/16-1 and/or other candidate genes

SOMATIC GENETIC MUTATIONS INCLUDE:

• NOTCH1 activating mutations - intermediate to high risk
• SF3B1 deleterious mutations - intermediate to high risk
• BIRC3 deleterious mutations - High risk

Question 14

Tell me about the Rai staging

Answer 14

Stage 0

• Lymphocytosis +
• Lymphocytes >15k/MCL +
• 40% lymphocytes in the BM

Stage I

• Lymphocytosis + lymphocytes >15k/MCL and >40% Lymphocytes in BM
• Enlarged LN present

Stage II

• Lymphocytosis
• Lymphocytes >15k/MCL
• 40% lymphocytes in BM
• Hepatomegaly +/- Splenomegaly or both

Stage III

• Lympohcytosis
• Lymphocytes > 15k/MCL
• lymphocytes > 40% in BM
• hepatomegaly +/- splenomegaly
• Hb 15k/MCL
• lymphocytes > 40% in BM
• Enlarged LN
• hepatomegaly+/-Splenomegaly
• Hb

Question 15

What is IgVH?

Answer 15

Immunoglobulin heavy chain variable gene

Question 16

What is Idelalisib?

Answer 16

PI3K inhibitor

Question 17

What is the International Prognostic index for CLL? (CLL-IPI)

Answer 17

5 components, predicts for OS:

1) Age
2) Clinical stage
3) del (17p) and/or TP53 mutation
4) IGHV mutation status
5) Beta-2microglobulin level

Question 18

How is ZAP70 level detected and what does it mean?

Answer 18

Detected by Flow cytometry or RNA expression

High level means high expression due to enhanced BcR signaling

Question 19

How does IgVH mutation status cor relate with survival?

Answer 19

Mutated survival >24 yrs

Unmutated survival 8-9 yrs

Question 20

What is CLL10

Answer 20

FCR>BR