CLL

Question 1

Monoclonal proliferation of mature B lymphocytes defined by an absolute number of malignant cells in the blood (5 × 109/mL)

Identical to SMALL LYMPHOCYTIC CELL (indolent B cell NHL)

Answer 1

CLL

NO DEFINITIVE LINKS with radiation or chemical exposures (unlike many other leukemias)

Question 2

Central to CLL pathogenesis

Answer 2

B-Cell Receptor (BCR) Signaling

Question 3

Features in CLL

Answer 3

low IgM expression

variable antigen response

tonic activation of anti-apoptotic pathways → tumor survival

Question 4

Presence of a clonal B-cell population in peripheral blood without CLL features

Answer 4

MONOCLONAL B-CELL LYMPHOCYTOSIS (MBL)

• no lymphadenopathy
• no organomegaly
• no cytopenias

Question 5

Leading cause of morbidity/mortality: 30–50% of deaths

immune dysfunction + therapy-induced immunosuppression

Answer 5

INFECTIONS

Question 6

Transformation of CLL → aggressive lymphoma (most commonly DLBCL; also HL or B-PLL)

Answer 6

Richter’s Transformation

Question 7

Diagnosis of Richter’s Transformation

Answer 7

rapid lymph node enlargement + B symptoms

↑ LDH

PET/CT scan: SUV >5 suspicious, ≥10 highly concerning

Question 8

Staging of CLL (RAI Staging System)

Lymphocytosis only

Answer 8

Low risk (stage 0)

Question 9

Staging of CLL (RAI Staging System)

Lymphocytosis with lymphadenopathy, with or
without splenomegaly or hepatomegaly

Answer 9

Intermediate risk (stage I/II)

Question 10

Staging of CLL (RAI Staging System)

Lymphocytosis with anemia or thrombocytopenia
due to bone marrow involvement

Answer 10

High risk (stage III/IV)

Question 11

Staging of CLL (Binet Staging System)

A

Answer 11

<3 areas of lymphadenopath

Question 12

Staging of CLL (Binet Staging System)

B

Answer 12

≥3 areas of lymphadenopathy

Question 13

Staging of CLL (Binet Staging System)

C

Answer 13

Hemoglobin ≤10 g/dL and/or platelets <100,000/μL

Question 14

Criteria for the Initiation of Therapy

Answer 14

symptomatic disease (fatigue, night sweats, weight loss)

cytopenias

rapid lymphocyte doubling time

organomegaly causing symptoms

Question 15

Inhibit BCR signaling, continuous therapy until progression

Answer 15

BTK inhibitors

Ibrutinib, Acalabrutinib

Ibrutinib + rituximab improves PFS/OS in younger pts. Acalabrutinib more selective → better tolerability

Question 16

1-year fixed duration therapy; effective in co-morbid patients (CLL14 study)

Answer 16

BCL2 inhibitor

Venetoclax + Obinutuzumab (VO)

Question 17

Mostly for relapsed CLL; toxicity limits frontline use

Answer 17

PI3K inhibitors

Idelalisib, Duvelisib, Umbralisib + Ublituximab

Question 18

Curative potential; high morbidity/mortality with myeloablative conditioning.

Answer 18

Allogeneic stem cell transplantation

Question 19

Definition of Minimal Residual Disease (MRD)

Answer 19

<1 CLL cell in 10,000 leukocytes (0.01%)

Question 20

The MC malignancy diagnosed during routine tests

Answer 20

CLL

Question 21

Confirms DIAGNOSIS of CLL

Answer 21

FLOW CYTOMETRY

B-cell markers: CD19, CD20, CD22, CD23
Aberrant T-cell marker: CD5
Surface immunoglobulin: dim expression (κ or λ)

Diagnosis threshold: ≥5 × 10⁹/L clonal B cells in peripheral
blood → CLL confirmed