Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Contents
• Introduction
• Risk Factor
• Etiology
• Signs and SX
• Diagnosis
• Staging
• Treatment
• Brunkisa
Introduction
• CLL and SLL is a neoplastic disease
characterized by proliferation and
accumulation (blood, marrow and
lymphoid organs) of morphologically
mature but immunologically
dysfunctional lymphocytes
• CLL vs SLL proliferation site
• The treatment for CLL and SLL is
very similar because they are both
caused by abnormal B cells.
Risk Factor

Exposure to
Age certain Family history
chemicals

A condition that
Gender Race/ethnicity causes excess
lymphocytes.
Etiology
• As is the case with most malignancies, the exact cause of CLL is
uncertain.
• Differences between normal lymphocytes and CLL cells.
• Cancers can be caused by DNA mutations that turn on oncogenes or
turn off tumor suppressor genes.
• Normal B lymphocytes are part of the immune system.
• Scientists think that CLL begins when B lymphocytes continue to
divide without restraint after they have reacted to an antigen
 Often none!

Non-specific (night sweats, fever, fatigue, weight loss)

Related to lymph node or spleen enlargement

Signs &
Symptoms Related to bone marrow involvement (cytopenia)

Infections

Skin involvement

High lymphocyte count does NOT cause symptoms

 Diagnosis
• CBC: Lymphocytosis
• Peripheral blood smear: smudge cells.
• Flow cytometry: looks for certain substances (markers) on
or in cells that help identify what types of cells they are.
• Flow cytometry can also be used to test for substances
called ZAP-70 and CD38 on the CLL cells. Studies
suggest that people who have few CLL with these
substances seem to have a better outlook.
• Bone marrow tests: Blood tests are often enough to
diagnose CLL, but testing the bone marrow can help tell
how advanced it is.
• Bone marrow aspiration and biopsy
Diagnosis
• Gene tests
• Cytogenetics: The most common deletions
occur in parts of chromosomes 13, 11, or 17.
• Fluorescent in situ hybridization (FISH):
Quicker than Cytogenetics
• Molecular tests: Immunoglobulins
• Lymph node biopsy: Rarely needed for CLL
• Imaging
• CT
• MRI
• Ultrasound
Staging

Rai Staging:
 CLL – Binet staging system

07/10/2023 12
 Staging: Rai and Binet staging systems for CLL
Clinical staging systems for CLL
Stage

Value Rai Binet Median survival

Lymphocytosis 150 months
0 -
(>15,000/mm3) (12.5 years)

Lymphocytosis plus nodal <3 101-108 months

involvement I A node groups (8.5-9 years)

Lymphocytosis plus >3 60-71 months

II B
organomegaly node groups (5-6 years)

III Hgb <10 g/dL 19-24 months

Anemia (RBCs) Hgb <11 g/dL (1.5-2 years)
C

Lymphocytosis plus IV
thrombocytopenia PLT <100,000/mm3
PLT <100,000/mm3
(platelets)
 When to start treatment?
• No advantage to treating CLL until symptoms develop regardless of
• genomic features

• IWCLL 2008 criteria for treatment (in primary and relapse)

• Enlarging, symptomatic lymph nodes (> 10 cm)
• Enlarging, symptomatic spleen (> 6 cm below costal margin)
• Cytopenias due to CLL (hemoglobin < 11 g/dL, platelets
• < 100,000 cells/µL)
• Constitutional symptoms due to disease (fatigue, B symptoms)
• Poorly controlled AIHA or ITP
• Progressive lymphocytosis with an increase of more than 50
percent over a two-month period
What are the treatment options?
Chemotherapy
• fludarabine
• bendamustine
• pentostatin Targeted
• cyclophosphamide Therapies
• chlorambucil • ibrutini
• …
b
Targeted Antibodies • Idelalisi
• rituximab b
• ofatumumab • ABT199
• obinutuzumab
• alemtuzumab
• others
• others
Targeted Therapy Drugs for CLL
• Bruton's tyrosine kinase (BTK) inhibitors
• BTK is a protein that normally helps some CLL cells to grow and survive. Drugs
that target this protein, known as BTK inhibitors, can be helpful in treating CLL

• Ibrutinib (Imbruvica)
• Acalabrutinib (Calquence)
• Zanubrutinib (Brukinsa)
Treatment Targets

syk inh
Zanubrutinib (Brukinsa)
• Zanubrutinib can be used in the initial treatment of CLL, or after other
treatments have been tried.
• Side effects can include:
• Low white blood cell count (with an increased risk of infection)
• Low blood platelet count (with an increased risk of bleeding and
bruising),
• Upper respiratory infections
• Muscle and joint pain
• Feeling tired
• Headache
• Cough
• Skin rash
• Diarrhea
Zanubrutinib (Brukinsa)
• More serious side effects can include:
• Bleeding (hemorrhage)
• Serious infections
• Heart rhythm problems
• Some people taking this drug have developed
skin or other cancers, so it’s important to use
sun protection when outside while taking this
drug.
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