Chronic Lymphocytic Leukemia: Epidemiology, Etiology, Pathophysiology, Diagnosis, Types of Medications, and Board Style Questions

This presentation provides an overview of Chronic Lymphocytic Leukemia (CLL) including its epidemiology, etiology, pathophysiology, diagnosis, types of medications, and board style questions. CLL is a chronic lymphoproliferative disorder that mainly affects older people. The real cause of CLL remains unknown, but a great deal about the variations between normal lymphocytes and CLL cells have been learned. Doctors can diagnose CLL by conducting blood tests, flow cytochemistry, and cytometry. Treatment options for CLL include watchful waiting, systematic therapy, target therapy, and stem cell transplantation/bone marrow transplantation.

CHRONIC
LYMPHOCYTIC
LEUKEMIA
Name
Institution

1. Epidemiology
• American Cancer Society presents the following estimates for leukemia in the US for the year
2018:
• Nearly 60,300 new instances of leukemia and almost 24,370 deaths from all kinds of leukemia
• Approximately 20,940 incidences of CLL (chronic lymphocytic leukemia)
• Nearly 4,510 deaths of lymphocytic leukemia
• The CLL makes up to ¼ of the new leukemia incidences.
• The average lifetime risk of getting CLL by a person is almost 1 in 175 or 0.57 percent.
• The risk of CLL is somewhat pronounced amongst men than in women (Rawstron et al., 2015) .
• CLL mainly affects older people.
• The average age at the point of diagnosis is about seventy years.
• CLL is seldom observed in individuals below forty years and highly infrequent in kids.

2. Etiology/Causes
• The real cause of incidences of CLL remains unknown.
• However, a great deal about the variations between normal lymphocytes and CLL cells have been learned.
• Healthy cells (human) grow and function primarily by information entailed in every chromosome of a cell.
• These are long DNA’s molecules.
• CCL results from a genetic mutation in DNA of blood-generating cells.
• Such mutations then cause blood cells to generate abnormal and ineffective lymphocytes.
• Apart from being inefficient, such abnormal lymphocytes endure to live and multiply, when the normal
ones would die (Abrisqueta et al., 2017).
• Abnormal lymphocytes collect in blood and some organs where they trigger complications.
• Healthy cells might then be crowded out of bone marrow and disrupt regular production of blood cells.

3. Pathophysiology
• CLL is amongst the chronic lymphoproliferative disorders or lymphoid
neoplasms. WHO classification indicate that B cell CLL is regarded to
be identical that is a single illness with various manifestations to
mature/peripheral B cells neoplasm small lymphocytic lymphoma (SLL).
It is indicated by the progressive functionally incompetent lymphocytes
accumulation that is often monoclonal in origin (Rawstron et al., 2018).
• The CLL molecular pathogenesis is a complicated, multistep process
culminating in a malignant clone of B-lymphocytes replication. Whereas
specific step in such a pathway has already been elucidated, a
significant number remains a mystery.

3. Pathophysiology Cont.
• It is a belief that almost all CLL incidences follow a premalignant B cell proliferative
illness known as MBL.
• It has CLL-phenotype in five-fifteen percent of the population above sixty and
progresses to SLL/CLL or associated malignancy at the rate of nearly one percent
per annum (Rawstron et al., 2015)).
• The CLL pathogenesis is conceptualized as follows:
• MBL establishment-whereas the inciting event remains a mystery, MBL seems to
develop due to various factors like a response to antigenic stimulation, gene
mutations, micro-environmental support, cytogenetic abnormalities and epigenetic
modifications (Gaidano, Foà & Dalla-Favera, 2012).
• The result is a B cells clone with the CLL phenotype.

4. Diagnosis of CLL
• Doctors can diagnose CLL. The following factors guide
CLL diagnosis:
• The type of suspected leukemia
• The symptoms and signs
• The age and medical condition
• The earlier medical test results

4. Diagnosis of CLL: Blood
Test
• The CLL diagnosis process often commences with a routine CBC test.
• This gives a measurement of the number of various cells types in a person’s blood
sample. One can have CLL if blood entails too much WBCs.
• Doctors use a high white blood cell count to detect which types of WBCs are surged
(Abrisqueta et al., 2017).
• CBC further measures RBCs and platelets. Individuals with CLL have low levels of
such cells.
• Low RBCs levels indicate anemia while low platelets count denotes thrombocytopenia.
• Blood tests are utilized to gather leukemia cells to test particular genetic markers
which are used in predicting the risk that the illness will worsen.

Diagnosis: Flow cytochemistry
and cytometry-
• The dyes/chemical are applied to cells of leukemia in laboratory.
• These give info regarding leukemia and its subtype.
• CLL cells have unique markers-cell surface protein, on the exterior side of cells
(Zhang & Kipps, 2014).
• Their pattern is referred as immunophenotype.
• Such tests remain utilized in distinguishing CLL from additional leukemia types
that also encompass lymphocytes.
• These two test are undertaken from a blood cell.
• Immunophenotyping/ flow cytometry remains the critical test in the CLL
diagnosis confirmation.

Diagnosis: Genomic and
Molecular testing.
• The doctor can suggest leukemia cells testing for particular genes,
chromosomes, proteins alterations and additional variables distinct to CLL
(Gaidano, Foà & Dalla-Favera, 2012).
• CLL divided very gradually and hence examining chromosomes usually is
helpful than utilizing tests to detect particular genetic mutations/changes.
• FISH assays together with genetic tests like polymerase chain reaction
are useful in finding genetic alterations.
• Such results determine how swiftly CLL shall progress and assist in
deciding treatment options (Zhang & Kipps, 2014).

5. Types/groups of medications
• CLL types/groups of medication
• Watch and wait/active surveillance for early-stage CLL
• Systematic therapy
• • Chemotherapy: Fludarabine
• • Chlorambucil
• • Cladribine
• • Cyclophosphamide
• • Pentostatin
• Systematic therapy
• Watch and wait/active surveillance for early-stage CLL

Types/Groups of medications Cont.
• Target therapy
• Combining systematic therapies:
• • Rituximab (Rituxan) and fludarabine
• • BR
• • FC
• FCR
• • Idelalisib and rituximab for CLL- recurrent patients
• • Obinutuzumab and chlorambucil (older patients)
• • PCR
• Stem cell transplantation/bone marrow transplantation

6. Board style questions.
• What Causes CLL?
• What Are the Symptoms of CLL?
• How Is CLL Diagnosed?
• How Does CLL Progress?

6. Board style questions Cont.
• How Is CLL Treated?
• I am on Watchful Waiting, How Do I Know When to Start
Treatment for CLL?
• What Are Potential Side Effects of Treatment for CLL?
• What Are the Goals of Treatment for CLL?
• Where Can I Get More Information About Chronic
Lymphocytic Leukemia?

References
Abrisqueta, P., Delgado, J., Alcoceba, M., González, M., Oliveira, A. C., Loscertales, J., ... & Medina, A. (2017). Clinical
Outcome and Prognostic Factors of Patients with Richter's Syndrome: Retrospective Multicenter Study of the
Spanish Chronic Lymphocytic Leukemia (CLL) Study Group (GELLC).
Gaidano, G., Foà, R., & Dalla-Favera, R. (2012). Molecular pathogenesis of chronic lymphocytic leukemia. The Journal of
clinical investigation, 122(10), 3432-3438.
Rawstron, A. C., Kreuzer, K. A., Soosapilla, A., Spacek, M., Gambell, P., McIver-brown, N., ... & Cedena, M. T. (2015).
Reproducible Diagnosis of Chronic Lymphocytic

References
Rawstron, A. C., Kreuzer, K. A., Soosapilla, A., Spacek, M., Stehlikova, O., Gambell, P., ... & Milani, R.
(2018). Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European
Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA)
Harmonisation project. Cytometry Part B: Clinical Cytometry, 94(1), 121-128.
Zhang, S., & Kipps, T. J. (2014). The pathogenesis of chronic lymphocytic leukemia. Annual Review of
Pathology: Mechanisms of Disease, 9, 103-118.