CLL Foundations Flashcards
what are chronic lymphoproliferative disorders?
CLPD are a group of diseases arising from a malignant clonal proliferation of lymphocytes
CLPD usually involves proliferation of mature B cells and rarely T cells
the malignancy can involve peripheral blood, bone marrow, spleen, and/or lymph nodes and other lymphoid tissues
what are the types of disorders that classify as chronic lymphoproliferative disorders?
- chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) - main one**
- hairy cell leukemia
- prolymphocytic leukemia
- large granulated lymphocyte leukemia
CLPD involves proliferation of what type of cells?
Mature B cells (and rarely, T cells)
what are the symptoms people with CLPD present with initially?
can be completely asymptomatic or present with lymphadenopathy, fevers/chills, night sweats, and/or weight loss
splenomegaly due to progressive growth of lymphatic tissue
in contrast to acute leukemia, these patients do not manifest the signs of bone marrow failure until late in the disease
what does the blood smear of someone with CLPD show?
- numerous lymphocytes
- leukocytosis
- smudge cells = lymphocytes that have been destroyed in the blood smear process
What cellular abnormalities are associated with CLL on a peripheral blood smear?
leukocytosis and smudge cells
how do you treat CLPD?
usually don’t cause pain, slow-growing and not immediately problematic
treatment is only required if symptoms of the lymphoproliferation are bothersome or progressive, and typically a “watch-and-wait” approach is taken
if you do have to treat it, then there are some drugs you can use to do so
what drugs are used to treat CLPD if you do have to treat it?
- chemotherapy
- radiation therapy
- monoclonal antibodies
- steroids
- ibrutinib (a small molecule inhibitor)
- idelalisib (works by inducing apoptosis)
- venetoclax (works by inducing programmed cell death)
what does ibrutinib do?
treats CLPD
a small molecule inhibitor
what does idelalisib do?
treats CLPD
works by inducing apoptosis
what does venetoclax do?
treats CLPD
works by inducing programmed cell death
What features of CLL/SLL make it the ‘poster child’ for chronic lymphoproliferative disorders?
CLL/SLL involves malignant clonal proliferation of mature lymphocytes, typically runs a prolonged and indolent course, and can involve the marrow, blood, or lymph nodes.
what is immunophenotyping?
a key diagnostic test used to differentiate the different lymphoproliferative disorders
how does immunophenotyping work?
it works is similar to a barcode scanner that reads a specific pattern of white and black lines to obtain details about a certain item in the grocery store
the same concept is used in medicine to identify unique proteins or antigens expressed by cells in order to classify them
antigens on the surface of leukemia cells are identified using special antibodies that bind to them specifically, allowing for their classification
the technique used is called flow cytometry immunophenotyping, which involves the measurement (-metry) of cellular (cyto-) properties as they are moving in a fluid stream (flow) past a fixed set of detectors
among the chronic lymphoproliferative disorders, specific disorders have characteristic cell surface markers. the detection of the specific groupings of cell surface proteins (labeled as CD for clusters of differentiation) on abnormal cells leads us to determine the specific type of leukemia or lymphoma
What does immunophynotyping detect on a test?
cell surface antigens
each disorder has its own immunophenotype!!!
what is the surface proteins detected on T-cells?
CD3
CD5
what is the surface proteins detected on helper T-cells?
CD4
what is the surface proteins detected cytotoxic T cells?
CD8
what is the surface proteins detected on B-cells?
Ig
CD10
CD23
CD19
CD19
CD20
CD21
what is the immunophenotye for CLL/SLL?
CLL/SLL is perhaps the best known of the chronic lymphocytic disorders and it will show:
- negative for TdT (terminal deoxynucleotidal transferase)
- positive for B-cell antigens CD19, CD20, CD21
- positive for monoclonal surface Ig
- Ppositive for T-cell antigen CD5
explain the absence of TdT in CLL/SLL
The absence of TdT makes sense, as this is an enzyme only found in lymphoblasts
here we have mature cells in a chronic disease
explain why B-cell antigens and monoclonal surface Ig are positive in CLL/SLL
B-cell antigens and the monoclonal surface Ig are expected since this is a B-cell disorder
explain why T-cell antigen CD5 is positive in CLL/SLL
for a short period of time during maturation, B cells actually express CD5
What is the immunophenotype of a B-cell?
B cells most commonly express immunoglobulin (Ig), CD19, CD20, and/or CD21
Many cases of chronic lymphoproliferative disorders are suspected from a routine CBC showing a lymphocytic predominant leukocytosis. Which of the following is the best next step to work-up our patient for a malignancy?
flow cytometry
the first step in working up a patient for a chronic lymphoproliferative disorder after initial suspicion from a CBC and/or smear is to obtain immunophenotyping on the blood
this will tell us what surface markers the cells are expressing and therefore help us determine if this is a benign or malignant leukocytosis
after flow cytometry is performed, a bone marrow biopsy is not required to confirm the diagnosis of a malignancy
Chronic lymphoproliferative disorders can often be suspected on a routine blood count, with diagnosis confirmed by further testing with immunophenotyping and marrow biopsy. Patients often have no symptoms at time of diagnosis. What is the best course for treatment when diagnosed with virtually no symptom burden?
watch and wait
chronic lymphoproliferative disorders can last for years without any clinical development.
therefore, frequent laboratory checks may be employed for a long while until the patient becomes symptomatic, which would then prompt treatment
A 65-year-old man is found to have an elevated WBC on a routine CBC. The peripheral smear shows many small, mature-appearing lymphocytes. Flow cytometry is then performed on the blood sample to further characterize these cells. What will the immunophenotype be if this population of cells is found to be benign?
lots of CD3+ cells, smaller amount of CD20+ cells
CD20 is a marker of B-cells, and CD3 is a marker for T-cells
the normal make-up of blood is about 60-80% T cells, 10-20% B cells, and 5-10% NK cells
hence, we would expect there to be more T cells (CD3) than B cells (CD20) in the population if this were a benign process
