Haem 8+9: Chronic Lymphocytic Leukaemia and Lymphoproliferative Disorders Flashcards
What is CLL? who is at increased risk?
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease -> mature B cells (essentially same process as ALL but just different presentation)
Commonest leukaemia in West – median 72y, M>F
7x increased risk if fhx of mutation
What is the presentation of CLL?
Usually asymptomatic (Picked up on routine blood tests)
Age >50 – incidence increases with age
2:1 in M:F
Can present with lymphadenopathy/splenomegaly
Can present with ITP / Haemolytic anaemias
What is the natural history of CLL
5-10y good health -> progression to 2-3y terminal phase, rapid progression to death <2-3y
Rule of 1/3s:
1/3 never progress;
1/3 progress + respond to rx;
1/3 progress + refractory + death from CLL
What is Richter’s transformation?
Transformation of CLL to aggressive disease (ALL / high grade lymphoma)
What might a FBC in CLL show?
Normally - no anaemia, no thrombocytopaenia and neutropaenia
Anaemia / thrombocytopaenia at presentation = more agressive disease or AIHA
High WCC with lymphocytosis (usually has lots of small mature cells)
What can blood film in CLL show?
Smear cells / Smudge cells - more vunerable to rupture when spreading the slide
Lymphocytosis
What other Ix (not blood film / FBC) is used in CLL diagnosis?
Flow cytometry:
- Identifying a “clonal” population of cells
- Will express same cell markers e.g. Kappa/Lambda light chains
Most frequently B-cells but can get T-cell CLL
Same pathology as Small Lymphocytic Lymphoma but different distribution of disease (blood/marrow vs lymph nodes)
Immunophenotyping = CD19+ve, CD5+ve
What is the staging for CLL?
Binet Staging:
A – no cytopenia, <3 areas of lymphoid involvement
B – no cytopenia, 3+ areas of lymphoid involvement
C – cytopenias
What is mx of CLL?
A – watch and wait
B – consider treatment
C – treat (also treat if there’s AI complications)
What medications can be used for CLL?
Venetoclax (BCL2)
Obinutuzumab (CD20)
Ibrutinib (Brutons TK inhibitor)
FCR (fludarabine, cyclophosphamide, rituximab)
Stem cell transplant
(Probs not needed for path)
What are the FBC findings in ALL + AML? how to tell the difference?
Both have:
- Low Hb
- High WCC (1-100)
- Low Plt
- Low Neutrophils
- Blast cells present
- BM >20% blasts
To tell the difference - AML = Auer rods on blood film
What are the FBC findings in CML + CLL? blood film?
Both have:
- Normal -> Low Hb
- High -> v.high WCC (10-400)
- <20% blasts in BM
CML:
- high / normal plt
- high neutrophils
- HIGH BASOPHILS, eosinophils (high/normal)
- High monocytes if CMML
- Myelocytes
- blast cells infrequent
- LEFT SHIFT on blood film
CLL:
- Normal plt,
- Normal neutrophils
- V HIGH LYMPHOCYTES
- SMEAR CELLS on blood film
What are lymphomas?
neoplasm of lymphoid cells
How can malignant lymphoproliferative disorders be classified?
Immature: ALL
Mature:
- Lymphoid leukaemai (CLL)
- Lymphoma: Hodgkins v Non-Hodgkins (B-cell v T/NK cell)
What are the general differences between Hodgkins and non-Hodgkins lymphoma?
Age, lymph nodes, disease course and prognosis?
Hodgkins:
- Young
- Enlarged lymph nodes in Mediastinum (anywhere) + PAINFUL on drinking alcohol
- Agressive cancer - quickly progresses
- Mostly curable
Non-hodgkins:
- Increases w/ age
- Enlarged lymph nodes anywhere
- Variable course and prognosis
How can lymphomas be classified?
Hodgkins (20%) v Non-hodgkins (80%)
B-cell v T-cell
V.high v high v low grade lymphomas (higher grade = easier to treat - better response to chemo)
How are lymphomas staged?
Ann-Arbor staging:
1 - One area of lymph nodes affected
2 - More than one area of lymph nodes affected however all on the same side of the diaphragm
3 - More than one area of lymphnodes affected and on a different side of the diagphragm
4 - Same as above + BM / spleen involvement
This plus b symptoms gives you 1a v 1b, 2a v 2b etc etc
What are “B symptoms”?
Fever >38 degrees
Drenching sweats at night
Unintentional weight loss >10% body weight in 6 months
What are the features of Hodgkins’s Lymphoma?
Affects many young people (M>F)
Presentation with lymphadenopathy or “B”-symptoms
Frequently mediastinal lymphadenopathy
REED-STERNBURG cells are diagnostic (only 1 needed) - lymph node biopsy!
can be associated w/ EBV
Diagnostic markers: CD30, CD15
What is the most common type of Hodgkin’s Lymphoma?
nodular sclerosing
Mx and prognosis of Hodgkins Lymphoma?
Treatment is with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine.) chemotherapy usually + radiotherapy
Most patients have a good chance of cure
Stem cell transplants for rare cases who fail treatment
Main features of non-hodgkins lymphoma?
Many sub-types – mostly B-cell origin, can be T-cell.
Present with B-symptoms or lymphadenopathy
Incidence increases with age
What are the 5 different types of NHL?
Burkitts
Diffuse large B cell lymphoma (DLBCL)
Mantle cell
Follicular
Adult T-cell leukemia/lymphoma (ATLL)
What is the most common indolent (slow) NHL? what genetic cause?
Follicular lymphoma - t(14,18) causes fusion of BCL2 gene (overexpression of bcl-2 (anti-apoptosis))
What are some features of follicular NHL? histopath? risk?
Small lymphocytic lymphoma is similar to CLL but with disease in nodes
Present with lymphadenopathy – usually few very large nodes
Risk of transformation to high grade lymphoma
HISTOPATH: Large numbers of centroblasts + centrocytes on lymph node biopsy
What are the most common high grade NHLs? presentation + risk of treatment - how does this risk present / how to avoid?
Most common “high grade” lymphoma is Diffuse Large B-Cell Lymphoma (DLBCL) ,mantle cell is another cause
Present with lymphadenopathy & frequently B-symptoms
May have Bone Marrow involvement
Risk of Tumour Lysis Syndrome (can show High potassium, high phosphate, and low calcium) with treatment - allopurinol used as prophylaxis
What is the mutation involved in mantle cell NHL + what is mx? what is produced in excess?
t(11;14) causes overexpression of Cyclin D1
Treatment is with chemotherapy
can have a leukemic phase when they show up in the blood
What is DLBCL associated w/ + what is Mx?
Mx = Rituximab-CHOP chemotherapy
Can be associated w EBV
Usually presents quite late hence hard to treat
What is a very high grade NHL? risk w treatment?
Burkitts lymphoma
High risk of tumour lysis syndrome w/ treatment -> leak out of
What features are associated w burkitts lymphoma?
“Starry sky” appearance on histology = “scattered tingible-body macrophages (macrophages filled with apoptotic remains) on a background of lymphoblasts”
Mostly associated with t(8;14)
Associated with EBV + HIV - seen in African areas
Large fast growing lymph nodes in the neck / elsewhere
Which NHLs are the least common? examples
T-cell lymphomas
Adult T-cell Leukaemia / Lymphoma
Cutaneous T-cell lympoma - even rarer and presents w/ weird rashes
What are the features associated w ATLL NHL? who’s at greater risk + blood film?
More common in far east
Associated with HTLV-1 ( human T-lymphotropic virus type 1) (more common in Japan and far east hence this tumour is more common there)
“flower cells” on blood fil
MDS v MPN?
Myelodysplastic - issue w quality of cells, they’ve become dysplastic (low amounts, low function)
Myeloproliferative - issue w amount of cells (proliferate too much) hence too many cells, normal ish function
