Haem 8+9: Chronic Lymphocytic Leukaemia and Lymphoproliferative Disorders

Question 1

What is CLL? who is at increased risk?

Answer 1

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

Question 2

What is the presentation of CLL?

Answer 2

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

Question 3

What is the natural history of CLL

Answer 3

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

Question 4

What is Richter’s transformation?

Answer 4

Transformation of CLL to aggressive disease (ALL / high grade lymphoma)

Question 5

What might a FBC in CLL show?

Answer 5

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)

Question 6

What can blood film in CLL show?

Answer 6

Smear cells / Smudge cells - more vunerable to rupture when spreading the slide

Lymphocytosis

Question 7

What other Ix (not blood film / FBC) is used in CLL diagnosis?

Answer 7

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

Question 8

What is the staging for CLL?

Answer 8

Binet Staging:
A – no cytopenia, <3 areas of lymphoid involvement
B – no cytopenia, 3+ areas of lymphoid involvement
C – cytopenias

Question 9

What is mx of CLL?

Answer 9

A – watch and wait
B – consider treatment
C – treat (also treat if there’s AI complications)

Question 10

What medications can be used for CLL?

Answer 10

Venetoclax (BCL2)
Obinutuzumab (CD20)
Ibrutinib (Brutons TK inhibitor)
FCR (fludarabine, cyclophosphamide, rituximab)

Stem cell transplant

(Probs not needed for path)

Question 11

What are the FBC findings in ALL + AML? how to tell the difference?

Answer 11

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

Question 12

What are the FBC findings in CML + CLL? blood film?

Answer 12

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

Question 13

What are lymphomas?

Answer 13

neoplasm of lymphoid cells

Question 14

How can malignant lymphoproliferative disorders be classified?

Answer 14

Immature: ALL

Mature:

• Lymphoid leukaemai (CLL)
• Lymphoma: Hodgkins v Non-Hodgkins (B-cell v T/NK cell)

Question 15

What are the general differences between Hodgkins and non-Hodgkins lymphoma?

Age, lymph nodes, disease course and prognosis?

Answer 15

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

Question 16

How can lymphomas be classified?

Answer 16

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)

Question 17

How are lymphomas staged?

Answer 17

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

Question 18

What are “B symptoms”?

Answer 18

Fever >38 degrees

Drenching sweats at night

Unintentional weight loss >10% body weight in 6 months

Question 19

What are the features of Hodgkins’s Lymphoma?

Answer 19

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

Question 20

What is the most common type of Hodgkin’s Lymphoma?

Answer 20

nodular sclerosing

Question 21

Mx and prognosis of Hodgkins Lymphoma?

Answer 21

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

Question 22

Main features of non-hodgkins lymphoma?

Answer 22

Many sub-types – mostly B-cell origin, can be T-cell.

Present with B-symptoms or lymphadenopathy

Incidence increases with age

Question 23

What are the 5 different types of NHL?

Answer 23

Burkitts

Diffuse large B cell lymphoma (DLBCL)

Mantle cell

Follicular

Adult T-cell leukemia/lymphoma (ATLL)

Question 24

What is the most common indolent (slow) NHL? what genetic cause?

Answer 24

Follicular lymphoma - t(14,18) causes fusion of BCL2 gene (overexpression of bcl-2 (anti-apoptosis))

Question 25

What are some features of follicular NHL? histopath? risk?

Answer 25

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

Question 26

What are the most common high grade NHLs? presentation + risk of treatment - how does this risk present / how to avoid?

Answer 26

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

Question 27

What is the mutation involved in mantle cell NHL + what is mx? what is produced in excess?

Answer 27

t(11;14) causes overexpression of Cyclin D1

Treatment is with chemotherapy

can have a leukemic phase when they show up in the blood

Question 28

What is DLBCL associated w/ + what is Mx?

Answer 28

Mx = Rituximab-CHOP chemotherapy

Can be associated w EBV

Usually presents quite late hence hard to treat

Question 29

What is a very high grade NHL? risk w treatment?

Answer 29

Burkitts lymphoma

High risk of tumour lysis syndrome w/ treatment -> leak out of

Question 30

What features are associated w burkitts lymphoma?

Answer 30

“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

Question 31

Which NHLs are the least common? examples

Answer 31

T-cell lymphomas

Adult T-cell Leukaemia / Lymphoma
Cutaneous T-cell lympoma - even rarer and presents w/ weird rashes

Question 32

What are the features associated w ATLL NHL? who’s at greater risk + blood film?

Answer 32

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

Question 33

MDS v MPN?

Answer 33

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