Haem - Lymphoma 2

Question 1

Which Ig are associated with B cell lymphomas

Answer 1

Follicular NHL: IgH-BCL2
Mantle Cell lymphoma: IgH-Cyclin D1
Burkitt Lymphoma: IgH-MYC

Question 2

What are the symptoms of lymphoma

Answer 2

Painless progressive lymphadenopathy (neck, axilla groin)
Compression symptoms
- Renal failure
- Obstructive jaundice
- Large blood vessels
- Bowel obstruction
- Trachea
- Oesophageal
Infiltration
- Brain: stroke, lOC, memory problems
- Skin rash: plaques, ulceration, nodules
- Ocular: blindess
- Liver: liver failure
Recurrent infections
B symptoms: fever, night sweats, weight loss

Question 3

What investigations should be done for lymphoma

Answer 3

Bloods:
- LDH: raised
- Albumin
- U&Es
- HIV, hep B serology ± HTLV-1 (ensure hep B will not reactivate)

Anatomical stage
- bone marrow biopsy
- CT/PET
- Lumbar puncture if risk of CNS involvement

Question 4

What is the epidemiology of Hodgkin’s lymphoma

Answer 4

1% of all cancer
Less common than non-Hodgkin’s
M > F
Bimodal age - 20-29yo (most common), >60yo (smaller peak)

Question 5

What is the prognosis for classical HL

Answer 5

Nodular sclerosing 80%: Good prognosis (causes the peak incidence in young women) - thick bands of nodular tissue
Mixed cellularity 17%: Good prognosis
Lymphocyte rich (rare): Good prognosis
Lymphocyte depleted (rare): Poor Prognosis

Question 6

Describe the features of nodular sclerosing HL sub-type (epidemiology, symptoms)

Answer 6

Seen in young women (F > M (20-29yo))
Neck nodes and a mediastinal mass; may have B symptoms
Mass may compress the SVC or trachea
Spreads contiguously

Question 7

Describe the staging of lymphoma

Answer 7

Ann Arbor Staging
A = B symptoms absent
B = B symptoms present
E = involvement of single, contiguous, or proximal extranodal site

I: One node region involved on 1 side of the diaphragm
II: 2+ ipsilateral regions involved on 1 side of the diaphragm
III: Bilateral node involvement on both sides of the diaphragm
IV:
HL: Involvement of extranodal sites beyond those designated by ‘E’ (below)
NHL: Disseminated/multifocal involvement of ≥1 extralymphatic site OR isolated extralymphatic organ involvement with distant node involvement

Question 8

Describe the treatment of Hodgkin’s lymphoma

Answer 8

Chemotherapy: ABVD (2-6 cycles, 4-weekly intervals) - adriamycin, bleomycin, vinblastine, DTIC (Dacarbazine)
± radiotherapy

Second line: salvage chemotherapy (high dose chemo + HSCT)

Third line: anti-CD30 (Brentuximab Vedotin)+ anti-PD1(nivolumab)

Question 9

What is the prognosis for Hodgkin’s lymphoma

Answer 9

Elderly patients do worse than the worst-prognosis HL (lymphocyte-depleted type)
It is a highly curable disease, but the prognosis depends on stage
Over 80% in stage I or II disease are cured
50% of stage IV are cured
10% die from relapse within 10 years and 10% die from complications after 10 years
More likely to die of secondary malignancy of CV complications after 5 years

Question 10

What is a common complication of Chemotherapy + radiotherapy for Hodgkin’s lymphom

Answer 10

Risk of damage to normal tissues (collateral damage)
Associated with increased risk of breast/lung/skin cancer, leukaemia/myelodysplasia

Question 11

What are the prognostic markers for NHL

Answer 11

LDH (marker of cell turnover)
Performance status
HIV serology
Hep B serology (treatment for lymphoma may cause a dormant hep B to reactivated → fulminant liver failure)

Question 12

What is the prognosis for NHL

Answer 12

Burkitt’s lymphoma – fastest growing human cancer
Follicular lymphoma (an indolent disease) – possible 25 year survival
HOWEVER, chance of being cured increases with more aggressive neoplasms

Question 13

What is the management for NHL

Answer 13

Chemotherapy: R-CHOP (6-8 cycles) - rituximab, cylophosphamide, adriamycin, vincristine, prednisolone

Second line: autologous HSCT

Question 14

Describe enteropathy associated T-cell lymphoma (cause and association, histology, presentation, response to treatment, prevention)

Answer 14

Caused by chronic antigen stimulation to gluten/gliadin → associated with coeliac disease
Histology: Mature T cells TdT, CD19
Presentation:
- Abdo pain, obstruction, perforation, GI bleeding
- Malabsorption
- Systemic symptoms

Responds poorly to chemotherapy, generally fatal
Can be prevented by strict adherence to a gluten-free diet

Question 15

What phenotype is indicative of CLL

Answer 15

Normal T cells are CD5 positive, and CD 19 and 20 negative. While normal B cells are the other way around.
CLL B cells have an unusual phenotype (Monoclonal lymphocytosis with abnormal expression of CD5 = highly suggestive of CLL)

Question 16

What is the phenotype of T cells

Answer 16

CD3 positive
CD4 or CD8 positive (Th-cell, CTL cell)
D19 NEGATIVE
CD5 POSITIVE

Question 17

What is the prognosis for CLL

Answer 17

In a disorder of elderly
- 1/3 never progress
- 1/3 Progress, respond to CLL Rx (death from unrelated disorder)
- 1/3 Progress, require multiple lines of Rx, refractory disease, death from CLL

Question 18

How is CLL staged

Answer 18

Rai and Binet staging
A: <3 lymphoid areas
B: >3 lymphoid areas
C Hb <100, Platelets <100

Question 19

What are the prognostic lab factors for CLL

Answer 19

Cytogenetics (FISH panel)
Immunoglobulin gene (IgHV) mutation status
- IgH mutated
- IgH unmutated (Bad)
17p deletion
p53 muted

Question 20

What are the complications of CLL

Answer 20

Non-functioning B cell production → hypogammaglobulinaemia → increased infection risk e.g. pneumonia, sinusitis
Metastasis to lymphoid organs e.g. lymph nodes, spleen
Bone marrow failure (anaemia, neutropenia thrombocytopenia)
Richter transformation → high grade lymphoma
Regulation of the surviving normal B cell population → autoimmune disease e.g. autoimmune haemolytic anaemia

Question 21

What is the management for CLL

Answer 21

1. Watch and wait
2. Supportive treatment
   - Vaccination: flu, pneumococcus (NOT live vaccines)
   - Anti-infective prophylaxis and treatment
3. if young: allogenic HSCT
4. If not, incurable by chemo → watch and wait

Richter transformation: high grade lymphoma R-CHOP
± new agents: ibrutinib (Bruton Tyroskine Kinase/BCR inhibitor), venetoclax (anti-Bcl2 oral agent), CAR-T (chimaeric antigen receptor T cells)

Question 22

What are the poor prognostic features of CLL

Answer 22

Deletion of 13q (~133 months survival)
Trisomy 12 (~114)
Deletion of 11q (ATM) (~79)
Deletion of 17p (TP53) - loss of p53 tumour