11. Lymphoproliferative disease

Question 1

Woman, middle aged, enlarged LYMPHS, mild aneamia, mildly raised CRP, mild eosinophila, PET CT shows areas of activity around the upper airways. What’s the diagnosis?

Answer 1

Classsical Hodgkin’s lymphoma

Question 2

What class of classical Hodgkin’s lymphoma does a woman from case 1 have?

Answer 2

2B

Question 3

How can you treat classical Hodgkin’s lymphoma

Answer 3

Very radiotherapy sensitive
Chemotherapy also very good, not primary treatment
Monoclonal antibodies, on its way
Stem cell transplant ion, alternative to bone marrow transplant

Surgical resection will NOT work a it’s a blood disease

Question 4

What is a lymphoma?

Answer 4

Cancers of lymphoid origin
Can present with enlarged lymph nodes or with exrranodL involvement or with bone marrow involvement

Also contains classic B symptoms

night sweats, priuitus, fatigue, (weight loss>10%)

Question 5

How do you diagnose lymphoma/leukaemia?

Answer 5

Biopsy tells you the type every time

Question 6

What is ALL?

Answer 6

Acute lymphoblastic leukaemia, occurs due to disease in the lymphoid progenitor cells

Question 7

What is a lymphoma, CLL?

Answer 7

Lymphoma/Chronic lymphoblastic leukaemia

Caused by disease in the germinal centres

Question 8

Where does acute leukaemia occur?

Answer 8

Bone marrow

Question 9

What is MM?

Answer 9

Multiple myeloma, occurs due to disease in the plasma cells

Question 10

What is Burkett lymphoma?

Answer 10

Clinical emergency, cancer that can double in size in 24 hours

Question 11

What is a common leukaemia in kids?

Answer 11

Acute lymphoblastic leukaemia

Question 12

What is ALL

Answer 12

Acute lymphoblastic leukaemia, cancerous disease of lymhoid progenitor cells

Normal=immature, rapidly proliferating cells that differentiate into lymphocytes

Leukaemia- no differentiation, instead rapid uncontrolled growth and accumulation

Usually in the bone marrow but can go anywhere

Question 13

Describe Acute lymphoblastic lymphoma?

Answer 13

75% occur in children under 6

Typically presents over 2-3 weeks, 1 month impaired visions, tiredness, anaemia, increased white and platelet count

Question 14

What are the pathological characteristics of ALL?

Answer 14

Large cells
Express CD19- all B cells have this
CD34, TDT- markers of very early, immature cells
Not much else, they haven’t matured and develop

Question 15

How do you treat ALL?

Answer 15

Induction chemotherapy to obtain remission- go into remission v quick
Consolidation therapy
CNS directed treatment- 
Maintenance treatment for 18 months
Stem cell transplantation (if high risk)

Question 16

What are the new therapies for ALL?

Answer 16

Harness the immune system to destroy the cancer using monoclonal antibodies

Massively activated T cells to kill lymphomas

CAR t-cells, patients healthy 3rd party T cells harvested.

Question 17

What are the side effects of the new T cell immunotherapies?

Answer 17

Cytokine release syndrome

Neurotoxicity

Question 18

What are the poor risk factors for ALL?

Answer 18

Increasing age
Increased white cell count
Cytogenetics/molecular genetics
slow/poor response to treatment

Question 19

What is CLL?

Answer 19

Chronic lymphocytic leukaemia, resemble normal lymphocytes, grow slowly or not at all, requires a lymphocyte count >5 for diagnosis

Question 20

What is the presentation of CLL?

Answer 20

Often asymptomatic

Bone marrow failure
Lymphadenopathy
Splenomegaly
Fever and swears

Less common findings: hepatomegaly, infections, weight loss

Haemolytic anaemia

Question 21

How do you stage CLL?

Answer 21

Stage A- <3 nodes in onvolved

Stage B- 3 or more lymph node areas

Stage Ç- anaemia and thrombocytopenia and 3 or more LYMPHS

Question 22

What are the indications for treatment of CLL?

Answer 22

Progressive bone marrow failure
Massive lymphadenopathy
progressive splenomegaly
lymphocyte double time

Question 23

What is the treatment of CLL?

Answer 23

Watch and wait, can’t cure it
Cytotoxic chemotherapy- fludarabine, bendamustine
Monoclonal antibodies- rituximab, obinatuzumab
Novel agents:
Bruton tyrosine kinase inhibitors
PI3K inhibit e.g. idelalisib
BCL-2 inhibitors e.g. venetoclax

Question 24

What are poor prognostic markers for CLL?

Answer 24

Advanced disease
Atypical lymphocyte morphology
Rapid lymphocyte doubling time
CD38 expression
Loss/mutation p53 del11q23 (ATM gene)— good answer for exams!
Unmutated IgVh gene status

Question 25

How do you stage lymphoma?

Answer 25

Ann arbour staging:

1- lymph involved

2- lymphs involved only on one side

3- lymphs involved on both side of the body

4- lymphs involved and cancer in non-nodal sites

Question 26

What is non- Hodkins lymphoma?

Answer 26

All lymphomas that aren’t Hodgkin’s lymphoma

Involved B or T cells (mainly B cells)

Question 27

What are low grade non hodkins lymphoma?

Answer 27

Indolent, often asymptomatic

Respond to chemotherapy but incurable

Question 28

What are high grade lymphomas?

Answer 28

Aggressive and fast growing
require combination chemo
can be cured

Question 29

What is diffuse B cell lymphoma?

Answer 29

Important form of non hodkins lymphoma, commonest lymphoma, high grade lymphoma.

Treated with combination chemotherapy and anti-CD20 monoclonal antibodies s

Question 30

What is follicular lymphoma?

Answer 30

2nd most common lymphoma, most common low grade Lymphoma

Treat with combination chemotherapy, typically anti-CD20 monoclonal, antibodies and chemo

Question 31

What is Hodgkin’s lymphoma?

Answer 31

30% of all lymphomas
Bimodal age curve- peaks at 15-35, 2nd peak in like (EBV associated)
Glandular fever makes it more likely to get Hodgkin’s lymphoma
More likely in developed world

Question 32

How do you treat hodkins lymphoma?

Answer 32

Combination chemotherapy (ABVD)
\+/- radiotherapy
Monoclonal antibodies (anti-CD30)
Immunotherapy (checkpoint inhibitors) 

PET scanning central to assessment or response