ATL Biology and Treatment

Question 1

where are lymphomas predominantly found?

Answer 1

lymph nodes; lymphoid organs; spleen or GALT

Question 2

What is involved in looking at the morphology of tumour cells?

Answer 2

architecture and cytology

Question 3

How is cytogenetics carried out?

Answer 3

convential karyotype; FISH

Question 4

How is the immunophenotype determined?

Answer 4

flow cytometry and immunohistochemistry

Question 5

What is stage I lymphoma?

Answer 5

one group of nodes

Question 6

What is stage II lymphoma?

Answer 6

> 1 group of nodes same side of diaphragm

Question 7

What is stage III lymphoma?

Answer 7

nodes above and below the diaphragm

Question 8

What is stage IV lymphoma?

Answer 8

spread beyond the lymphatic system eg bone marrow, liver

Question 9

What does the suffix E in lymphoma staging mean?

Answer 9

started outside the lymph nodes

Question 10

What are the known RFs for lymphoma?

Answer 10

constant antigenic stimulation; viral infection; immunosuppression

Question 11

Chronic stimulation with H.pylori antigen increases the risk of which type of lymphoma?

Answer 11

gastric MALT

Question 12

Chronic stimulation with antigen in coeliac disease increases the risk of what?

Answer 12

small bowel T cell lymphoma

Question 13

Why is there a 60x increase in non-hodgkins lymphoma in HIV?

Answer 13

loss of T cell regulation of EBV infected B cells

Question 14

Why are immune cells particularly at risk of malignant transformation?

Answer 14

have rapid and multiple cell division steps; lymphocytes cut and mutate their own DNA; normal development relys on apoptosis

Question 15

what is a high prevalence of HTLV-1?

Answer 15

> 1% of adult population

Question 16

Which subtype accounts for 70% of the ATLL cases in the UK?

Answer 16

lymphoma

Question 17

What is seen on blood film with ATLL?

Answer 17

flower cell morphology

Question 18

Where are the lesions foudn in smouldering ATLL?

Answer 18

skin or lungs

Question 19

What are the clinical features of ATLL?

Answer 19

generalised lymphadenopathy; hepatosplenomegaly;skin lesions; lytic bone lesions; hypercalcaemia and OI

Question 20

What is the proviral load?

Answer 20

% of PBMCs infected

Question 21

What transmission route is required for the development of ATLL?

Answer 21

mother-to-child

Question 22

What are the RFs for ATLL development?

Answer 22

Fhx; smoking; high provirla load (HLA type)

Question 23

What is considered a high proviral load?

Answer 23

> 4%

Question 24

How many asymptomatic carriers are high load?

Answer 24

25%

Question 25

How many high load carrier develop ATL?

Answer 25

20%

Question 26

What HLA class I allele is detrimental to host protection against HTLV1

Answer 26

HLA-B*5401

Question 27

What are the HTLV-1 serology tests available?

Answer 27

ELISA and western blot

Question 28

How do you distinguish between ATL and peripheral T cell lymphoma in asymptomatic carriers?

Answer 28

for ATL need to demonstrate a monoclonal provirus in tumours

Question 29

Why may HTLV1 infection have to happen in infancy in order to develop ATL?

Answer 29

before immune system has developed?

Question 30

Why is loss of tax expression the last hit before malignancy?

Answer 30

allows infected cells to escape the immune system, mutations acquired meaning Tax is no longer needed

Question 31

What is the oligoclonality index?

Answer 31

the spread of clones- how many of each clone present in an individual

Question 32

What is clonal succession?

Answer 32

if a subclone occupying an environmental niche is lost, another population will fill its place

Question 33

What is the treatment for lymphoma and bulky acute forms of ATLL in the UK?

Answer 33

chemo- CHOP-like regimen; allo HSCT

Question 34

What is the treatment for both acute and chronic leukaemic forms of ATL?

Answer 34

AZT and IFNa

Question 35

What killed patients qith chronic ATL?

Answer 35

half die of OI; half transform to agggressive subtype

Question 36

What is hte name of hte anti-CCR4 antibody?

Answer 36

mogamulizumab

Question 37

What is the effect of mogamulizumab in chronic ATL?

Answer 37

proviral load drops by 3-4 logs by end