ATL Biology and Treatment Flashcards
where are lymphomas predominantly found?
lymph nodes; lymphoid organs; spleen or GALT
What is involved in looking at the morphology of tumour cells?
architecture and cytology
How is cytogenetics carried out?
convential karyotype; FISH
How is the immunophenotype determined?
flow cytometry and immunohistochemistry
What is stage I lymphoma?
one group of nodes
What is stage II lymphoma?
> 1 group of nodes same side of diaphragm
What is stage III lymphoma?
nodes above and below the diaphragm
What is stage IV lymphoma?
spread beyond the lymphatic system eg bone marrow, liver
What does the suffix E in lymphoma staging mean?
started outside the lymph nodes
What are the known RFs for lymphoma?
constant antigenic stimulation; viral infection; immunosuppression
Chronic stimulation with H.pylori antigen increases the risk of which type of lymphoma?
gastric MALT
Chronic stimulation with antigen in coeliac disease increases the risk of what?
small bowel T cell lymphoma
Why is there a 60x increase in non-hodgkins lymphoma in HIV?
loss of T cell regulation of EBV infected B cells
Why are immune cells particularly at risk of malignant transformation?
have rapid and multiple cell division steps; lymphocytes cut and mutate their own DNA; normal development relys on apoptosis
what is a high prevalence of HTLV-1?
> 1% of adult population
Which subtype accounts for 70% of the ATLL cases in the UK?
lymphoma
What is seen on blood film with ATLL?
flower cell morphology
Where are the lesions foudn in smouldering ATLL?
skin or lungs
What are the clinical features of ATLL?
generalised lymphadenopathy; hepatosplenomegaly;skin lesions; lytic bone lesions; hypercalcaemia and OI
What is the proviral load?
% of PBMCs infected
What transmission route is required for the development of ATLL?
mother-to-child
What are the RFs for ATLL development?
Fhx; smoking; high provirla load (HLA type)
What is considered a high proviral load?
> 4%
How many asymptomatic carriers are high load?
25%
How many high load carrier develop ATL?
20%
What HLA class I allele is detrimental to host protection against HTLV1
HLA-B*5401
What are the HTLV-1 serology tests available?
ELISA and western blot
How do you distinguish between ATL and peripheral T cell lymphoma in asymptomatic carriers?
for ATL need to demonstrate a monoclonal provirus in tumours
Why may HTLV1 infection have to happen in infancy in order to develop ATL?
before immune system has developed?
Why is loss of tax expression the last hit before malignancy?
allows infected cells to escape the immune system, mutations acquired meaning Tax is no longer needed
What is the oligoclonality index?
the spread of clones- how many of each clone present in an individual
What is clonal succession?
if a subclone occupying an environmental niche is lost, another population will fill its place
What is the treatment for lymphoma and bulky acute forms of ATLL in the UK?
chemo- CHOP-like regimen; allo HSCT
What is the treatment for both acute and chronic leukaemic forms of ATL?
AZT and IFNa
What killed patients qith chronic ATL?
half die of OI; half transform to agggressive subtype
What is hte name of hte anti-CCR4 antibody?
mogamulizumab
What is the effect of mogamulizumab in chronic ATL?
proviral load drops by 3-4 logs by end
