Diffuse Large B cell Lymphoma (NON-HODGKIN LYMPHOMA) Flashcards
What are lymphoma?
Malignancies that tend to occur in lymphoid cells
-in mature, differentiated lymphocytes
What is the function of the lymphatic system
- removes and destroys waste
- removes excess fluid from interstial spaces
- returns proteins and tissue fluids to the blood
- absorbs fats and fat-soluble vitamins and delivers it to the cells
- important component of immune response
What is the lymphatic system
- it is not a closed system like the heart
- there are:
generative:
-thymus and bone marrow responsible for developing cells
peripheral:
-responsible for transport and storage of lymphocytes in lymph
Compare B and T lymphocytes
B lymphocytes:
-once exposed to soluble antigen it becomes sensitised to the antigen
division of B lymphocytes:
-plasma cells - produce antibody against specific antigen
-memory cells - responsible for sustained immunity
T lymphocytes:
-recognise non-self cell e.g cancer cell
variety of subsets with specific function:
-Helper T cell: recognises self vs non-self
-Suppressor T cell - prevents hyper sensitivity when exposed to non-self
-cytotoxic T cell - lyses/kills antigen cell
What is the classification of non-Hodgkin lymphoma
High grade:
- aggressive
- sensitive to chemo
- curative intent
- bit like acute leukaemia
Indolent:
- like chronic leukaemia
- non-curable
- may be watch and wait approach first
What is the most common origin of malignancy
B cell
What are the signs and symptoms of non-Hodgkin lymphoma
Common symptoms:
-superficial lymphadenopathy - painless asymmetrical enlargement of one or more peripheral lymph nodes
Constitutional symptoms occurs in up to 50% of patients:
- weight loss
- fever
- night sweats
Other symptoms:
- Dyspnoea
- Abdominal symptoms e.g enlarged spleen
- Bone marrow involvement e.g anaemia, thrombocytopenia and neutropenia
- neurological symptoms e.g spinal cord compression by lymph nodes
What investigations are carried out for diffuse large cell B lymphoma
Blood evaluation including ‘lactate dehydrogenase’ - increase level suggest disease activity bad
- biopsy
- Imagine
- Prognostic evaluation
What is the staging for non-Hodgkin lymphoma
Ann Harbour staging
Stage 1 - One lymph node affected
Stage 2 - multiple lymph node affected on one side of the diaphragm
Stage 3 - multiple lymph nodes involved on both side of the diaphragm
Stage 4 - spread disease not contained in the lymph system anymore
What are the IPI risk factors for aggressive non-Hodgkin lymphoma
- Age >60yrs
- Ann Harbour stage 3/4
- More than 1 extra nodal site
- serum lactate dehydrogenase levels above normal
- ECOG performance status ≥2
What is the risk group according to the IPI score for non-Hodgkin lymphoma
Low risk - IPI score 0-1
Low-intermediate risk - IPI score 2
High intermediate risk - IPI score 3
High risk - IPI score 4-5
What is the common regimen for diffuse large cell B lymphoma
R-CHOP
- Rituximab - effective in causing B cell lysis
- Cyclophosphamide
- Doxorubicin
- Vincristie
- Prednisolone
What are the supportive therapy for diffuse large cell B lymphoma
- Anti-emetic therapy - Ondansetron (w/therapy and take home) and metoclopramide. could also give dexamethasone if the regimen does not contain steroid
- Prophylaxis for tumour lysis syndrome - 1st cycle
- Gastro-protection for prednisolone
- Pre-meidcation for hypersensitivity reactions e.g paracetamol and Chlorphenamine (hydrocortisone - can cause sleepiness so take at night)
- prophylaxis of urothelial toxicity with cyclophosphamide - Mesna
What is Rituximab and its common side effects
its a monoclonal antibody against B cell surface antigen CD20 (CD20 is present in 98% of NHL)
Side-effects:
- fever
- malaise
- nausea
- vomiting
- flushing
- urticaria
pre-medication for it:
paracetamol and Chlorphenamine (hydrocortisone)
What is the MOA of Rituximab
- recognises CD20 on B cell (works extracellular)
- depletes and reduces size of lymphoma through 3 ways
Complement dependent cytotoxicity (CDC)
- Rituximab-CD20 (antibody-antigen) complex activates a large group of plasma protein -destroy evading pathogen and antigen
- causes the formation of membrane attack complex (MAC) which allows the contents of the cell to escape
Antibody-dependent cell-mediated cytotoxicity (ADCC)
- Binding of Rituximab recruits natural killer cells which bind to Rituximab’s tail
- causes a release of granules filled with cytotoxic molecules which penetrate the B-cell membrane and destroys cell nucleus thus allowing the contents to spill out
Apoptosis:
-Rituximab binds to CD20- signals are sent for apoptosis to occur and cell content is released and killed
