Lecture 20 - Graft vs. Host Disease Flashcards
What is graft vs host disease
- donor cells mount a response against host
- graft cells are immunocompetent
- host cells foreign to graft
- host cells unable to eliminate graft cells
What are risk factors for graft vs host
HLA mismatch, age, sex disparity, multiparous female donors, type of transplant and source, insufficient prophylaxis, host conditioning
What donor cells are involved in graft vs host
T lymphocytes
NK cells
APCs
B cells
What is the pathophysiology of acute GVHD
phase I - APC activation
phase II - donor T cell activation
phase III - inflammatory phase
What is the pathophysiology of chronic GVHD
complex and not well understood
What are the characteristics of acute GVHD
- within days
- usually more severe
- high mortality rate
- seen more often with transfusion
What are the characteristics of chronic GVHD
- long term ( >100 days)
- solid organ transplant
- varies in severity
- morbidity and mortality related to severity
What is phase 1 of acute GVHD
- activation of host antigen presenting cells pre-transplant
- priming of host by host
- host tissue damage
What is involved in phase 1 GVHD
- TNF
- IL1
- chemokines CCL2-5, CXCL9-11
- fever, inflammation, increased adhesion molecules, increased TNF, increased MHC
What is phase 2 of acute GVHD
- donor t cells undergo activation, proliferation, differntiation, migration
- donor t cells interact with APC
What is involved in phase II acute GVHD
- IL2, IFN, TNF, IL- 4 -5 -10 -13
- CD8 and NK cells enhanced
- increased MHC
What is phase III acute GVHD
- tissue damage caused by donor cytotoxic t cells and macrophages
What are symptoms of GVHD
fever, rash, diarrhea, vomiting, nausea, liver disfunctionw
What is the staging of GVHD
0 - no rash, TBil <35
1- rash <25%, Tbil 35-50, mild GI symptoms
2 - Rash >25%, Tbil 50-100, moderate GI symptoms
3 - rash with bullous formation, desquamation, Tbil 100-225, mod-severe GI
4 - exfoliative dermatitis, Tbil 100-225, mod-severe GI
How to prevent GVHD
prophylaxis
using irradiated cellular products for transfusion
What is the treatment for GVHD
immunosupression with corticosteroids
anti-histamines
manage infection
What is chronic GVHD
- common in stem cell transplant
- less severe than acute
- pathophysiology complex and not well understood
- immunodeficiency, organ failure, decrease function of the graft
- treatment with immunosuppression
What are risk factors for transfusion GVHD
- preterm infants
- primary immunodeficiencies
- immunsuppresed patients
- HLA matched
