Mar28 M1-GVH and Rejection Flashcards
allogeneic transplant charact
- host receives graft from non-self donor
- fully or partially HLA matched
- host is immunosuppressed to prevent GVHD or rejection
3 types of GVHD
- after allogeneic stem cell transplant (most common)
- following solid organ transplant (uncommon)
- following blood transfusion (transfusion-associated GVHD) (uncommon)
cause of GVHD
donor T lymphocytes attack recipient tissues (respond to HLA I and II expressed on MHC
conditions for GVHD to occur (Billingham’s criteria)
- graft must contain immunologically competent donor cells
- host must be unable to reject, eliminate the donor cells of the graft (NO REJECTION)
- host and graft must be antigenically different from each other (NOT IDENTICAL TWINS)
what do we mean by ‘‘graft must contain immunologically competent donor cells’’ for GVHD
- mature T lymphocytes in donor
- tolerant to self
- intolerant to non-self HLA (major histoc complex)
- intolerant to HLA identical molecules complexed to foreign peptides (like minor histoc complex)
what do we mean by host must be unable to reject, eliminate the donor cells of the graft
- host is immunosuppressed
- host must be genetically identical similar to the donor (some kind of matching was done) so won’t REJECT
cause of GVHD after solid organ transplant (SOT)
- transplant of organ with lot of mature T cells like bowel and liver
- immune competent cells in graft attack cells in immunosuppressed host
- these T cells will wipe out the hematopoietic cells in the BM
risk factors of GVHD after SOT
- HLA mismatch
- older age of patient
clinical manifestations of GVHD after SOT
- pancytopenia (bc of BM aplasia)
- skin rash
- fever
- diarrhea and gut dysfunction
in what GVHD types do the donor T cells wipe out hematopoietic cells of the BM and in what types do they not
- wipe them out in GVHD after SOT and in transfusion associated GVHD
- don’t in allogeneic SC transplant bc the patient had no immune system in the 1st place. we’re giving them an immune system. nothing to wipe out.
treatment of GVHD after SOT
systemic steroids
cause of death in GVHD after SOT
severe cytopenias and BM failure = infections
why get much more rejection cases than GVHD, especially in SOT
it’s a question of dose. how much host has immune cells + how much host is immunocompetent VS how much immune cells are in the graft
% of GVHD and rejection in allogeneic SC transplant (ASCT)
GVHD in 20-80% of cases
rejection in 5% of cases
cause of TA (transfusion associated GVHD)
- viable T lymphocytes in donated blood product
- attack non HLA identical cells of the host
- host can’t neutralize the attack bc is immunocompromised or genetically identical to the donor
normal transfusion conditions and why GVHD doesn’t occur
host (recipient) is not immunocompromised so T cells of the recipient destroy the donor lymphocytes
what do we mean by ‘‘the host can’t neutralize the attack in TA-GVHD because it is genetically identical to the donor’’
- donor HLA haplotype is AA and recipient is AB
- recipient recognizes A of donor as self
- donor recognizes B of recipient as foreign
who’s at risk of having TA-GVHD
- immune suppressed (disease, drug, chemo)
- granulocyte transfusion recipient
- premature neonate
- partial HLA match or relative
how TA-GVHD is avoided
irradiation of fresh blood products to inactivate T lymphocytes
SCT (stem cell transplant) def
- infuse healthy hematopoietic cells (SCs included) in blood stream of pt who got immunosuppressive chemo or radiation
- replaces part or whole host BM
- replaces an unhealthy immune system
3 types of SCT donors
- syngeneic or identical twins
- autologous transplant (to self. in high risk lymphoma or multiple myeloma)
- allogeneic transplant (matched)
3 sources of stem cells (hematopoietic) for a SCT
- bone marrow
- peripheral blood
- umbilical cord blood (extracted at birth and frozen)
timeline of allogeneic SCT
- 2 months before, match
- 10 days before, chemo and radiation to immunosuppress host
- after transplant, give calcineurin inhibitor for 4 months
- CBC normal after 4 weeks (30 days)
acute vs chronic SCT-GVHD
- in first 100 days after transplant = acute
- after 100 days after transplant = chronic
- can be acute and then become chronic when go over 100 days
