Mar28 M1-GVH and Rejection

Question 1

allogeneic transplant charact

Answer 1

• host receives graft from non-self donor
• fully or partially HLA matched
• host is immunosuppressed to prevent GVHD or rejection

Question 2

3 types of GVHD

Answer 2

• after allogeneic stem cell transplant (most common)
• following solid organ transplant (uncommon)
• following blood transfusion (transfusion-associated GVHD) (uncommon)

Question 3

cause of GVHD

Answer 3

donor T lymphocytes attack recipient tissues (respond to HLA I and II expressed on MHC

Question 4

conditions for GVHD to occur (Billingham’s criteria)

Answer 4

• 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)

Question 5

what do we mean by ‘‘graft must contain immunologically competent donor cells’’ for GVHD

Answer 5

• 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)

Question 6

what do we mean by host must be unable to reject, eliminate the donor cells of the graft

Answer 6

• host is immunosuppressed

- host must be genetically identical similar to the donor (some kind of matching was done) so won’t REJECT

Question 7

cause of GVHD after solid organ transplant (SOT)

Answer 7

• 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

Question 8

risk factors of GVHD after SOT

Answer 8

• HLA mismatch

- older age of patient

Question 9

clinical manifestations of GVHD after SOT

Answer 9

• pancytopenia (bc of BM aplasia)
• skin rash
• fever
• diarrhea and gut dysfunction

Question 10

in what GVHD types do the donor T cells wipe out hematopoietic cells of the BM and in what types do they not

Answer 10

• 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.

Question 11

treatment of GVHD after SOT

Answer 11

systemic steroids

Question 12

cause of death in GVHD after SOT

Answer 12

severe cytopenias and BM failure = infections

Question 13

why get much more rejection cases than GVHD, especially in SOT

Answer 13

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

Question 14

% of GVHD and rejection in allogeneic SC transplant (ASCT)

Answer 14

GVHD in 20-80% of cases

rejection in 5% of cases

Question 15

cause of TA (transfusion associated GVHD)

Answer 15

• 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

Question 16

normal transfusion conditions and why GVHD doesn’t occur

Answer 16

host (recipient) is not immunocompromised so T cells of the recipient destroy the donor lymphocytes

Question 17

what do we mean by ‘‘the host can’t neutralize the attack in TA-GVHD because it is genetically identical to the donor’’

Answer 17

• donor HLA haplotype is AA and recipient is AB
• recipient recognizes A of donor as self
• donor recognizes B of recipient as foreign

Question 18

who’s at risk of having TA-GVHD

Answer 18

• immune suppressed (disease, drug, chemo)
• granulocyte transfusion recipient
• premature neonate
• partial HLA match or relative

Question 19

how TA-GVHD is avoided

Answer 19

irradiation of fresh blood products to inactivate T lymphocytes

Question 20

SCT (stem cell transplant) def

Answer 20

• 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

Question 21

3 types of SCT donors

Answer 21

• syngeneic or identical twins
• autologous transplant (to self. in high risk lymphoma or multiple myeloma)
• allogeneic transplant (matched)

Question 22

3 sources of stem cells (hematopoietic) for a SCT

Answer 22

• bone marrow
• peripheral blood
• umbilical cord blood (extracted at birth and frozen)

Question 23

timeline of allogeneic SCT

Answer 23

• 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)

Question 24

acute vs chronic SCT-GVHD

Answer 24

• 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

Question 25

T-F: GVHD is not reported in identical twin (syngeneic) SCT

Answer 25

True.

Question 26

3 phases of acute GVHD pathophysiology

Answer 26

1. effects of conditioning: inflam activation 2. donor T cell activatio: Ag directed T cell attack 3. effector phase (cell injury, target tissue death)

Question 27

acute GVHD symptoms

Answer 27

``` skin = red rash, bullae, desquamation. painful and pruritic liver = cholestasis gut = anorexia, nausea, vomiting, diarrhea, abd pain NOT pancytopenia (that's in TA-GVHD or SOT-GVHD) ```

Question 28

how to dx acute GVHD

Answer 28

clinical picture + bx

Question 29

treatment of acute GVHD

Answer 29

- topical therapy only in grade 1 (skin stage below 2) | - systemic steroids in grade 2+

Question 30

pathophgy of chronic GVHD

Answer 30

- inflam, cell and humoral immunity, fibrosis | - starts like acute GVHD

Question 31

symtpoms of chronic GVHD

Answer 31

ressembles autoimmune diseases (scleroderma, Sjogren's, PBC and PSC, immunodeficiency)

Question 32

organs where see symptoms in GVHD

Answer 32

- skin - mouth - liver - eyes - gut

Question 33

(IMPORTANT) #1 risk factor for acute GVHD of grade >2 and also the #1 risk factor for chronic GVHD

Answer 33

HLA ressemblance (less ressemblance = higher risk)

Question 34

treatment of GVHD

Answer 34

- systemic steroids | - therapy based on organs involved

Question 35

prognosis of aGVHD

Answer 35

- related to grade - higher grade = less survival - 50% respond to systemic steroids - no response = poor prognosis

Question 36

prognosis of cGVHD

Answer 36

depends on number of organs involved and high risk factors like low platelets, poor response to steroids, progressive onset, and BSA over 50%

Question 37

good thing about GVHD

Answer 37

The worse the GVHD, the lower the chance of relapse for CML or AML (best to worse: twin, T depletion, no GVHD, aGVHD alone, cGVHD alone, aGVHD and cGVHD)

Question 38

(imp?) first manifestation of GVHD that you see usually

Answer 38

skin involvement

Question 39

treatment of all GVHD (basically comes back to one thing)

Answer 39

systemic steroids