Hem. Stem Cell Transplant

Question 1

Types of HSC Transplantation: • Reduced intensity transplant • Less intensive chemotherapy before transplantation of allogeneic stem cells

Answer 1

Non-myeloablative

Question 2

Types of HSC Transplantation: • Patient’s own hematopoietic stem cells are used • Fewer side effects

Answer 2

Autologous

Question 3

Graft-Versus-Tumor Effect pathogenesis: T-cell interacts with a dendritic cells and releases 1) –> leads to apoptosis of the tumor cell.

Answer 3

1) granzyme and perforin (CD8+)

Question 4

Do not get GVHD

Answer 4

Identical twin donors

Question 5

GVHD primarily 1) mediated, but contributions of other cells types

Answer 5

1) T cell

Question 6

Higher risk of relapse

Answer 6

Identical twin donors

Question 7

Recipient T-cell recognizes donor peptides shown in the context of a RECIPIENT MHC and dendritic cell

Answer 7

Indirect Allorecognition:

Question 8

Autologous transplant mobilized PBPCs (peripheral blood stem/progenitor cells) are superior b/c they have:

Answer 8

(a) accelerated engraftment. (b) Require fewer RBC and platelet transfusions. (c) Results in a shorter hospital stay.

Question 9

increased serum bilirubin.

Answer 9

Acute GVHD and chronic

Question 10

Plays a role in ACUTE rejection

Answer 10

Direct Allorecognition:

Question 11

dry oral mucosa with ulcerations

Answer 11

Chronic GVHD

Question 12

Mimic features of SLE, sicca syndrome, eosinophilic fasciitis, RA, PBS

Answer 12

Chronic GVHD

Question 13

most important in initiation of GVHD

Answer 13

HLA-A, B, and DR

Question 14

HSC Donors: Identical twin donors–> • Do not require 1) • Do not get 2) • Higher risk of relapse

Answer 14

1) post-transplant immunosuppression 2) GVHD 3)

Question 15

GVHD Unrelated donors with serologic match may have 1) leading to incompatibility

Answer 15

1) different alleles

Question 16

Traditional source of HSC for allogeneic and autologous transplants

Answer 16

bone Marrow

Question 17

• Restricted to cells of immune system • HLA-DQ, DR, DP

Answer 17

MHC class II

Question 18

Preferred donor for allogeneic transplants are:

Answer 18

Matched related donors such as siblings

Question 19

Use of peripheral precursor cells rather than bone marrow inc. risk of:

Answer 19

chronic GVHD

Question 20

human platelet antigen 3

Answer 20

minor histocompatibility antigens and difference in host and recipient may cause GVHD

Question 21

CXCR4 antagonist AMD3100

Answer 21

Mobilizes HSC from marrow into BLOOD

Question 22

Acute GVHD vs. chronic time period

Answer 22

acute–>First 100 days post-transplant chronic–>After 100 days post-transplant

Question 23

polymorphism of PECAM (platelet endothelial cellular adhesion molecules)

Answer 23

human platelet antigen 3

Question 24

Mismatched related donors: Associated with higher risk of 1)

Answer 24

1) GVHD

Question 25

If recipient and donor are matched for MHC antigens, GVHD is initiated by differences in 1) presented in the context of MHC

Answer 25

1) minor histocompatibility antigens

Question 26

Maculopapular rash

Answer 26

Acute GVHD

Question 27

Previous splenectomy inc. risk of

Answer 27

Chronic GVHD

Question 28

Hematopoietic Stem Cells (HSC) specific markers

Answer 28

CD34+Thy-1+

Question 29

CMV seropositivity inc. risk of:

Answer 29

chronic GVHD

Question 30

• Potential minor histocompatibility antigens include 1) • Minor differences in these peptides compared with the native peptide may result in partial activation

Answer 30

1) class I myosin family member, human platelet antigen 3, a polymorphism of PECAM

Question 31

• On all nucleated cells • HLA-A, B, C

Answer 31

MHC class I

Question 32

Risk factors Chronic GVHD

Answer 32

Prior acute GVHD

Question 33

Chronic GVHD s/s.

Answer 33

Skin issues like lichen planus or scleroderma, dry oral mucosa with ulcerations, sclerosis of GI tract, and increased serum bilirubin.

Question 34

what is one clinical use of allorecognition?

Answer 34

Graft-Versus-Tumor Effect--\> the cells that may not have been killed off w/ chemotherapy and radiation are killed off by graft cells

Question 35

Dendritic cell from the graft (i.e. donor’s cell) interacts w/ recipient T-cell

Answer 35

Direct Allorecognition:

Question 36

GVHD pathogenesis: Stress causes 1) to mature; Recipient mature DC present antigen to 2) 2) becomes T helper cell which activates 3) Result--\> Recipient tissue damage aka GVHD

Answer 36

1) RECIPIENT DC 2) DONOR CD4+; 3) DONOR CD8+ T-cells;

Question 37

Sources of HSC for Transplantation: -Immunologically relatively naïve, which may extend donor pool • Limitation = small number of cells per unit

Answer 37

Umbilical cord blood

Question 38

10X greater number of T cells increases risk of GVHD

Answer 38

Allogeneic transplant with BLOOD as source of marrow

Question 39

Occurs \>50% of long-term survivors of HLA-identical sibling transplants

Answer 39

Chronic GVHD

Question 40

Sources of HSC for Transplantation: Blood: HSC mobilized from DONOR marrow into blood by 1); and then the progenitor stem cells, now in the peripheral blood, collected via 2)

Answer 40

1) chemotherapy, G-CSF, GM-CSF, IL-3, thrombopoietin, and CXCR4 antagonist AMD3100 2) apheresis

Question 41

• In GVHD, principal antigenic targets of graft T cells are 1) if they differ • If graft is matched at MHC, 2) underlie GVHD

Answer 41

1) host MHC molecules 2) minor histocompatibility antigens

Question 42

Normally, Self MHC molecule presents foreign peptide to T-cell to recognize self MHC-foreign peptide complexes Allorecognition: T-cell recognizes an 1) (i.e. MHC from the donor; this structure resembles self MHC-foreign peptide complex); leads to inappropriate immune reponse.

Answer 42

1) allogeneic MHC molecule

Question 43

Types of HSC Transplantation: Donor’s hematopoietic stem cells are used

Answer 43

Allogeneic

Question 44

Graft-versus-Host Disease (GVHD) Basic requirements: • Graft contains 1) • Host possesses antigens lacking in the graft, which appear as non-self • Host must be incapable of mounting a reaction against graft for a period sufficient to allow graft cells to attack the host

Answer 44

1) immunologically competent cells

Question 45

Acute GVHD s/s

Answer 45

Maculopapular rash, abdominal cramps w/ diarrhea, and increased serum bilirubin.

Question 46

Matched related donors • Typically are 1)

Answer 46

1) siblings