Wk 5 CAR T Therapy HSC Transplantation

Question 1

Allo

Answer 1

=other than self

Question 2

Process of autologous transplantation

Answer 2

Take blood
Do chemo
Return blood to patient as rescue therapy

Question 3

Process of allogeneic transplantation

Answer 3

Purpose is to reconstitute blood system and provide cancer-killing cells
Graft vs tumor effect

Question 4

What are 3 ways progenitor cells are collected for patient or donor?

Answer 4

1. Bone marrow harvest (aspirate) -~ week recovery.
2. Peripheral blood - collected w/ centrifuge closeby to filter out WBCs. Remaining plasma returned to pt. Quick recovery. Injected first w/ growth factors.
3. Umbilical cord blood - often for patients w/o well matched donor

Question 5

What is leukapheresis?

Answer 5

Process of filtering out WBCs

Question 6

How are stem cells infused?

Answer 6

Like a simple RBC transfusion

Question 7

When are autologous transplants done?

Answer 7

Hodgkin’s
NHL
MM
Testicular
Stave IV Neuroblastoma
Ewings Sarcoma (peds)

Question 8

In what malignant diseases are allogeneic transplants done?

Answer 8

AML
ALL
CML
Juvenile myelomonocytic leukemia
MDS
Myeloproliferative Disease

Question 9

What non-malignant diseases are allogeneic transplants done for?

Answer 9

Question 10

What is the goal of an allogeneic HCT?

Answer 10

induction of tolerance

Question 11

What is the minimum requirement for HLA match?

Question 12

What are the major HLA molecule classes?

Answer 12

All on chromosome 6:
Class I (HLA-A, B, C) interact w/ CD8 cytotoxic T cells
Class II (HLA-DR, DQ, DP) interact w/ CD4 Helper T- cells

Question 13

Are identical twins good matches?

Answer 13

No b/c major AND minor HLA matched -> no GVL effect

Question 14

BMT eligibility

Answer 14

Question 15

5 steps of transplant process

Answer 15

1. conditioning - 7-10 days
2. stem cell infusion
3. neutropenic phase
4. engraftment phase
5. post-engraftment period

Question 16

Explain the conditioning phase of transplant

Answer 16

7-10 days
goals:
1. eliminate malignancy
2. provide immune suppression to prevent rejection of new stem cells
3. create space for new cells

-might be done w/ radiation and chemo

Question 17

What is the neutropenic phase?

Answer 17

2-4 weeks when pt has no effective immune system
-poor healing, highly susceptible to infection
-empiric antibiotics

Question 18

What is the engraftment phase?

Answer 18

ANC > 500 x 3 days
Pltls > 20k x 3 days w/o plt transfusions
-several weeks, healing begins, fever subsides

Question 19

What is the post-engraftment phase?

Answer 19

months to years
gradual tolerance, weaning off immunosuppression, management of chronic GVHD

Question 20

What is graft vs host disease? (GVHD)

Answer 20

cytokine storm
-translocation of LPS in the GI system
-alloreactivity of donor cells (extent of MHC disparity)
-T cell polarization (Th1 vs Th2)

Question 21

GVHD prophylaxis and tx

Answer 21

Prophylaxis:
1. Tacrolimus and methotrexate
2. post-transplant cyclophosphamide
3. T cell depletion of the graft

Tx:
1. high dose steroids
2. Ruxolitinib
3. clinical trials

Question 22

What is a primary target for CAR T therapy?

Answer 22

CD19 (only on B-cells, not expressed on stem cells)
-antibodies against CD19 to inhibit tumor growth

Question 23

What is a primary target for CAR T therapy?

Answer 23

CD19 (only on B-cells, not expressed on stem cells)
-antibodies against CD19 to inhibit tumor growth

Question 24

Toxicities of CAR T therapy

Answer 24

1. cytokine release syndrome (CRS)
2. immune-effector cell-associated neurotoxicity syndrome (ICANS)