Heme #27: Hematopoietic Stem Cell Transplant

Front 1

What are some characteristics of HSC (Hematopoietic Stem Cells)?

Back 1

- capable of differentiating
- capable of self renewing (asymmetric replication)
- mark for CD34+ (early progenitors)

Front 2

What is the difference between bone marrow and stem cell transplant?

What are 3 sources of HSC?

Back 2

Difference is WHERE the cells come from (BM- cells come from BM, SC- cells taken from peripheral blood).

Bone Marrow
Peripheral Blood stem cells
Umbilical cord cells

Front 3

Where is bone marrow harvested from?

What is the limitation to using umbilical cord blood?

Back 3

PSIC (Posterior superior iliac crest)

Umbilical cord blood is limited in number of cells (can only use what's in the cord)

Front 4

How do you prep someone for peripheral stem cell harvest?

How does "time to engraftment" compare to "degree of graft vs. host disease"

Back 4

Give them G-CSF--> take blood and plasmapherese to remove only CD34+ cells --> transplant to recipient

More days to engraft = typically less chronic graft vs. host disease (ex: cord blood = longest to engraft but has least GVHD).

Front 5

What is an Autologous transplant?

For what diseases is autologus transplant curative? for what diseases does it cause progression free survival?

Back 5

Autologous = patients given high dose chemo to remove bone marrow and use their own stem cells to repopulate.

Multiple Myeloma = progression free survival (but not cure)
NHL, HD, Amyloidosis = Autologous transplant can be curative

Front 6

What is the major disadvantage to using Autologous transplant?

Back 6

Concern for relapse (we are not sure if we are reinfusing patient with diseased marrow). However, low toxicity AND can lead to possible cure.

Front 7

MHC Class I is found on what cells? What type of T cell is it targeted by?

MHC Class II is found on what cells? What type of T cell is it targeted by?

Back 7

MHC I --> expressed on almost all cells. Targeted by CD8.
MHC II --> on B-cells, Dendritic Cells, Monocytes. Targeted by CD4+.

Front 8

What is the difference between Full Allogeneic, Non-Myeloablative "mini" allogeneic, or Haplo allogeneic transplants?

Back 8

Full allogeneic --> complete ablation of bone marrow

Mini --> chemo will not completely remove bone marrow, but rely on Graft vs. Leukemia to wipe out remaining leukemia.

Haplo--> Use stem cells from a donor that's a half match (ex: parent). Immune reaction will hopefully put cancer cells into remission (but you're at increase risk of GVHD)

Front 9

How is HLA typing inherited? What is the chance of the identical HLA antigens as your sibling?

Does blood type need to be matched?

Back 9

HLA typing inherited by Mendelian Genetics (thus siblings have 1/4 chance of having identical HLA antigens).

Blood type does NOT need to be matched!

Front 10

Would a older patient be a better or worse donor? a better or worse recipient?

Why do men make better donors than women, in general?

Back 10

Older patient- higher risk as donor (more antigenic exposure), and as patient (higher risk of GVHD).

Men have less antigenic exposure (women have been pregnant!).

Front 11

What conditions are ideal for Allogeneic Bone Marrow Transplants?

Back 11

AML, ALL, CML, CLL
Multiple Myeloma
Sickle Cell, Thalassemia
Myelodysplastic syndrome
Aplastic Anemia (where BM has been completely wiped out)

Front 12

What is the major disadvantage of Allogeneic Transplant?

Back 12

High mortality rate --> Graft vs. Host disease

There is a risk for graft rejection and you must have a match in order to undergo transplant

Front 13

Describe the pathogenesis of how the condition above occurs (post-transplant).

What other body systems are affected

Back 13

Graft vs. Host disease- donor T-cells attack native organs on the recipient (recognizes them as foreign)

- Skin (rash)
- Gut (diarrhea and gastric ulcerations)
- Mouth ulcers
- Eyes (sicca syndrome)

Front 14

In what type of transplant do we see Graft vs. Leukemia (GVL) effect?

Back 14

Allogeneic transplant --> New T cells from donor will sruvey and attack malignant cell.

Front 15

The staging of acute GVHD is based on what three findings?

What is "Acute GVHD" defined as?

Back 15

1) Area of skin damaged
2) volume of diarrhea
3) level of bilirubin

Acute = <100 days post transplant
Chronic = >100 days post transplant

Front 16

How do you treat GVHD?

What is the major difference between morbidities associated with Autologous transplant and morbidities associated with Allogeneic transplants?

Back 16

- Immunosuppression (Steroids - 1mg/kg prednisone).
- If that fails use others- cyclosporine, tacrolimus, etc.
- Rituximab (unknown how it works)

ONLY with Allogeneic do you get GvH and Acute Renal Failure / Veno-occlusive disease (much less sxs with Autologous transplant)

Front 17

What is it critical to workup on a patient undergoing Pre-transplant screening?

Back 17

- HLA typing (if allogeneic)
- All organ system checks (Echo, EKG, PFTs)
- Infectious Serologies (HIV, Hepatitis, CMV)
- Detal screening

Front 18

What is the time course for a typical allogeneic transplant procedure?

Back 18

7 days of conditioning (pts. get chemo to deplete BM counts)
Day 0: stem cells delivered from blood bags- monitor for anaphylaxis
Day 1-28: monitor counts, on immunosuppresion (can get toxicity)

Front 19

What are complications of allogeneic grafting procedure?

What is Veno-occlusive disease?

Back 19

Immunosuppression: CMV, PCP, and VZV reactivation
Engraftment syndrome: From cytokine release after neutrophils engraft (fever, rash, pulmonary edema)

VoD= inflammation/damage to hepatic sinusoids. Leads to clotting. Pts get weight gain, ascites, and increased bilirubin.

Front 20

When you think of lymphomas, should you recommend autologous or allogeneic transplant?

Back 20

Autologous transplant 1st (if patient fails, then do allogeneic transplant).