Stem Cell Transplantation

Question 1

What are the two phases of hematopoietic stem cell transplant and why do we do it?

Answer 1

1. Administration of high dose chemotherapy / radiation to eliminate tumor and all of patient’s bone marrow
2. Infusion of HSC to reconstitute the entire system

We do it because doses to eliminate malignancies via chemotherapy are too high to not kill your own cells.

Question 2

What is autologous vs allogeneic vs syngeneic transplant?

Answer 2

Autologous - patient’s own marrow cells removed, cryopreserved, and reinfused after chemo

Allogeneic - stem cells or marrow from a donor

Syngeneic - stem cells or marrow from an identical twin

Question 3

What are the eligible matches for allogeneic stem cell transplant?

Answer 3

1. HLA matched sibling donor
2. HLA mismatched family donor
3. HLA matched unrelated donor

Question 4

What is the last source of stem cell transplant? Why is it advantageous?

Answer 4

Cord blood - advantageous because stem cells are immunologically naive
-> less likely to have graft rejection on a pure match compared to HLA-matched bone marrow

Question 5

How common are HSC in bone marrow? What marker are they positive for? Why are they super useful? How are they stored?

Answer 5

Rare, about 1/10000

Positive for CD34

Super useful because only a small amount is capable of reconstituting the entire lymphohematopoietic system

Can be stored for long periods by cryopreservation

Question 6

How are stem cells usually harvisted?

Answer 6

Although direct harvest from posterior iliac crest is possible, usually a peripheral harvest is done

Mobilize stem cells in peripheral blood by increased proliferation by G-CSF and drawing them about 1 week after starting administration

Question 7

Once you’ve harvested HSCs, how do you put them in the marrow?

Answer 7

If you put them in via IV, they will just automatically home into the bone marrow

Question 8

What diseases are commonly treated by HSCT?

Answer 8

1. Hodgkins Lymphoma
2. Non-Hodgkins Lymphoma
3. Multiple Myeloma
4. AML
5. ALL
6. MPD / MPN
7. MDS

Question 9

What diseases are non-malignant but can be treated by HSCT?

Answer 9

1. Marrow failure / aplastic anemia
2. Hemoglobinopathies / Sickle cell disease / Thalassemias
3. Enzyme deficiencies

Question 10

What are the advantages and disadvantages of autologous stem cell transplant?

Answer 10

Advantages: Patient is donor, so less toxicity / rejection

Disadvantages - patients own marrow cells may be abnormal due to contamination or previous chemotherapy (damage)

Question 11

What are diseases frequently treated by autologous transplantation?

Answer 11

1. Hodgkins Lymphoma
2. Non-Hodgkins Lymphoma
3. Multiple Myeloma

Question 12

What disease are frequently treated by allogeneic transplantation?

Answer 12

1. AML
2. ALL
3. MPD / MPN
4. MDS
5. Aplastic anemia
6. Hemoglobinopathies

Question 13

What are the advantages and disadvantages of allogeneic transplantation for treatment of malignancies?

Answer 13

Advantages:
No risk of contamination
New cells will recognize cancer cells as foreign (graft vs tumor activity)

Disadvantages:
Difficulty finding a donor
Toxicity

Question 14

What chromosome are the HLA antigens located on and what antigens do we need to match?

Answer 14

Chromosome 6

Need to match HLA-A,B,C, and HLA-DR

8/8 match is best

Question 15

What are chances of HLA matching with your sibling?

Answer 15

25%

Need to both be passed the same chromosome 6 by your parents

Question 16

What is done in the conditioning phase of both allogeneic and autologous stem cell transplant?

Answer 16

Both - chemotherapy and radiation to reduce tumor burden

Allogeneic only - immunosuppress patient to allow engraftment

Question 17

When is the transplant done? How long does it take for cells to come online?

Answer 17

Whenever the WBC count is about to drop to 0 due to chemo / radiation

• cells start functioning about two weeks after the infusion

Question 18

What is done in the recovery phase of stem cell transplant? What does recover coincide with?

Answer 18

Intense supportive care with platelets and transfusions

Reversible damage occurs to skin, liver, GI tract, and lung. Infections are common due to disrupted mucosal barriers and immunosuppression

Recovery coincides with recovery of WBC count

Question 19

What viral and fungal infections are common in the recovery?

Answer 19

Viral - HSV, CMV, EBV, VZV

RSV and influenza from healthcare workers

Fungal - Candida and aspergillus

Question 20

Why does graft-versus-host disease occur in HLA matched donations? How does this relate to graft rejection within and outside a family?

Answer 20

There are many minor antigens which the donor cells can attack on the recipients cells

-> Bone marrow donations from related donors do better because there are fewer small antigen mismatches and less graft versus host disease

Question 21

What are the common manifestations of GVHD in terms of which tissues are affected?

Answer 21

1. Skin -> often maculopapular rash acutely, with dermal fibrosis chronically
2. Liver -> often jaundice due to injured bile ducts
3. GI Tract -> Mucosal surfaces like GI tract, eyes, and mouth can be damaged leading to N/V, eye dryness

Later - lymphoid organs -> destruction of thymus and LN