Stem Cell Transplantation Flashcards
What are the two phases of hematopoietic stem cell transplant and why do we do it?
- Administration of high dose chemotherapy / radiation to eliminate tumor and all of patient’s bone marrow
- 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.
What is autologous vs allogeneic vs syngeneic transplant?
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
What are the eligible matches for allogeneic stem cell transplant?
- HLA matched sibling donor
- HLA mismatched family donor
- HLA matched unrelated donor
What is the last source of stem cell transplant? Why is it advantageous?
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
How common are HSC in bone marrow? What marker are they positive for? Why are they super useful? How are they stored?
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
How are stem cells usually harvisted?
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
Once you’ve harvested HSCs, how do you put them in the marrow?
If you put them in via IV, they will just automatically home into the bone marrow
What diseases are commonly treated by HSCT?
- Hodgkins Lymphoma
- Non-Hodgkins Lymphoma
- Multiple Myeloma
- AML
- ALL
- MPD / MPN
- MDS
What diseases are non-malignant but can be treated by HSCT?
- Marrow failure / aplastic anemia
- Hemoglobinopathies / Sickle cell disease / Thalassemias
- Enzyme deficiencies
What are the advantages and disadvantages of autologous stem cell transplant?
Advantages: Patient is donor, so less toxicity / rejection
Disadvantages - patients own marrow cells may be abnormal due to contamination or previous chemotherapy (damage)
What are diseases frequently treated by autologous transplantation?
- Hodgkins Lymphoma
- Non-Hodgkins Lymphoma
- Multiple Myeloma
What disease are frequently treated by allogeneic transplantation?
- AML
- ALL
- MPD / MPN
- MDS
- Aplastic anemia
- Hemoglobinopathies
What are the advantages and disadvantages of allogeneic transplantation for treatment of malignancies?
Advantages:
No risk of contamination
New cells will recognize cancer cells as foreign (graft vs tumor activity)
Disadvantages:
Difficulty finding a donor
Toxicity
What chromosome are the HLA antigens located on and what antigens do we need to match?
Chromosome 6
Need to match HLA-A,B,C, and HLA-DR
8/8 match is best
What are chances of HLA matching with your sibling?
25%
Need to both be passed the same chromosome 6 by your parents
What is done in the conditioning phase of both allogeneic and autologous stem cell transplant?
Both - chemotherapy and radiation to reduce tumor burden
Allogeneic only - immunosuppress patient to allow engraftment
When is the transplant done? How long does it take for cells to come online?
Whenever the WBC count is about to drop to 0 due to chemo / radiation
- cells start functioning about two weeks after the infusion
What is done in the recovery phase of stem cell transplant? What does recover coincide with?
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
What viral and fungal infections are common in the recovery?
Viral - HSV, CMV, EBV, VZV
RSV and influenza from healthcare workers
Fungal - Candida and aspergillus
Why does graft-versus-host disease occur in HLA matched donations? How does this relate to graft rejection within and outside a family?
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
What are the common manifestations of GVHD in terms of which tissues are affected?
- Skin -> often maculopapular rash acutely, with dermal fibrosis chronically
- Liver -> often jaundice due to injured bile ducts
- 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
