Hematopoietic Stem Cell Transplant

Question 1

What is hematopoiesis?

Answer 1

The process of formation and development of cells of the blood and immune system from a common hematopoietic stem cell

Question 2

What are hematopoietic progenitor cells (HPCs)?

Answer 2

They are the precursor cells for RBCs, WBCs, and platelets. They have the surface marker CD34 and can be transplanted to replace or regenerate bone marrow.

Question 3

What is an autologous HPC transplant?

Answer 3

When a patient’s own HPCs are used for transplant

Question 4

What are reasons to undergo an autologous HPC transplant?

Answer 4

Adults with lymphoproliferative or plasma cell disorders, children with solid tumors, rescue bone marrow after high-dose chemotherapy

Question 5

What is an allogeneic HPC transplant?

Answer 5

HPCs from another individual used for transplant

Question 6

What are reasons to undergo an allogeneic HPC transplant?

Answer 6

Malignant myeloproliferative processes, Sickle Cell Anemia, Congenital immune deficiencies

Question 7

Why can allogeneic transplants lead to Graft-vs-Host Disease?

Answer 7

Donor cells that are transplanted can recognize the recipient as foreign and attack them. This is why it is necessary to HLA match bone marrow transplant patients.

Question 8

What are the symptoms of acute GVHD?

Answer 8

Skin rash, transaminitis, gastroenteritis

Question 9

What are the symptoms of chronic GVHD?

Answer 9

Dry eyes and mouth, joint contractures and reduced mobility, scleroderma-like changes in skin, lung damage

Question 10

What is an umbilical cord blood (HPC-C)?

Answer 10

It is stem cells collected from the placenta and umbilical cord at delivery

Question 11

What are the benefits and risks of HPC-C?

Answer 11

Benefits include a greater tolerance of HLA disparity and lower risk of GVHD. The risk is a longer time until engraftment occurs.

Question 12

What is a bone marrow HPC-M?

Answer 12

HPCs collected from bone marrow under anesthesia. This is done using a needle to access the posterior iliac crest.

Question 13

What are the benefits and risks of HPC-M?

Answer 13

The benefit is a lower risk of GVHD than HPC-A. The risk is a higher risk to the donor.

Question 14

What is peripheral blood stem cells collected by apheresis (HPC-A)?

Answer 14

These are HPCs that are collected from the donor through apheresis. Growth factors are administered to the donor before donation to increase the number of HPCs in peripheral blood before collection. They then use flow cytometry to collect the HPCs. This is the most common HPC product used.

Question 15

What are the benefits and risks of HPC-A?

Answer 15

The benefits are faster engraftment of neutrophils and platelets than HPC-M. There is also a better graft-vs-leukemia affect than HPC-M. There is however a higher risk of GVHD than HPC-M.

Question 16

What are the requirements/testing that must be performed on HPC donors?

Answer 16

Pass screening questionnaire, pass physical exam, review of medical records, infectious disease testing including HIV, Hepatitis B and C, HTLV-I, II, Syphilis, CMV, and HLA testing including HLA-A, HLA-B, HLA-C, and HLA-DRB1

Question 17

What testing is performed on the HPC product?

Answer 17

CBC, WBC differential, CD34 enumeration, and viability studies

Question 18

What is the amount of CD34+ cells required in an HPC product?

Answer 18

2x10^6-6x10^6 CD34+ cells/kg of recipient body weight

Question 19

How would you prepare HPCs for long term storage?

Answer 19

Cryopreserve the product by adding a cryoprotectant (DMSO) to prevent all the water from leaving the cell when freezing. It should then be stored in a liquid nitrogen freezer at -196°C.

Question 20

How is an HPC product infused?

Answer 20

If needed, the product is first thawed in a water bath and then possibly washed. Infusion occurs through a central venous catheter. The circulating HPCs will enter the bone marrow by the CD34 reacting with bone marrow stroma.

Question 21

What are the symptoms of DMSO toxicity?

Answer 21

Coughing, flushing, rash, nausea, vomiting, cardiovascular instability, wheezing

Question 22

Why is it unnecessary to match donor and recipient’s blood types?

Answer 22

HPCs lack ABO antigens

Question 23

What is a major ABO mismatch?

Answer 23

Anti-donor ABO antibodies are present in the recipient such as an O recipient with an A donor.

Question 24

What are the potential complications of a major ABO mismatch?

Answer 24

There can be acute hemolysis of any RBCs in the HPC product due to recipient ABO antibodies attacking the red cells. There can be delayed RBC production after transplant because the recipient ABO antibodies are destroying newly formed red cells of the donor type. There is also delayed granulocyte and platelet production. Pure red cell aplasia can also occur which is when red cell maturation stops occurring. There will be no erythroblasts in the bone marrow, but WBC and platelet levels remain ok.

Question 25

If a patient has not converted yet to their donor blood type after a major ABO mismatch, what blood type should be given to the patient for a red cell transfusion?

Answer 25

The recipient’s ABO blood type

Question 26

What is a minor ABO mismatch?

Answer 26

When the donor lymphocytes can produce anti-recipient red blood cell antibodies such as an A recipient with an O donor.

Question 27

What are the potential complications of a minor ABO mismatch?

Answer 27

Acute hemolysis can occur if donor plasma in HPC products has a high ABO titer. This can be reduced by removing as much plasma as possible before donation. Hemolysis of recipient RBCs due to passenger lymphocyte syndrome is also a risk. Here the transfused donor lymphocytes will recognize the recipient as foreign and manufacture more antibodies against the recipient RBCs.

Question 28

If a patient has not converted yet to their donor blood type after a minor ABO mismatch, what blood type should be given to the patient for a red cell transfusion?

Answer 28

The donor’s blood type. This way any recipient antibodies present will not bind to the transfused red cells.

Question 29

What is a bidirectional ABO mismatch?

Answer 29

If both donor and recipient have antibodies direct against ABO blood group antigens of each other.

Question 30

What are the potential complications of a bidirectional ABO mismatch?

Answer 30

They have the risk of complications of both the major and minor crossmatch.

Question 31

If a patient has not converted yet to their donor blood type after a bidirectional ABO mismatch, what blood type should be given to the patient for a red cell transfusion?

Answer 31

Group O red cells. This should reduce complications of both major and minor crossmatches.

Question 32

When does a major Rh mismatch occur?

Answer 32

When the recipient is Rh negative and the donor is Rh positive (recipient has antibodies to donor red cells).

Question 33

What are the potential complications of a major Rh mismatch?

Answer 33

Recipient could be sensitized and form anti-D

Question 34

When does a minor Rh mismatch occur?

Answer 34

When the recipient is Rh positive and the donor is Rh negative (the donor could make antibodies against recipient red cells).

Question 35

What are the potential complications of a minor Rh mismatch?

Answer 35

Donor could have anti-D which is passively transferred to the patient

Question 36

What is Passenger Lymphocyte Syndrome (PLS)?

Answer 36

Donor lymphocytes are infused and recognize foreign RBC antigens in the recipient. The donor lymphocytes then manufacture antibodies against recipient RBCs. This results in hemolysis of recipient RBCs.

Question 37

What causes immune mediated platelet refractoriness?

Answer 37

The recipient makes antibodies against HLA antigens and removes platelets positive for those antigens from circulation stopping the post-transfusion platelet counts from increasing. HLA matched platelets should be transfused.

Question 38

What causes non-immune platelet refractoriness?

Answer 38

Can occur due to splenomegaly, sepsis, fever, DIC, medications, GVHD