Hematopoietic Stem cells and Progenitor Cells Flashcards
Which of the following growth factors is used to mobilize progenitor cells to the peripheral circulation for collection?
a. G-CSF
b. Erythropoietin
c. IL-11
d. Thrombopoietin
Correct : G-CSF
In most normal adults, HPC and HSC do not appear in the peripheral circulation so we have to mobilize the bone marrow to release them to the periphery. Giving the donor G-CSF prior to the donation should result in a sufficient harvest of cells during the apheresis collection. The most common administration is daily for 3-5 days prior to the donation, but there is a newer form of the drug which requires only a single administration
Adequacy of peripheral blood progenitor cell collection is best assessed by counting the number of cells bearing which of the following markers?
a. CD33
b. CD4
c. CD55
d. CD34
Correct: CD34
Stem cells and Progenitor cells have CD34 markers which are used as a means to measure the harvest of cells. We need to test the harvested unit to be sure that there was an adequate collection that will best treat the patient.
Typically the goal is to harvest 2 X 106 CD34+ cells/kg but we typically try to target 5 X 106.
All of the following are true regarding cryopreserved HPC transplantation except:
a. Dimethyl sulfoxide (DMSO) is used for cryopreservation?
b. HPCs are thawed at 37C and must be used within 24 hours
c. Volume reduction of HPCs may be performed before cryopreservation to reduce the storage space needed.
d. Cryopreserved HPC are shipped in containers charged with liquid nitrogen
Correct: HPCs are thawed at 37C and must be used within 24 hours
The question is asking for the answer that is NOT true.
DMSO is used as the cryopreservative for most HPC collections. HPC may be volume reduced prior to cryopreservation to reduce the amount of freezer space needed. This is fairly common in umbilical cord banking. Cryopreserved HPC are shipped frozen in containers charged with liquid nitrogen which can maintain the integrity of the frozen HPC for up to 2 weeks.
While it is true that the HPC are thawed at 37C, there is no mandate to transfuse within 24 hours. Typically the unit is not thawed until it is needed, so the outdate is not an issue. Because the product is so special, and the handling is so customized, there is no expiration date for thawed products. It is exceedingly rare that the HPC would be thawed and not infused within 24 hours anyway.
This is the exact thing that can trip you up on the SBB exam. We are so accustomed to a 24 hour outdate for thawed or washed products, that we are assuming the outdate is the same for the HPC or HSC products. Be careful about this on the SBB exam.
A patient is to undergo autologous HSC collection. He is tested prior to HSC collection and found to be positive for Hepatitis C on EIA. The infection is confirmed by RIBA. Which of the following statements concerning his donation is true?
a. He is not eligible for collection and an allogeneic donor should be identified
b. He is eligible for collection and the unit must have a biohazard sticker placed on it.
c. The donor should receive treatment for HCV infection. Once the infection has resolved, the autologous HSC many be collected.
d. He is not eligible for transplantation and therefore a collection should not be performed using either autologous or allogeneic cells.
Correct: He is eligible for collection and the unit must have a biohazard sticker placed on it.
FDA does not require testing of autologous HSC donations, but the AABB does require HCV testing. However, the autologous donor does not have to react negative on viral marker tests in order to be drawn. the purpose of the viral marker testing is to identify those units that should be stored separately from nonreactive units. In addition the final component needs a biohazard sticker applied.
The minimum number of CD34+ cells in a peripheral blood progentitor cell collection required for prompt engraftment is closest to:
a. 1.0 x 106 CD34+ cells/kg
b. 2.0 x 106 CD34+ cells/kg
c. 2.0 x 107 CD34+ cells/kg
d. 2.0 x 105 CD34+ cells/kg
Correct: 2.0 x 106 CD34+ cells/kg
This is the minimum number, but many facilities strive for closer to 5.0 X 108/kg.
I included 1.0 X 106 because that is the number we use for leukoreduction. Remember to label a component as leukoreduced we must prepare the unit in such a way that less than 1.0 X 106 WBC remain. It is easy to get these two numbers confused, and it can trip you up on the SBB exam.
Which cell type mediates Graft vs Host Disease?
a. B cells
b. T cells
c. Monocytes
d. Granulocytes
Correct: T cells
Graft vs Host Disease (GVHD) occurs when T cells from an engraftment launch an immune response to the host cells.
When collecting HPC via bone marrow aspiration, what factor determines the volume of the harvest?
a. Donor weight
b. Recipient weight
c. There is no variation in volume harvested. We always collect 500ml of bone marrow
d. The volume of harvest is determined by collection bag size
Correct: Recipient Weight
We use the recipient weight as a guide to determine how much volume we need from the patient. However we cannot exceed collection of 20/ml/kg of donor weight at any one time.
Another way to assess the volume to be collected is to estimate it based on the Total nucleated cell count of the donor. Here is a quote from an article cited below. It explains the concept here better than I can!
” Total nucleated cell (TNC) count per recipient body weight is an important factor predicting engraftment following bone marrow transplantation. Larger TNC counts can be collected by harvesting larger marrow volumes. This may risk donor complications from prolonged anesthesia time and increased blood loss. Multiple factors affect the marrow TNC concentration. A concentration of 0.183e8 TNC/mL has been recommended to estimate the volume of marrow to be collected (estimated volume). Measuring actual TNC concentrations during the harvest procedure may optimize outcomes by assuring an adequate number of TNC and allow for a smaller marrow collection for donors with higher TNC concentrations.”
Richart, J. et. al. (2017) The Role of Total Nucleated Cell Concentration in Bone Marrow Collections. Biology of Blood and Marrow Transplantations. 23 (3). S192.
https://www.bbmt.org/article/S1083-8791(16)30847-3/fulltextLinks to an external site.
Which choice below best represents donor screening requirements for autologous HCT donors?
a. Facilities must use the AABB form for HPC-Apheresis and HPC-Bone Marrow donor questionnaire for autologous HCT donors.
b. Autologous donors are screened to assess if they are healthy enough to tolerate the HCT donation procedure
c. Autologous HCT donor screening must include an assessment for risk of viral diseases.
d. Both the FDA and AABB have requirements for autologous HCT donor screening.
Correct: Autologous donors are screened to assess if they are healthy enough to tolerate the HCT donation procedure .
The FDA does not have regulations regarding autologous HCT donation screening but the AABB does have standards which can be found in the 8th edition of Standards for Cellular Therapy Services as well as in the Standards for Blood Banks and Transfusion Services.
It is not necessary to screen for history of viral markers or behavior that puts the donor at risk for infectious disease, nor is it necessary to use the full DHQ that is in place for allogeneic donors.
Which of the following is the most important factor for successful outcome of HPC transplant?
a. ABO/Rh matching between donor and patient
b. gender and age matching of donor and patient
c. HLA matching of donor and patient
d. all of the above are equally important
Correct: HLA matching of donor and patient
Because the HLA system is so highly polymorhic, matching for as many alleles as possible between patient and donor promotes a successful outcome. HLA antibodies can cause rejection of the graft.
There have been some studies showing that younger donor age can result in better patient outcomes, but there is no reason to match age or gender between patient and donor.
What is the purpose of giving G-CSF prior to an HCT donation?
a. To increase production of stem cells
b. To increase production of progenitor cells
c. To mobilize the release of CD34+ cells from the bone marrow into the peripheral circulation
d. To cause the RBCs to sediment out of the HPC product when it is collected.
Correct: To mobilize the release of CD34+ cells from the bone marrow into the peripheral circulation
G-CSF, or granulocyte colony stimulating factor, or filgrastim. The G-CSF causes the bone marrow to release cells that are CD34+, stem cells and progenitor cells, to the peripheral circulation. The purpose is to increase the amount of HCs that are harvested.
In many cases the donor receives several doses over a period of 2-4 days before the donation. To be clear, this is given ONLY to those donors who are being harvested via apheresis.
If the collection is via bone marrow, there is no need to give the G-CSF since the CD34+ cells are already in the bone marrow in adequate numbers. The issue is that with collection from the peripheral circulation, the HSC and HPC are not present in sufficient quantities to produce a viable unit with a minimum count of 2.0 X 106/kg of CD34+ cells.
Define Hematopoietic Stem Cells (HSC):
Hematopoietic Stem Cells (HSC): cells with potential to produce any cell line (uncommitted). Capable of unlimited self renewal
The blueprint for any cell line!
Define Hematopoietic Progenitor Cells (HPC):
Hematopoietic Progenitor Cells (HPC): cells that have COMMITTED to the blood-cell lineage (WBC, RBC, Plts) and have limited self renewal properties
Collections of Hematopoeitic Cell Transplants (HCTs):
will contain a mixture of committed and uncommitted cells
Define Pluripotency:
Pluripotency means the potential to become any cell type and is a potential observed in stem or progenitor cells at the beginning of the differentiation process. This potential is slowly lost as the cell differentiates and gains specialized functions. The differentiation process alters the cell dramatically, its shape, size, and energy requirements.
Cell differentiation is a result of the integration of different stimulus in a spatiotemporal fashion. Cell differentiation is sensitive to both mechanical and chemical stimulus from the environment.
Which cell type has delayed recover after allogeneic transplantation with major-ABO-mismatched HPCs?
a. lymphocytes
b. granulocytes
c. platelets
d. red cells
e. all of the above
Answer: D (Page 328)
- Allegeneic transplantation with ABO-major-mismatched marrow results in delayed red cell recovery due to destruction of engrafted red cell proginators (donor) by recipient isohemagglutinins.
- Engraftment and recovery of the other cell lines is not affected by ABO compatability.
