Hematopoietic Progenitor Cells (Transplant) Flashcards
who oversees HPC marrow transplants that have been minimally manipulated and collected from unrelated donors?
Health Resources and Services Administration
who oversees HPC marrow transplants that have been more than minimally manipulated?
FDA
cells in the bone marrow that are capable of becoming any of the mature cells
hematopoietic stem cells
cells capable of differentiation and self-renewal, not committed to particular blood cell lineage
hematopoietic stem cells
cells not capable of differentiation and self-renewal; more mature cells that are multi-potent or committed to a particular blood cell lineage
hematopoietic progenitor cells
most common indication for HPC transplant
malignant diseases
what percentage of circulating white cells are stem cells (CD34+)?
<0.05%
what are stem cell mobilization regiments used for?
to increase levels of circulating CD34+ cells in preparation for HPC collection of peripheral blood by apheresis
is stem cell mobilization typically used for bone marrow harvesting?
no
what is used for stem cell mobilization in allogeneic donors?
G-CSF
what is used for stem cell mobilization in patients with malignant diseases undergoing autologous stem cell transplant?
chemotherapy
indication for autologous HPC transplantation
rescue of patient with patient’s own HPCs following otherwise lethal or near-lethal dose of radiation or chemotherapy given to treat malignancies or marrow and metastatic or recurrent solid tumors
what CBC parameter decreases during autologous HPC apheresis collection?
platelets
apheresis collection goal of CD34 cells for single autologous transplant
2x10^6 CD34 cells/kg to 5x10^6
in what type of HPC transplant are the host and donor the same individual?
autologous
what is the risk of graft rejection in autologous HPC transplant?
low (no immunologic rejection)
what is the risk of GVHD is autologous HPC transplant?
none
autologous HPC transplant donor eligibility screening concerns:
medical condition of patient
sensitivity of malignancy to myeloablative regimen
possibility of tumor cells in harvested marrow
sufficient number of cells collected to reconstitute the marrow after myeloablation
how long is posttransplant immunosuppression for allogeneic HPC transplant?
6 months
what transplant type is useful in genetic and all stem cell diseases?
allogeneic
related MHC match allogeneic transplant
host and donor are fully genotypically matched at the MHC locus
related MHC partial match allogeneic transplant
host and donor differ at least one major MHC locus
unrelated MHC match allogeneic transplant
host and donor may be phenotypically partially or fully MHC matched but are genotypically disparate
T-cell depleted allogeneic transplant
cells are manipulated to remove T-cells or T-cell subset
transplant type in which host and donor and fully matched at both major and minor histocompatibility antigens, usually due to host and donor being identical twins
syngeneic
transplant type in which host and donor are disparate individuals who may or may not match at major histocompatibility complex locus and are usually not matched at minor histocompatibility loci
allogeneic
when is syngeneic transplant indicated?
acquired diseases in which entire progenitor cell population is abnormal
type of transplant with human recipient and live HPCs from nonhuman animal source or human cells with no ex-vivo contact
xenogeneic
sources of HPC
bone marrow
peripheral blood
umbilical cord blood
traditional source of progenitor cells
bone marrow
what HPC source is used predominantly in allografting?
bone marrow
HPC source used predominantly in autografting
peripheral blood
target collection for autologous transplant
> 2.0x10^8 nucleated cells per kg recipient body weight
target collection for allogeneic transplant
> 3.0x10^8 nucleated cells per kg of recipient body weight
what is used in combination with G-CSF for mobilization of CD34 cells in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma
adhesion-blocking agents and cytokines
what defines poor HPC mobilization?
failure to achieve minimum level of 5-20 CD34 cells/uL in PB after completion of mobilization regiment
OR
inability to collect at least 1x10^6 CD34 cells/kg during single apheresis procedure
OR
failure to collect total of 5x10^6 CD34 cells/kg in all collections
what is the current most popular source for HPC collection in both autologous and allogeneic transplants in adults?
apheresis
is apheresis or marrow collection more practical currently?
apheresis
infectious disease testing of autologous and allogeneic donors should be done in what time frame?
within 30 days of scheduled collection
donor testing included in autologous and allogeneic transplant
HBsAg anti-HBc anti-HTLV anti-HIV-1 anti-HIV-2 HIV-1 p24 antigen anti-HCV syphilis CMV
what is one of the leading causes of posttransplant mortality in allogeneic setting?
CMV infection
tumor purging
removal or destruction of tumor cells than can contaminate an autologous product
what cell causes GVHD?
T cells
autologous HPC storage
refrigerated or cryopreserved until infused
expiration date of HPC for marrow transplant
no expiration date defined
storage of allogeneic HPC of un-manipulated marrow
3 days at 2-8C or 18-24C for vitality
purpose of cryopreservation
to freeze HPC marrow products that will be capable of maintaining viability and potency of stem and progenitor cells
what preservative are HPCs stored in?
DMSO and hydroxyethyl starch
storage temp of cryopreserved HPC
- 180C or colder at liquid phase
- 145 to -185C in vapor phase
transport storage of cryopreserved components
liquid nitrogen dry shipper that can maintain temp at -180C for 10-14 days with continuous temp monitoring
HPC infusion rate
5-20 ml/min
side effects of HPC infusion
bradycardia, diarrhea, flushing, nausea, hypertension, abdominal pain
what percentage of HPC show signs of bacterial contamination?
0.2-4%
QC of HPC
cell counts viability microbial culture CD34 enumeration cytoplasmic aldehyde dehydrogenase colony-forming cell assays bioluminescence assays tumor cell detection engraftment data
best QC test predictor of engraftment
CD34+ cell dose
what does measurement of cytoplasmic aldehyde dehydrogenase correlate to in transplant?
speed of neutrophil engraftment
what cells have been found to be responsible for short-term engraftment?
committed progenitor cells
what cells have been found to be responsible for long-term, sustained engraftment?
pluripotent stem cells
what aspect of transplant correlates with intracellular adenosine triphosphate concentration?
cell proliferation
transplant success rate depends on what?
disease of patient stage of disease degree of disease prior to treatment age and condition of patient degree of HLA match between patient and donor (in allogeneic patients)
overall survival rates of HPC transplant
30-60% for otherwise fatal diseases
what is the most important risk factor for GVHD?
MHC incompatibility between donor and recipient
all donors and recipients are typed for what HLA antigens?
HLA class I (-A, -B, -C) and HLA Class II (-DR, -DQ, -DP)
optimal allele-level match important mainly for what HLA antigens?
HLA-A, -B, -C, -DR
HLA match degree: A
4 antigens match
HLA match degree: B1U
3 antigens detected in donor, all match
HLA match degree: B1X
3 donor antigens match, 1 cross-reactive
HLA degree match: B2U
2 antigens detected in donor, both match
HLA degree match: B2UX
3 antigens detected in the donor, 2 match and 1 cross-reactive
HLA degree match: B2X
2 donor antigens match, 2 cross-reactive
HLA degree match: C
1 antigen in donor not present in recipient and not cross-reactive
HLA degree match: D
2 antigens in donor not present in recipient and not cross-reactive
what is best donor choice for HPC transplant?
HLA-identical siblings
3 requirements for development of GVHD
graft must contain immunologically competent cells
recipient must be incapable of rejecting transplanted cells
recipient must express tissue antigens that are not present in donor
broad attack against host tissues mediated by donor T lymphocytes
graft vs host disease
acute GVHD occurs when after transplant
a few days to 100 days
chronic GVHD occurs when after transplant
100 days
2 approaches employed with major ABO incompatibilities in HPC transplant
1) removal of or decrease in isoagglutinin levels in recipient through large-volume plasma exchange
2) removal of red cells in donor marrow
resolution of minor ABO incompatibility in transplant
removing incompatible plasma by centrifugation before transplant
is ABO incompatibility a risk factor for GVHD?
no
what allows successful engraftment of HPC transplant regardless of ABO compatibility between recipient and donor?
non-committed and very early committed HPCs do not possess ABH antigens
major red cell incompatibility
recipient has antibodies against donor red cell antigens (Ex: group O recipient and group A donor)
minor red cell incompatibility
donor has antibodies against recipient red cell antigens (Ex: group A recipient and group O donor)
allogeneic transplant with ABO ___ mismatch results in delayed red cell recovery due to destruction of engrafted red cell progenitors by recipient isohemagglutinins
major
in ABO ___ mismatch transplant, red cell recovery is generally delayed 40-60 days after transplant and correlates with decreased anti-donor isoagglutinin levels
major
recipients of ABO ___ incompatible transplant may experience delayed hemolysis mediated by donor lymphocytes 7-14 days after infusion; red cell recovery is not delayed
minor
autologous HPC transplant recipients receive blood components that are:
ABO identical or compatible
