INDEX
A
information flow, 87–90
patient support in the search and transplant process, 91–92
physician support in the search and transplant process, 91
probability of finding a donor, 90–91
Accreditation, 96–102
American Association of Blood Banks, 96–97
Foundation for the Accreditation of Cellular Therapy, 97–99
new organization, 102
NMDP standards, 99
self-reported, 162
Accreditation recommendations, 99–102
accrediting organization, 102
collection site, 100
cord blood banks, 100–101
transplant facility, 101
Administrative costs, 234
Adverse events, 101
Advisory Council on Cord Blood Donation, 95
African American donors, 37, 50, 87, 95, 124, 248, 258
African American recipients, 235–236
Algorithm for selection, of bone marrow versus umbilical cord blood, 89–90
Allele frequencies, 247–248
Allele levels, 254
Alleles, 297
identified at each HLA locus, 245
which encode specific HLA proteins (or antigens), 255
Allocation systems, 280
Allogeneic transplantation, 21, 38–43, 297
indications for stem cell support, 39–40
outcomes of transplantation of HPCs from unrelated donors, 38–43
Alloreactive T cells, 257
Allorecognition, 257
American Association of Blood Banks (AABB), 25, 79, 96–97, 102
Standards Committee, 97
American Red Cross (ARC), 24, 87, 199
Cord Blood Program, 80
American Society for Histocompatibility and Immunogenetics (ASHI), 248
Standards for HLA Testing, 249
American Society of Blood and Marrow Transplantation (ASBMT), 97–98
Anticoagulants
citrate dextrose solution, formula A (ACD-A), 205
citrate-phosphate-dextrose (CPD), 81, 205
isotonic, 82
Antigen presentation function, 244–245
Aplastic anemia, 21
Asian American donors, 50, 87, 248
standards for, 98
Aspergillis, 59
Aspilt@, 251
Australian donors, standards for, 98
Autoimmune diseases, treating, 57
Autologous transplantation, 43–44, 297
indications for stem cell support, 39–40
Available units, across all banks, 166
B
Banks. See Cord blood banks
Beta thalessemia, clinical use of cord blood in treating, 62
Biological characteristics, of umbilical cord blood, 33–38
“Biological life insurance,” 78
Biological Response Modifiers Advisory Committee (BRMAC), 93–94
failures treatable by transplantation of cord blood, 63
Bone Marrow Donors Worldwide (BMDW), 122–123, 258
Bone marrow transplantation (BMT), 47, 172
aftermath of, 209–210
Brain injury, 67–68
non-stroke-related brain damage, 67–68
stroke, 67
umbilical cord blood in, 67–68
C
California donors, 87
Canadian donors, standards for, 98
Cardiac repair, umbilical cord blood in, 65–66
Cardiac stem cell precursors, 66
Cardiomyocytes, 212–213
Carolinas Cord Blood Bank, 48, 80
Caucasian donors, 37, 50, 87, 236, 238, 248
Caucasian recipients, 235
CD34* cell counts, 40, 50, 58, 61, 67, 82–83, 93–94, 171
Cell viability, 171
transport of cord blood and, 83–84
Cellular Therapies Standards Program Unit, 96
Center for International Blood and Marrow Transplant Research (CIBMTR), 34–35
Centers for Disease Control (CDC), Health Information for International Travel, 191
Central nervous system disease, umbilical cord blood in, 66
double, 59
hematological, 68
Circulating cells, contribution to nonhematopoietic tissues in clinical specimens, 212
Citrate dextrose solution, formula A (ACD-A), an anticoagulant, 205
Citrate-phosphate-dextrose (CPD), an anticoagulant, 81, 205
Clinical Laboratory Improvement Amendments (CLIA), 248
Clinical testing and quality control, 248–249
Clinical use of cord blood in treating inherited diseases, examples of effective, 62
Colitis, ulcerative, 68
Collection of cord blood units, 82–83, 100, 151–156, 179
centers for, 297
costs, 233–234
sites for, 100
Colony-forming units (CFUs), 84
granulocyte-macrophage (CFU-GM), 83
megakaryocyte (CFU-M), 33
mixed (CFU-MIX), 78–79
Commissioned papers, 146, 208–271
Committed progenitor cells, 33
Committee on Establishing a National Cord Blood Stem Cell Bank Program, 6, 30, 79, 90
meetings, 146–147
site visits conducted by, 145
Confidentiality, of donors, protecting, 116
Confirmatory typing (CT), 197, 263
Congenital adrenal hyperplasia (CAH), 190
Consent practices. See also Informed consent of donors
for agencies currently involved with cord blood, 108
Consolidated Appropriation Act, 5
Cord blood (CB)
consent practices for agencies currently involved with, 108, 209–217
major components in the process of collection, banking, and transplantation, 77
searches for, 25
Cord Blood Accrediting Organization, 83, 86
Cord Blood Banking and Transplantation (COBLT) study, 1–2, 10, 14, 40, 43, 48–50, 133, 233, 273–276
eligibility for, 48–50
stratification variables for, 49
Cord blood banks (CBBs), 100–101, 297.
See also Private cord blood banks;
Public cord blood banks;
individual cord blood banks
applying uniform quality standards to all, 297
cost recovery by, 125
currently collecting units, 166
defined, 76–79
developing, 23–24
funding to promote inventory growth, 17, 137, 198–199
options for, 78
reputation of, 123
responding, 160
selecting, 138
that offer both private and public, 161
in the United States, list of, 24n
Cord Blood Center. See National Cord Blood Coordinating Center
Cord blood collection, establishing uniform standards for, 8, 83
Cord Blood Coordinating Center. See National Cord Blood Coordinating Center
Cord blood donors. See Donors
Cord Blood Family Trust, 80–81
Cord blood lymphocytes, 47
Cord blood storage, 84–86, 151–156, 179, 204–205
costs of, 233–234
methods, 81
motives for, 76
storage length, 233
Cord blood (CB) transplantation, 38–50, 67, 209, 297
after nonmyeloablative therapy, 57–58
allogeneic transplantation, 38–43
autologous transplantation, 43–44
graft versus host disease, 45–47
outcomes of transplantation of HPCs from related donors, 44–45
Cord blood units (CBUs), 297
collecting, 82–83
establishing FDA licensure of, 8, 94
Coriell Institute for Medical Research, 95
Cost-benefit of increasing cord blood inventory levels, 221–241
conclusion, 239
equity, 235–237
incremental cost-effectiveness, 235
introduction, 221–222
patient survival time, 222–231
sensitivity analyses, 237–238
Cost estimates, 234–235
by inventory level, 235
Cost model, 231–232
parameters, 233
Cost per life year gained, as a function of cord inventory, 236
associated with increasing the inventory, 125–126
recovering, 125
of transplantation, 234
of typing, 254
Creutzfeldt-Jakob disease (CJF), 191
Criteria
for data sharing, establishing, 18, 138
to determine which units are for transplant, 172–175
to determine which units are suitable for banking, 168–171
Crohn’s disease, 68
Cryobanks International, Inc., 80
Cryopreservation, 85
Cryopreservative agents, dimethyl sulfoxide, 81, 85, 205
Cumulative proportion alive (engrafted), 279–281
Current bank status, 79–81
collection processes, 80–81
size of identified banks, 80
storage methods, 81
Current good tissue practice (cGTP), 92
Current inventory, expanding, 11, 127
Current transplant technology
approaches to accelerate immune recovery, 59
coinfusion of mesenchymal stem cells, 60–61
cord blood transplantation after nonmyeloablative therapy, 57–58
ex vivo expansion of cord blood derived from hematopoietic progenitor cells, 58–59
improving, 56–61
multiple cord blood unit transplantation, 59–60
upregulation of homing receptors, 61
Cytomegalovirus (CMV) infection, 59, 169, 273–274, 279
D
Danielle Martinez Act, 95
Data sharing, establishing criteria for, 18, 138
Databases, outcomes, 16–17, 136
De-identification, 118
Detroit donors, 87
Deviations, 101
Differentiated myeloid cells, 215
Dimethyl sulfoxide (DMSO), a cryopreservative agent, 81, 85, 205
Discard rate, 233
Disclosure, of information regarding screening and other risks, 112–114
Discount rate, 234
Discrepancies, major, clouding the cord blood field, 214–215
Diseases, 256–257.
See also Autoimmune diseases;
Central nervous system disease;
Genetic diseases treatable by transplantation of cord blood;
Immune deficiency diseases;
Infectious disease;
Inherited diseases
Distribution systems, for hematopoietic progenitor cells, 10, 130
DNA-based testing, 114, 243, 250–251, 254–256, 261
Donor cell contribution to nonhematopoietic tissues after whole bone marrow transplantation, in animal models, 210
Donor identification, removal of, 117
Donor records, maintenance of, 114–117
Donor selection, 258–264
defining a “match,” 258–259
defining a mismatch, 260
HLA matching to optimize outcome in marrow transplantation, 36, 260
HLA testing at recruitment and at the time of donor selection, 261–263
selection of potential HLA matches by registry search algorithms, 263–264
Donors, 106
clarifying potential options and outcomes of donation for, 9, 111–112
permanent unavailability of, 23
protecting confidentiality and privacy of, 116
transient unavailability of, 23
unavailability of, 23
understanding the limitation of their rights, 9, 118
Duchene muscular dystrophy, 214
Carolinas Cord Blood Bank, 48, 80
E
EMBASE, 143
Engraftment
lack of, 213
long-term, 62
Epitopes, serologic, 250
Equity, 235–237
Ethical and legal issues, 19, 106–119
cord blood research, 5, 117–118
disclosure of information regarding screening and other risks, 112–114
informed consent of donors, 107–112
maintenance of donor records and patient privacy, 114–117
European donors, 22
standards for, 98
European Federation for Immunogenetics (EFI), 248
European Group for Blood and Marrow Transplantation (EBMT), 41n, 172
European Research Project on Cord Blood Transplantation (Eurocord), 35, 42
registry, 44–45
Exclusion criteria, 180–183
Existing cord blood inventory, 122–124
likelihood of finding a match, 123–124
racial and ethnic representation, 124
total number of usable units, 123
Expanded Access Protocol, 50
Extended haplotypes, 247
F
Fanconi anemia, umbilical cord blood in, 62
Federal Advisory Committee Act, 14, 133
Financial support, for infrastructure development, providing, 17–18, 137–138
Findings, number of new units needed, 137
Florida Center for Universal Research to Eradicate Disease, 96
Florida Public Health Provision, 95
Follow-up, on neonatal health status, 200
Foundation for the Accreditation of Cellular Therapy (FACT), 25, 79, 97–99, 102, 172
banks meeting standards of, 50
standards of, 99
Funding, of cord blood banks to promote inventory growth, 17, 137, 198–199
G
Gastrointestinal disorders, umbilical cord blood in, 68
Genetic diseases treatable by transplantation of cord blood, 63, 69
bone marrow failures, 63
immune deficiency diseases, 21, 63
metabolic storage disorders, 21, 63
Genetic screening, 184
Good tissue practice (GTP), 92
Government regulations, 92–96
FDA regulation of human cell, tissue, and cellular and tissue-based products, 92–94
state-legislated programs, 94–96
Graft-versus-host disease (GVHD), 2, 21–22, 24, 35–36, 38, 41–47, 56–60, 213, 298
preventing, 44
relapse and graft-versus-leukemia effect, 47
Graft-versus-leukemia (GVL) effect, 47
relapse and, 47
Granulocyte-macrophage colony-forming units (CFU-GM), 83
Growth. See Inventory growth
H
Haemolysis, elevated liver enzymes, low platelets (HELLP), 181, 183, 206
extended, 247
frequencies of, 247–248
predicting, 247
uncommon, 264
Health Care Financing Administration (HCFA), 249
Health care payment systems, 17
Health insurance, 113
Health Insurance Portability and Accountability Act (HIPAA)
de-identification rules under, 117–118
Privacy Rule of, 115
Health Resources and Services Administration (HRSA), 5, 7–8, 11, 13–14, 26, 80, 102, 132
Hematological chimerism, 68
Hematological malignancies, 60
Hematopoietic progenitor cell (HPC), 1–7, 13, 56–57, 59, 63–69, 75, 97, 127, 298
distribution systems for, 10, 130
donating, 23
ex vivo expansion of cord blood derived from, 58–59
homing receptors, 61
multipotent, 33
sources of, 5
Hematopoietic progenitor cell (HPC) transplantation
continued evolution of, 120
experimental, 106–107
facilities for, 98
Hematopoietic stem cell (HSC), 209–217
formation of multiple peripheral blood cells from multipotent, 34
Hematopoietic stem cell (HSC) transplantation, 5, 33–55
biological characteristics of umbilical cord blood, 33–38
cord blood transplantation, 38–50
Hepatitis B core antibody (hbcAb), 171
Hepatitis B virus (HBV), 85, 169
Hepatitis C virus (HCV), 169, 190
Hepatocytes, marrow-derived, 68
Hespan, 85
High resolution (HR) level, 27, 254
mismatches, 260
Histocompatibility, 121
HLA Nomenclature Committee, 249
Homing receptors, upregulation of, 61
HPCs, developing an outcomes database for all sources of, 16–17, 136
Human cellular and tissue-based products (HCT/Ps), 92–93
Human histocompatibility genes, 37, 246
Human immunodeficiency virus (HIV), 169, 190
Human leukocyte antigen (HLA), 2–3, 21, 36, 244–266, 298
alleles, 246
allorecognition, 257
antigens, 21
assignment of nomenclature, 249
in disease and transplantation, 256–257
disparities among, 57, 91, 125, 266
genes, 245
haplotypes, 246–247
matched units, 60, 91, 123–124, 127–128, 260, 276–281
mismatched units, 3, 10, 42, 56, 120, 125, 137, 266, 276, 279
as molecules, 242–243, 249–252
responsibilities of banks regarding, 100
testing, 117
testing at recruitment and at the time of
donor selection, 261–263
typing, 6–7, 25, 34, 36–37, 43, 59, 75–76, 90, 136, 246–256
typing assignments carried by volunteer donors on registries, 16, 261
Human leukocyte antigen (HLA) overview, 242–266
donor selection, 258–264
key observations on HLA and hemotopoietic stem cell transplantation, 242–243
probability of finding an allele match for HLA loci, 264–266
research, 266
sources of hematopoietic stem cell donors, 257–258
testing methodology, 249–251
testing resolution, 252–254
tissue typing, 248–256
Human leukocyte antigen (HLA) system, 244–248
allele and haplotype frequencies, 247–248
antigen presentation function, 244–245
MHC-encoded HLA proteins, 244
Human transplantation data, 211–212
Hurler syndrome, umbilical cord blood in, 62
I
Illinois donors, 95
Immune deficiency diseases, 21
treatable by transplantation of cord blood, 63
Immune recovery, approaches to accelerate, 59
Incremental cost-effectiveness, 235
Informatics, 178
Information
about donors’ options, providing clear, 9, 111
flow of, 87–90
medical, promoting the security of, 9, 116–117
regarding screening and other risks, disclosure of, 112–114
Information Technology Working Group, 258
Informed consent of donors, 5, 107–112
clarifying potential options and outcomes of donation, 111–112
requirements for consent, 107–110
standards for obtaining, 112
timing of consent, 110–111
Infrastructure development, providing financial support for, 17–18, 138
Inherited diseases
beta thalessemia, 62
effective clinical use of cord blood in treating, 62–63
Fanconi anemia, 62
Hurler syndrome, 62
osteopetrosis, 62
severe combined immunodeficiency, 62
sickle cell anemia, 62
umbilical cord blood as effector cells, 63
Wiskott-Aldrich syndrome, 62
Institute of Medicine (IOM), 1, 5–6, 27, 30, 79, 90, 120, 122n, 130, 133, 233
Statistical Report, 229
Institutional review boards (IRBs), 112, 117, 172
Intermediate resolution level, 171, 253–254
Internal audits, 101
International Bone Marrow Transplant Registry (IBMTR) scale, 34, 45, 225, 229, 274
International Cord Blood Transplant Registry (ICBTR), 34
International Histocompatibility Workshops, 249
International registries and cord blood banks, 258
International Society for Cellular Therapy (ISCT), 97
International Society of Blood Transfusion (ISBT), 177
International Society of Hematotherapy and Graft Engineering (ISHAGE), 98
Interstate commerce, applicability of, 92
Inventory, 150–151
database and unit selection, 136
initial, 234
Inventory growth
expanding the current, 11, 127
funding of cord blood banks to promote, 17, 137, 198–199
Inventory of a National Cord Blood Stem Cell Bank Program, 19, 120–128
costs associated with increasing the inventory, 125–126
existing cord blood inventory, 122–124
practical considerations, 124–126
recommendations, 126–128
summary, 128
Inventory policy. See also National Cord Blood Policy Board
Investigational new drugs (INDs), 94, 101, 116
applications for, 8, 106–107, 117
Isotonic anticoagulants, 82
J
Japanese Cord Blood Banking Network (JCBBN), 35
Japanese donors, 22
Joint Accreditation Committee ISCT EBMT (JACIE), 172
Joint Commission for Accreditation of Healthcare Organizations (JCAHO), 249
K
Karmanos Cancer Institute, 87
L
Labor and delivery, obtaining informed consent prior to, 9, 111
Legal issues. See Ethical and legal issues
Legislation, 27.
See also individual acts
Leukemia, 21.
See also Graft-versus-leukemia effect
Life years gained, 229–231
from marrow and cord transplantation, 230
total, for transplant candidates, 231
Lifebank USA, 80
LifeCord, 79
Limitation, of the rights of cord blood donors, 9, 118
Literature search, 143–144
Low resolution (LR) level, 37, 264
generic or serologic or antigen, 253
mismatches, 260
at serological broad, 252
at serological split, 253
Lymphohematopoiesis, 22
Lymphomas, 21
M
Major histocompatibility complex (MHC), 244–246
Maryland donors, 95
Massachusetts donors, 87
Match probabilities, 222–224, 259
for pediatric patients, 224
by race, 237
Matches
defined, 258–259
likelihood of finding, 123–124
Maximum likelihood estimates, standard errors, and probabilities main effects model, 277
McCarthy Cord Blood Bank, 87
Medical information, promoting the security of, 9, 116–117
Medium-chain acyl-CoA dehydrogenase (MCAD), 190
Medline, 143
Megakaryocyte colony-forming units (CFU-M), 33
Mesenchymal stem cells (MSCs), 67
coinfusion of, 60–61
Metabolic storage disorders, treatable by transplantation of cord blood, 21, 63
Methodologies, 143–148
commissioned papers, 146
committee meetings, 146–147
literature search, 143–144
raw data analysis, 146
site visits, 144–145
survey, 145
MHC-encoded HLA proteins, 244
Milano Cord Blood Bank, 233
Minority consent, 109
Mismatches
defined, 260
high resolution, 260
low resolution, 260
major, 260
minor, 260
“permissive,” 260
Mixed colony-forming units (CFU-MIX), 78–79
Mixed-type banks, 78–79, 161, 298
MSC-like cells, 65.
See also Mesenchymal stem cells
Multiple cord blood unit transplantation, 59–60
Multipotent hematopoietic stem cells, formation of multiple peripheral blood cells from, 34
Muscular dystrophy, 214
Myeloid cells, 214
differentiated, 215
N
National Bioethics Advisory Commission, 115
National Board. See National Cord Blood Policy Board
National Bone Marrow Donor Registry (NBMDR), 24
National Cord Blood Bank Program. See National Cord Blood Stem Cell Bank Program
National Cord Blood Coordinating Center, 13, 18, 121, 133–139
needing policies regarding who must provide consent, 9, 109–110
National Cord Blood Policy Board, 13, 16, 18–19, 69, 122, 132–136, 138
National Cord Blood Stem Cell Bank Program, 2, 4, 8, 11–14, 80, 102–103, 121, 129–139
as envisioned by the Institute of Medicine committee, 132
key functions, 13
summary of recommendations for establishing, 19
National Heart, Lung, and Blood Institute (NHLBI), 40, 273–276
analysis of the cord blood data from, 273–282
Cord Blood Banking and Transplantation study, 1–2, 10, 14, 40, 43, 48–50, 133, 233, 273
National Institutes of Health (NIH), 11, 27, 69
Office of Human Research Protection, 115–116
National inventory policy. See also National Cord Blood Policy Board
National Marrow Donor Program (NMDP), 1, 10, 12, 14, 24, 26, 40, 79, 86, 91, 99, 102, 130–131, 133, 135, 172, 197, 222, 225, 243, 248–249, 256, 258, 260, 263–264, 273–274
analysis of the cord blood data from, 273–282
banks approved by, 49
standards, 99
views on an ideal National Stem Cell Cord Blood Bank program from, 28
National oversight, 132–133
Native American donors, 87, 95
Natural killer (NK) cells, 47, 63, 257
Neonatal health status follow-up, 200–203
Neoplastic transformation, 215
banks meeting standards of, 50
Neural cell phenotypes, 66
Neutrophil recovery, 38, 40, 60–61
New Jersey Cord Blood Bank, 95
New Jersey donors, 95–96
New Mexico donors, 96
New York Blood Center (NYBC), 1, 10, 24, 27, 40, 49, 62, 91, 93, 273–276
analysis of the cord blood data from, 273–282
National Cord Blood Program of, 1, 13, 26–27, 80, 102, 132, 274
views on an ideal National Stem Cell Cord Blood Bank program from, 28
Non-Caucasian donors, 22–23, 236, 238, 276
Non-stroke-related brain damage, 67–68
Nonclinical units, for research use, developing a mechanism to make available, 18–19, 69
Nonhematopoietic applications, 65
Nonhematopoietic disease, 214
Nonhematopoietic repair. See also Potential nonhematopoietic differentiation from bone marrow cells;
Potential nonhematopoietic uses for stem cells in cord blood
determining usefulness of cord blood in, 216
Nonhematopoietic tissues
in clinical specimens, circulating cells contribution to, 212
differentiation from HSCs, 210–211
mechanism of HSC-derived incorporation in, 213–214
Nonmyeloablative therapy, 58
preparatory regimens, 62
North American Task Force (NATF), 98–99
Numbers of annual transplants, by cord blood inventory level, projected, 228
Numbers of units
collected, stored, and transplanted, 163–164
collected and shipped, 191–195
O
Office of Human Research Protection (OHRP), 115–116
Oklahoma donors, 95
Optimizing registry size, to find a match, 265–266
Options, providing donors with clear information about, 9, 111
Organ Procurement and Transplantation: Assessing Current Policies and the Potential of the DHHS Final Rule, 130
Organ Procurement Transplantation Network, 133
Organ Transplants Amendment Act of 1988, 24
Osteopetrosis, clinical use of cord blood in treating, 62
developing for all sources of HPCs, 16–17, 136
Outcomes of transplantation of HPCs
continuing to conduct research on, 11, 127
from an unrelated donor, 38–41
from related donors, 44–45
from unrelated adult donors, 41–43
P
Panel on Cost-Effectiveness in Medicine and Health, 234
Parameter values for costs, 232–234
administrative costs, 234
collection and storage costs, 233–234
cost of transplantation, 234
discard rate, 233
discount rate, 234
initial endowment, 234
initial inventory, 234
storage length, 233
Patient survival time, 222–231
life years gained, 229–231
match probabilities, 222–224
numbers of transplants, 225–229
Patients
maintaining privacy of, 114–117
in the search and transplant process, 91–92
supporting, 139
Pentaspan, 85
“Permissive” mismatches, 260
Phenotypes, neural cell, 66
Phenylketonuria (PKU), 190
Physician support, in the search and transplant process, 91
Policies. See also National Cord Blood Policy Board;
National inventory policy
regarding who must provide consent, cord blood centers needing, 9, 109–110
Polymorphic sequences, 246, 250
Potential nonhematopoietic differentiation from bone marrow cells, 209–214, 263–264
after bone marrow transplantation, 209–2210
human transplantation data, 211–212
lack of engraftment reported, 213
mechanism of HSC-derived incorporation in nonhematopoietic tissue, 213–214
nonhematopoietic differentiation from HSCs, 210–211
prevalence of “transdifferentiation,” 213
Potential nonhematopoietic uses for stem cells in cord blood, 208–217
abstract, 208–209
determining usefulness of CB in nonhematopoietic repair, 216
differences between stem cells in cord blood and bone marrow, 216–217
evidence, 214–215
implications for cell therapy using CB or BM transplantation, 215–216
introduction, 209
major discrepancies clouding the field, 214–215
summary, conclusions, and recommendations, 217
respect for autonomous choice by, 110
PreMedline, 143
Privacy, of donors, protecting, 116
Privacy Rule, of the Health Insurance Portability and Accountability Act, 115
Private cord blood banks, 78, 103, 158, 161, 298
Probabilities
of finding a donor, 90–91
of finding an allele match for HLA loci, 264–266
optimizing registry size to find a match, 265–266
Processing procedures, 81–86
collection of cord blood units, 82–83
screening maternal donors and cord blood, 81–82
storage, 84–86
transport of cord blood and cell viability, 83–84
Proposed structure of a national program, 15
Public cord blood banks, 76, 78, 158–159, 161, 298
Public Cord Blood Tissue Bank, 94–95
Pulse duplicator bioreactors, 65
Q
Quality assurance systems, 100
Quality of life of patients, 120
R
Racial and ethnic compositions, 124
of the units in cord blood banks, 86–87, 167
Raw data analysis, 146
Receptor contact residues, 246
Recombinant human stem cell factor (rHuSCF), 61
Recommendations, 19
applying uniform quality standards to all cord blood banks, 8, 103
cord blood centers needing policies regarding who must provide consent, 9, 109–110
cord blood donors understanding the limitation of their rights, 9, 118
developing a mechanism to make nonclinical units available for research use, 18–19, 69
developing an outcomes database for all sources of HPCs, 16–17, 136
establishing a National Cord Blood Coordinating Center, 14–16, 133–134
establishing a National Cord Blood Policy Board, 14, 132–133
establishing a national inventory policy, 10, 126–127
establishing criteria for data sharing, 18, 138
establishing FDA licensure of cord blood units, 8, 94
establishing uniform quality assurance systems, 8, 86
establishing uniform standards for cord blood collection, 8, 83
expanding the current inventory, 11, 127
funding banks to promote inventory growth, 17, 137
identifying a Cord Blood Accrediting Organization, 8, 80
obtaining informed consent prior to labor and delivery, 9, 111
promoting the security of medical information, 9, 116–117
providing donors with clear information about their options, 9, 111
providing financial support for infrastructure development, 17–18, 138
Recommended direction for accreditation, 99–102
an accrediting organization, 102
collection site, 100
cord blood banks, 100–101
transplant facility, 101
Recommended structure of a national program, 129–139
national oversight, 132–133
structure and governance, 133–139
Regenerative potential, 68
Registries, 298
cord blood banks as repositories, 266
international, 258
optimizing size to find a match, 265–266
Registry search algorithms, selection of potential HLA matches by, 263–264
Regression analysis, 83
Relapse risk, 44
and graft-versus-leukemia effect, 47
Related donors, 257
Relationships that the IOM committee envisions under the governance structure described in its recommendations, 135
Replicative capacities of cells, 35
developing a mechanism to make nonclinical units available for, 18–19, 69
developing research priorities, 69
effective clinical use of cord blood in treating inherited diseases, 62–63
genetic diseases treatable by transplantation of cord blood, 63
improving current transplant technology, 56–61
registries/cord blood banks as repositories, 266
umbilical cord blood in regenerative medicine, 64–69
Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, 115
Results. See also Survey results
confirming, 282
Rights, of cord blood donors, limiting, 9, 118
S
San Diego donors, 87
Scientific Advisory Committee for Organ Transplantation, 133
Screening completed prior to storage, 184–191
genetic screening, 184
infectious disease testing, 185–187
other exclusions, 188–191
Screening maternal donors, and cord blood, 81–82
Search strategy for patients, 227
Security, of medical information, promoting, 9, 116–117
Selection of potential HLA matches by registry search algorithms, 263–264
Self-reported accreditation, 162
Sensitivity analyses, 237–238
Sequence specific, 249
Serologic epitopes, 250
Serologic typing, 243, 249–250, 252, 255–256
defining antigens and DNA-defined types, relationships between, 253
Severe combined immunodeficiency (SCID), 67
clinical use of cord blood in treating, 62
Sibling Cord Blood Program (CHORI), 80n, 81
Sickle cell anemia, clinical use of cord blood in treating, 62
Site visits, conducted by the Committee, 144–145
Size of identified banks, 80
Solid-organ transplants, 57, 133
Sources of hematopoietic stem cell donors, 135, 257–258
international registries and cord blood banks, 258
related donors, 257
SouthEastern Organ Procurement Foundation (SEOPF), 249
Spinal cord injury, umbilical cord blood in, 66–67
St. Louis Cord Blood Bank, 80
Standards, 139
for cord blood collection, establishing uniform, 8, 83
for obtaining informed consent of donors, 112
Standards for Blood Banks and Transfusion Services, 96
Standards for Cellular Therapy Product Services, 96
Standards for Cord Blood Services, 96
Standards for Hematopoietic Progenitor Cells, 96
Standards for HLA Testing, 249
State-legislated programs, 94–96
Danielle Martinez Act, 95
Statistical Report, 229, 273–282
Status of current banks, 79–81
Stem cells in cord blood and bone marrow, 298–299
differences between, 216–217
potential nonhematopoietic uses for, 208–217
StemCyte International Cord Blood Banks, 80–81
Steps in donor selection, 262
Stigmatization, 113
Storage containers, for cryopreservation of cord blood units, example of, 84
Storage of cord blood units. See Cord blood storage
Stroke, 67
Stromal cells, 213
Structure and governance of a national program, 133–139
cord blood bank selection, 138
finances, 137–138
inventory database and unit selection, 136
outcomes data, 136–137
patient support, 139
source of transplanted material, 135
standards, 139
Sudden acute respiratory syndrome (SARS), 191
Summaries
of current research, 64
of HLA matches, 264–265
of recommendations for establishing a National Cord Blood Stem Cell Bank program, 19
of statistics cell dose, age, and HLA mismatch, 281
of statistics predictors by outcomes, 275
status of current banks, 79–81
Survey results, 160–205
available units across all banks, 166
banks that responded, 160
banks which are currently collecting units, 166
collection process, 179
costs, 196–197
criteria to determine which units are for transplant, 172–175
criteria to determine which units are suitable for banking, 168–171
exclusion criteria, 180–183
funding of public banks, 198–199
informatics, 178
neonatal health status follow-up, 200–203
numbers of units collected, stored, and transplanted, 163–164
numbers of units collected and shipped, 191–195
racial makeup of inventory, 167
screening completed prior to storage, 184–191
self-reported accreditation, 162
storage of the units, 204–205
total units collected, by bank, 165
tracking units, 177
types of banks, 161
units that are not usable for transplant, 176
T
alloreactive, 257
receptor contact residues, 246
recognition of, 245
suppressing responses of, 61
T-regulatory cells, 59
Testing methodology, 249–251
DNA-based methods, 250–251
impact of allele discovery and genotype summarization on, 254–255
serology, 249–250
Testing resolution, 252–254
allele level, 254
high-resolution level, 254
intermediate resolution level, 253–254
low resolution at serological broad, 252
low resolution at serological split, 253
low resolution (generic or serologic or antigen) level, 253
Texas Cord Blood Bank, 96
Texas donors, 95
Thawing, 101
Timing of consent, 110–111
Tissue typing, 248–256
clinical testing and quality control, 248–249
comparison of typing methods, 252
correlation of DNA-based and serologic types, 255–256
cost of typing, 254
HLA assignments—nomenclature, 249
impact of allele discovery and genotype summarization on test interpretation, 254–255
testing methodology, 249–251
testing resolution, 252–254
Total body irradiation/cytokine (TBI/Cy), 49
Total nucleated cell (TNC) count, 80, 222, 274, 278–279, 282
Total number of usable units, 123
Total units collected, by bank, 165
Toxic liver injury, umbilical cord blood in, 68
Tracking units, 177
Transdifferentiation events, 65, 69, 210, 214
prevalence of, 213
Transient donor unavailability, 23
Transient warming events (TWE), 86
Transit time, 83
Transplant Amendments Act of 1990, 24
Transplant-related mortality (TRM), 278
Transplants (tx)
facilities for, 101
numbers of, 225–229
Transport of cord blood, and cell viability, 83–84
Types of banks, 161
banks that offer both private and public, 161
private banks, 161
public banks, 161
Typing methods, comparison of, 252
U
Ulcerative colitis, 68
Umbilical cord blood (UCB), 299
biological characteristics of, 33–38
as effector cells, 63
Umbilical Cord Blood Banking Act, 96
Umbilical cord blood (UCB) banks and banking, 19, 75–105.
See also Cord blood banks
accessing units, 87–92
accreditation, 96–102
definition of a cord blood bank, 76–79
government regulations, 92–96
private banks, 103
processing procedures, 81–86
racial and ethnic compositions of the units in cord blood banks, 86–87
status of current banks, 79–81
Umbilical cord blood (UCB) in regenerative medicine, 64–69
brain injury, 67–68
cardiac repair, 65–66
central nervous system disease, 66
gastrointestinal disorders, 68
gene therapy, 69
spinal cord injury, 66–67
toxic liver injury, 68
Unavailability, of donors, 23
Uniform quality assurance systems, establishing, 8, 86
Uniform standards for cord blood collection, establishing, 8, 83
United Network for Organ Sharing (UNOS), 249
United States Pharmacopeia (USP) grading, 205
University of California, Los Angeles (UCLA), 48
Upregulation, of homing receptors, 61
U.S. Congress, 27
U.S. Department of Health and Human Services (DHHS), 4, 7, 13–14, 26, 112n, 130–133
Scientific Advisory Committee for Organ Transplantation, 133
U.S. Food and Drug Administration (FDA), 7–8, 93–94, 101, 106–107, 113–114, 117
establishing licensure of cord blood units, 8, 94
regulation of human cell, tissue, and cellular and tissue-based products, 18, 92–94, 102, 112n, 136
V
Variant Creutzfeldt-Jakob disease (vCJF), 191
Viacord, 80
Volunteers carrying the same allele, A*0201, examples of, 256
W
West Nile virus (WNV), 169, 190
White blood cell (WBC), 38
Wiskott-Aldrich syndrome, clinical use of cord blood in treating, 62
Women. See Pregnant women
World Health Organization (WHO), 251
HLA Nomenclature Committee, 249
World Marrow Donor Association (WMDA), 172, 258
X
Xenogenic transplantation, 68
Y
Y-chromosome-positive cells, 211–213