INDEX

A

Accessing units, 49, 87–92

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



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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program INDEX A Accessing units, 49, 87–92 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 Bar coding, 84, 177 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 Bone marrow (BM), 45, 209–217 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 Chimerism, 58, 212, 297 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 processes used, 80–81, 179 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 research in, 5, 117–118 searches for, 25 Cord Blood Accrediting Organization, 83, 86 identifying, 8, 80 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 Costs, 196–197, 231–235 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 Duke University, 62, 87 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 Federal Register, 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 donors, 87, 94–99 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 Haplotypes, 23n, 37, 247, 298 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 therapeutic promise of, 20–22, 26, 38, 94, 121

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 Hemoglobinopathies, 169, 298 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 Hispanic donors, 50, 87, 95 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 and HLA matching, 10, 36 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 Immunosuppression, 22, 298 Incremental cost-effectiveness, 235 Infectious disease, 22, 169 testing for, 180–183, 185–187 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 obtaining prior to labor and delivery, 9, 111

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 establishing, 10, 126–127 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 searching for, 22–23, 156–158 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 establishing, 14–16, 133–134 needing policies regarding who must provide consent, 9, 109–110 National Cord Blood Policy Board, 13, 16, 18–19, 69, 122, 132–136, 138 establishing, 14, 132–133 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 inventory of, 19, 120–128 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 establishing, 10, 126–127

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 NetCord, 25, 98, 102 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 Outcomes data, 4, 136–137 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program initial inventory, 234 storage length, 233 Paternal objections, 107, 109 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 Pregnant women, 9, 106 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 establishing uniform, 8, 86 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 continuing to conduct outcomes research, 11, 127

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 Research, 19, 56–74, 266 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program Search strategy for patients, 227 algorithms for, 25, 263–264 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 Survey, 145, 149–159 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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 T cells, 45, 47, 62 alloreactive, 257 receptor contact residues, 246 recognition of, 245 suppressing responses of, 61 T lymphocytes, 244, 257 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) centers for, 261, 299 facilities for, 101 numbers of, 225–229 solid organ, 57, 133 Transport of cord blood, and cell viability, 83–84 Types of banks, 161 banks that offer both private and public, 161 mixed, 78–79, 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

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Cord Blood: Establishing a National Hematopoietic Stem Cell Bank Program 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