Saving your baby s s cord blood: Is this good insurance? 32 th SEMINAR ON PERINATAL MEDICINE CONTROVERSIES IN PERINATAL MEDICINE: EVIDENCE FOR CURRENT PRACTICE Sante Fe, New Mexico Mervin C. Yoder, MD Richard and Pauline Klingler Professor of Pediatrics and Professor of Biochemistry and Molecular Biology and Cellular and Integrative Physiology Indiana University School of Medicine
Disclosure I serve as a Medical Director for The Genesis Bank and am a paid consultant to this cord blood company
Outline 1) Cord blood and vessel origins 2) Stem cell types and sources 3) Use of cord blood as alternative source of hematopoietic stem cells 4) History of cord blood studies 5) Cord Blood Banking 6) Recommendations
Umbilical cord
Vein Arteries
Umbilical cord in a 26 day old human embryo
Umbilical cord in a 36 day old human embryo
Stem cell potential in cord blood and umbilical cord 1. Alternative source of hematopoietic stem cells for allogeneic stem-cell transplantation for the treatment of acquired or inherited diseases 2. Source of cardiac, hepatic, pancreatic, and epidermal progenitor/precursor cells 3. Potential source of neurons and glial cells 4. Alternative source of postnatal mesenchymal stem cells: osteoblast,, smooth muscle, adipocytes,, bone 5. Endothelial progenitor cells: vessel forming ability 6. Very small embryonic like stem cells: pluripotent cells derived from the blood 7. Multipotent stem cells: universal stem cell : pluripotent cells derived from the Wharton s s jelly
Source of hematopoietic stem cells for allogeneic transplantation Hematopoietic stem cells for transplantation may be derived from the patients themselves (autologous transplant) or from another person (allogeneic( transplant) Only 25-30% of patients requiring a transplant find a fully matched sibling donor. therefore unrelated donor cells are sought
Source of hematopoietic stem cells for allogeneic transplantation An alternate to a related donor involves seeking an unrelated HLA-matched adult donor outside the family The National Marrow Donor Program registry has 7 million potential allogeneic donors 50-60% of patients are unable to find a fully matched donor Non-white donors least successful (lack of genetic heterogeneity due to few non-white donors) Umbilical cord blood has emerged as an alternate source of allogeneic stem cells
Source of hematopoietic stem cells for allogeneic transplantation Umbilical cord blood has been successfully utilized as an alternative source of hematopoietic stem cells for related and unrelated donor stem cell transplants. Advantages of cord blood as a stem cell source: no risk to the donor no donor attrition immediate availability lower incidence and severity of GVHD
Source of hematopoietic stem cells for allogeneic transplantation The one year survival has been as high as 80-90% for sibling HLA-matched cord blood transplants and 40-80% for unrelated partially HLA-matched transplants Unrelated donor transplants have greater associated toxicity due to infectious complications, increased incidence and severity of graft versus host disease (GVHD), and greater incidence of graft failure. How did the field of cord blood transplantation evolve?
History of cord blood studies Greenfield AD, et al. The rate of blood flow in the umbilical cord. Lancet 8:2(10):422, 1951 Greenfield AD, et al. The relationship between the blood flow in the umbilical cord and the rate of foetal growth in sheep and guinea pig. J Physiol 115(2):158, 1951 Since 1951 there have been more than 21,000 articles archived in PubMed under the search: Umbilical cord blood
History of cord blood studies Synthesis of fetal and adult hemoglobins in culture by human umbilical cord blood erythropoietic progenitors. Kidoguchi K et al. Hemoglobin 2(6):503, 1978 One of the first papers to attempt to culture human umbilical cord blood hematopoietic progenitors
History of cord blood studies HPP-CFC LPP-CFC Colony forming assays permit distinction of a hierarchy of proliferation/differentiation
History of cord blood studies Hematopoietic colony-forming cells in umbilical cord blood with extensive capacity to generate mono- and multipotent hematopoietic colony-forming cells Nakahata T and Ogawa M. J Clin Invest 70:1324, 1982 This report identified a unique class of human hematopoietic CFC with extensive ability to generate blast cell colonies: blast cells displayed features of stem-like cells with capacity to generate secondary hematopoietic CFC.
History of cord blood studies Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Broxmeyer HE, et al. PNAS 86:3828, 1989 These investigators examined > 100 cord blood collections: 1) CFC survived < 72h at 4 o or 23 o C but not at 37 o C 2) CFC frequency vastly exceeded adult marrow or blood 3) CFC in cord blood responded to growth factors like CFC isolated from human adult bone marrow 4) Recovery of CFC fell into the range of values that were known to be sufficient for human engraftment The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous or allogeneic human reconstitution.
History of cord blood studies Gluckman E, et al. Hematopoietic reconstitution in a patient with Fanconi s anemia by means of umbilical cord blood from an HLA-identical sibling. N Engl J Med 1989; 321:1174 >7000 cord blood transplants have since been conducted
Indications for hematopoietic stem cells for allogeneic transplantation Cancer Marrow Failure Lymphoblastic leukemia Blackfan-Diamond anemia Myelogenous leukemia Aplastic anemia Juvenile CML Fanconi anemia Burkitt s lymphoma Kostmann s syndrome Liposarcoma Dyskeratosis congenita Hemoglobinopathies Inborn Errors of Metabolism Sickle cell disease Adrenoleukodystrophy β-thalassemia Batten disease Hunter disease Hurler disease Immunodeficiencies Other diseases
Limitations of cord blood stem cells for allogeneic transplantation Limitations of cord blood as a stem cell source: Limited amount of material (around 80 ml) Delayed neutrophil engraftment (25-32d)[18d] Delayed platelet engraftment (54-85d)[32d] Reduction in graft versus leukemia effect?
Limitations of cord blood stem cells for allogeneic transplantation Potential strategies to increase cord blood hematopoietic stem cells for transplantation: 1. Improvements and standardization of cord blood collection 2. Ex vivo expansion of stem cells 3. Use of multiple units of cord blood
Limitations of cord blood stem cells for allogeneic transplantation In 2000 NetCord (cord blood banking arm of the Eurocord registry for Blood and Marrow transplant) and FACT (Foundation for accreditation of cell therapy) published comprehensive standards for Cord Blood Banking. The third edition of NetCord-FACT International Standards for Cord Blood Collection, Processing, Testing, Banking, Selection, and Release was published 12/08/06. These standards permit accreditation process for all Banks and will facilitate proper regulatory control for the field.
Public Cord Blood Banking Numerous Cord Blood Banks have been established in this country and abroad.. Public programs New York Blood Center established in 1991 for the collection, typing, screening, and freezing of cord blood for potential transplantation Funding for public banks has come from NIH, National Marrow Donor Program, American Red Cross, and some academic programs in not-for-profit sites
Public Cord Blood Banking The C. W. Bill Young Cell Transplantation Program was authorized in December 2005, when the Stem Cell Therapeutic and Research Act of 2005 was passed by Congress and signed by President Bush. The federal program also will provide federal funding to multiple cord blood banks to increase the number of cord blood units available for matches with the long-term goal of providing an additional 150,000 cord blood units for public use. The creation of a national cord blood program provides great opportunity in the treatment of many lifethreatening blood disorders, said U.S. Rep. C. W. Bill Young (R- Fla.), for whom the program is named. The increase in cord blood units provides additional options for patients and their doctors, particularly for minority patients.
Public Cord Blood Banking This law helps patients by: Expanding federal support for bone marrow, peripheral blood and umbilical cord transplant and research Authorizing $79 million in federal funding to collect and store an additional 150,000 cord blood units for public use Establishing a public cord blood bank network Establishing a system that provides transplant doctors an efficient single point of access to both adult volunteer donors and cord blood units for their patients
Public Cord Blood Banking Six cord blood banks have been awarded National Cord Blood Inventory contracts in 2006 to increase the inventory of cord blood units: Carolinas Cord Blood Bank Duke University Medical Center Durham, N.C. M.D. Anderson Cord Blood Bank Houston, Texas New York Blood Center National Cord Blood Program New York, N.Y. Puget Sound Blood Center Seattle, Wash. StemCyte International Cord Blood Center Arcadia, Calif. University of Colorado Cord Blood Bank Aurora, Colo. Cord blood units from these banks will be listed on the NMDP Registry along with those from all NMDP Network cord blood banks
Private Cord Blood Banking Private for-profit companies have also formed to bank cord blood: Recent internet screen identified >12 private companies Fees range from $1,250 2,120 for processing, freezing, and storage
Private Cord Blood Banking One of the strategies to encourage parents to bank their children s cord blood is to state that the stored material could be used in the future by the infant (autologous) or a member of the infant s family (allogeneic). This would constitute a form of biological insurance.
Private Cord Blood Banking What evidence exists that autologous cord blood is safe or effective for the treatment of malignant neoplasms? No evidence that autologous cord blood is safe or effective to treat malignant neoplasms. Johnson FL. Placental blood transplantation and autologous Banking.caveat emptor. J Ped Hema Oncol 19(3):183, 1997 DNA mutations in cord blood of children who later develop leukemia Gale KB, et al. Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 94(25):13950, 1997
Private Cord Blood Banking What is the likelihood that a child whose cord blood is banked will need the stem cells for transplantation? No accurate estimates for the risk of the development of a malignant disorder that is amenable to transplantation, but the range of estimates is from 1:1,000 to 1:200,000. Johnson FL. Placental blood transplantation and autologous Banking.caveat emptor. J Ped Hema Oncol 19(3):183, 1997
What should we recommend? Physicians consulted by prospective parents about cord blood banking can provide the following information: Cord blood donation should be discouraged when cord blood stored in a bank is to be directed for later personal or family use, because most conditions that may be helped by a cord blood transplant are already resident in the stem cells. Cord blood donation should be encouraged when there is knowledge of a full sibling in the family with a medical condition (malignant or genetic) that could potentially benefit from cord blood transplantation. Policy statement. Cord Blood Banking for Potential Future Transplantation. Pediatrics 119:165, 2007
What should we recommend? Physicians consulted by prospective parents about cord blood banking can provide the following information: Cord blood donation should be encouraged when the cord blood is stored in a bank for public use. Since the blood will be tested for karyotypic and infectious abnormalities, they may be contacted. Parents need to understand that the unit donated may not be available for future private use. Policy statement. Cord Blood Banking for Potential Future Transplantation. Pediatrics 119:165, 2007
What should we recommend? Physicians consulted by prospective parents about cord blood banking can provide the following information: Cord blood Banks should comply with national accreditation standards: Foundation for the Accreditation of Cell Therapy US Food and Drug Administration Federal Trade Commission Policy statement. Cord Blood Banking for Potential Future Transplantation. Pediatrics 119:165, 2007
Recommendations for Cord Blood Banks Cord blood banking recruitment practices should be developed with an awareness of the possible emotional vulnerability of pregnant women and their families and friends. Permission for obtaining cord blood should be obtained before onset of active labor.
Recommendations for Cord Blood Banks Policies should be developed to disclose to the parents any abnormal findings during screening. Specific permission for maintaining demographic medical information should be obtained and potential risks of breaches of confidentiality should be disclosed.
Recommendations for Cord Blood Banks The cord blood collection process should not alter routine practice for the time of cord clamping. If the cord blood bank is conducting research an institutional review board must review and approve recruitment strategies and consent forms. Targeted efforts should be made to recruit underserved minorities in public cord blood banking programs to extend to them potential treatments afforded other segments of society.
Recommendations for Cord Blood Banks Physicians or other professionals who recruit pregnant women and their families for private cord blood banking should disclose any financial interest or other potential conflict of interest they have in the procedure. Professionals affiliated with organizations that promote for-profit cord blood banking should make annual financial and conflict of interest statements to appropriate institutional review committees that possess oversight authority.
Summary Saving your babies cord blood: Is this good insurance? No evidence to support autologous cord blood banking for use as a source of transplantable stem cells for treating a hematopoietic malignancy in the donor: We should discourage this form of biologic insurance but when there is a family member who has a disorder that would benefit, then encourage donation.