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Umbilical Cord Blood Donation: Implications for the Obstetrician

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Umbilical Cord Blood Donation: Implications for the Obstetrician

  1. 1. H A Y WO O D L . B R O WN , M D R O Y T . P A R K E R P R O F E S S O R A N D C H A I R D U K E U N I V E R S I T Y J U N E 2 0 1 3 UMBILICAL CORD BLOOD DONATION IMPLICATIONS FOR THE OBSTETRICIAN
  2. 2. HISTORY OF STEM CELL RESEARCH • 1960’s • Researchers discover bone marrow contains two types of cells • hematopoietic stem cells – forms all types of blood cells • Bone marrow stromal cells – mixed cells that generate bone, cartilage, fat, fibrous connective tissue
  3. 3. STEM CELL RESEARCH • 2000’s • Stem cell research gets “political” primarily as a result of the sources for obtaining embryonic stem cells and their use. • Politics and Stem cell – Abortion controversy
  4. 4. CORD BLOOD LEGISLATION • 2005 – CW Bill Young Transplantation Program, the Stem Cell Therapeutic and Research Act of 2005 created the National Cord Blood Inventory (NCBI) with the goal of increasing the national supply of publicly donated cord blood units
  5. 5. STEM CELLS • What are Stem Cells (Properties) • Capable of dividing and renewing themselves for long periods • Unspecialized • Can give rise to specialized cell types
  6. 6. PATIENT KNOWLEDGE OF CORD BLOOD BANKING • Perlow. J reprod med 2006;51:642-648 • Survey of 425 patients • Older patients with higher education more knowledgeable • Greatest disparity of knowledge among Native Americans • 50% were misinformed that UCBB was only for “the child that I will deliver.” • Only 14% of patients were educated about UCBB by nurse or obstetrician.
  7. 7. AWARENESS OF UCBB PERLOW 2006 • Education % p • < 8th grade 21.9 <0.00001 vs. all levels • High School 59.1 0.039 HS vs. College • College degree 70.6 • Graduate degree 77.6 0.021 HS vs. Graduate • Race/Ethnicity • Caucasian 73.8 <0.0001 vs. All races • Hispanic 43.2 <0.0001 vs. Caucasian • African American 48 <0.001 vs. Caucasian • Native American25 <0.0001 vs. Caucasian • Asian 50 NS
  8. 8. UMBILICAL CORD BLOOD BANKING • Perlow. J Reprod Med 2006 • If physicians are unaware of the benefits of UCBB and/or not informing patients of their options in this regard,… potential therapeutic options can be missed
  9. 9. NORTH CAROLINA CORD BLOOD EDUCATION LEGISLATION • North Carolina Jun 9, 2009 ... North Carolina Governor Beverly Perdue signs cord blood education legislation • The Department of Health and Human Services shall make online materials available and will encourage healthcare professionals to educate all pregnant patients on their cord blood options, to ensure every family has the opportunity to make an informed choice. • The law also encourages physicians to make the information available to expectant parents early enough in the pregnancy so that they can make an informed decision about whether to participate in a public or private cord blood banking program.
  10. 10. STATES WITH CORD BLOOD LEGISLATION
  11. 11. BIPARTISAN LEGISLATION PROMOTING LIFE-SAVING MEDICAL ADVANCES CLEARS SENATE • The Stem Cell Therapeutic and Research Reauthorization Act of 2010 (S. 3751), unanimously approved by the Senate today, reauthorizes the original 2005 act and extends the C.W. Bill Young Cell Transplantation and National Cord Blood Inventory (NCBI) programs through Fiscal Year 2015.
  12. 12. ACOG COMMITTEE OPINION # 399. FEBRUARY 2008 • Recommendations (Information to Patient) • balanced and accurate information on advantages and disadvantages of public vs. private • Remote chance of autologous unit being used of 1 in 2700 individuals • Disclosure that demographic data will be maintained, maternal infectious disease and genetic testing, ultimate outcome of poor quality units • Provider not obligated to obtain consent for private banking • Collection should not alter routine delivery practices • Disclose any financial and conflict of interest for for-profit UCBB
  13. 13. STEM CELLS • Embryonic Stem Cells • Derived from four to five day old embryos • Adult Stem Cells • Undifferentiated cells found among differentiated cells in a tissue or organ
  14. 14. EMBRYONIC STEM CELLS Human Embryonic Stem Cells • Obtained from donated embryos that have developed from eggs fertilized in vitro (in the lab) • Potentially unlimited capacity to replenish themselves and are pluripotent, meaning that they can differentiate into any cell type found in the adult body. • Embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease.
  15. 15. STEM CELLS • Embryonic • Blastocysts cells • Isolated in the laboratory by transferring inner cell mass into tissue culture • Inner cell mass proliferates and divides and are replated (subculture) • Over six months the original 30 cells become millions of undifferentiated embryonic stem cells that are pluripotent
  16. 16. CORD BLOOD STEM CELLS • Cord blood contains embryonic-like stem cells. • Cord blood stem cell is not quite as primitive as the controversial embryonic stem cells, which can give rise to any tissue type of the body. • CB cells are more versatile than adult stem cells such as those found in bone marrow.
  17. 17. ADULT STEM CELLS • An adult stem cell is an undifferentiated cell found in a tissue or organ. • Produces more stem cells and can also give rise to specialized cell types of the tissue or organ they are located in. • The main job of an adult stem cell is to maintain and repair the tissue in which it is found. • When compared to embryonic and cord blood stem cell, adult stem cells are believed to be more limited in the type of cells that they can generate.
  18. 18. ADULT STEM CELLS • Adult (somatic) stem cells • An undifferentiated cell found among differentiated cells in a tissue or organ • Can renew itself • Can differentiate to yield specialized cell types • Role is to maintain and repair tissue in a living organism • Origin in mature tissue is unknown • Growing adult stem cells from culture can be challenging
  19. 19. STEM CELLS • Primary Differences in Embryonic and Adult Stem Cells • PROLIFERATION • Embryonic stem cells can proliferate without differentiating but adult stem cells cannot.
  20. 20. STEM CELL TRANSPLANTATION • National Bone Marrow Donor Program • 5.5 million adult donors • Unrelated donor matching uses low resolution typing in the 80% race for whites, Hispanics and Asians. • African American matches only around 60% • Affiliated with 15 umbilical cord blood banks with inventory of over 40,000 units. • In 1999, NBMDP established network of banks listing their units on the NMDP Registry and the Center for Cord Blood in 2005
  21. 21. BONE MARROW DONOR MATCHING BY RACE • Likelihood of finding a donor • African American – 66% • Hispanic or Latino – 72% • Asian and Pacific Islander – 82% • White – 93%
  22. 22. CORD BLOOD FOR TRANSPLANTATION • Hematopoietic progenitor (stem) cells from cord blood have advantages over bone marrow • Unlimited supply • Ethnic diversity easier to achieve • Painless collection • Higher proliferative capacity • Lower rate of acute graft vs. host disease (a greater HLA mismatch is better tolerated) • No donor attrition as with bone marrow
  23. 23. ADVANTAGES OF CORD BLOOD • Biologically, a greater degree of human leukocyte antigen mismatch between the donor and recipient is tolerated by patients, allowing more patients, including those from diverse racial and ethnic background, to receive a cord blood transplant • Relevant to African Americans • The incidence of acute and chronic graft versus host disease is decreased with UCBD • Cord blood is stored and readily available for those needing transplantation.
  24. 24. CORD BLOOD TRANSPLANTATION • Compared to Bone marrow • CD 34+ cells have higher rate of proliferation • Greatest limitation is lower total nucleated cells or CD 34+ count • Lower number of CD 34+ leads to longer interval for neutrophil and platelet recovery • Signs of engraftment • Transplanted cell dose ~ 10% of marrow transplants • CD8+ lymphocytes is reduced in cord blood leading to less graft vs. host
  25. 25. CORD BLOOD TRANSPLANTATION • Cord blood progenitor cells and lymphocytes subsets in cord blood influenced by: • # of nucleated red cells • Greater CD34+ with higher nucleation • Caucasian ethnicity • Higher CD3+/CD38- in Caucasians than AA, Asians • Infant Gender • Male infants have fewer CD3+/CD4+, C19+ but higher CD3+/CD8+ • Type of delivery • Higher # of total CFU’s with cesarean delivery but lower CD3+/CD4+, CD3=/CD8+, and CD 19+
  26. 26. CORD BLOOD TRANSPLANTATION • Disadvantages • Inability to obtain additional cells for second transplant • Small volumes • Slower engraftment
  27. 27. CORD BLOOD TRANSPLANTATION • Disadvantages • Studies underway to evaluate methods to overcome limited cell dose • Combining two or more closely matched cord blood units • Co-infusion of mesenchymal cells or • Ex vivo expansion of the cells
  28. 28. CORD BLOOD TRANSFUSION
  29. 29. CORD BLOOD TRANSFUSION • CIBMTR data • Lifetime probability of undergoing a transplant with one’s own hematopoietic stem cells in US from marrow, peripheral blood and cord blood • 1 in 400 if the indications for autologous HSCT do not change • Nietfield JJ. Biol blood Marrow Transplant, 2-8,14:316-322
  30. 30. CORD BLOOD TRANSFUSION
  31. 31. CORD BLOOD BANKING • Types of Cord Blood Banks • Private Banking • Public Banking • Directed Donor Banks
  32. 32. CORD BLOOD BANKING • Private Banking • Direct patient advertising and recruitment • “Biology insurance” • College savings plans • Discounts for second and third child
  33. 33. CORD BLOOD BANKING • Private Banking • Over 24 private banks in the U. S. • Collected on site by obstetrician for autologous use Limited testing for infectious diseases • Initial HLA typing not performed • Initial fees $1100 - $1750 with yearly fees for storage of $115 - $125 • If used processing and shipment fees paid by insurance (OB $$$$ for collection)
  34. 34. CORD BLOOD TRANSPLANTATION • Realities for chances of need and use • For majority of blood cancers and blood diseases, an autologous unit would not be used if the donor ultimately needed a transplant because the disease may be present in the cord blood cells • The best source of cells for a transplant is from a fully matched sibling, or if unavailable, an unrelated donor (allogeneic transplant)
  35. 35. CORD BLOOD BANKING • Private Banking • ACOG Committee Opinion • “Parents should not be sold this service without a realistic assessment of their likelihood of return on investment” • Cord blood stem cells survive after freezing for up to ~ 15 years
  36. 36. CORD BLOOD BANKING • Some public banks will accepts units from any provider through shipment by an overnight express courier
  37. 37. CORD BLOOD TRANSPLANTATION • Private Banking • Legal concerns for the obstetrician • Liability for collection of poor quality units if later required for transfusion • Patent infringement • Public Banking • Greater access by the general public • More cost effective • Will accept patient donations
  38. 38. CORD BLOOD TRANSPLANTATION • Used in both children and adults • Limited amount of blood forming cells • Smaller patients need fewer cells • Larger patients need combined cord blood units • Emerging technology • Laboratory methods to grow the number of cells before transplanting
  39. 39. INDICATIONS FOR TRANSPLANTATION • Malignant Hematopoietic Diseases • Acute leukemia: Lymphoblastic or myelogenous • Hodgkin’s lymphoma and non-Hodgkin’s lymphoma • Chronic myelogenous leukemia • Nonmalignant/Heriditary Hematopoietic • Sickle cell anemia and thalassemia • Fanconi’ Anemia • Chronic granulomatous disease • Severe congenital neutropenia
  40. 40. INDICATIONS FOR TRANSPLANTATION • Emerging Indications • Neurological injuries, including cerebral palsy • Type 1 insulin-dependent diabetes mellitus
  41. 41. UMBILICAL CORD BLOOD TRANSPLANT
  42. 42. UCB AND HURLER’S SYNDROME • Hurler’s • Inherited metabolic disease with lack of enzyme lysosomal α-L-iduronidase • Cord blood increases the level of lysosomal a-L-iduronidase
  43. 43. CORD BLOOD TRANSPLANTATION • Hurler’s Syndrome • 258 infants and children from age 2 mo-18years (median age 16 mo) of which ½ received unrelated cord blood transplants (81% from mismatched donors) • Higher rate of donor cell engraftment (complete replacement of bone marrow with donor cells), normal enzyme levels than those of matched sibling cells or matched/unmatched bone marrow • 98% of UCB recipients with successful engraftment had normal enzyme levels • Boelens et al. Blood, 2013
  44. 44. CORD BLOOD TRANSPLANTATION • Case Report • Treatment of Krabbe Disease (Globoid Cell Leukodystrophy) with cord blood transplantation. • Krabbe Disease • Progressive cerebral degenerative disease • Clinical onset before 6 months of age with death by age 2 years • Autosomal recessive with carrier testing and prenatal diagnosis availability
  45. 45. CORD BLOOD TRANSPLANTATION • Krabbe Disease • McGraw et al. Radiology 2005;236:221 • 15 newborns with transplantation for Krabbe disease • Normal myelination and neurological development after transplantation
  46. 46. CORD BLOOD TRANSPLANTATION • Ongoing Research for Cord Blood Use • Birth Asphyxia • Transfusion could lead to regeneration of damaged neural tissue • Stroke • Transplantation enhance recovery from stroke • Myocardial damage after MI • Transplantation may enhance healing of heart • Genetic Predisposition to chronic disease • Transplantation possible prevent onset
  47. 47. CORD BLOOD TRANSPLANTATION NEURAL CONDITIONS • Case Report • Treatment of infant with severe hydrocephaly from aqueductal stenosis • Implications for regeneration of neural tissue
  48. 48. CORD BLOOD TRANSPLANTATION • Cerebral palsy • 1 in 500 children in US diagnosed annually • No known treatment • Therapeutic benefits of UCB stem cell trans-fusion using autologous blood being studied at Duke University.
  49. 49. CORD BLOOD TRANSPLANTATION FUTURE DIRECTIONS • Prevention of Atherosclerosis • Progenitor cell-based therapy to prevent or cure established disease • Reserve the health consequences of atherosclerosis in adults • Immune ablation required for transplantation poses certain risk • Ethical issues for human trials for those without obvious injury *Working Group on Ethics of Progenitor Cell base strategies for disease prevention
  50. 50. CORD BLOOD BANKING IMPLICATIONS FOR PROVIDERS • Be informed about potential for transplantation and indications for collection • A sibling or parent in need of stem cell transplantation when HLA identical bone marrow or stem cell donation from a sibling or parent is unavailable
  51. 51. CORD BLOOD BANKING IMPLICATIONS FOR PROVIDERS • Allogeneic transplantation is treatment of choice for a child with no HLA –identical sibling or donor • Allogeneic transplantation in young adults with hematologic malignancies in urgent need of transplantation • Altruistic donation for public banking for allogeneic transplantation
  52. 52. CORD BLOOD BANKING IMPLICATIONS FOR PROVIDERS • “Safe management of obstetric delivery should never be compromised to facilitated cord blood collection” Armson BA. J Obstet Gynaecol Can 2005,3:263
  53. 53. SUMMARY • Advantages • Abundantly available • No ethical concerns (i.e. embryonic ) • Ethnic balance • Low viral contamination with CMV and EB virus • Cryoperserved, banked and available on demand • No observed malignant transformation of UCB observed • Undistorted accumulation of HLA genotypes because stored UCB has no attrition except use • Frozen UCB easily shipped, thawed and used
  54. 54. THE BOOZER’S FAMILY STORY • Twins, who do not have sickle cell disease, presented a chance of a cure for their brother. Using umbilical cord blood from the twins, 17- month-old Carmani underwent a successful stem cell transplant.

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