Cord Cor Blood Banking Scott N. Furlan, MD Ellen S. Plummer, Plummer MD

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1 Cord Blood Banking Scott N. Furlan, MD Ellen S.Plummer, MD

2 Overview Background Biology of Stem Cell Transplant Opportunities i at Parkland Logistics of Banking Potential Barriers

3 Indications for HCT Cancer Hodgkin lymphoma Non-Hodgkin lymphoma Neuroblastoma Ewing Sarcoma Medulloblastoma Breast Cancer Testicular cancer Renal cell carcinoma Multiple myeloma Acute lymphoblastic leukemia Chronic lymphoblastic leukemia Acute myelogenous leukemia Chronic myelogenous leukemia Juvenile myelomoncytic leukemia Central Nervous System Disease Amyotrophic Lateral Sclerosis Alzheimer's Disease Huntington's Disease Parkinson's Disease Immunodeficiencies, histiocytoses and metabolic disorders Severe combined immunodeficiency Chronic granulomatous disease Chediak-Higashi Hemophagocytic lymphohistiocytosis Langerhans cell histiocytosis MPS I (Hurler) MPS II (I cell) Adrenal leukodystrophy Metachromatic leukodystrophy Globoid cell leukodystrophy α mannosidosis Traumatic injury Spinal cord injury Stroke recovery Organ repair (Kidney, Liver, Lungs, Heart) Disorders of the bone marrow Myelodysplastic syndrome Refractory anemia Essential thrombocytosis Polycythemia vera Aplastic anemia Fanconi anemia Dyskeratosis congenita Diamond-Blackfan anemia Thalassemia major Sickle Cell Anemia Auto-Immune Diseases Juvenile arthritis Rheumatoid arthritis Crohn's Disease Evan s syndrome Juvenile Dermatomyositis Scleroderma

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5 Transplant Sources Direct Bone Marrow Harvest Peripheral Stem Cell Harvest Umbilical Cord Blood

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7 What is a Stem Cell?

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9 Why is MHC important A hematopoietic stem cell transplant will always have a number of donor T cells in circulation MHC Peptide With greater discordance in HLA between donor and host the greater probability of high avidity binding of TCR to MCH regardless of peptide - Self - Non-self (viral) TCR The result is a massive immune attack against the recipient (GVHD) Attack T Cell T Cell

10 All in the Family Generally need at least 5 out of 6 loci (HLA-A, A - B, and DR) From within the family A 25% chance that each sibling is a match C 30% of patients have a matched sibling B 70% of patients require a non-related donor DR DR 11 million donors on international registries DQ DQ Match for ~75% of Western European patients DP DP Only 20-30% chance for other ethnic groups

11 Finding an HLA match for a HCT 100% a Match % Finding 80% 60% 40% 20% Caucasian Native American Multiracial / Other Hispanic Asian / Pacific Islander 0% African American Year African American 2.83 Asian 2.05 Hispanic 1.73 RR of a partial or mismatched transplant 2005

12 Benefits of Cord Blood Noninvasive source of hematopoetic stem cells and mesenchymal stem cells Allogeneically transplanted UCB has immune tolerance Less GVHD Less nonrelapse mortality Tolerate less HLA match Faster availability Median time for URD BMT = 49 days Median time for URD UCBT = 13.5 days

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14 Deliveries at Parkland Caucasian African Hispanici Other American (3%) 764 (9%) 7402 (86%) 164 (2%) (3%) 1416 (9%) (86%) 287 (2%) (3%) 1457 (9%) (86%) 324 (2%) (2% (10%) (86%) 355 (2%) (2%) 1639 (10%) (85%) 426 (3%) (3%) 1751 (11%) (84%) 452 (3%)

15 Deliveries at Parkland Caucasian African American 40 Hispanic Other

16 What we re proposing Info on Texas Cord Blood Bank Identify person collecting Emphasize no cost to mother or baby bb

17 Consent Logistics Currently obtained in L&D Possible distribution in clinic with follow up by Cord Blood Facilitator Blood stored at room temperature Blood for banking collected daily by Texas Cord Blood Bank Funding through Texas Cord Blood Bank No cost to mother or baby Texas Cord Blood Bank Research Associate

18 Barriers to Donation Patient Perspective Lack of awareness Pamphlets supplied by Texas Cord Blood Bank at no cost Cost of donation Lack of opportunity to donate

19 Barriers to Donation Hospital Perspective L&D very busy would need to streamline into system Competition for research If unit of cord blood does not meet banking criteria, may be used for research if mom consents Costs to the hospital Educate staff Storage

20 Questions?

21 References Aplenc, Richard et al. Ethnicity and survival in childhood acute myeloid leukemia: A report from the Children s Oncology Group. Blood 108: (2006). Barker, Juliet N. et al. Searching for Unrelated Donor Hematopoietic Stem Cells: Availability and Speed of Umbilical Cord Blood versus Bone Marrow. Biology of Blood and Marrow Transplantation 8: (2002) Cox, S.T. et al. Further Diversity at HLA A and B loci identified in Afro Caribbean potential bone marrow donors. Tissue Antigens 57: (2001) Dehn, Jason, et al. Unrelated Donor Hematopoietic Cell Transplantation: Factors Associated with a Better HLA Match. Biology of Blood and Marrow Transplantation 14: (2008) Fisk, Nicholas M. et al. Can Routine Commercial Cord Blood Banking Be Scientifically and Ethically Justified? PLoS Medicine 2(2): (2005) Hurley, Carolyn Katovich et al. National Marrow Donor Program HLA Matching Guidelines for Unrelated Marrow Transplants. Biology of Blood and Marrow Transplantation 9: (2003). Trigg, ME et al. Ten year experience ofunrelated bone marrow donor transplants in Children with malignant and non malignant conditions. Pediatric Transplantation 3: (1999).