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



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

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

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

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

http://www.marrow.org/physician/urd_search_and_tx/number_of_allogeneic_tx_perfor/index.html

What is a Stem Cell?

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

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

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 1988 1990 1992 1994 1996 1998 2000 Year African American 2.83 Asian 2.05 Hispanic 1.73 RR of a partial or mismatched transplant 2005

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

Deliveries at Parkland Caucasian African Hispanici Other American 2009 234 (3%) 764 (9%) 7402 (86%) 164 (2%) 2008 418 (3%) 1416 (9%) 13568 (86%) 287 (2%) 2007 431 (3%) 1457 (9%) 14123 (86%) 324 (2%) 2006 375 (2%0 1624 (10%) 14029 (86%) 355 (2%) 2005 368 (2%) 1639 (10%) 13759 (85%) 426 (3%) 2004 410 (3%) 1751 (11%) 13325 (84%) 452 (3%)

Deliveries at Parkland 90 80 70 Caucasian 60 50 African American 40 Hispanic 30 20 Other 10 0 2009 2008 2007 2006 2005 2004

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

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

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

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

Questions?

References Aplenc, Richard et al. Ethnicity and survival in childhood acute myeloid leukemia: A report from the Children s Oncology Group. Blood 108: 74 80 (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 8:257 260 (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: 70 72 (2001) Dehn, Jason, et al. Unrelated Donor Hematopoietic Cell Transplantation: Factors Associated with a Better HLA Match. Biology of Blood and Marrow Transplantation 14:1334 1340 (2008) Fisk, Nicholas M. et al. Can Routine Commercial Cord Blood Banking Be Scientifically and Ethically Justified? PLoS Medicine 2(2): 0087 0090 (2005) Hurley, Carolyn Katovich et al. National Marrow Donor Program HLA Matching Guidelines for Unrelated Marrow Transplants. Biology of Blood and Marrow Transplantation 9: 610 615 (2003). Trigg, ME et al. Ten year experience ofunrelated bone marrow donor transplants in Children with malignant and non malignant conditions. Pediatric Transplantation 3: 49 59 (1999). http://www.marrow.org