Siriraj Cord Blood Banking Project Introduction Hematopoietic stem cell transplantation was first established in Thailand in 1986 at Siriraj Hospital. Since then, more than 1000 lifes were saved in 4 medical centers in the country. Allogeneic1 stem cell transplantation needs a donor to donate HLA-matched stem cells to the patient. Although some patients have a family member who can donate cells, nearly 75% of patients will not find a matching donor in their family. Thus, Cord blood donations can give more patients hope of finding a match In recent years, umbilical cord blood, which contains a large number of hematopoietic stem cells, has been used successfully for allogeneic transplantation to treat a variety of pediatric genetic, hematologic, and oncologic disorders. It is a potential alternative when autologous or allogeneic transplantation with HLA-matched marrow is unavailable for children. This advance has resulted in the establishment of cord blood banking programs for autologous and allogeneic transplantation. The American Academy of Pediatrics1 has makes recommendations about appropriate ethical and operational standards, including informed consent policies, for the institutions that operate a program of cord blood banking. The Faculty of Medicine, Siriraj Hospital’s policy is committed to supporting the health of Thai people. Recruitment of as much cord blood unit as possible would increase the chance of finding a suitably matched donor. Even though more than 100,000 cord blood unit registed worldwide, most of the Thai patients still can’t find a matched because some tissue traits are more likely to be found among people of a particular racial or ethnic heritage, not to mention the extremely high cost and the complicated process to access. That is why a pressing need remains for more cord blood donations among the Thai community. The Thai Red Cross Society has established a National Stem Cell Donor Registry Program since May 2003 from the list of adult blood donor volunteers. The program registed more than 5000 adult stem cell donors (peripheral blood or bone marrow donation) within 3 years, but the expansion of cord blood donation is very limited. Siriraj Hospital is the most suitably qualified and experienced institute for setting up a public cord blood banking in Thailand. Not only that Siriraj has a large number of birth per year, but also it has the competency and full complement of other facilities, including Blood bank, clinical departments, stem cell transplantation units and all essential laboratories. As per Executive Board of Siriraj’s vision to be a leading health institute in South-East Asia, this project is to set up the first International Standard Umbilical Cord Blood Bank in Thailand. Its difference resource of Hematopoietic stem cells from the Thai Red Cross Society will benefit the Nation’s Stem Cell Donor Policy. 1 From other person Name Siriraj Cord Blood Stem Cell Bank Project. Vision “New life, new chance” Mission Siriraj CBSCB project will expand and maximize the national cord blood inventory in Thailand Objective To establish a public cord blood bank in Siriraj Hospital Action Plan 1. Establish a UCB Policy Board and Financial Support Committee 2. Establish a Cord Blood Coordination Center 3. Establish a public umbilical cord blood bank (UCBB) at Siriraj Hospital by the year 2007 4. Join the National Donor Registry Networking in Thailand The Policy A Policy and Ethic Committee should be set up by the faculty to make recommendations about appropriate ethical and operational standards, including inform consent policies, the security of medical information and cord blood donor’s rights. The Process Registry All of the data in the Registry are managed by the Siriraj UCBB center by using a proprietary software system to track detailed patient history and maintains donor information. Collecting Cord Blood Donations The collecting of cord blood from the Department of Ob-Gyn through a standard institutional protocol. Informed Consent The umbilical cord blood is considered to belong to the infant, and the mother gives consent on behalf of her child. The mother must sign an informed consent to donate the cord blood is collected. Donation must be voluntary, confidential and uncompensated. Collection Procedures The goal when collecting cord blood is to collect the maximum number of hematopoietic progenitor cells possible while in no way disrupting the normal activities of the obstetrician in the peripartum period. The number of cells is important to the success of the transplant. The transplant recipient's time to neutrophil recovery is strongly correlated with the dose of cryopreserved nucleated cells, CFU-GM and the dose of thawed CD34+ cells (3). To accept a CBU for storage and Registry listing, the total CBU nucleated cell count must be 4x107 - 750x107 at start of processing and 12x107 - 750x107 frozen. Cord blood can be collected from the placenta either while the placenta is still in utero after the cord is clamped and cut and the baby is removed from the area, or after the placenta has been delivered, referred to as ex utero. Most in utero collections occur in a closed system using blood collection bags to minimize the risk of contamination. In ex utero collections, the cord blood is collected after the placenta has been delivered and has been moved to a location outside the delivery room. To collect the blood, the surface of the umbilical cord is disinfected and the umbilical vein is punctured. The blood can be collected by gravity drainage into a prepared blood bag or it can be drawn into a 60 cc syringe containing an anticoagulant. The collection can be completed within 10 minutes (4). A delay of more than 10-15 minutes could result in a decreased volume of cord blood and a decreased number of hematopoietic cells . Processing and Storing Cord Blood Units The CBU is often not processed immediately after collection because of the unpredictable timing of deliveries and because the CBUs must be transported to the laboratory for processing. Current guidelines suggest the CBU be processed within 24 hours after collection. The processing of the CBU includes the testing described below for quality control and often includes removing red blood cells and plasma to reduce the volume of the stored CBU. Processed CBUs are stored in plastic or vinyl bags and cryopreserved in a liquid nitrogen (vapor or liquid phase) storage freezer. One study has shown no significant loss of cell viability in CBUs stored for up to ten years . Screening To ensure that CBUs accepted by a cord blood bank are safe and effective for transplantation, the following evaluations are made: Review of a maternal and family health history Laboratory testing of mother's blood sample for infectious diseases Laboratory testing of the CBU for quality control, including the followings o Alpha and beta thalassemia screening (DNA) o Common genetic disorders in Thai population o Infectious screening accordig to AABB standard The goal of the maternal health history is to assess family medical history and maternal risk factors to identify risks for the CBU to transmit genetic or infectious diseases such as cancer, leukemia, immune disorders, neurological disorders, hepatitis or AIDS. Any responses that indicate potential risks must be evaluated to determine the suitability of storing the CBU. In some cases the CBU will be deferred. In others, the CBU may be stored with information indicating the potential risks noted in the NMDP Registry record for the CBU. This information is then communicated to any transplant physician and patient considering the CBU so that the risks can be weighed in the decision to proceed to transplant. Cord blood donations are rigorously screened and tested much the same way donations of whole blood are. However, just as donated whole blood cannot be guaranteed 100% free of infectious diseases, the risk of the CBU transmitting an infectious disease to a recipient cannot be completely eliminated. Tests for infectious diseases carried out on the maternal blood sample generally include: Human immunodeficiency virus 1 and 2 (HIV-1, HIV-2) Hepatitis B virus Hepatitis C virus Cytomegalovirus Syphilis Samples from the CBU are tested to assure quality and provide the data necessary for listing on Siriraj Registry. Testing of the CBU includes: Volume of the CBU prior to processing and volume of additives at processing Bacterial and fungal cultures ABO blood group and Rh type HLA type (DNA high resolution) Nucleated cell and CD34 counts RESEARCH Registries/Cord Blood Banks as Repositories of Extensive HLA Data As large repositories of HLA and often clinical data, registries/banks should have the resources to analyze this information to direct registry recruitment (e.g., evaluate HLA diversity to serve searching patients), to refine search and matching algorithms, to create search tools, and to define matching requirements for optimal outcome. Access to expertise in informatics, population genetics, and histocompatibility is essential to capitalize on this wealth of information. The Budget and Financial Plan ( see details in Appendix A) The Outcome and KPI 1. By the year 2006, an international standard UCB banking will be established at Siriraj Hospital. 2. Expected number of public cord blood storage at this site would be 500 by the year 2006 1500 by the year 2007 3000 by the year 2008 10,000 by the year 2015 3. The UCB registry established at Siriraj Hospital will join the networking National networking by the year 2006 International Networking by the year 2010 4. The average likelihood of finding a potential unrelated HLA-matched donor for the Thai increased from 0.003 % (year 2005) to at least 10 % by the year 2008 25 % by the year 2015 Bibliography 1. American Academy of Pediatrics; Work group on cord blood banking. Cord blood banking for potential future transplantation: Subject review. Pediatrics, 1999;104(1):116-8. 2. Gluckman E, Locatelli F. Umbilical cord blood transplants. Curr Opin Hematol, 2000; 7(6): 353-7. 3. Laughlin MJ, Barker J, Bambach B, et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med, 2001; 344(24): 1815-22. 4. 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Working Group on Ethical Issues in Umbilical Cord Blood Banking. JAMA, 1997; 278(11): 938-43. 10. Surbek DV and Holzdreve W. Fetal cells from cord blood as stem cell source: current status and possible implications in gynaecologic oncology. Eur. J. Gynaec. Oncol., 2001; 22(1): 6-12.