A Public Cord Blood Bank for South Africa? i

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1 No. 42/2007 A Public Cord Blood Bank for South Africa? i By Dr Robert Crookes MBChB (Wits), Dip. Internal Medicine (American Board of Internal Medicine, USA) Transfusion Medicine Consultant. South African National Blood Service. Johannesburg Professor Ernette du Toit MBChB, MD (Cape Town) Head of Laboratory for Tissue Immunology and Medical Director of the South African Bone Marrow Registry. Cape Town Professor Machteld Oudshoorn PhD (Cape Town), MSc (Leiden) Associate Professor, Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre. Director of the Europdonor Foundation Umbilical cord blood (UCB) contains a multiplicity of cell types. A small percentage of these cells are haematopoietic stem and progenitor cells (HPC s). Cord blood also contains endothelial and mesenchymal stem cells that are able to give rise to cell types other than blood cells. The progeny of haematopoietic stem cells includes erythroid cells, granulocytes, monocytes / macrophages, platelets, lymphocytes, natural killer cells and dendritic cells whereas mesenchymal stem cells (MCS s) and unrestricted somatic stem cells (USSC s), present in cord blood, are able to give rise to cells such as osteoblasts (bone), chondroblasts (cartilage), adipocytes (fat) and neural cells (including astrocytes and neurons). 1

2 The successful use of umbilical cord blood as a source of haematopoietic stem cells for transplantation to children and adults with malignant and non-malignant haematologic disease, and for the treatment of genetic immune deficiency disorders, has been extensively documented. 1,2,3 The ability to perform stem cell transplants from cord blood is dependent on the establishment of banks of cord blood cells (similar in concept to the establishment of blood banks ). Banked cord blood cells must however be stored in a frozen (cryopreserved) state. Umbilical cord blood banks have been established in countries throughout Europe, Asia, North and South America and Australasia. There is currently no public cord blood bank in Africa. An HLA matched sibling donor is available in only 30% of patients in need of an allogeneic haematopoietic stem cell transplant, which has led to the recruitment of unrelated volunteer donors through international Bone Marrow and Cord Blood Registries. The South African Bone Marrow Registry has more than 60,000 potential haematopoietic stem cell donors registered and, worldwide, the HLA phenotypes of more than 11 million donors are available through coordinated matching programs. Approximately 260,000 HLA phenotyped cord blood units are recorded in registries around the world. 4,5 The transplantation of cord blood units continues to increase and currently about 20% of stem cell products provided to patients are cord blood units. There is also an increase in the use of more than one (double) cord blood unit for the treatment of adult patients. More than 7,500 unrelated cord blood transplants have been performed to date. 4 The advantages of cord blood as a clinical source of stem cells (compared to bone marrow or peripheral blood stem cells) include: Abundant availability No donor attrition from the Registry. (Over 25% of potential bone marrow donors, whose names appear on Bone Marrow Registries worldwide, are unfortunately not available when requested. This is similar for the SABMR)

3 Collected at no risk to mother or infant Available at short notice Correctly processed grafts can be stored for many years Lower incidence of acute graft-vs-host disease Tolerance of HLA mismatches The establishment of a volunteer public umbilical cord blood bank in South Africa would expand the currently available pool of allogeneic donors for patients requiring a haematopoietic stem cell transplant. The targeted selection of cord blood collections from individuals who are genetically representative of the broad Southern African population will significantly increase the likelihood that an African patient will have a well matched UCB graft available for transplantation. UCB units collected and stored in cord blood banks in other countries (and stem cells from donors available through international Bone Marrow Registries) are predominantly representative of Caucasian HLA types and HLA genotypes from other ethnic backgrounds (and are not likely to be a match for African patients). An umbilical cord blood bank in Southern Africa is also likely to make suitably HLA matched transplants available to individuals of African descent who reside in countries outside of Africa. There is currently a shortage of banked cord blood from these population groups making it less likely that such patients will find a match and reducing their access to this potentially life saving treatment. The American Academy of Pediatrics recommends that targeted efforts should be made to recruit Black individuals to donate their newborn s cord blood to public cord blood banks. 6 It has been proposed that a network of cord blood stem cell banks be established and that public cord blood banking should be more widely adopted. 1,7,8 A view has been expressed by South African paediatric haematologists and oncologists that a public cord blood bank in South Africa is imperative if patients in this country are to have access to optimal future treatment options. The required number of cord blood units stored in a South African UCB bank will need to be determined. It is however considered that at least 5,000 banked cord blood units would provide a foundation for the provision of haematopoietic stem cells, from this source, for patients requiring transplantation in Southern Africa. The cost of collection and storage, in the vapour phase of liquid nitrogen, as well as HLA

4 typing and infectious disease marker testing, is estimated to be R6,000 R7,000 (six thousand to seven thousand rand) per cord - in the start up phase. A model to ensure financial viability in the start-up and maintenance phases of a cord blood bank should take into account the funding that may accrue from international searches of the registry (for HLA matching) and the funding that would accrue with the provision of suitably matched UCB units nationally and internationally. If a network of cord blood banks were initially established in three major cities in South Africa (e.g. Cape Town, Johannesburg and Durban) sufficient representative units could be collected. Taking into account the number of births in the regions (more than 17,000 natural births and more than 4,000 Caesarian sections are carried out annually at the Chris Hani Baragwanath Hospital alone), it is likely that if mothers throughout the country are encouraged to donate their cord to a public bank, there will be little difficulty in obtaining informed consent to obtain the number of collections required to achieve the initial critical mass of banked units. A public cord blood bank operating in Sub-Saharan Africa will need to comply with international quality standards for the accreditation of such facilities. It is well known that South Africa has one of the highest prevalence rates of HIV (and HBV) in the world. The protocols for screening donated UCB for transmissible infections will need to be carefully considered. Testing UCB units for HIV, HBV and HCV by individual donation nucleic acid technology ID NAT (as currently performed on all blood donations in South Africa) would be optimal. As can be seen from the above data, only about 3% of cord blood units banked worldwide have been transplanted. The funders of such a project will need to accept that the establishment and maintenance of a public cord blood bank is expensive and that the future clinical potential of such a bank in South Africa remains uncertain. The future clinical indications for cord blood transplantation will be dependent on evidence-based developments in the management of patients with malignant and non-malignant haematologic disease and on the decision by local and overseas treating clinicians to undertake this treatment option (for paediatric and adult patients). The availability of HLA matched cells from a public cord blood bank in Southern Africa will extend the use of stem cell transplantation to patients for whom this treatment would be life saving.

5 REFERENCES 1. Broxmeyer HE. Umbilical cord blood stem cells: Collection, processing, and transplantation in Blood Banking and Transfusion Medicine. Second edition. Ed. Hillyer CD., Silberstein LE., Ness PM., et. al. Philadelphia, PA., Churchill Livingstone (Elsevier) 2007; pp Laughlin MJ., Eapen M., Rubenstein P., et. al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. New England Journal of Medicine 2004; 351: Rocha V., Labopin., Sanz G., et. al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. New England Journal of Medicine 2004; 351: World Marrow Donor Association (WMDA) Annual Report (2006) 5. Bone Marrow Donors Worldwide (2007) 6. Kuehn BM. Pediatrics Group recommends public cord blood banking. JAMA 2007; 297: Mica M. Cord blood stem cell network proposed. JAMA 2005; 293: Carpenter RJ. Public cord blood banking should be more widely adopted. (Letter) BMJ 2006; 333:919 i The views expressed in this paper are those of the author and do not necessarily reflect the views of the Centre for International Political Studies (CiPS) or the University of Pretoria