Review Article

Cord Blood Banking: Ethical Considerations

Hossam E. Fadel, MD Editor-in-Cheif, JIMA Clinical Professor, Medical College of Georgia Augusta, Georgia

Abstract Umbilical (UCB) is a valuable source of both hematopoietic and pluripotent stem cells. It is a readily available, easily collected source that does not cause inconvenience or harm to the donor. It has been shown to be useful in the treatment of several serious neoplastic and non-neoplastic diseases. blood transplants have proven to be life saving in many of these conditions. Umbilical cord blood transplants result in better survival rates and fewer cases of graft-versus-host disease (GVHD) than the traditional bone mar- row transplants. It probably can fill the gap that is caused by the lack of a suit- able bone marrow match. Umbilical cord blood can be collected and cryopre- served in blood banks for at least 15 years. The family, when donating cord blood, chooses whether it prefers a public or private blood bank. Health-care providers should provide detailed and balanced information to aid the parents in their decision. Health authorities should support the development of the pub- lic banks, because by their nature they do not make money and they provide the much-needed help to those who cannot afford private banking. Ethical concerns, including proper informed consent, linkage of the donor to the donated units, truth in advertising by the private banks, and distributive justice, are discussed. Also discussed is the question of the appropriateness of selective conception of a baby to be a potential donor. There is no ethical or moral objection to its use. Umbilical cord blood donation should be encouraged.

Key words: Umbilical cord blood, cord blood bank, medical ethics, regenerative medicine, cord blood transplants, stem cells

tem cells are undifferentiated cells that through Human embryonic stem cells are capable of indefi - replication have the capacity of both self- nite ex-vivo proliferation, and they can differentiate renewal and differentiation into mature spe - into any specialized cell in the human body. Adult cSialized cells. There are two types of stem cells: stem cells are located in tissues throughout the body embryonic stem cells (ESCs) and adult stem cells. and function as a reservoir to replace damaged or Human embryonic stem cells (hESCs) are isolated aging cells. Under physiologic circumstances they from the 4- to 5-day-old postfertilized blastocyst. differentiate only into the cell lineage of the organ system in which they are located. Umbilical cord Correspondence should be directed to blood (UCB) is a source of “adult” stem cells. It was discovered about 30 years ago to have hematopoiet - Hossam E. Fadel, MD ic stem cells. These cells were found to be function - ally comparable to those in the bone marrow. They

JIMA: Volume 38, 2006 - Page 1 have been used in marrow transplants and in the the blood and immune system, bone marrow failure, treatment of leukemias and other hematologic dis - and genetic diseases such as hemoglobinopathies, eases. This raised the possibility of using UCB for the inborn errors of metabolism and immune deficien - treatment of the same. The first successful trans - cies. 15 The National Institutes of Health (NIH) web plant using UCB was done in Paris in 1988 to treat site, clinictrials.gov, lists 236 clinical trials involving Fanconi anemia in a sibling. 1 Since then UCB trans - the use of UCB. 16 plants were successfully used in a multitude of hematologic and immunologic diseases. 2 Current Applications of UCB Transplants While hESCs offer the greatest promise and ver - The traditional hematopoietic trans - satility, they are the subject of great ethical contro - plant involves stem cells harvested from bone mar - versy, as obtaining them entails the destruction of 4- row. Because of the shortage of suitable bone mar - to 5-day-old human pre-embryos, even though they row donors, efforts have been made to use unrelated are usually extras developed during the process of in or related donors whose human leukocyte antigen vitro fertilization (IVF) and, in most cases, would (HLA) is only partially matched with the recipient, have been discarded. 3 In any event, this controversy with less-than-optimal results. With the availability resulted in attempts to secure other sources of stem of UCB, the gap can be filled with UCB transplants. cells to be used for both research and therapy. Actually, UCB offers more advantages over bone Umbilical cord blood seems to be a promising such marrow. Umbilical cord blood is more easily source. In this paper, the discussion is limited to UCB obtained; does not cause pain or inconvenience to as a source of stem cells. the donors, in contrast to bone marrow donors As mentioned above, UCB has already been used requiring aspiration of their marrow; and UCB cells to treat a variety of life-threatening malignant and are more easily harvested and more readily avail - nonmalignant hematologic and immunologic condi - able, and, most important, are immunologically tions. Scientists continue to expand research efforts naïve. Bone marrow cells are more difficult to har - on other pluripotent cells present in the cord blood, vest, take months to procure, and are more mature specifically, the ability of the mesenchymal cells to immunologically, making them more prone to cause differentiate beyond their tissue lineage into other graft-versus-host disease (GVHD), specially the more types of cells e.g. neurons, hepatocytes, myocardio - severe types (grades 3 and 4). While in bone marrow cytes, and pancreatic islet beta cells, a process called transplants 6/6 match of HLA loci are required, only transdifferentiation. When successful, this will pave a 4/6 or even 3/6 match is acceptable in UCB trans - the way to treat various chronic diseases that plantation. In a study by Rocha et al, comparing the heretofore have no cure; for example diabetes type incidence of both acute and chronic GVHD in 1, cerebral palsy, Parkinson disease, Alzheimer dis - patients receiving trans - ease, other neurologic diseases as well as spinal cord plants, they reported that both were significantly injury, etc., heralding a new field of medicine i.e. less in those who received UCB than in those who regenerative medicine. 4-13 These lofty goals have not received bone marrow transplants. 17 Beatty et al yet been achieved, but research continues. using low resolution HLA typing reported a 75% Umbilical cord blood stem cells also can be chance that a sibling will be at a least a 3/6 hap - potentially used in gene therapy. Normal genes can loidentical match, which is the threshold of trans - be introduced ex-vivo in cord blood stem cells of an plantation, a 40% chance of at least a 4/6 haploiden - infant born with a genetic defect of the bone marrow tical match, and a 25% chance of being a perfect 6/6 or blood, and then infused into the patient. This has match with a sibling. 18 An additional advantage of been effective in children with severe combined UCB over bone marrow transplantation is that it can immunodeficiency syndrome, although some be virtually free of cytomegalovirus (CMV), which in patients developed serious complications. the past has been responsible for 10% of deaths fol - Nevertheless, devising new approaches continues. 14 lowing bone marrow transplantation. 19 Recently, it has been estimated that approximately Broxmeyer et al in a study suggested that UCB 10,000 UCB transplants have been used in the treat - can be frozen and stored for at least 15 years with ment of more than 70 diseases, including cancers of highly efficient recovery of viable and highly func -

JIMA: Volume 42, 2009 - Page 2 tional human stem cells, which are needed for suc - been associated with congenital hematologic disor - cessful UCB stem cell transplants. 20 More recent data ders are discovered on physical examination of the suggest that longer-term storage is feasible and does newborn, the collected unit should be disqualified. 23 not compromise the quality of the engraftment abil - ity of the UCB unit. 21 The great therapeutic potential Umbilical Cord Blood Banks of UCB and the demonstration of the feasibility of There are two types of blood banks for collection cryopreserving collected units and their utility for and storage of UCB: public and private. The first pub - up to 15 or more years led to the development of lic bank in the United States was established in the cord blood banks. New York Blood Center in 1991. Several others were One important disadvantage of UCB use is that established since then. The cord blood units are relatively fewer stem cells are present in a unit. donated, collected, and stored for public use. There However, the use of combined units allows it to be are no fees charged to the donor’s family and thus used for adult hematopoietic transplants. Studies are the expectant mother/donor family has no owner - now underway to evaluate the feasibility of ex-vivo ship rights. In 1999, the National Bone Marrow expansion of the units. In a study by Jaroscak et al, Donor Program (NBMDP) established a network of they showed that this is possible using an automated these banks listing their units for potential trans - continuous perfusion culture device. There was a plants. It also established the Center for Cord Blood 2.4-fold increase in the number of nucleated cells in 2005. 24 In the United States, federal legislation and an 82-fold increase in the number of colony- was passed in December 2005 to provide funding for forming units. The administration of the ex-vivo- the establishment of a national inventory of cord expanded cells was well tolerated by the 28 patients blood units. Subcommittees have been formed to they studied. 22 address standards, quality improvement, donor recruitment, collection, testing, and processing Collection of Cord Blood methodology. 15,23,25 Public banks promote allogenic Cord blood is collected at the time of delivery. (related or unrelated) donation, analogous to the The cord is wiped clean and held slightly away from current collection of whole blood units in the United the perineum to avoid contamination with maternal States. These banks are typically associated with a blood. It is then prepped with povidone iodine and local network of obstetric hospitals that send their alcohol. A large bore needle is then inserted in the units of collected cord blood to a central processing umbilical vein. This is connected to a closed collec - facility. A minority of public banks accept units of tion bag that contains an anticoagulant (citrate- cord blood from any provider through shipment via phosphate-dextrose). As much blood as possible is overnight express couriers. Umbilical cord blood obtained, without changing the timing of cord units collected for public banking must meet rigor - clamping routine. Usually, 60 mls can be obtained. ous standards of donor screening and infectious dis - The procedure is the same for collection of blood at ease testing as outlined by U.S. Food and Drug cesarean section deliveries with obvious attention to Administration (FDA). It does not accept units that the sterile technique. Cord blood is usually not col - are <60 mls. Some will require the presence of at lected from pregnancies less than 34 weeks gestation least 1 x 109 total nucleated cells. The criteria are so because of the smaller volume of blood that can be strict that approximately half of the collections are collected. Also excluded are multiple pregnancies discarded (or used for research). Initial HLA typing because of the possibility of cross contamination and allows these units to be entered into computerized issues of the proper labeling of the cord blood units registries so that a specific unit can be rapidly locat - (from which fetus the blood is collected). Cord blood ed for a patient when the need arises. The main should not be collected if chorioamnionitis, active objective of public blood banks is to archive the UCB genital herpes is suspected, in the presence of a mal - units that they collect, so that these units are avail - odorous placenta, or in extensive vaginal or perineal able to any patient. Some public banks restrict their condylomata. Any major structural abnormality or activities to support research on stem cell biology or known chromosomal anomaly contraindicate cord on therapeutic uses of the stem cells. The UCB donat - blood collection. If more subtle anomalies that have ed to those banks is used for research and not for

JIMA: Volume 42, 2009 - Page 3 transplantation. The cost of UCB collection, process - ters. They reported a two-fold increase in one-year ing, and cryopreservation in U.S. dollars is about survival rates and a two-fold decrease in the risk of $2,000 per unit. The banks partially retrieve their GVHD with the use of the former. 27 expenses by charging the transplant institution $25,000-35,000 per unit transplanted. They also sell Ethical Issues the unqualified units to research labs or centers and UCB Donation is a Virtue receive grants and/or donations. 23 Up until recently, the placenta and its content of Private blood banks, on the other hand, store blood was considered a waste byproduct of the birth blood for autologous use i.e. for use by the same indi - process and was discarded. Knowing what we know vidual from whom it was obtained at birth, if he or now, cord blood is a valuable product that is poten - she develops a treatable disease later in life, but also tially life-saving. Donating cord blood is a generous can be used for another family member. The family gift that basically does not cause harm or inconven - pays a fee ($1,100-1,750) for the initial collection, ience to the donor and may save or improve the processing, and storage and an annual fee for storage quality of someone’s life. We as Muslims should ($115-125). 23 While an autologous unit can be used in encourage UCB donation. The Qur’an reminds us a multitude of conditions, it cannot be used for the that treatment of inborn errors of metabolism or other genetic diseases in the same individual, because the “... and if anyone saved a human life it would genetic mutation would already be present in the be as if he saved the life of all mankind... .” 28 stem cells. They cannot be used for the treatment of childhood leukemia because chromosomal translo - Physicians, specifically obstetricians, should cations in fetal blood have been detected in some encourage families to bank cord blood at birth. This children who ultimately develop leukemia. 25 In addi - should be seriously considered when there is a spe - tion, the use of autologous stem cells will negate the cific diagnosis of disease known to be treatable by beneficial graft-versus-leukemic effect that occurs stem cell transplant in an immediate family member. with allogenic stem cell transplants. 25,26 The chance However, there is an important ethical concern that that a donor will use the donated blood is difficult to is related indirectly to UCB donation. A case in point estimate. Prior estimates of the probability of using is that of a baby who was specifically conceived to an autologous unit have ranged from 1 in 2700 to 1 in serve as a donor for his sister who was suffering from 200,000. 14 Private cord blood banks claim a higher the hereditary fatal Fanconi anemia. The mother possibility than seems to be likely. Some quote unre - conceived through IVF. The resulting embryos were alistic odds. One private bank cited a frequency of 1 subjected to preimplantation genetic diagnosis in 27. 23 Private banks do not perform all the screen - (PGD). Only the embryo that tested negative for the ing tests that are performed by the public banks, disease and was an adequate HLA match to the sick specifically HLA typing. They do not have a stringent sister was implanted. At delivery UCB was obtained minimum volume requirement. If the day comes that from the newborn and was successfully used for the a unit is required to be transplanted to the donor (or treatment of his sister. 19 Bioethicists in that institu - to a family member), the transplant physician may tion ruled that this was ethically acceptable. The decide not to use it because it fails a test e.g. contam - question is whether the child was used as a commod - inating bacteria or a hepatitis virus, etc., or it is of ity. But is bringing a human being to life while in the poor quality, i.e. if the volume is <40 mls or if it is process saving another life (especially that the new - between 40 and 60 ml, but the nucleated cell count is born did not encounter any risk) Islamically accept - <6 x 108.23 On the other hand, the transplantation of able? In my opinion it is acceptable as long as we UCB stem cells from a related donor (guaranteed by accept that IVF is permissible and that most Islamic banking in a private bank) is associated with a better scholars agree that PGD is also acceptable. 29 outcome in terms of survival rates and the risk of However, this may be a subject of further debate. GVHD. 27 This study involved 143 transplants, 78 from related sources and 65 from unrelated sources over Whether to Donate to Public or Private Banks? the course of 8 years in 45 European transplant cen - The merits of each type have been discussed. The

JIMA: Volume 42, 2009 - Page 4 families should be given detailed information of the the blood bank is responsible for inquiring about the therapeutic potential, realistic expectation of the health of the donor. The blood bank should also noti - benefit that can be derived to their families if they fy the family about the advent of new tests. That is decide to donate to a private bank as well as the why the identity and contact information of the if they donate to a pub - donor/family should be kept. It also implies that UCB ﷻ great reward from Allah lic bank, ensuring that the human resource they units are to be quarantined for a certain time, usual - are donating will serve the greater good for ly 6-12 months, before being released. The length of mankind rather than only a small possibility of this period has to be balanced with the advantage of benefit to themselves. This amounts in my opin - having the unit available for use soon after procure - ion to Ihsan (a higher level of virtue). It is estimat - ment. Linkage is thus important, but it has to be ed in a study by Johnson in 1997 that if 200,000 noted that it does pose a risk to the privacy of the UCB units are stored for the exclusive use of the donor. The donor may be contacted at a later date to donor (autologous transplant), only 74 units will solicit a bone marrow donation of his or her be so utilized, and the remaining 199,926 units “unique” stem cells. It is recommended that demo - would be taken out of circulation for use by graphic data should be kept separate from other data patients who need allogenic transplants. 26 while linkage is maintained. 31

Truth in Advertising Consent Private banks, being for-profit entities, are The expectant mother should be given detailed involved in aggressive marketing. They should not and accurate information about the utility of donat - be promising “biologic insurance” for the newborn ing the cord blood and clearly given the option of not or use the slogan “stop cord waste.” Ironically that is donating it. She should be counseled about the pros what is happening with random autologous stor - and cons of private versus public banking. The age. 26 The issues of the possibility of future use, qual - health-care provider who is providing prenatal care ity control, long-term availability, and cost should be and who is going to be present at the time of delivery addressed in their literature and marketing. The is the best person to give this information and obtain American College of Obstetricians and Gynecologists consent. The best time to do this is during the third (ACOG) committee opinion in 1997 states “Parents trimester, and it is best affirmed during labor. There should not be sold this service without realistic may be a question about who actually owns the cord assessment of their likelihood of return on their blood. Is it the mother’s or the newborn’s? As far as investment.” 30 It has been stated that private bank - the consent this question is immaterial because par - ing is really indicated for families with a child who is ents are custodians of their children and can make already afflicted with a disease treatable by stem cell health decisions for their newborns. In the United transplant only and for families where the two par - States, the consent of the expectant mother is all ents are known to be heterozygous for a potentially that is needed, especially since she has to give a lethal disease treatable by stem cell transplantation blood sample at the time of delivery for various tests. even if they have not yet had an affected child. 26 In Muslim countries, both parents probably would be involved in this decision. Linkage of the UCB Units to the Identity of the Donor The primary purpose of this linkage is to assure Distributive Justice that unsafe units are identified and not used for Another aspect of private banking is that it transplantation. For example, if the donor develops a allows the “privileged” parents to pay for the collec - disease, metabolic or infectious, which was not iden - tion of stem cells for their “own,” while the less tified at birth and that may be detrimental to a financially able society members would have no potential transplant recipient, that unit would be access to this valuable resource. This concern, com - disqualified. Or if a new genetic test is developed, the bined with the many units of UCB that are potential - donor can be tested to rule out this particular genet - ly wasted in the autologous donation approach pro - ic disease. This implies the family is responsible for moted by the private banks, tilts the balance in favor notifying the blood bank of this development, and public banks.

JIMA: Volume 42, 2009 - Page 5 In a measure to support public banks and to In conclusion, cord blood is a very valuable address this issue of unequal access, the Stem Cell source of both hematopoietic and pluripotent stem Therapeutic and Research Act was passed in 2005 in cells. It is a readily available, easily collected source the United States. This bill established a network of that does not cause inconvenience or harm to the cord blood banks to facilitate the use of cord blood donor. It has been shown to be useful in the treat - for transplantation and appropriated $79 million ment of several serious neoplastic and non-neoplas - between 2006 and 2010 to establish a national inven - tic diseases. Umbilical cord blood transplants have tory of 150,000 UCB units. The bill also calls for the been proven to be lifesaving in many of these condi - U.S. Federal Drug Administration (FDA) to develop tions. It results in better survival rates and fewer licensing requirements for cord blood banks that will cases of GVHD than the traditional treatment with contribute cord blood units to the inventory. It is bone marrow transplants. It probably can fill the gap hoped private banks will also abide by these regula - that is caused by the lack of a suitable bone marrow tions. 23 match. There is no ethical or moral objection associ - The American College of Obstetrics and ated with its use. Umbilical cord blood donation Gynecologists (ACOG), in its latest committee opin - should be encouraged. It can be collected and cryop - ion on the subject issued in February 2008, did not reserved for at least 15 years in public or private express a recommendation for or against private blood banks. The pros and cons of public and private banking but argued for the need for provision of bal - banks have been described. The family, when decid - anced and accurate information regarding the ing to donate cord blood, has to choose which type it advantages and disadvantages of public versus pri - prefers. Detailed and balanced information should be vate banks. It further stressed that the remote given to the parents by their health-care providers chance of an autologous UCB unit being used (1:2700) before they make that decision. Health authorities should be disclosed to the expectant mother. 25 The should support the development of the public banks American Academy of Pediatrics suggested because they are not-for-profit entities and provide “...Private storage of cord blood for biologic insur - much-needed help to those who cannot afford pri - ance is unwise.” 32 Private blood banking has been vate banking. Ethical concerns include proper banned in Italy since 2002. 3 The Royal College of informed consent, linkage of the donor to the donat - Obstetricians and Gynecologists states that “Routine ed units, truth in advertising by the private banks, directed commercial cord blood collection and stem and distributive justice. Also discussed is the ques - cell storage cannot be recommended at this time ... .” 33 tion of the appropriateness of selective conception The French National Consultative Ethics Committee of a baby to be a potential donor. recommended that the decision makers “encourage a considerable extension of cord public banks for References essentially allogenic purposes, rather than subscrib - 1. Gluckman E, Broxmeyer HA, Auerbach AD, et al. ing to the creation of private banks for strictly autol - Hematopoietic reconstitution in a patient with ogous purposes... .” 34 In March 2004, the European Fanconi’s anemia by means of umbilical-cord blood Group on Ethics in Science and New Technologies from an HLA-identical sibling. N Engl J Med. 1989 Oct stated its position: “The legitimacy of commercial 26;321(17):1174-8. cord blood banks for autologous use should be ques - 2. Moise KJ Jr. Umbilical cord stem cells. Obstet tioned as they sell a service that has presently no Gynecol. 2005:106:1393-407. real use regarding therapeutic options. Thus, they 3. Fadel HE. Prospects and ethics of stem cell promise more than they can deliver. The activities of research: an Islamic perspective. J Islam Med Assoc. such banks raise serious ethical criticisms.” 35 The 2007;39:73-83. Maternal/Fetal Medicine Committee of the Society 4. Haller MJ, Viener H-L, Brusko T, et al. Insulin of Obstetricians and Gynecologists of Canada recom - requirements, HbA1c, and stimulated C-peptide fol - mended that “altruistic donation of cord blood for lowing autologous umbilical cord blood transfusion public banking and subsequent allogenic transplan - in children with T1D. Paper presented at: The tation should be encouraged when UCB banking is American Diabetes Association’s 67th Scientific considered by childbearing women ... .” 36 Sessions; June 22-26, 2007; Chicago, IL. Abstract 0313-

JIMA: Volume 42, 2009 - Page 6 OR. 18. Beatty PG, Boucher, KM, Mori, M. Probability of 5. Davis EC. Cord blood: a weapon against cerebral finding HLA mismatched, related or unrelated mar - palsy? Los Angeles Times. April 7, 2008. http://arti - row or cord blood donors. Hum Immunol. cles.latimes.com/2008/apr/07/health/he-cpalsy7. 2000;61:834-40. Accessed September 22, 2008. 19. Kline RM. Whose blood is it, anyway? Scientific 6. Sanberg PR, Willing AE, Garbuzova-Davis S, et al. American. 2001;284(4):42-9. Umbilical cord blood-derived stem cells and brain 20. Broxmeyer HE, Srour EF, Hangoc G, et al. High repair. Ann N Y Acad Sci. 2005;1049:67-83. efficiency recovery of functional hematopoietic pro - 7. Nan Z, Grande A, Sanberg CD, et al. Infusion of genitor and stem cells from human cord blood cry - human umbilical cord blood ameliorates neurologic opreserved for 15 years. Proc Natl Acad Sci USA. deficits in rats with hemorrhagic brain injury. Ann N 2003;100:645-50. Y Acad Sci. 2005;1049:84-96. 21. Scaradavou A, Stevens CE, Dobrila L, et al. 8. Staba SL, Escolar ML, Poe M, et al. Cord-blood National Cord Blood Program. “Age” of cord blood transplants from unrelated donors in patients with (CB) unit: impact on long term cryopreservation and Hurler’s syndrome. N Engl J Med. 2004 May storage on transplant outcome. Amer Society of 6;350(19):19609. Hematol 49th Annual Meeting and Exposition. 9. U.S. National Institutes of Health. Umbilical cord December 8-11, 2007, Atlanta, GA. Abstract 2033. blood infusion to treat type 1 diabetes. Available at: 22. Jaroscak J, Goltry K, Smith A, et al. Augmentation www.clinicaltrials.gov/ct/show/NCT00305344?orde of umbilical cord blood (UCB) transplantation with r=1. Accessed September 20, 2006. ex vivo-expanded UCB cells. Results of phase 1 trial 10. Haller MJ, Cooper SC, Brusko T, et al. Autologous using the AastromReplicell System. Blood. cord blood transfusion associated with prolonged 2003;101:5061-7. honeymoon in a child with type 1 diabetes. Diabetes. 23. Moise KJ Jr. Umbilical cord stem cells. In: 2005;54(suppl 1): Poster A485. Queenan JT. High-risk pregnancy. Washington, DC: 11. Meier C, Middelanis J, Wasielewski B, et al. Spastic American College of Obstetricians and Gynecologists; paresis after perinatal brain damage in rats is 2007:3610-76. reduced by human cord blood mononuclear cells. 24. National Marrow Donor Program. Where to Pediatr Res. 2006 Feb;59(2):244-9. donate cord blood. Minneapolis (MN) NMDP; 2007 12. Ende N, Chen R. Parkinson’s disease mice and available at http://www.marrow.org/HELP/Donate- human umbilical cord blood. J Med. 2002;33(1-4):173- cord-blood-share-life/how-to-donate-cord- 80. blood/CB-participating-hopsitals/nmdp-cord- 13. Ende N, Chen R, Ende-Harris D. Human umbilical blood-hospitalspl.retrieval 8/22/07. cord blood cells ameliorate Alzheimer’s disease in 25. Committee on Obstetric Practice; Committee on transgenic mice. J Med. 2001;32(3-4):241-7. Genetics. ACOG committee opinion number 399, 14. Barnhard Y, Bahceci E, Bayer-Zwirello L, et al. February 2008: umbilical cord blood banking. Obstet Family cord blood banking: what you need to know. Gynecol. 2008 Feb;111(2 Pt 1):475-7. OBG Management. 2007;19(11 Suppl):S1-S8. 26. Johnson FL. Placental blood transplantation and 15. Rebarber A, Slatzman D. An OB’s guide to cord autologous banking-conveat emptor. J Pediatr blood banking. Contemp Ob Gyn. 2008 October Hematol Oncol. 1997;19:183-6. Supplement; S2-S14. 27. Gluckman E, Rocha V, Boyer-Chammard A, et al. 16. ClinicalTrials.gov. http://clinicaltrials.gov. Outcome of cord blood transplantation from related Accessed August 19, 2009. and unrelated donors. EuroCord Transplant Group 17. Rocha V, Wagner JE Jr., Sobocinski KA, et al. and the European Blood and Marrow Graft-versus-host disease in children who have Transplantation Group. N Engl J Med 1997;337:373- received a cord-blood or bone marrow transplant 81. from an HLA-identical sibling. Eurocord and 28. The Glorious Qur’an, Chapter 5, Verse 32. International Bone Marrow Transplant Registry 29. Fadel HE. Preimplantation genetic diagnosis: Working Committee on Alternative Donor and Stem rationale and ethics, an Islamic perspective. J Islam Cell Sources. N Engl J Med. 2000;342:1846-54. Med Assoc. 2007;39:150-7.

JIMA: Volume 42, 2009 - Page 7 30. American College of Obstetricians and 2009 Aug 19. Gynecologists. Routine storage of umbilical cord 34. French National Consultative Ethics Committee blood for potential future transplantation. ACOG for Health and Life Sciences. Umbilical cord blood Committee Opinion 183. Washington, DC: ACOG; banks for autologous use or for research. Opinion 1997. #74. Available at: http://www.ccne- 31. Sugarman J, Kaalund V, Kodish E, et al. Ethical ethique.fr/docs/en/avis074.pdf. Accessed 2009 Aug issues in umbilical cord banking. JAMA. 19. 1997;278:938-43. 35. European Group on Ethics in Science and New 32. Cord blood banking for potential future trans - Technologies. Ethical aspects of umbilical cord blood plantation: subject review. American Academy of banking. Available at: http://ec.europa.eu/euro - Pediatrics. Work Group on Cord Blood Banking. pean_group_ethics/docs/avis19_de.pdf. Accessed Pediatrics. 1999;104:116-8. 2009 Aug 19. 33. Royal College of Obstetricians and Gynaecologists 36. Armson BA, Maternal/Fetal Medicine Committee, Scientific Advisory Committee. Umbilical cord blood Society of Obstetricians and Gynaecologists of Canda. banking. Opinion paper 2. Available at: Umbilical cord blood banking: implications for http://www.rcog.org.uk/files/rcog-corp/uploaded- Perinatal care providers. J Obstet Gynaecol Can. files/SAC2UmbilicalCordBanking2006.pdf. Retrieved 2005;27;263-90.

Appendix Indications of Umbilical Cord Blood Transplants

Thalassemias • Lymphomatoid granulomatosis • Hemoglobin H disease • Myelodysplasia syndrome • Thalassemia major (hydrops fetalis) Hematologic disorders • Thalassemia major (Cooley's anemia) • Amegarakarocytic thrombo-cytopenia • Thalassemia intermedia • Autoimmune neutropenia (severe) • E-thalassemia • Congenital dyserythropoietic anemia • E-B thalassemia • Cyclic neutropenia Sickle cell disorders • Diamond-Blackfan anemia • Sickle cell anemia (hemoglobin SS) • Evans syndrome • HbSC disease • Fanconi’s anemia • Sickle thalassemia • Glanzmann disease • Sickle B-thalassemia • Hypoproliferative anemia Oncologic disorders • Juvenile dermatomyositis • Thalassemia major (Cooley’s anemia) • Juvenile xanthogranulomas • Thalassemia intermedia • Kostmann’s syndrome • Acute lymphoblastic leukemia • Pancytopenia • Acute myeloid leukemia • Red cell aplasia • Chronic myeloid leukemia • Refractory anemia • Autoimmune lymphoproliferative syndrome • Shwachman syndrome • Burkitt’s lymphoma • Severe aplastic anemia • Cytopenia related to monosomy 7 • Systemic mastocytosis • Familial histocytosis • Severe neonatal thrombocytopenia • Juvenile myelomonocytic leukemia • Congenital sideroblastic anemia • Hemophagocytic lympho-histiocytosis • Thrombocytopenia-absent radius syndrome • Hodgkin’s disease Immune deficiencies • Non-Hodgkin’s lymphoma • Ataxia telangiectasia • Langerhans cell histiocytosis • Cartilage-hair hypoplasia

JIMA: Volume 42, 2009 - Page 8 • Chronic granulomatous disease • Metachromatic leukodystrophy • DiGeorge syndrome • Krabbe’s disease • Hypogammaglobulinemia • Gunther disease • IKK delta deficiency • Hermansky-Pudlak syndrome • Immune dysregulation polyendocrinopathy • Hurler’s syndrome • Mucolipidosis, type II • Hurler-Scheie syndrome • Myelokathexis • Hunter’s syndrome • X-linked immunodeficiency • Sanfilippo’s syndrome • Severe combined immune-deficiency • Maroteaux-Lamy syndrome • Adenosine desaminase deficiency • Mucolipidosis types II, III • Wiskott-Aldrich syndrome • Alpha mannosidosis • X-linked agammaglobulinemia • Niemann-Pick disease, types A and B • X-linked lymphoproliferative syndrome • Sandhof’s disease Metabolic disorders • Tay-Sachs disease • Adrenoleukodystrophy • Gaucher's disease (infantile) Modified from K. J. Moise, JR, 2007. 23

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