Version May 2024
INTRODUCTION — Reconstitution of the bone marrow is an important and potentially curative treatment option for a wide variety of malignant and nonmalignant diseases, including acute and chronic leukemia, lymphoma, aplastic anemia, sickle cell anemia, thalassemia major, and a number of other genetic and acquired disorders. The pluripotent hematopoietic stem cells required for this procedure are usually obtained from the bone marrow, peripheral blood, or umbilical cord blood of an allogeneic (non-self) related or unrelated donor. In some situations where extensive myeloablative chemotherapy is required to treat a malignancy not involving the bone marrow, autologous (self) stem cells may be used.
Engraftment and survival rates following hematopoietic cell transplantation (HCT) are optimized when the donor and recipient are genetically compatible. The risk of graft-versus-host disease (GVHD) correlates with the level of human leukocyte antigen (HLA) disparity. Unfortunately, finding an HLA-matched donor is not always possible, especially for underrepresented racial or ethnic groups. While autologous hematopoietic stem cells provide perfectly compatible tissue, this type of transplantation is not appropriate in many cases, due to the presence of the disease to be treated in the collected autologous stem cells. Each full sibling potential donor has only a 25 percent chance of being fully HLA-matched with a sibling who requires a transplant. Therefore, many patients do not have an HLA-identical relative.
When a suitable related donor is not available, a search is conducted to identify a potential unrelated HLA-matched donor. Finding an appropriate donor through a national registry is a lengthy process that is not always successful, especially for individuals who are not of Northern European descent. As a result, many patients who might benefit from HCT are not afforded this opportunity or die during the extended process of securing a donor. (See "Donor selection for hematopoietic cell transplantation", section on 'Unrelated donors'.)
Because of the lack of matched related donors and the risk of severe GVHD that accompanies mismatched unrelated bone marrow or peripheral blood HCT, alternative sources of hematopoietic stem cells have been sought. Umbilical cord blood, the blood remaining in the umbilical cord and placenta following the birth of an infant, has emerged as a potential alternative source of hematopoietic stem cells in allogeneic HCT. Collection, storage, and ethical issues regarding the use of cord blood for HCT will be discussed here. Other issues related to umbilical cord blood transplantation are discussed separately, including the advantages and limitations to cord blood as a stem cell source and the administration of cord blood transplantation in adults using myeloablative and non-myeloablative preparative regimens. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation" and "Umbilical cord blood transplantation in adults using myeloablative and nonmyeloablative preparative regimens" and "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells" and "Donor selection for hematopoietic cell transplantation".)
CORD BLOOD AS A RESOURCE — Unrelated umbilical cord blood offers many practical advantages over unrelated donor bone marrow or mobilized peripheral blood progenitor cells as a source of hematopoietic stem cells including an expanded donor pool, ease of procurement and lack of donor attrition, lack of need for a complete human leukocyte antigen (HLA) match, and decreased graft-versus-host disease for the degree of HLA disparity. Limitations to umbilical cord blood include an increased risk of graft failure, delayed immune reconstitution, limited stem cell number, and unavailability of the donor for additional donations (ie, donor lymphocyte infusions). This is discussed in more detail separately. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation", section on 'Features of UCB grafts'.)
Generation of immune effector cells from cord blood, such as NK cells or viral-specific T cells, for clinical use following allogeneic transplantation are under investigation [1,2].
Cord blood units that are privately banked for potential autologous use have only a remote chance of being used for the intended purpose. A very low percentage of umbilical cord blood units that are collected and stored privately are used for the child or another relative. (See 'Estimating need for cord blood' below.)
CORD BLOOD BANKS — Two main types of cord blood banks exist for the purpose of storing cord blood for potential future transplantation: public cord banks and private cord banks. It is estimated that several hundred thousand cord blood units are stored in such banks worldwide (www.bmdw.org) [3,4]. In addition to these two main types of cord blood banks, some private and public cord blood banks provide a service called directed cord blood banking in which cord blood is reserved for a sibling or other close relative with a known potentially transplant-treatable disease.
Public cord blood banks — Public cord blood banks collect and store cord blood units for use by any individual who has a medical indication for hematopoietic stem cell transplantation and for whom a suitably matched unit is available. These banks perform collections at a limited number of hospitals throughout the world [3-7], meaning that a mother can choose to donate her infant's cord blood to a public cord blood bank only if the infant is delivered at a hospital with access to such a bank. California, Connecticut, and a number of other states have developed more disseminated collection programs. Programs have been developed that allow for the remote site collection of cord blood units with shipment to centralized banking facilities, thereby providing additional options for related individuals to donate cord blood. Following collection, each cord blood unit is characterized, and the parameters (eg, HLA profile, total nucleated cell count) are placed in a public database accessible to health care providers. Public cord blood banks are usually non-profit, although a few for-profit cord blood banks bank both privately and publically. (See 'Processing and preservation' below.)
Private cord blood banks — Private cord blood banks are for-profit enterprises that facilitate the collection of cord blood for relatives who are willing and able to pay for such a service [7]. Typically, an infant's cord blood is stored to serve as a source of hematopoietic stem cells for the child or a relative should the need arise. Private cord blood banks supply a collection kit and then generally depend on the mother's obstetrician or midwife to collect the umbilical cord blood upon delivery and transport it to the company's stem cell processing laboratory. The cord blood unit is reserved for use by relatives who pay a fee for the initial collection and processing and then annually for the continued storage of their child's cord blood unit. However, given the lack of experience or interest on the part of those collecting the cord blood, the collection volume may be inadequate for transplantation purposes despite their subsequent storage. Information regarding the stem cell count in the collected cord blood unit is often not provided to relatives.
Directed cord blood banking — In addition to these two main types of cord blood banks, private as well as public cord blood banks provide a service called directed or sibling cord blood banking for a child who has a potentially transplant-treatable disease and the parents are expecting another child [8]. A program providing such a service either facilitates or performs the cord blood collection, and then processes, characterizes, and cryopreserves the unit, which is reserved for exclusive use by the donor's relatives. These collection and banking services, whether private or public, are most often performed free of charge. (See 'Additional information sources for parents' below.)
DONOR RECRUITMENT — Strategies for donor recruitment and consent depend on the type of program performing the banking. For public banks, it is vital that high standards of selection are employed in order to ensure the safety and quality of the cord blood supply. To this end, many banks utilize a questionnaire like that conducted for blood donation in the United States. This questionnaire serves to screen potential donors and their sexual partners for risk factors for infectious diseases, inherited immunologic and hematologic diseases, certain genetic diseases, cancer, and other conditions that could be transmissible by blood or hematopoietic stem cells [9]. Staging procedures for obtaining consent in public banks are under consideration to eliminate the time and cost of obtaining consent on cord blood units that have an insufficient volume to bank. In these procedures, the first step is to obtain approval for collection. The second step, which includes the complete medical history and laboratory screening, is done only on the 30 to 50 percent of units that have sufficient volume to bank.
In addition to historical medical information, maternal blood testing is performed to screen for hepatitis B, hepatitis C, HIV-1 and -2, HIV p24, cytomegalovirus, syphilis, and in some programs human T-lymphotropic virus (HTLV)-I/II, malaria, Chagas disease, and West Nile virus [10,11]. Finally, upon delivery of the infant, the mother's and neonate's hospital charts are reviewed for signs or symptoms of congenitally acquired infection and for labor and delivery factors that could put the infant donor, and thus the collected stem cell product, at risk for infection.
For private banks, and for those medically indicated sibling directed donations, in which cord blood is reserved for use by relatives only, a unit may be banked regardless of the results of the maternal history, serologies, and infant evaluation. In this case, if the unit is requested for release, the transplant center makes a determination regarding the safety and adequacy of the unit for transplantation.
Maternal (donor) consent — During their pregnancies, many expectant parents become aware of the possibility of banking their infant's cord blood for potential future use [12]. They are encouraged to call upon their health care providers to help them decide whether or not to donate their infant's cord blood, or to pay to preserve it for private use. If the infant will be delivered at a hospital providing philanthropic donation to a public, non-profit cord blood bank at no cost to relatives, such donation is encouraged. Donation is also encouraged for full siblings of a child with a potentially transplantable illness.
The parents, however, may want to consider the following privacy issues associated with public banking:
●How will infectious and genetic disease testing results be conveyed to the donor's relatives?
●What measures does the bank take to protect donor confidentiality?
●What is the quality of the collected cord blood?
●How is the unit collected and stored?
●How many units have been released for transplantation and what has been the outcome of the transplantation?
The process of obtaining informed consent from donors differs among banks. Private banks utilize a standard consent process that is completed during the prenatal period. Public banks, on the other hand, employ a variety of consent procedures in order to optimize expense and logistic variables. Some seek consent for cord blood donation during prenatal care; others utilize a phased consent process, in which mothers are preliminarily consented during labor, the cord blood is collected following delivery of the placenta, and complete signed consent is obtained after collection. In some hospitals, the placenta and umbilical cord are considered discarded material allowing for the collection of cord blood following delivery of the placenta with consent obtained only after successful collection is performed. Each of these consent protocols has financial and ethical ramifications [13].
In all cases, the bank has the legal and ethical responsibility to provide adequate information to the mother so that she can make an informed, appropriate decision. Consent information should be provided in the mother's preferred language. At a minimum, the consent process for public banks should review the maternal testing required, the altruistic nature of the donation, and the potential laboratory or research use of samples that are not suitable for clinical use. (See "Informed procedural consent".)
CORD BLOOD COLLECTION AND PROCESSING
Cord blood collection — Protocols for umbilical cord blood collection are designed to avoid interfering with the delivery of the baby, while still preserving the sterility and maximizing the volume, and thus the number of hematopoietic stem cells collected in the cord blood unit. Importantly, cord blood collection should never compromise the safety of the mother or infant during childbirth. Standard obstetric procedures for determining the mode of delivery and timing of cord clamping should not be altered in an attempt to optimize cord blood collection. Delayed cord clamping improves infant iron stores but compromises the size and cell dose of collected cord blood units. As such, delayed cord clamping is usually avoided in term infants when collection of cord blood is planned.
Collection may be performed either prior to ("in utero") or following ("ex utero") delivery of the placenta. An example of each type of collection procedure is described below. Ex utero collection is preferred because it is technically easier and safer for the clinician obtaining the sample, without compromising sample volume or sterility [14]. Regardless of the technique employed, the earlier the blood is collected, the less likely it is that clotting will occur and the greater the chance of obtaining a maximal volume [15]. Of importance, especially in the anemic or hypovolemic newborn, immediate cord clamping reduces the volume of placental blood transfused to the infant, which can have deleterious effects (eg, low blood volume and worsening anemia) [16]. (See 'Importance of unit volume' below and "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Early versus delayed cord clamping'.)
●In utero collection – For "in utero" collection, the obstetrician or midwife receives the collection supplies in the form of a kit weeks before delivery. The kit is opened, and the contents are surveyed in order to confirm that they are complete. Following delivery of the infant, the umbilical cord is clamped and cut in the usual manner. Prior to delivery of the placenta, a four- to eight-inch area of the cord is cleansed with an antiseptic solution provided in the kit. A 16-gauge needle, connected to a cord blood collection bag containing an anticoagulant solution, is inserted into the umbilical vein at the cleansed site, and the blood is allowed to drain into the bag by gravity. In utero collection can be performed by the obstetrician in the course of vaginal delivery or cesarean section.
●Ex utero collection – For "ex utero" collection, the collection supplies are kept in a room outside the delivery room. Following delivery of the placenta, it is immediately taken to the collection room, suspended from a collection stand, and the clamped umbilical cord is cleansed with antiseptic solution. A 16-gauge needle, connected to a cord blood collection bag containing an anticoagulant solution, is inserted into the umbilical vein at the cleansed site, and the blood is allowed to drain into the bag by gravity. Ex utero collection is usually performed by trained technicians.
Some kits provided by for-profit companies utilize a syringe to collect the cord blood. If necessary, the needle may be repositioned, turned, or even removed and reinserted more proximal to the placenta in order to maximize the volume of blood collected. If the needle is reinserted, the new insertion site must be thoroughly cleansed prior to insertion.
With either in utero or ex utero collection, when all the residual blood has been collected, the flow stops, and the cord appears empty and mostly white. This usually occurs after a minimum of two to four minutes [16]. At this point, the tube between the needle and blood bag is clamped, the needle is removed from the umbilical cord and cut from the tubing and the bag is sealed and labeled. Ideally, at least 40 to 60 mL of blood (in addition to anticoagulant) will be collected. A volume below 40 mL is unlikely to contain sufficient numbers of cells to be used for transplantation. The cord blood is stored at room temperature in order to preserve cell viability until it is shipped or otherwise transported to the processing laboratory [17-19].
Follow-up studies — A maternal blood sample is obtained within seven days of cord blood collection to screen for infections that might be transmitted to the infant and therefore might be found in the cord blood. This examination commonly includes testing for maternal HLA type, HIV (antibody and polymerase chain reaction), hepatitis C, hepatitis B (surface antigen, core antigen, and polymerase chain reaction), human T-lymphotropic virus (HTLV)-I/II, treponema pallidum hemagglutination assay, West Nile virus, and cytomegalovirus IgG. Some cord banks also require testing for malaria and Chagas disease [11]. This testing is restricted to publicly banked cord blood units.
Some public banks also require a saliva swab from the infant in order to screen for the presence of cytomegalovirus. Some also request a follow-up examination at six months to determine such relevant factors as seroconversion, the infant's postnatal history, or existence of potentially transmittable genetic disease. These conditions might lead to discarding of the stored cord blood unit or using it for research purposes [20].
Importance of unit volume — Transplantation outcome is significantly affected by the number of hematopoietic stem cells present in the cord blood unit as measured by the total number of nucleated cells (TNC) or the number of CD34+ stem cells. Importantly, the collection volume roughly correlates with both the TNC and the number of CD34+ stem cells present [21,22]. It is not clear whether the collected cord blood volume, the TNC, or the number of CD34+ stem cells is significantly altered by the mode of delivery. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation", section on 'Cell dose'.)
Collection volumes and cell counts vary greatly [22]. A study of 542 umbilical cord blood collections at several hundred hospitals throughout the United States found that the mean collection volume was 103 mL, including 35 mL of anticoagulant solution, with a mean of 9 x 108 nucleated cells per collection [8]. Individual public cord blood banks use different TNC cutoffs to determine whether a particular unit will be stored for clinical use. Larger units with higher TNC numbers are preferred and a cutoff of 1 x 109 TNC per unit is commonly used [11].
Various predictors of cord blood unit volume and cell count have been investigated [22-27]. As examples:
●Maternal and fetal characteristics – Heavier babies, larger placentas, and women with fewer previous live births had higher cell counts, while longer gestation correlated with greater TNC counts but lower CD34+ cell counts [22,23,28].
●Fetal distress – One study has suggested that umbilical cord blood collected following cesarean delivery performed because of nonreassuring fetal heart rate tracing increases the number of mobilized stem cells [29]. Similarly, umbilical cord blood from newborns with meconium-stained amniotic fluid also contains higher TNC counts and CD34+ cells [30,31].
●Mode of delivery – In one study, the average volume of cord blood obtained in 29 cesarean deliveries versus 126 vaginal deliveries was 104 and 84 mL, respectively [32]. Since the percent of CD34+ cells was similar in the two groups, cord blood collected during cesarean deliveries had a higher absolute number of CD34+ cells per unit.
●Technical aspects of collection – In other studies, a shorter time between delivery of the infant and clamping of the umbilical cord resulted in larger collection volumes and greater cell counts [24,25]. A shift towards more routine delayed cord blood clamping would therefore be expected to result in smaller cord blood units and lower cell counts. Leaving a longer length of umbilical cord attached to the placenta may result in the collection of larger blood volumes [33]. It is unclear whether larger volumes are obtained when cord blood collection is performed prior to delivery of the placenta. Some studies report that in utero collection provided larger volumes and increased cell counts [15,34-36], while others have shown no significant difference between in utero and ex utero collection [14,37]. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Early versus delayed cord clamping'.)
●Cord blood units collected from African Americans have lower cell counts than those collected from White Americans [38]. The mechanism responsible for this is not known, but it is likely similar to that which explains the low neutrophil count in African Americans compared with White Americans.
Cord blood collection should never compromise the safety of the mother or infant during childbirth. In general, ex utero collection is preferred, especially for public banking, because it is technically easier and safer for the clinician obtaining the sample, without compromising sample volume or sterility. In utero collection is often used for private collections. Standard obstetric procedures for determining the mode of delivery and timing of cord clamping should not be altered in an attempt to optimize cord blood collection. (See 'Cord blood collection' above.)
Processing and preservation — After collection, cord blood units should be tested, processed, and stored for future use, typically within 48 hours of collection. Because of the relatively unregulated nature of cord blood banking, cord blood unit characterization and processing procedures vary. In general, public cord blood banks must perform more extensive testing in order to maintain databases searchable by transplant centers. Procedures and quality standards for the safe collection, processing, testing, storage, selection, exchange, and clinical use of cord blood are provided by various organizations. New regulations developed by the US Food and Drug Administration will insure standardized procedures for cord blood safety. (See 'Regulatory aspects' below.)
Complete characterization of a cord blood unit should include the following assays [39]:
●Unit volume and weight, total nucleated cell count with differential, as well as an assessment of the unit's hematopoietic potential (eg, CD34+ cell count or colony forming unit count) after processing.
●ABO/Rh blood type and human leukocyte antigen (HLA) class I (-A, -B) and class II (-DRB1) haplotypes.
●Testing for hepatitis B, hepatitis C, HIV-1 and -2, HIV p24, syphilis, cytomegalovirus, and bacterial culture.
●Hemoglobin electrophoresis to screen for the presence of a hemoglobinopathy in the donated specimen [10,40].
●At public banks, mononuclear cells, plasma, and DNA from the cord blood unit may be stored in an aliquot separate from the main unit for future infectious and/or genetic disease testing.
While some banks store cord blood units with little or no processing, others remove the majority of the plasma and red blood cells in order to store the units in a smaller volume [39,41-43]. In general, processed units are preferred. This is principally because cord blood samples that have not had their red cells removed require washing prior to administration to remove red cell debris and free hemoglobin that may cause significant infusion reactions [44]. While the exact cause of the infusion reactions in such cases is not known, dilution in human serum albumin-dextran 40 may play a role in these infusion reactions [45,46]. In addition, unprocessed cord blood units will typically contain more dimethyl sulfoxide (DMSO), which can result in hypersensitivity reactions [11]. When possible, a split product should be collected so that part of the cord blood specimen can be used for ex vivo expansion studies. After testing and processing are completed, the viability of the hematopoietic stem cells is preserved by storing each unit in either liquid or vapor-phase nitrogen.
Processing and storage can be successfully performed at remote sites. Accordingly, a network of community collection sites targeted at particular ethnic groups and serviced by a central processing and storage facility could maximize the genetic diversity of banked cord blood units in a cost-effective fashion [47-49]. Shipping procedures are critical so that units are processed and stored within 48 hours.
Shelf-life of units — It is not known how long umbilical cord blood cells remain viable when stored in this manner; quality control procedures for testing viability are in their infancy [50]. However, other stem cell sources have been stored for many years and retained viability and engraftment potential.
●In one study, human cord blood cells stored for 21 to 23 years had an engraftment potential in mice similar to that of freshly-obtained cells [51].
●In a second study, cord blood stored for up to 12 years showed minimal loss of hematopoietic progenitor cells by in vitro testing, with recoveries >90 percent at 10 years [52].
●In a report of 93 children who received cord blood transplants varying in storage time from three months to 11 years, there was no correlation between storage time and time to engraftment [53]. For those children who failed to engraft, length of storage time did not appear to be a contributing factor.
There is no accepted "shelf life" of cord blood units and the age of a stored unit does not usually affect unit selection. However, given otherwise equivalent cord blood units, a more recently collected unit may be preferred due to changes in standards for collection, processing, and storage over time.
Release of units for transplantation — Transplant centers search public databases to locate both donors and cord blood units that are appropriate for patients in need of HCT. If an appropriate cord blood unit is located and a decision is made to proceed with transplantation, the unit is shipped to the transplant center in its cryopreserved state and thawed and infused into the recipient according to the standardized protocols. (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation" and "Donor selection for hematopoietic cell transplantation", section on 'Other considerations'.)
Appropriate labeling and confirmation HLA typing of the unit are critical. In one report, 2 of 871 units (0.2 percent) sent to a single medical center for transplantation were mislabeled and potentially would have been transplanted incorrectly [54].
Cord blood units should be available to the transplant center in one to two weeks, a time frame that is several months shorter than that for stem cells obtained by the standard National Marrow Donor Program (NMDP) process.
Regulatory aspects — Establishments that are involvement in the collection, processing, testing, storage, and distribution of unrelated donor cord blood must register with the US Food and Drug Administration (FDA) and are subject to FDA inspection [55,56]. The Association for the Advancement of Blood & Biotherapies (AABB; formerly known as the American Association of Blood Banks), the Foundation for the Accreditation of Cellular Therapy (FACT), NETCORD (NetCord-FACT), and the National Marrow Donor Program have each developed standards for banking procedures and quality control that banks may elect to follow [57].
More rigorous regulatory control could help ensure product quality and consistency, thereby facilitating the exchange of units between cord blood banks and transplant centers. However, any increase in regulatory scrutiny carries financial implications for cord blood banks.
Costs — Private banking fees vary greatly. Typically, companies in the United States charge approximately $2000 for processing the initial specimen [58]. In general, this fee does not include reimbursement for the collection procedure performed by the mother's obstetrician or midwife. Each company also charges a storage fee of approximately $125 per year per unit.
It is difficult to assess the per-unit cost of public cord blood banking, as the financial model of these banks is quite different from that of private banks [59]. It is certain, however, that the high cost of public cord blood banking raises the question of financial viability. Public banks are sometimes able to obtain compensation from cord blood transplant recipients and/or their insurance companies upon release of a cord blood unit but may rely on financial support from an external source (eg, an affiliated organization or a grant from the federal government). Unfortunately, less than 50 percent of cord blood units collected publicly have cell counts that are sufficient for banking. Thus, costs associated with public banking place constraints on program sustainability.
ETHICAL AND LEGAL ISSUES — Because cord blood banking is relatively new, the legal aspects are actively evolving, while the ethical issues raised by both public and private banking have not yet been resolved. A thorough discussion of these topics can be found elsewhere [60-67]. However, a number of these issues are illustrated via the questions posed below:
●Who owns a given cord blood unit: the child or the parents? Do the parents have the right to give the units away or sell them, or should they be held exclusively for the donor until adulthood?
●If the cells are to be used for someone other than the person from whom they came, must both parents agree or is consent from one adequate? What happens if the parents disagree?
●What happens to a unit stored by a for-profit company when there is a dispute among relatives regarding its disposition? What should be done with a privately banked unit if storage fees are not paid?
●When a cord blood unit is donated to a public bank, how can the privacy of the donor be protected without compromising the safety of the unit? Should a long-term link be maintained between units and donors, so that donors can alert the bank if they develop a disease that could be transmitted via the unit? Should the recipient be able to contact the donor in case additional blood cells may be needed (eg, hematopoietic stem cells, donor lymphocytes)? Alternatively, should all identifying links be destroyed, in order to preserve donor confidentiality?
●How shall the conflict of interest between donation for public banking purposes and banking for autologous use be resolved? What are the ethical implications of the fact that many cannot afford to bank their children's cord blood through a for-profit company, but do not have access to a bank that stores blood for public use?
●When infectious disease (eg, HIV and other viral testing) and genetic testing is required for banking purposes, who should be informed of the results (eg, mother, father, child)? If nonpaternity is discovered in the course of testing, should that information be disclosed, and to whom (eg, mother, father, or child)?
●Are for-profit cord blood banking companies exploiting parents at a vulnerable time in their lives, or providing a valuable service [7,16,68]? What sort of truth in advertising should be expected of these companies?
●What are the ethical ramifications of preimplantation genetic testing and HLA typing for the purpose of producing a child who can supply a cord blood unit for an ill relative [69,70]?
●What liability for the quality of the cord blood unit is carried by a cord blood bank? What is the liability of the physician or midwife who performs the collection for private banking purposes?
●Should we as a society be concerned about the commodification or commercialization of cord blood, a substance of increasing value? Is cord blood banking more akin to blood banking or organ donation?
COUNSELING EXPECTANT PARENTS — During their pregnancies, many expectant parents become aware of the possibility of banking their infant's cord blood for potential future use [12]. They may call upon their health care providers to help them decide whether or not to donate their infant's cord blood, or to pay to preserve it for private use. In particular, many parents confront the question of whether to bank their infant's cord blood through a private, for-profit company. Many pediatricians relate a general lack of knowledge with regards to counseling parents about cord blood banking. Given the current uncertainties of this technology, the American Academy of Pediatrics does not recommend that parents routinely store their infant's umbilical cord blood for future use unless there is an immediate medically indicated use for a sibling [16,71]. The American College of Obstetricians and Gynecologists states that patients who request information on umbilical cord blood banking should be provided with "balanced and accurate information regarding the advantages and disadvantages of public versus private banking" and be informed that the chance that a child or relative will develop a condition that could be treated with autologous unit of umbilical cord blood is low and that the routine storage of umbilical cord blood as 'biologic insurance' against future disease is not recommended [72]. Parents should be warned that autologous cord blood will not be selected if the donor child develops leukemia as the cord blood will have genetic markers of leukemia. Private cord banking is not allowed in Italy and France, and other European committees (eg, European Commission's Group on Ethics in Science and New Technologies, Royal College of Obstetricians and Gynecologists, World Marrow Donor Association) have indicated their concern about the ethical status of private cord banks [7,68].
The emotional vulnerability of parents who want to do "everything possible" to ensure the future welfare of their children must be recognized while making this decision. The promotional literature from private for-profit companies often does not accurately convey the potential benefits and limitations of cord blood banking and transplantation. Most of the reported cases of successful cord blood transplants utilizing cord bloods banked in private banks, as indicated on websites and not in peer reviewed publications, have been when a sibling is transplanted with the banked cord blood.
Parents considering private cord blood banking should be informed of the following issues:
●The indications for cord blood transplant are limited to certain genetic, hematologic, and malignant disorders. (A complete list is provided on the NMDP website.)
●Routine storage of umbilical cord blood as "biologic insurance" against future disease is not recommended.
●Cord blood banked is much more likely to be used by the donors' siblings than by the donor.
●Private storage of umbilical cord blood should be considered if there is a relative with a current or probable future need for transplantation.
If, despite being given the above information, the parents decide to proceed with cord blood banking through a private agency, it is wise for them to thoroughly investigate available companies. There are various online resources available to guide parents in this process. At a minimum, parents should be advised to do the following:
●Read all contracts thoroughly and know all costs associated with banking through a given company.
●Understand whether the stored cord blood will be available for autologous use only, or whether another relative, such as a sibling, could utilize the unit should the need arise.
●Confirm that the company is financially and otherwise stable, since the cord blood may be stored for years to decades before being used.
●Inquire whether the company is accredited by a reputable regulatory agency (eg, AABB, FACT).
●Know how long the company has been involved in cord blood storage, how many samples they currently have in storage, whether any units banked through the company have been used for transplantation, and their outcomes.
Estimating need for cord blood
Autologous donation — It is difficult to estimate a child's risk of requiring hematopoietic cell transplantation (HCT) [73]. Estimating the lifetime probability that an individual will need to undergo autologous or allogeneic HCT, given the current indications for HCT, is similarly difficult, and may be 2 to 10 per thousand [74].
However, the chance that a child or relative would ever benefit from HCT using his or her own cord blood has been estimated as one in 2700 individuals or less [39,73]. One source estimated that 1 in 20,000 collections performed without any medical indication might be used for autologous transplantation [63].
In addition, not all patients who develop a disease that can be treated with HCT will benefit from using their own cord blood cells. Autologous stem cells may be less effective than allogeneic stem cells in some medical situations. As examples:
●In the case of leukemia and other malignancies, the graft-versus-tumor effect that occurs with allogeneic transplants can be essential to the success of the transplant. (See "Biology of the graft-versus-tumor effect following hematopoietic cell transplantation" and "Hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) in adults", section on 'Graft-versus-leukemia'.)
●The genetic abnormalities underlying many transplant-treatable diseases, including leukemia and the hemoglobinopathies, are either believed or known to be present in the genetic material of hematopoietic stem cells present at conception, rendering autologous cord blood transplantation either undesirable or completely inappropriate as a treatment option for these diseases [75-77]. In such cases, even if a child's cord blood is stored and the child develops a transplant-treatable disease, the stored cord blood might not provide an appropriate source of mutation-free hematopoietic stem cells for transplantation. (See "Acute myeloid leukemia: Pathogenesis", section on 'Two-hit hypothesis of leukemogenesis'.)
In the absence of effectively proven procedures to expand the number of stem cells in cord blood, use of cord blood as the sole source of stem cells is limited based upon the recipient's weight. There are several clinical trials evaluating use of cord blood stem cell infusions for conditions such as cerebral palsy and diabetes. However, at the present time, the data from these studies are extremely preliminary and do not support a recommendation for private cord blood banking. Indeed, while advances in ex vivo cell expansion, gene therapy, and regenerative medicine may someday provide therapeutic options for a wide variety of diseases, there is no scientific basis to advise relatives to bank a child's cord blood on the assumption that such technology will develop to the point of broad clinical utility.
Allogeneic donation — Individuals with a known transplant-treatable disease (eg, thalassemia major, sickle cell disease, Diamond Blackfan anemia) have a potential need for cord blood. In these cases, cord blood storage should be encouraged and is available, even with private cord blood banks, at no cost [78]. (See 'Directed cord blood banking' above and "Hematopoietic stem cell transplantation in sickle cell disease", section on 'Alternative donors' and "Hematopoietic stem cell transplantation for transfusion-dependent thalassemia".)
Alternatives to cord blood — Depending on the medical condition of the potential recipient, there are a number of alternatives to the use of autologous or allogeneic cord blood. The majority of individuals with transplant-treatable diseases are initially managed with other medical programs, such as chemotherapy and radiation therapy for malignant diseases, and supportive care for some congenital hemolytic anemias (eg, transfusion, hydroxyurea for sickle cell disease).
If the individual has obtained a reasonable clinical response and quality of life with these treatments, this may outweigh the potential morbidity and mortality associated with hematopoietic cell transplantation. However, in the hemoglobinopathies, the long-term chronic illness-associated complications must be considered as these diseases have been cured by transplantation of mobilized peripheral blood progenitor cells, bone marrow and/or cord blood.
Finally, if hematopoietic cell transplantation is contemplated, a number of other donor options are available, including HLA-matched related or unrelated donors, as well as HLA-mismatched or haploidentical related or unrelated donors. (See "Donor selection for hematopoietic cell transplantation".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Labor and childbirth (The Basics)")
Additional information sources for parents — Additional noncommercial information concerning the potential benefits and limitations of cord blood donation and transplantation is available from the National Marrow Donor Program website.
SUMMARY AND RECOMMENDATIONS
●Description – Umbilical cord blood, the blood remaining in the umbilical cord and placenta following the birth of an infant, has emerged as an alternative source of hematopoietic stem cells in allogeneic hematopoietic cell transplantation (HCT). (See "Selection of an umbilical cord blood graft for hematopoietic cell transplantation", section on 'Increased demand for UCBT'.)
●Cord blood banks – Two main types of cord blood banks exist for the purpose of storing cord blood for potential future transplantation:
•Public cord blood banks collect and store cord blood units for use by any individual who has a medical indication for HCT and for whom a suitably matched unit is available. These banks perform collections at a limited number of hospitals throughout the world, meaning that a mother can choose to donate her infant's cord blood to a public cord blood bank if the infant is delivered at a hospital associated with such a bank. Several of these banks also have outreach programs supporting public cord blood donation. (See 'Public cord blood banks' above.)
•Private cord blood banks are for-profit enterprises that facilitate the collection of cord blood for those who are willing and able to pay for such a service. Typically, an infant's cord blood is stored as a source of hematopoietic stem cells for the child or another relative if the need should arise. (See 'Private cord blood banks' above.)
●Directed banking – A number of public and private cord blood banks provide a service, called directed cord blood banking, for those with a relative with a potentially transplant-treatable disease and who are expecting another child. (See 'Directed cord blood banking' above.)
●Safety – Cord blood collection should never compromise the safety of the mother or infant during childbirth. Standard obstetric procedures for determining the mode of delivery and timing of cord clamping should not be altered in an attempt to optimize cord blood collection. While collection may be performed either prior to ("in utero") or following ("ex utero") delivery of the placenta, ex utero collection is generally preferred because it is technically easier and safer for the clinician obtaining the sample, without compromising sample volume or sterility. (See 'Cord blood collection' above.)
●Testing, processing, and storage – After collection, cord blood units should be tested, processed, and stored for future use within 48 hours of collection. Because regulations regarding cord blood banking are relatively new, cord blood unit characterization and processing procedures still vary. A maternal blood sample should be obtained within seven days of cord blood collection to screen for infections that might be transmitted to the infant and therefore might be found in the cord blood. (See 'Follow-up studies' above and 'Processing and preservation' above.)
●Counseling – Parents considering private cord blood banking should be informed of the following issues (see 'Counseling expectant parents' above):
•The indications for cord blood transplant are currently limited to certain genetic, hematologic, and malignant disorders.
•Routine storage of umbilical cord blood as "biologic insurance" against future disease is not recommended.
•Cord blood is much more likely to be used by the donors' siblings than by the donors.
•Private storage of umbilical cord blood should be considered if there is a relative with a current or probable future need for transplantation.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Bertram H Lubin, MD, who contributed to an earlier version of this topic review.
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