Cord blood banking 2002: 112,010 of 7,914,773 chances (2002)

On July 6, 2002, while surfing through a number of internet websites related to hemopoietic stem cell (HSC) transplantation, I reached the Bone Marrow Donors Worldwide website, where a summary table indicated that a patient in need of bone marrow replacement and with no suitable family related donor(s) may find a compatible unrelated donor in a number of registries including a total of 7,914,773 individuals. Of these, 112,010 were children of mothers who had generously consented to donation of their newborns' placental blood (or cord blood) for long-term cryopreservation in 28 banking programs. The program names indicated a US location in 8 cases and a European location in 17 cases, which globally accounted for 55,560 and 44,693 units, respectively, or 49.6 percent and 39.9 percent of the total inventory. Moreover, there were 6449 units listed from Australia (5.8 percent) and 5238 from China (4.7 percent). Ten years ago, not only was the global number of HSC donors much smaller, but also no placental blood was available. To my knowledge, it was in fact in 1993 that the first three programs aimed at the implementation of large repositories of cryopreserved cord blood regularly collected from healthy newborns (cord blood banking) were started in New York, Milan, and Düsseldorf by Pablo Rubinstein, Girolamo Sirchia, and Peter Wernet, respectively. Following the development of these programs, it soon became apparent that cord blood banking and traditional blood banking share a number of similarities related to staff, facility, equipment, data processing, and risk management. For this reason, the facilities of many cord blood banking programs have found their natural location within or close to a large blood center. This may have facilitated a broadening of the interests of a number of professionals involved in transfusion medicine toward cord blood banking. It is therefore not surprising that this issue of TRANSFUSION, a leading forum for transfusion medicine, hosts four papers dealing with different aspects of cord blood banking. The fresh information provided by these papers also shows that, besides many similarities, cord blood banking and traditional blood banking show a number of important differences (Table 1). The article by Vawter et al.1 describes a phased consent policy for cord blood donation. The authors define the phased consent process as “a process that permits consent during early labor to the ex utero collection of cord blood followed by consent postcollection to donation.” In comparison to routine blood donation, where consent is a unique action, it is proposed that consent to cord blood collection is given in a different moment from that in which consent to donation is expressed. The rationale of the phased consent policy proposed by Vawter et al.1 and the requirement to seek consent not only to donation but also to collection stem from consideration of the emotional stress of the parents before and during labor, as they may have “deep cultural, religious, or personal objections to the handling and disposition of the placenta and/or the blood it contains.” Besides proposing a new modality for the collection of consent to cord blood donation, the article by Vawter et al.1 stresses the importance of distinguishing between in utero and ex utero collection. This is appropriate in view of the important legal and operational differences between the two modalities of cord blood collection. Moreover, the article provides a detailed and useful discussion of consent policies or views of a number of organizations, including the New York State Council on Human Blood and Transfusion Services, the Foundation for the Accreditation of Cell Therapy (formerly the Foundation for the Accreditation of Hematopoietic Cell Therapy), the American Academy of Pediatrics, the AABB, the National Marrow Donor Program, the American Medical Association's Council on Ethical and Judicial Affairs and the American College of Obstetricians and Gynecologists. Ethical and policy issues are also the main focus of the article by Askari et al.,2 who performed a retrospective review of all cord blood units collected between November 1999 and October 2000 at the American Red Cross Cord Blood Bank in St. Paul, Minnesota. The aim of this study was to assess the value of the paternal health history in making cord blood safer. Accordingly, the investigators determined the proportion of cord blood units deferred based solely on paternal health history. It was found that a paternal health history was available in 46 percent of the 655 cord blood units collected and in 79 percent of the 339 cord blood units banked. Moreover, only 3 of the 301 units in which the paternal history was available were discarded based only on paternal history. The three risk factors reported were: 1) gave money or drugs for sex; 2) traveled to a high-risk area; and 3) did not answer high-risk questions. Based on these findings, the authors correctly conclude that obtaining paternal history—a logistically difficult and expensive procedure—does not appear to be justified, as it has an “overall indistinct and unconvincing role in minimizing infectious disease transmission risk” in cord blood banking. The issue of ex utero versus in utero collection is addressed again in the study by Lasky et al.3 These authors move the focus from the ethical and policy issues discussed in the previous articles to an assessment of the quality of cord blood units collected with the two methods. The importance of this study derives from the different implications—in terms of staff qualification, operation and costs—of using trained obstetricians and midwives versus trained laboratory personnel. In fact, the former are required with in utero collections, while the latter may be used if collections are performed ex utero. The study was carried out between October 1999 and December 2000 at five American Red Cross centers located in Massachusetts (where cord blood was collected in utero), and in California, Minnesota, Ohio and Oregon (where collections were performed ex utero). During the 14 months of study, large numbers of units—from 513 to 848—were collected in each program. Similar to other reports, including our own study, the percentage of discarded units ranged from 34 to 52.6 percent of those collected (i.e., a large proportion). This multicenter investigation showed significant differences among the programs in regard to the unit volume, number of nucleated and mononuclear cells, CFU-GM, and CD34+ cells. Nonetheless, based on limited variations of the medians detected at each program for each of the considered parameters, the authors conclude that most differences are not of practical importance or that they may be due to differences in the measurement process at each center. Based on these findings, these investigators reached the conclusion that cord blood can be collected successfully using either the in utero or ex utero methods. This conclusion may be particularly relevant and valuable in some settings like our own, where the large number of delivery suites engaged in cord blood collection for our bank (19 at the time of this writing) and their distance from the cryogenic facility located in Milan (1-120 miles) would make the use of our personnel difficult and quite costly. For these reasons, from the onset of our activities in 1993 we elected to rely on the generous efforts of qualified midwives collecting cord blood in utero during the phase after the delivery of the baby and before the delivery of the placenta. Despite its justification, our choice is not free of difficulties, because the management of periodic qualification of a large number of midwives as required by our ISO 9002 certified quality system is an intense and expensive task. The observation that the reasons for cord blood unit discard were not significantly associated with the baby's race at any of the centers participating in the study by Lasky et al.3 may serve as an introduction to the last of the four articles dealing with cord blood banking that are published in this issue of TRANSFUSION. Ballen et al.4 investigate the racial and ethnic composition of 9020 volunteer cord blood donors and match it with that of 417,676 unrelated bone marrow donors in comparable geographical areas. The study was triggered by a frequently quoted presumed advantage of cord blood, its ability to increase minority recruitment, which has been substantiated with limited data so far. This investigation has the particular merit of providing experimental evidence indicating that this purported advantage, although theoretically correct and potentially exploitable, cannot be taken for granted in all geographic areas. In fact, Ballen et al.4 showed that minorities were less represented among cord blood donors than among bone marrow donors in California, Florida and Massachusetts, while minority recruitment was equivalent in New York and Colorado. Although the study has some limitations that are extensively discussed by the authors, Ballen et al. correctly point out in their conclusions that better strategies are needed to recruit minority donors and suggest that some efforts developed by the National Marrow Donor Program to increase minority recruitment among bone marrow donors can be adapted to cord blood donors. One important feature needing consideration in this regard, which might facilitate the new efforts by psychologically well-trained cord blood donor recruiters, is that the target of recruitment for cord blood donors is the well-defined population of mothers close to delivery. This is a less polymorphic group than the general population from which bone marrow donors are usually recruited. In conclusion, this issue of TRANSFUSION publishes important contributions to the field of cord blood banking, a recent specialty not only characterized by unique features but also sharing a number of similarities with traditional blood banking. It is now the duty of the scientific and medical communities at large to fully exploit the new therapeutic perspectives offered by cord blood. In this regard, it is encouraging to note that not only have more than 2300 allogeneic cord blood transplants been already performed, mainly in the unrelated pediatric setting and for hematologic conditions, but also that promising reports specifically addressing cord blood transplantation in adults have been recently published.5 Interested readers may find more detailed information on the source of units for 2058 cord blood transplants so far performed at the website of NETCORD, an organization developed to improve the international standards of cord blood banking and use, which can be reached at http://www.office.de.netcord.org. Finally, we should open our minds to the astounding discoveries of stem cell plasticity and transdifferentiation, which might hopefully transform cord blood and other tissues into a potential source of manipulated cells for human tissue repair.6–8 With wise prudence, of course.9