Pediatric HCT physicians are currently the main group of clinicians who might employ privately banked cord blood in clinical care. They are often asked by families and by other clinicians for advice regarding prophylactic cord blood banking. We surveyed these physicians about their prior use of and views on privately banked cord blood. We found limited experience with and enthusiasm for prophylactic private cord blood banking among respondents.
Several observations from this survey stand out. First, despite the fact that cord blood banked prophylactically surely accounts for the preponderance of units stored in private cord blood banks, transplants using cord blood banked preemptively have substantially outnumbered transplants using cord blood banked prophylactically. Second, allogeneic transplants using privately banked cord blood have substantially outnumbered autologous transplants. In the allogeneic setting, because the sibling typically can serve postnatally as a hematopoietic stem cell donor, the transplant can generally proceed even if cord blood was not banked. Third, very few pediatric transplant physicians would recommend prophylactic cord blood banking to prospective parents. Importantly, willingness to recommend increases only marginally when the parents are of different minority ethnic groups, a circumstance that reduces the likelihood of finding a suitably matched unrelated-donor stem cell source should the need for HCT arise.(20
Respondents were reluctant to use autologous cord blood to transplant a child with ALL, the most common malignancy of childhood and the most common indication for allogeneic HCT in children in North America (unpublished data, CIBMTR). This reluctance may be attributed to the established importance of an allogeneic “graft-versus-leukemia” effect for survival after HCT for ALL,(21
) or to the observation that leukemic clone-specific molecular genetic markers may be present at birth in children who subsequently develop ALL.(22
) The same considerations would likely affect clinical decision-making for pediatric acute myeloid leukemia.(23
) The one circumstance in which a majority of respondents indicated willingness to use stored autologous cord blood to treat relapsed ALL is the child who lacks a suitable MSD or URD stem cell source. However, the likelihood that a healthy newborn will ultimately face such a situation is remote. First, approximately 25% of children who require an allogeneic HCT have an HLA-matched sibling.(12
) For those who lack a matched sibling, availability of a suitable unrelated-donor graft varies according to ethnicity, with a match identified for approximately 85% of Caucasians and 60% of African-Americans.(20
) Given the annual incidence of ALL in children aged 0–19 years (30.6/million for Caucasians and 15.9/million for African-Americans),(24
) and relapse and re-induction rates of approximately 20% and 90%, respectively,(25
) the probabilities of a healthy newborn 1) developing ALL during childhood, 2) experiencing a relapse, 3) achieving a second remission, and 4) being unable to find a suitable allogeneic donor are approximately 12.4/million for Caucasians and 17.2/million for African-Americans.
Severe aplastic anemia, with an annual incidence for all ages combined of approximately 3/million,(27
) is the most common non-malignant indication for allogeneic HCT in childhood (unpublished data, CIBMTR). Currently, MSD HCT is indicated for children with newly diagnosed SAA, whereas URD HCT is reserved for those with an inadequate response to immunosuppressive therapy.(28
) Historically, survival has been approximately 90% after MSD HCT and 50–60% after URD HCT.(29
) The poorer reported outcomes after URD HCT likely underlie the willingness of 55% of respondents to use the autologous cord blood rather than an URD graft for transplantation. More recent reports, however, demonstrate improved survival after URD HCT for SAA.(31
) Other factors, such as the absence of benefit related to graft-versus-tumor effect in SAA, may also contribute to respondents’ willingness to consider banked autologous cord blood as a stem cell source for treatment.
High-risk neuroblastoma, with an annual incidence of approximately 3–5/million children under 15 years of age in the United States,(32
) is the most common indication for autologous HCT in children (unpublished data, CIBMTR). Molecularly detectable contamination of the autologous stem cell graft with neuroblastoma cells is frequent,(34
) and has been shown to contribute to relapse post-transplant.(35
) The chance of graft contamination is likely lower with cord blood collected at birth, prior to the clinical diagnosis though not necessarily the development of neuroblastoma. Hence a majority (55%) of respondents said they would choose the autologous cord blood as a graft in this scenario. However, this majority decision was dependent on adequate cellularity of the stored cord blood unit, a variable affected by the skill of the personnel collecting and storing the cord blood as well as by other factors.(36
This study has several limitations. First, there is no comprehensive list of pediatric HCT physicians in the United States and Canada. The sampling frame for this survey included 152 pediatric HCT physicians who were listed with the CIBMTR. We believe this population to be representative of pediatric HCT physicians in these countries. Indeed, the preponderance of program leaders among respondents strengthens our confidence in our findings, both because these physicians are best able to report their prior institutional experience and because they are likely to make decisions regarding stem cell source in unusual clinical circumstances. Second, our findings might have been influenced by response bias if views on private banking of cord blood or on therapeutic use of autologous cord blood differed between respondents and non-respondents. Third, it is possible that additional transplants using privately banked cord blood have been performed, either by non-respondents to our survey, by physicians who were not included in our sample, or since the survey was fielded. However, these estimates are commensurate with those provided by cord blood banks themselves in their promotional materials.(17
) In addition, because several physicians responded from some centers, it is possible that we double-counted several transplants. Had we discounted transplants with the same type of graft and the same disease indication as one already reported by another respondent from the same center, there would have been a total of 7 autologous and 36 allogeneic transplants reported. Fourth, our data do not directly address the value of prophylactically stored cord blood for stem cell transplantation among adults. Finally, while pediatric HCT physicians are uniquely qualified to address the clinical experience with and utility of privately banked cord blood, their opinions concerning how prospective parents should spend their private funds should not be considered determinative. Nevertheless, the fact that pediatric HCT physicians are frequently asked for their advice regarding storage of cord blood suggests that their views on this issue are valued by parents and other physicians alike.
Although we did not ask HCT physicians about their views regarding public cord blood banking, there is growing recognition that unrelated-donor cord blood obtained from public banks represents an invaluable stem cell source for both pediatric and adult patients in need of transplantation.(39
) Cord blood units are particularly useful for patients from racial and ethnic minority groups, due to the less stringent requirements for HLA matching with the use of cord blood as a stem cell source as compared with marrow from unrelated adult donors.(20
) In recognition of the value of unrelated-donor cord blood, the U.S. Congress has funded a National Cord Blood Inventory Program, with plans to build an inventory of 150,000 cord blood units.(42
) This source of funding, which supplements income derived from releasing cord blood units to recipients, is nevertheless inadequate to cover the full costs of maintaining a cord blood bank.(39
) The role of alternative models of supporting public cord blood banks, including joint public-private banks,(43
) remains to be clarified.