A case of mistaken identity

If doubts remain regarding the importance of quality management systems that conform with comprehensive internationally agreed standards for collecting and handling cord blood (CB) units, this article by McCullough et al will provide the missing evidence.¹  Establishment of public cord blood banks was triggered by the finding that cord blood transplantation can be successful despite a relatively high degree of human leukocyte antigen (HLA) incompatibility. More than 20 000 CB transplantations have been performed worldwide, and in some countries up to 50% of unrelated transplantations involve the use of cord blood stem cells. Some of the advantages of using cord blood cells include their ready availability and the complete absence of any risk for the donor.²  Moreover, the various tests for safety, identity, and efficacy can be carried out at leisure, which means that quality can eventually be defined with some precision. One recent report suggested that for a medium-sized country with a moderately diverse ethnic make-up, a cord blood bank with 50 000 units could offer stem cells for a significant proportion of patients requiring allogeneic transplantation but lacking match.³  But despite great progress with CB bank standardization, some pitfalls remain. Most of the errors are related to what we might call a “bank learning curve” and involve units processed before 2001, when the standards were published.⁴ 

In this issue of Blood, McCullough et al report 2 cases of mislabeled CB (error rate of 0.4%; ie, 1 of 249 patients would receive an incorrect unit) that were recognized as such only by rapid ABO and HLA typing after thawing, thereby avoiding what might otherwise have been a catastrophic outcome. In both cases the CB units had no physically attached mini-tube or “segment” containing small aliquots of the stored cells (see figure). The investigators had previously reported considerable variability in the quality and consistency of CB units provided for transplantation.⁵  In practice, some banks are still not yet formally accredited and in many cases adherence to standards still leaves much to be desired. There are various possible strategies for improving the situation. First, CB containers should be manufactured with enough attached tubing to allow several segments to be filled with cells, yet each would remain attached to the main bag. This would allow laboratory staff to test viability and perform progenitor cell assays using published methodology.⁶  To confirm the actual identity of a given CB unit before it is used, McCullough et al propose that it should be routine practice to thaw a small aliquot and carry out rapid blood group and serologic HLA typing—a very logical suggestion. Moreover, a back-up unit of CB should have been selected and made available at short notice if required. Unfortunately, it may be difficult to persuade all transplantation centers to adopt these policies.

The McCullough paper raises some relevant questions. Who is responsible for errors that may occur, and how can the causes be traced if the unit originated in another country? There must be effective lines of communication among the transplantation centers, the data banks, and the banks where the cord blood units are stored. These require a high level of cooperation among the various international regulatory bodies considering that the number and volume of biologic products that now cross international boundaries are increasing exponentially. A report from the last meeting of the World Marrow Donor Association indicated that about 3000 CB units had been shipped and 40% of those had been provided internationally during 2007.⁷ 

In summary, these findings provide a warning signal. The CB bank community needs to work toward use of bags designed with physically linked segments. Apart from recognizing those cord blood banks that meet appropriate international standards, we also need to identify any individual CB unit that does not meet current safety and efficacy criteria, because many of the units stored years ago may prove to be inadequate by today's standards. Such measures should help transplantation centers select the best units for their patients.