Issues in the quality of umbilical cord blood stem cells for transplantation: challenges in cord blood banking quality management
2005; Wiley; Volume: 45; Issue: 6 Linguagem: Inglês
10.1111/j.1537-2995.2005.05116.x
ISSN1537-2995
Autores Tópico(s)Polyomavirus and related diseases
ResumoAs cord blood is becoming a major alternative hematopoietic stem cell source for transplantation, the cord blood banking community is transitioning from the research-based laboratory to the clinical cellular therapy production laboratory. Historically, quality assurance measures that are considered standard practice in the cellular laboratory have not been uniformly applied to cord blood. In an article in this issue, McCullough and colleagues performed a systematic review of the cord blood products imported for transplantation at their center using a tool developed for cellular therapy products.1 They identified many variances and/or deviations at all stages of production and release that could impact transplant outcome. Although one could argue the importance and/or relevance of some of the quality issues identified, it is inarguable that communication about the cord blood product was incomplete before acceptance of the unit. It is important to note that cord blood units are typically shipped just before starting the transplant-preparative regimen, a time point at which it is frequently difficult to alter treatment decisions. In reading the article, one asks why was there such a high incidence of quality issues being identified in the screening of units at time of transport to the treating facility. The answers to this question hold the key to future approaches for quality programs for cord blood banks. My observation as a person active in both cord blood banking and transplantation is that there is an underappreciated third party in the cord blood transplant team—the transplant institution's cellular therapy laboratory. The clinical decision to use a cord blood unit is typically made by the transplant team who is reviewing lists of HLA types, cell doses, and possibly a limited other number of data fields (ethnicity, cytomegalovirus status, and length of storage) in registries of cord blood banks. Once a potential unit is identified, the transplant program will request a comprehensive report from the cord blood bank that may or may not address the quality indicators discussed in the article by McCullough et al. Cord blood banks and transplant teams have a varying level of understanding of and/or acceptance of the now commonly accepted quality indicators. Frequently the role of the cellular therapy laboratory is limited to notification of shipment time to their laboratory and request date for transplantation. It is the cellular therapy laboratory team who is practiced in the production and qualification of cellular therapy products. They can and should provide guidance to the transplant team on product suitability issues. Early involvement of the cellular therapy laboratory in the cord blood selection process is critical. There is no return of cord blood units back to the cord blood center once they have been shipped. The cord blood banking community has been working systematically to raise the quality standards for cord blood banks. As mentioned in the article, the efforts of FACT and the AABB have provided a platform of at least minimum standards for banking. The NMDP Cord Blood Committee, a collaboration of 12 NMDP US public cord blood banks, has active quality, collection, and proficiency subcommittees. The banks are transitioning from having an extremely limited inventory to having a large and increasing inventory of cord blood units. Hence variances from banking standards perceived as low risk for the patient and once accepted given the high risk of death that the patient was facing without a stem cell source are becoming more difficult to defend. Newly banked units currently being listed with the NMDP are negative for bacteriologic and fungal cultures and maternal infectious screening and testing and have had hematologic assays which include viability measurement, CD34 and CFU quantitation, and hemoglobinopathy screening. The NMDP TransLink application, which is available real time to the transplant center and used for cord blood unit match, review, and selection, displays the processing, testing, and screening information that has been collected on the unit. Other banks and banking collaborative groups are also applying similar standards to new inventory. It is important to appreciate that the definition of a quality issue varies in the eyes of community members and depends on the glasses that are being worn at the time. For patients in dire clinical need for whom there is no other suitably matched hematopoietic stem cell product, clinical and cellular therapy laboratory personnel will accept some of the variances as low risk to the patient and use the unit. Examples of acceptable low-risk options would be a family history of thyroid disease or the presence of α-thalassemia trait in the cord blood unit. This decision needs to be made prospectively by the transplant team; ideally with guidance by the cellular therapy laboratory, before acceptance of a cord blood unit for transplantation. For significant variances from current practices, it is important that this cellular therapy product be considered an exceptional product and that there be documentation of recipient knowledge of the quality concern. The definition of what is an indication for cord blood unit deferral versus a reported variance is one that is under active discussion in the regulatory, cord blood banking, and transplant communities. Much guidance has been received from the new FDA guidance documents. Areas that need further discussion include exclusion criteria for maternal travel to areas where Creutzfeldt-Jakob disease (CJD) has been reported. Given the lack of evidence for vertical transmission of CJD, it is difficult to rationalize the exclusion of cord blood units based on maternal travel history. This issue becomes important because in our global networking of cord blood banks, several excellent banks would have their entire inventory ineligible because of their geographic location. Such an action would not be of benefit to the transplant community because of the inheritance of HLA alleles is linked to ethnicity. The transplant community does not have a consensus as to what type of family history of cancer should be an indication for deferral. There are many difficult questions on donor screening for inherited disorders that need to be addressed, ideally with an evidence-based approach. The focus of the discussion being whether the transplanted hematologic and/or immunologic system would be impacted by these disorders. The best approach at present is for banks to collect detailed family genetic, cancer, and/or infectious histories and disclose these findings to the transplanters and cellular therapy lab at time of search. Communication of all the collection, processing, and storage information on the unit should be standard practice and not available only if the right probing questions are asked. Not addressed in this article is an evolving quality issue in cord blood banking—that of long-term storage. Cord blood is processed and stored either in liquid or vapor-phase nitrogen. It is a common standard that freezer conditions be maintained and documented through the length of storage. Cord blood units that were collected 5, 10, and even 20 years ago were banked with the quality standards of the time. Considerable changes, hopefully improvements, in banking procedures have resulted in improved qualification for units before listing that were not present at the time the older units were prepared. Thus, many of the quality issues identified by McCullough and colleagues will continue to be issues for the transplant community for years to come. Transplant centers and their cellular therapy labs will need to be diligent to ensure that they have all the product information available about a unit before acceptance of products for transplantation. It is important for the transplant and cellular therapy community to appreciate that testing of hematopoietic potential and viability of the unit that is reported in the cord blood product reports is performed before freezing. To date there is no standard approach to validate that the unit being shipped has retained its viability through the storage process. Although cellular products have been shown to maintain viability over years2 for a given unit, one does not know the quality of the frozen storage process or whether that unit experienced thawing conditions. Efforts are ongoing in the cord blood banking community to develop release testing for cord blood before shipping for transplantation.3 The NMDP proficiency committee is evaluating the possibility of utilizing the attached segment on the cord blood unit to perform identity confirmation and a measure of hematopoietic potential. This type of testing would potentially add to the quality of cord blood units being released for transplantation. The successful cord blood transplant also hinges on the cellular therapy laboratory having experience in cord blood thawing and infusion. These transplants are being performed with limited cell doses; thus it is critical to maximize cell yield and viability at thaw. Cord blood banks should provide recommended thaw procedures for their products. These may vary depending on the manipulation of the cord blood unit before freezing—most important being whether the products were red cell–depleted before freezing. Most banks are recommending thaw procedures similar to those developed by Rubinstein and colleagues.4 All banks should provide cord blood units for practice thaws by the cellular therapy laboratory before that laboratory accepts a cord blood unit. A validated cord blood thaw procedure must be in place in the institutional cellular therapy laboratory before acceptance of cord blood units for transplantation. Educational opportunities are available for cellular therapy laboratories that would like to develop proficiency in handling cord blood. Although the cord blood unit banked several years ago may not meet the GTP of today, the units currently being banked are meeting higher standards. All FACT/AABB-accredited banks and the NMDP network of banks have extensive product qualification standards that address maternal screening and testing, infant health, processing, testing, and release. It is important that cord blood banks, transplant programs, and their cellular therapy laboratories nurture an active dialogue and continue to work together to provide a seamless information exchange to assure that all products are safe and potent at time of infusion. The review performed by McCullough and colleagues is an important contribution to this evolving process.
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