v. QUALITY ISSUES

1. Issues in the quality of umbilical cord blood stem cells for transplantation. McCullough J, McKenna D, Kadidlo D, Schierman T, Wagner J. Transfusion. 2005;45:832-41.

The authors report on a quality assurance monitoring system that was used to evaluate 268 UCB units provided to a single transplant center by UCB banks in the United States and Europe.

The authors point out that, because standards have evolved over time, cord blood banks contain units that have different levels of quality. Some units have been placed in the usable inventory with incomplete test results and/or documentation or that may not meet the bank's own current criteria. Information about any quality or operating procedure deviation should be provided in sufficient detail and at the initiation of the search process so that transplant physicians can consider these quality issues against the unique value of a particular UCB unit.

The authors' quality assurance monitoring system detected quality issues in 151 (56%) of 268 units, and there were a total of 246 specific issues in 151 units. The issues involved quality control (54%), medical history (40%), and labels and documentation (6%).

Examples of medical history issues include maternal residence in or recent travel to an area endemic for malaria, recent maternal tattoo placement and body piercing (less than 12 months before delivery), maternal human immunodeficiency virus (HIV) risk factors, and maternal history of herpes, chlamydia, human papillomavirus, or use of donor sperm for the pregnancy. Four units had a factor on the "possible disease and/or medical history" that could relate to the effectiveness of the UCB for transplantation. These include a mean corpuscular volume of 101.6 fL suggestive of possible α-thalassemia because the parents are of Mediterranean ancestry, hemoglobin (Hb) Bart's, sickle cell trait, and juvenile diabetes. Forty-two units included comments about the medical history of the extended family. Most of these dealt with cancer. Four comments described risk factors in the father and 11 comments dealt with other maternal health issues such as polycystic kidneys or hypothyroidism that would not necessarily relate to transmissible disease risk.

Quality control issues regarding transmissible disease testing included the fact that the transplants center received 21 units of UCB for potential transplantation from the useable inventory of UCB banks with a total of 28 transmissible diseases tests incomplete or pending or with positive results. Test results were missing for HIV antigen, serologic test for syphilis, cytomegalovirus, human T-lymphotropic virus (HTLV), and hepatitis B core antigen (HBc) antibody. Other quality control issues involved bacterial contamination, transportation and shipping, UCB processing methods, and miscellaneous issues.

Fifteen units had issues related to labeling and/or documentation. The authors point out that, at the time of transfer to the transplant facility, the label on the unit must contain the following information: a unique numeric or alphanumeric identifier; proper name "cord blood"; ABO and Rh type; name and volume of any additive such as anticoagulant, electrolyte solutions, or cryoprotectant; approximate volume of the unit; any methods used to manipulate the UCB unit (e.g. depletion, positive selection, gene manipulation); recommended storage temperature range; name and address of processing facility; and a biohazardous label if indicated. The label should also contain statements to indicate the intended recipient, that unit identification must occur before infusion, and a warning that the unit might transmit infectious agents.

Interestingly, engraftment issues did not occur more frequently in recipients of UCB units with quality issues. Most patients did not have engraftment problems. Quality issues occurred in 72 percent of transplants with and 72 percent without engraftment problems. UCB units with quality issues were involved in 66 percent (31/47) of patients with and 62 percent (137/221) of patients without engraftment problems. Although no patient was harmed as a result of these quality issues described, they consumed large amounts of time to resolve and created great uncertainty by both the clinical transplantation and cell therapy laboratory staffs.

The authors make specific recommendations to transplant centers and UCB banks so that potentially lifesaving UCB units may be used while minimizing risks. They recommended that available units that do not meet present levels of expected quality should be identified by the cord blood bank, and that this information should be transmitted to the transplant center early in the search process. Search systems should be designed to promote communication between the transplant center and the bank.

(This is a well-written and detailed article which points out specific problems encountered at a transplant center regarding the quality of units that are received from cord blood banks. Unfortunately, even if all of the issues raised in this article were to be corrected, transplant centers are still left with the bigger issue that there are no standard methods for evaluating the post-thaw quality of the progenitor cells in cord blood units (see Citation #2 below).

The fact that none of the units with quality issues seemed to have an adverse effect in the authors' patients is of interest. If the quality issues do not affect patient care, but consume large amounts of time and create great uncertainty one should assess the value of such issues. Indeed, the authors make several recommendations for elimination of specific compliance issues. For example, if the only quality factor regarding contamination is a positive culture, and even that does not preclude banking the unit, it appears that labor history issues could be eliminated. Also, they suggest it might be timely for a review of the donor health history for cord blood to determine whether all of the present efforts are necessary.)

2. Issues in the quality of umbilical cord blood stem cells for transplantation: challenges in cord blood banking quality management. Wall DA. Transfusion. 2005;45:826-8.

This editorial is by a physician experienced in both cord blood banking and transplantation. The author's comments relate, in particular, to the article by McCullough et al (see Citation #1 above). She states that, although one could argue the importance and/or relevance of some of the quality issues identified by McCullough et al, 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.

She argues that the transplant institution's cellular therapy laboratory can and should provide guidance to the transplant team on product suitability issues. This can be provided for many aspects of quality of the cord blood unit being considered for transplantation, as pointed out by McCullough et al. However, testing of hematopoietic potential and viability of the unit that is reported in the cord blood product reports is performed before freezing, and to date there is no standard approach to validate that the unit being shipped has retained its viability through the storage process.

Efforts are ongoing in the cord blood banking community to develop release testing for cord blood before shipping for transplantation. 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.

3. Cord blood units for adult transplantation: child's play no longer. Snyder EL, Haley NR. Transfusion. 2005;45:829-31.

This editorial briefly reviews the early history of cord blood transplantation, and cites other articles in the same issue of the Journal regarding key quality issues. The authors emphasize that the current "climate of quality" in the cord blood field is intense. "Indeed, the transplant field's insistence on cord blood unit quality approaches a degree of enthusiasm generally seen only at major sporting events."