Response: the controversy of red blood cell–replete cord blood units

We welcome the opportunity to formally debate the issue of assessment of progenitor cell dose in cord blood (CB) units from public banks. Drs Petz and Chow raise an important question: how should transplant centers compare CB units processed with various methodologies of plasma plus or minus red blood cell (RBC) depletion? There are essentially no data to guide decision-making and, therefore, our review¹  has highlighted the current practice in relation to RBC-replete CB units: “… to permit comparison of such units with RBC depleted units, many TCs correct the TNC dose of RBC replete units (J.N.B., personal communication with multiple US investigators, 2004-2009). Unfortunately, this strategy is controversial, and the most appropriate correction factor is unknown.”^(p2334)

Drs Petz and Chow state that “… all processing methods that produce RBC-reduced units lose significant numbers of progenitors.” However, CB banks use a variety of manual and automated methods and such an oversimplification is not accurate. For example, the AutoExpress Processing System recovers more than 95% of CD34⁺ cells and CFU with excellent viabilities (unpublished data, National Cord Blood Program, New York Blood Center, December 2008). Furthermore, Drs Petz and Chow acknowledge that RBC-replete units have TNC doses approximately 25% higher than RBC-depleted units, because no neutrophils have been removed. It is logical that in the absence of data, transplant centers would apply a correction factor to permit comparison of these units with RBC-depleted units. However, they maintain that no correction factor is necessary and show some data to this effect. We encourage formal analysis of a larger number of units with reporting of postthaw yield, replication by independent investigators, and publication in peer-reviewed scientific literature. Only such studies will be able to potentially answer this question given that retrospective analyses will be flawed by the inability of transplant centers or banks to standardize CD34⁺ cell and colony-forming unit assays. Ultimately, the field requires new measurements of progenitor cell content that could replace TNC measurements and be easily standardized.

A further issue that is not addressed by Drs Petz and Chow is the challenge of thawing RBC-replete products, their postthaw cell yield, the final product hematocrit, and the safety of infusion. RBC-replete products are more complicated to wash given that cellular debris and free hemoglobin can interfere with the demarcation of the interface between mononuclear cells and the supernatant, and can contribute to viscosity and clumping. To avoid cell loss and product manipulation with wash, we have investigated an albumin-dextran dilution-only thaw technique. However, in an initial study of 54 patients, all 3 recipients in whom one unit of a double-unit graft was RBC-replete exhibited infusional toxicity that was of clinical concern.²  Subsequently, multiple severe or life-threatening infusion-related adverse events occurring at other centers using unwashed RBC-replete units have been reported to the National Marrow Donor Program (NMDP). As patient safety is of paramount importance, this prompted a detailed analysis by and subsequent alert from the NMDP in 2009 recommending the wash of RBC-replete CB products as a prudent safety measure while the investigation of these events was conducted. A safety report was also made to the Food and Drug Administration. We, therefore, have maintained our practice of albumin-dextran dilution (ie, no wash) of RBC-depleted products in recipients weighing more than 20 kg with good success, but we now wash all RBC-replete units. And although we value the significant global inventory of RBC-replete products, we are concerned about the difficulties of the wash of a RBC-replete unit. Moving forward, we must work together with strong bank-transplant center collaboration to define the optimal quality of CB products and the best procedures for their use.