Analysis of the CD34+ Cell Content of 126, 341 Cord Blood (CB) Units in the NMDP be the Match Inventory: Implications for CB Transplantation and Public Banking

Background: Infused CD34+ cell dose is a critical determinant of the speed & success of engraftment after single & double unit CBT, & analyses have demonstrated that the cryopreserved CD34+ cell dose can reliably predict the post-thaw CD34+ yield in most units. Accordingly, incorporation of the CD34+ dose into unit selection is now recommended. The CD34+ content of the current unrelated donor NMDP Be the Match® CB inventory has not been analyzed. Methods: We examined the CD34+ cell content of CB units originating from U.S. CB Banks listed in the NMDP registry. This preliminary analysis was limited to RBC-depleted units with a total TNC content of ≥90 × 10e7, a cryovolume of 24-55 mls (1 or 2 bags), & units banked between 1/2007-9/2017. TNC & CD34+ data was obtained from the existing NMDP Database. Results: 126, 341 units collected by 20 public banks fulfilled criteria. The median pre-cryopreservation TNC content was 127 × 10e7 (IQR 108-156) & CD34+ cell content was 44 × 10e5 (IQR 29-67). The median CD34+ (×10e5)/TNC (×10e7) ratio was .34% (IQR .23-0.48) & the distribution of the CD34+/TNC ratio in the analyzed units is shown (Figure 1). Table 1 shows the relationship between TNC versus CD34+ content of the CB units. This demonstrates there is not a strict correlation between CB unit TNC & CD34+ cell content. Thus, in a patient's search there could potentially be many units with a high TNC but low-intermediate CD34+ content. For example, of the CB units with TNC ≥ 210 × 10e7 (N = 7, 175 CB units, shown in bold in Table 1), only 47% have CD34+ content ≥100 × 10e5 (gray area, Table 1). However, some units have an unexpectedly high CD34+ content for a given TNC. Table 2 shows the number of units that fulfill dose criteria for a single unit graft (designated as TNC ≥ 2.5 × 10e7/kg & CD34+ cells ≥ 1.5 × 10e5/kg) by patient weight. The number of units that would be acceptable as a single unit graft for adult sized patients is small. For example, only 5, 424 units (4% of the analyzed inventory) have TNC & CD34+ dose adequate for a patient weighing 70 kg.Table 1TNC & CD34 Cell Content of the Analyzed Inventory (Data Reflects Number of Units Fulfilling Each Cell Content Level, Total N = 126,341)Table 1TNC & CD34 Cell Content of the Analyzed Inventory (Data Reflects Number of Units Fulfilling Each Cell Content Level, Total N = 126,341)Table 2Number of Units with Minimally Acceptable TNC & CD34+ Cell Dose by Patient WeightTable 2Number of Units with Minimally Acceptable TNC & CD34+ Cell Dose by Patient Weight Conclusions: These findings require detailed validation & could be limited by changes in CD34+ assays & lack of accounting for viability. Nonetheless, they have important implications. The CD34+/TNC ratio presented in this analysis could provide transplant center guidance as to the range of the expected CD34+ content relative to the reported pre-cryopreservation TNC. Also, given both TNC & CD34+ doses should now be taken into account in unit selection, centers should be aware that units with the highest TNC dose do not necessarily have the highest CD34+ dose. Conversely, units with very high CD34+ content should be questioned & verified. The fact that the inventory of CB units with adequate TNC & CD34+ doses for patients of at least 70 kg is very small supports the continued use of double unit grafts in larger patients, the need to focus on banking high dose units, & new technologies such as ex vivo expansion.