Targeting Cord Blood Units with Higher Total Nucleated Cell Count for Inclusion in a Public Cord Blood Bank: Impact on Inventory Diversity and Self-Sustainability (2016)

Public cord blood banks (CBB) aim to procure quality, racially diverse, cord blood units (CBU) for hematopoietic stem cell transplantation (HSCT). Selection for HSCT is based on the cryopreserved total nucleated cells (TNCC). The National Cord Blood Inventory (NCBI) subsidizes CBUs with a post processing (post) TNCC ≥0.9x109 and has an inventory of >80,000 CBUs with a median post TNCC 1.2x109. However, the median post TNCC of CBUs selected for HSCT is 1.75x109. As such, some have proposed to limit banking to larger CBUs. Raising the TNCC threshold would affect the cost per CBU banked and inventory diversity. We examined the experience of the Carolinas CBB (CCBB) to model interactions between volume, TNCC and inventory diversity. We also modeled the financial impact on CBB self-sustainability. The CCBB has operated since 1998, using varying volume (range 40-80mL) and preprocessing (pre-) TNCC thresholds (range ≥0.6-1x109) over time. Currently CBUs with a pre-TNCC ≥1x109 are processed. CBUs with a post TNCC ≥0.9x109 are cryopreserved. We created a database of all collected, counted, processed and cryopreserved CBUs from 1998-2015. The expected discard rate at various pre-TNCC thresholds was compared by fitting curves to volume and race-specific TNCC distributions using the gamma family of probability distributions. We then modeled the impact of increasing the pre-TNCC threshold on manufacturing costs. The CCBB collected 106,957 CBUs in the study time; 51,539 (48%) CBUs met volume specifications and were sent for pre-TNCC measurement. CBUs meeting TNCC specifications were processed and cryopreserved. While up to 25% of CBUs were later excluded for other reasons (e.g. donor eligibility, viability, sterility, etc), we utilized this data to define TNCC and volume interactions. At all volumes, fewer Black/African American (AFA) CBUs achieved the target TNCC as compared to other races (Table 1). Targeting the pre-TNCC, 40% of collected CBUs would have ≥1x109 cells. Factoring in donor race, 43% of Caucasian (CAU) but only 33% of AFA CBUs meet the ≥1x109 target. Raising the TNCC threshold to ≥1.75x109, only 18% and 11% of CAU and AFA collections, respectively, would be processed. We modeled the financial impact of higher pre- and post TNCC thresholds (pre-TNCC ≥1.75x109 to yield a post TNCC ≥1.5x109). With stable collections, 62% fewer CBUs would be banked. Operating costs would decline by 18%, but the cost per banked CBU would increase by 115%. To maintain banking diversity targets with the TNCC ≥1.75x109, yearly collections would need to expand from 6300 to >21000 including 7000 from non-CAU donors. Operating and per banked CBU costs would both raise 24%. Increasing TNCC banking thresholds results in fewer CBUs banked with a less racially diverse inventory. Increasing collections from minority donors can overcome this barrier but only if public CBBs funding is expanded for these added collections.Table 1Predicted probability of a CBU meeting volume specifications achieving a pre - TNCC target*Pre - TNCC Threshold (x109)RaceCollection Volume (mL)>40 – 60>60 - 80>80 - 100>100 - 125>125 - 150>150N%N%N%N%N%N%1.00All3,56531.712,00968 015.80388 112.50795 55,03198 62.60599 5CAU2,0843435,59274 29.3758927,42196.03,03498 81,59899 6AFA73321 32.56454.12.31281.31,91092 574797.137798.71 75All3,5651.312.0095 715.80321.512.50746 35,03169 72,60587 0CAU2,0841.45,592649 37522.77,42148.43,03472 01,59888.4AFA7330 72.5643.62,31214.01,91037.174761.337782 8CBU - cord blood unit; TNCC – total nucleated cell count; CAU – Caucasian; AFA – Black/African American.*Predictions are based on curves fit to race and volume-specific distributions of TNCC using the gamma family of probability distributions.ˆFischer exact test.At a threshold of 1×109, the odds of a CBU achieving the target pre - TNCC are 2.16 times higher for Caucasians than African Americans after controlling for the collection volume (OR=2.16, 95% CI: 2.02-2.31), P < 0.0001.At a threshold of 1.75×109, the odds of a CBU achieving the target pre-TNCC are 1.68 times higher for Caucasians than African Americans after controlling for the collection volume (OR=1 68, 95% CI: 1.57 - 1.80), P< 0.0001. Open table in a new tab CBU - cord blood unit; TNCC – total nucleated cell count; CAU – Caucasian; AFA – Black/African American. *Predictions are based on curves fit to race and volume-specific distributions of TNCC using the gamma family of probability distributions. ˆFischer exact test. At a threshold of 1×109, the odds of a CBU achieving the target pre - TNCC are 2.16 times higher for Caucasians than African Americans after controlling for the collection volume (OR=2.16, 95% CI: 2.02-2.31), P < 0.0001. At a threshold of 1.75×109, the odds of a CBU achieving the target pre-TNCC are 1.68 times higher for Caucasians than African Americans after controlling for the collection volume (OR=1 68, 95% CI: 1.57 - 1.80), P< 0.0001.