Evaluation of Cord Blood (CB) Unit TNC & CD34+ Cell Content & Donor-Recipient High-Resolution 8 HLA-Allele Match By Patient Ancestry: An Evaluation of 513 CB Units in a Racially & Ethnically Diverse Population of Adults with Hematologic Malignancies
Authors: Mazis Christopher , Politikos Ioannis , Devlin Sean M , Maloy Molly , Davis Eric , Cooper Candice , Nhaissi Melissa , Suri Beth , Wells Deborah , Giralt Sergio , Shah Gunjan L. , van den Brink Marcel R.M. , Kernan Nancy A. , Scaradavou Andromachi , Barker Juliet 
Published: October 2019

Abstract
Introduction: Optimal CB unit selection guidelines recommend consideration of CD34+ cell dose & 8-allele donor-recipient HLA-match. How graft characteristics for these parameters vary by patient (pt) race/ ethnicity, however, is not known.
Methods: We analyzed the infused graft & back-up unit cryopreserved total nucleated cell (TNC) x 107 & CD34+ x 105 cell content, the cell dose (incorporating pt weight), & 4-6/6 & 8-allele HLA-match by pt ancestry in CB transplant (CBT) recipients transplanted 1/2014-6/2018. Units were chosen based on banking practices (e.g. RBC depleted, standard cryo volumes), TNC & CD34+ dose & 4-6/6 & 8-allele HLA-match with dose usually taking priority over match given pt size at our center. The analysis included transplanted units (considered the best choice) & the next best high resolution typed back-up units (reserved but not shipped). Pt racial/ ethnic origins were prospectively obtained by detailed family history & grouped as previously described (Barker J. et al. BBMT 2010).
Results: The characteristics of 513 units chosen for 136 CBT recipients by pt ancestry are shown (Table 1). Pts had highly diverse origins including 70 (51%) non-Europeans. The 513 units included 270 units infused as the graft (134 doubles & 2 singles) & 243 back-up units (109 pts had 2 back-ups, 25 pts had one & 2 had none). Thus, 4 best units were analyzed in 109 pts (all double unit recipients), 3 best in 25 pts (all doubles), & 1 unit in 2 pts (both singles). The median weight of the 136 pts was 81 kg. Asian pts (median 68 kg) had a lower weight than other groups. The median TNC content of units for the 66 European pts was higher than that for the 70 Non-Europeans (218 vs 196, p = 0.004). Units chosen for Northwestern (NW) Europeans had the highest median TNC content (235) with lower TNC content in units for Southern Europeans (202), Asian (193), African (191) & White Hispanic (189) pts. Units chosen for European pts also had a higher median CD34+ cell content (162) than Non-Europeans (138), p = 0.004. NW Europeans had units with a higher median CD34+ content (198) & the lowest CD34+ content were those for African (124) & Middle Eastern pts (124). When patient weight was considered, median TNC/kg dose per unit was similar in European and Non-European pts (2.7 vs 2.6, p = NS). Units for NW Europeans had the highest median TNC dose (3.0) whereas those for African pts had the lowest TNC dose (2.4). Units for Europeans had a higher median CD34+ dose (2.0) than Non-Europeans (1.7) although this difference was not significant (p = 0.15). Additionally, similar to TNC dose, median CD34+ dose was highest in units for NW European pts (2.2) & lowest in units chosen for African pts (1.5). 89% of chosen units were 4/6 HLA-matched with no differences between Europeans & non-Europeans. Furthermore, the median 8 allele HLA-match was 5/8 (range 2-8/8) with no overall differences between units for Europeans and Non-Europeans (p = NS).
When only transplanted units were analyzed (Table 2), the median TNC & CD34+ contents were significantly lower in non-Europeans than Europeans (238 vs 216, p = 0.01 & 184 vs 160, p = 0.016). Overall, however, units received by Europeans vs non-European pts had similar TNC & CD34+ doses (p = NS). However, differences in the CD34+ content combined with differences in pt weights resulted in disparities in CD34+ doses by ancestry sub-group. NW Europeans (high weight, high CD34+ content) received the best CD34+ doses; lower CD34+ content in Asian pts was compensated for by their lower weight. African pts (high weight, low CD34+ content) received the lowest CD34+ doses. The median 8 allele HLA-match for all was 5/8 (range 3-8/8) with the exception of African pts [median 4/8 (range 3-7/8)]. Moreover, while 108 (40%) of transplanted units were 3-4/8 HLA-matched overall, there were marked differences between pt sub-groups with only 23% of units for NW Europeans being 3-4/8 vs 42% for southern Europeans, 46% for white Hispanics & 53% for Africans.
Conclusions: While CB significantly extends transplant access to racial & ethnic minorities, differences in cellular content translates to many minority pts receiving lower dosed units. There are also marked racial/ ethnic differences in HLA-match grade with African pts the most likely to receive highly mismatched units. This data supports ongoing funding of public CB banks to further increase the inventory of high dosed & better matched units for all but especially racial & ethnic minority pts.

Disclosures
Shah: Janssen: Research Funding; Amgen: Research Funding. Kernan:National Cancer Institute: Research Funding.