Anthony Nolan Cell Therapy Centre, Nottingham, UK.
Anthony Nolan Cell Therapy Centre, Nottingham, UK.
Cytotherapy. 2022 Oct;24(10):1060-1066. doi: 10.1016/j.jcyt.2022.03.012. Epub 2022 May 31.
In this study, the authors sought to assess whether cord blood units (CBUs) collected from donors of non-European ethnic backgrounds are utilized for umbilical cord blood transplantation (UCBT) at a different rate than those of European ethnic backgrounds. The authors also examined potential methods of enriching these under-represented ethnic backgrounds in cord blood bank (CBB) inventories without increasing financial overheads and without compromising total inventory utilization or post-transplant outcomes.
Data from N = 6506 searchable or shipped Anthony Nolan Cell Therapy Centre grafts were used in this study. Banked grafts were graded from A+ to D based on total nucleated cell and CD34+ cell content. Utilizations of each grade group were further stratified by graft ethnic background. The Mantel-Cox log-rank test was performed in conjunction with Kaplan-Meier survival analysis to compare utilization rates and post-transplant outcomes. For shipped grafts, levels of HLA matching at HLA-A, HLA-B and HLA-DR loci were also analyzed by graft ethnic background and grade using data from the Eurocord/EBMT registry.
Overall utilization of non-European grafts did not significantly differ from that of European grafts (2.5% versus 2.2%, P = 0.23). However, significant differences were found when stratifying utilization rates by cell content. The probability of non-European D grade grafts being utilized was 3-fold higher than that of European D grade grafts (1.1% versus 0.4%, P = 0.03) and comparable to that of European C grade grafts (1.1% versus 0.9%, P = 0.90). No significant differences were found between D and C grade grafts in terms of overall survival (OS) (P = 0.12), in part due to a disproportionate utilization of D grade grafts for pediatric UCBT (74% versus 39%, age difference P < 0.001). Furthermore, non-European graft shipments were 4-fold less likely to be a 6/6 HLA match to their recipients relative to European graft shipments (7% versus 29%).
The authors have identified a niche for CBUs of low cell content collected from donors of non-European ethnic backgrounds that has been overlooked by previous studies. Banking of these CBUs for pediatric UCBT instead of CBUs from European donors containing modestly higher cell content is an ethical approach to increasing the ethnic diversity of CBB inventory-and, consequently, the probability of non-European recipients finding a 6/6 HLA-matched graft-without compromising post-transplant OS or overall rate of inventory utilization.
本研究旨在评估非欧洲裔供者来源的脐血单位（CBU）在用于脐带血移植（UCBT）时的利用率是否与欧洲裔供者来源的 CBU 不同。作者还研究了在不增加财务负担、不影响总库存利用率或移植后结果的情况下，增加 CBB 库存中代表性不足的少数民族群体的潜在方法。
本研究使用了 N=6506 例可搜索或已发货的 Anthony Nolan 细胞治疗中心移植物的数据。根据总核细胞和 CD34+细胞含量，将储存的移植物从 A+分级到 D 级。根据移植物的种族背景，进一步对每个分级组的利用率进行分层。使用 Eurocord/EBMT 注册处的数据，通过移植的种族背景和分级，对 HLA-A、HLA-B 和 HLA-DR 基因座的 HLA 匹配水平进行了 Mantel-Cox 对数秩检验和 Kaplan-Meier 生存分析。对于已发货的移植物，还根据 Eurocord/EBMT 注册处的数据，按移植物的种族背景和分级，分析了 HLA-A、HLA-B 和 HLA-DR 基因座的 HLA 匹配水平。
非欧洲裔移植物的总体利用率与欧洲裔移植物无显著差异（分别为 2.5%和 2.2%，P=0.23）。然而，当按细胞含量对利用率进行分层时，发现了显著差异。非欧洲裔 D 级移植物的利用率是欧洲裔 D 级移植物的 3 倍（分别为 1.1%和 0.4%，P=0.03），与欧洲裔 C 级移植物的利用率相当（分别为 1.1%和 0.9%，P=0.90）。在总体生存（OS）方面，D 级和 C 级移植物之间无显著差异（P=0.12），部分原因是儿科 UCBT 中更多地使用了 D 级移植物（分别为 74%和 39%，年龄差异 P<0.001）。此外，与欧洲裔移植物发货相比，非欧洲裔移植物发货的 6/6 HLA 匹配率低 4 倍（分别为 7%和 29%）。
作者发现了一个以前的研究中被忽视的来自非欧洲裔供者的低细胞含量 CBU 的利基市场。为儿科 UCBT 储存这些 CBU，而不是储存来自欧洲供者的细胞含量略高的 CBU，是一种增加 CBB 库存种族多样性的伦理方法，从而增加非欧洲裔受者找到 6/6 HLA 匹配移植物的概率，而不会影响移植后 OS 或总体库存利用率。
