ExCellThera, Inc., Montreal, Quebec, Canada; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec, Canada.
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec, Canada.
Transplant Cell Ther. 2022 Jul;28(7):410.e1-410.e5. doi: 10.1016/j.jtct.2022.03.016. Epub 2022 Mar 18.
Cord blood (CB) stem cell transplantation offers a greater tolerance to HLA mismatches compared to adult-derived stem cell transplants (i.e., bone marrow or peripheral blood stem cells). Indeed, 4/6 or 5/8 HLA-matched CB transplantations are regularly performed for patients lacking a matched unrelated donor. Unfortunately, most banked CB units contain a stem cell dose that is too small to treat adult patients, resulting in only 4% to 5% of available CB units offering an adequate cell dose for prompt engraftment for adult patients. Ex vivo stem cell expansion appears to be an attractive strategy to circumvent this cell dose issue, while also enabling the selection of better HLA-matched CB units. In this study, we retrospectively performed HLA matching simulations to assess how the minimal cell content requirements associated with UM171 CB expansion may improve usability of existing CB unit inventories and donor availability for patients of different races and ethnicities. We analyzed a dataset of 58,971 adults for whom a donor search was initiated through the National Marrow Donor Program Be The Match registry against 142,942 CB units from major U.S. public CB banks listed on the Be The Match registry. Our results show that by enabling selection of smaller CB units, UM171-expanded CB transplantation increases donor availability from 72% to 84% for all patients compared to single unmanipulated CB transplantation. Furthermore, the low cell dose criteria for UM171-expanded CB also increases donor availability compared to double CB transplantation, while enabling better HLA matching between donor and recipient. UM171 expanded CB appears particularly beneficial for racial and ethnic minority patients as CB availability increases from 53% to 78% for African Americans, from 66% to 85% for Hispanics, and from 68% to 84% for Asians and Pacific Islanders, compared to single unmanipulated CB transplantation. In addition, UM171 expansion dramatically improves usability of CB units currently in inventories, as only 4.3% and 0.6% of banked CBs have sufficient cell doses for a 70 kg and 100 kg patient, respectively. UM171 raises this proportion to 53.8% and 20.2%, respectively, making CB banks potentially more cost effective. In conclusion, UM171 expansion allows the use of smaller CB units while also improving access to transplantation for racial and ethnic minorities.
脐带血(CB)干细胞移植与成人来源的干细胞移植(即骨髓或外周血干细胞)相比,对 HLA 不匹配具有更高的耐受性。实际上,对于缺乏匹配的无关供体的患者,经常进行 4/6 或 5/8 HLA 匹配的 CB 移植。不幸的是,大多数库存的 CB 单位包含的干细胞剂量太小,无法治疗成年患者,导致只有 4%到 5%的可用 CB 单位为成年患者提供足够的细胞剂量以进行快速植入。体外干细胞扩增似乎是一种有吸引力的策略,可以解决这个细胞剂量问题,同时还可以选择更好的 HLA 匹配的 CB 单位。在这项研究中,我们回顾性地进行了 HLA 匹配模拟,以评估与 UM171 CB 扩增相关的最小细胞含量要求如何提高现有 CB 单位库存和不同种族和族裔患者供体可用性的使用。我们分析了通过美国骨髓捐赠计划 Be The Match 注册表为 58971 名成年人发起供体搜索的数据,这些成年人与列出在 Be The Match 注册表上的 142942 个来自美国主要公共 CB 银行的 CB 单位进行了 HLA 匹配。我们的结果表明,通过允许选择较小的 CB 单位,与单未处理的 CB 移植相比,UM171 扩增的 CB 移植将供体可用性从 72%提高到所有患者的 84%。此外,UM171 扩增的 CB 较低的细胞剂量标准也提高了与双 CB 移植相比的供体可用性,同时在供体和受体之间实现更好的 HLA 匹配。UM171 扩增的 CB 对非裔美国人、西班牙裔、亚洲人和太平洋岛民等少数族裔患者尤其有益,与单未处理的 CB 移植相比,CB 的可用性从 53%增加到 78%,从 66%增加到 85%,从 68%增加到 84%。此外,UM171 扩展极大地提高了库存中当前 CB 单位的可用性,因为只有 4.3%和 0.6%的库存 CB 具有足够的细胞剂量分别用于 70 公斤和 100 公斤的患者。UM171 将这一比例分别提高到 53.8%和 20.2%,使 CB 银行更具成本效益。总之,UM171 扩增允许使用较小的 CB 单位,同时也改善了少数族裔患者获得移植的机会。