Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Transplant Cell Ther. 2023 Feb;29(2):129.e1-129.e9. doi: 10.1016/j.jtct.2022.11.007. Epub 2022 Nov 15.
Greater use of umbilical cord blood (UCB) for hematopoietic cell transplantation (HCT) is limited by the number of cells in banked units. Ex vivo culture strategies have been increasingly evaluated in controlled studies, but their impact on transplantation-related outcomes remains uncertain owing to the small patient numbers in these studies, necessitating an updated systematic review and meta-analysis. A systematic literature search was conducted using the MEDLINE, Embase, and Cochrane databases to March 18, 2022. Nine cohort-controlled phase I to III trials were identified, and data of 1146 patients undergoing umbilical cord blood transplantation (UCBT) were analyzed (308 ex vivo expanded and 838 unmanipulated controls). Expansion strategies involved cytokine cocktails plus the addition of small molecules (UM171, nicotinamide [NiCord], copper chelation, Notch ligand, or Stem regenin-1 [SR-1]) and coculture with mesenchymal stromal cells in a single-unit transplant strategy (5 studies) or a double-unit transplant strategy with 1 unmanipulated unit (4 studies). The included trials reported a median ex vivo expansion of CD34 cells from 28-fold to 330-fold. Eight of the 9 studies demonstrated a significantly faster time to initial neutrophil and platelet engraftment using expanded cells compared with controls. Studies using UM171 and NiCord in single-unit UCBT and SR-1 or NiCord double-unit UCBT demonstrated long-term donor chimerism of the expanded unit at 100 days to 36 months post-transplantation in all single-unit recipients and in 35% to 78% of double-unit recipients. Our meta-analysis revealed a lower risk of death at the study endpoint in patients who received ex vivo expanded grafts (odds ratio [OR], .66; 95% confidence interval [CI], .47 to .95; P = .02), while the risk of grade II-IV acute graft-versus-host disease was unchanged (OR, .79; 95% CI, .58 to 1.08; P = .14). This review indicates that UCBT following ex vivo expansion can accelerate initial engraftment. Durable donor chimerism can be achieved after transplanting cord blood units expanded using NiCord, UM171, or SR-1; however, long term outcomes remain unclear. Larger studies with longer-term outcomes are needed to better understand the merits of specific expansion strategies on survival.
为了进行造血细胞移植（HCT），更多地使用脐带血（UCB）受到存储单位中细胞数量的限制。在对照研究中，越来越多地评估了体外培养策略，但由于这些研究中的患者数量较少，它们对移植相关结果的影响仍不确定，因此需要进行更新的系统评价和荟萃分析。使用 MEDLINE、Embase 和 Cochrane 数据库进行了系统的文献检索，检索时间截至 2022 年 3 月 18 日。确定了 9 项 I 期至 III 期队列对照试验，并对 1146 例接受脐带血移植（UCBT）的患者的数据进行了分析（308 例经体外扩增，838 例未经处理的对照）。扩增策略包括细胞因子鸡尾酒加小分子的添加（UM171、烟酰胺[NiCord]、铜螯合、Notch 配体或 Stem regenin-1[SR-1]）以及与间充质基质细胞共培养在单个单位移植策略（5 项研究）或使用 1 个未经处理的单位的双单位移植策略（4 项研究）。纳入的试验报告称，CD34 细胞的中位数从 28 倍扩增至 330 倍。9 项研究中的 8 项表明，与对照相比，使用扩增细胞可显著加快初始中性粒细胞和血小板植入的时间。在使用 UM171 和 NiCord 的单个单位 UCBT 以及使用 SR-1 或 NiCord 的双单位 UCBT 中，在移植后 100 天至 36 个月，所有单个单位受者和 35%至 78%的双单位受者中均检测到扩增单位的长期供体嵌合体。我们的荟萃分析显示，接受体外扩增移植物的患者在研究终点的死亡风险较低（优势比[OR]，0.66；95%置信区间[CI]，0.47 至 0.95；P=0.02），而 2 级至 4 级急性移植物抗宿主病的风险保持不变（OR，0.79；95%CI，0.58 至 1.08；P=0.14）。该综述表明，UCBT 后进行体外扩增可以加快初始植入。使用 NiCord、UM171 或 SR-1 扩增的脐带血细胞移植后可实现持久的供体嵌合体；然而，长期结果尚不清楚。需要进行更大规模的长期结局研究，以更好地了解特定扩增策略对生存的影响。
