University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA.
University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA.
Cytotherapy. 2020 Nov;22(11):613-616. doi: 10.1016/j.jcyt.2020.05.006. Epub 2020 Jun 26.
Adequate cryopreservation techniques are critical to ensure optimal recovery of functional progenitor cells in hematopoietic cell (HC) transplantation, minimize risk of contamination and prevent infusion-related adverse events (irAEs). In this article, we provide graft function and infusion safety results observed by decreasing the concentration of dimethyl sulfoxide (DMSO) in cryopreservative media and by minimizing processor-dependent formulation.
Ten HC products, collected after standard mobilization of multiple myeloma patients, were cryopreserved with PRIME-XV FreezIS (FreezIS) and compared with products previously cryopreserved with media formulated in-house to achieve a final DMSO concentration of 10% (Std10) and 5% (Std5). At infusion, HCs were analyzed for recovery of CD34+ cells and viability; irAEs and time to engraftment of neutrophils and platelets were also monitored.
Median CD34+ cell recovery for HC cryopreserved with Std10, Std5 and FreezIS was 38%, 78% and 68%, respectively (P = 0.0002). There were less frequent irAEs with Std5 and FreezIS (10%) compared with Std10 (80%) (P ≤ 0.0001). Median time to neutrophil engraftment was comparable (11 days) for all three groups, while platelet engraftment occurred at a median of 20, 19 and 17 days, respectively (p-values not significant).
FreezIS, a Good Manufacturing Practice-grade, pre-constituted cryopreservative with low DMSO content, maintains functional viability of the HC product while reducing the incidence of irAEs compared with 10% DMSO solutions. The pre-constituted nature of this agent also decreases processor-dependent handling, hence decreasing the risk of variability and infection.
充分的冷冻保存技术对于确保造血细胞（HC）移植中功能性祖细胞的最佳恢复、降低污染风险和预防输注相关不良事件（irAE）至关重要。在本文中，我们通过降低冷冻保存介质中二甲基亚砜（DMSO）的浓度并尽量减少处理器依赖性配方，提供了观察到的移植物功能和输注安全性结果。
对多发性骨髓瘤患者进行标准动员后收集的 10 个 HC 产品，用 PRIME-XV FreezIS（FreezIS）进行冷冻保存，并与以前用内部配方制成的介质冷冻保存的产品进行比较，以达到最终 DMSO 浓度为 10%（Std10）和 5%（Std5）。在输注时，分析 HC 中 CD34+细胞的恢复和活力；还监测 irAE 和中性粒细胞和血小板植入的时间。
用 Std10、Std5 和 FreezIS 冷冻保存的 HC 的中位 CD34+细胞恢复率分别为 38%、78%和 68%（P=0.0002）。Std5 和 FreezIS（10%）的 irAE 发生率低于 Std10（80%）（P≤0.0001）。所有三组的中性粒细胞植入中位时间相当（11 天），而血小板植入中位时间分别为 20、19 和 17 天（p 值无显著性）。
FreezIS 是一种符合良好生产规范的预配方冷冻保存剂，DMSO 含量低，与 10%DMSO 溶液相比，可保持 HC 产品的功能活力，同时降低 irAE 的发生率。该试剂的预配方性质还降低了处理器依赖性处理的风险，从而降低了变异性和感染的风险。
