Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Statagize LLC, Thousand Oaks, California.
Transplant Cell Ther. 2022 Apr;28(4):215.e1-215.e10. doi: 10.1016/j.jtct.2022.01.010. Epub 2022 Jan 15.
In response to the widespread COVID-19 pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear. In this study, we compared outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 and 60 consecutive patients who received fresh allografts before the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment and graft failure (GF), and secondary outcomes were overall survival (OS), relapse-free survival (RFS) and nonrelapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved and prospectively collected fresh apheresis samples. Compared with recipients of fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced-intensity conditioning (RIC) allo-HCT, with a median time to engraftment of 24 days versus 18 days (P = .01) for neutrophils and 27 days versus 18 days (P = .069) for platelets. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) versus only 1 of 60 patients (1.7 %) in the fresh cohort (P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid, and T cell donor chimerism at 1 month. OS and RFS were inferior for cryopreserved graft recipients (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.00 to 4.67) and HR, 1.90; 95% CI, 0.95 to 3.79, respectively. Using an extended immunophenotype analysis, we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both a decrease in total cell viability and a significantly reduced absolute number of natural killer cells (CD3CD56) in the cryopreserved apheresis samples. In this single-institution study, we found delayed engraftment and a trend toward clinical inferiority of cryopreserved allografts compared with fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.
针对广泛存在的 COVID-19 大流行,我们实施了同种异体供体外周血造血干细胞产品的低温保存,以减轻供体可用性和产品运输方面的挑战。虽然在物流方面具有优势,但低温保存对临床结果和移植物组成的影响尚不清楚。在这项研究中,我们比较了同种异体造血细胞移植(allo-HCT)中冷冻保存的同种异体移植物与新鲜同种异体移植物的结果和移植物组成。我们回顾性分析了 2020 年 3 月至 8 月期间接受冷冻保存同种异体移植物的 30 例连续患者和在 COVID-19 大流行之前接受新鲜同种异体移植物的 60 例连续患者的临床结果。主要终点是造血植入和移植物失败(GF),次要终点是总生存率(OS)、无复发生存率(RFS)和非复发死亡率(NRM)。此外,我们对冷冻保存和前瞻性采集的新鲜外周血样本进行了扩展免疫表型分析。与接受新鲜同种异体移植物的患者相比,接受冷冻保存的减低强度预处理(RIC)allo-HCT 的患者中性粒细胞和血小板恢复延迟,中性粒细胞植入的中位时间为 24 天,而 18 天(P=0.01),血小板为 27 天,而 18 天(P=0.69)。我们观察到冷冻保存组中有 4 例(13.3%)患者发生原发性 GF,而新鲜组中仅有 1 例(1.7%)患者(P=0.03)。冷冻保存的 RIC allo-HCT 在 1 个月时总、髓系和 T 细胞供者嵌合率明显降低。冷冻保存移植物受者的 OS 和 RFS 较差(风险比[HR],2.16;95%置信区间[CI],1.00 至 4.67)和 HR,1.90;95%CI,0.95 至 3.79)。通过扩展免疫表型分析,我们比较了冷冻保存组的 14 个样本与 6 个前瞻性采集的新鲜外周血供体样本。这些分析表明,冷冻保存的外周血样本中总细胞活力降低,且自然杀伤细胞(CD3CD56)的绝对数量显著减少。在这项单中心研究中,我们发现与新鲜同种异体移植物相比,冷冻保存同种异体移植物的植入延迟,且临床结果有下降趋势。进一步评估冷冻保存同种异体移植物的使用及其对临床和实验室结果的影响是必要的。