Wan Bo Angela, Lindo Lorenzo, Mourad Yasser Abou, Chung Shanee, Forrest Donna, Kuchenbauer Florian, Nantel Stephen, Narayanan Sujaatha, Nevill Tomas, Power Maryse, Rodrigo Judith, Sanford David, Song Kevin, Stubbins Ryan J, Sutherland Heather, Toze Cynthia L, White Jennifer, Roy Claudie, Hay Kevin A
Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Terry Fox Laboratory, BC Cancer Research Institute, Vancouver, British Columbia, Canada.
Cytotherapy. 2024 Oct;26(10):1210-1216. doi: 10.1016/j.jcyt.2024.05.009. Epub 2024 May 8.
Allogeneic hematopoietic stem cell transplant (alloHSCT) is a mainstay of treatment for hematologic malignancies such as acute leukemias and aggressive lymphomas. Historically, fresh hematopoietic progenitor cell (HPC) products have been preferred to cryopreserved products (cryo-HPC) due to concerns of loss of stem cell viability and number with the cryopreservation procedure.
We aimed to analyze the outcomes of patients who received cryo-HPCs during the COVID-19 pandemic and compare this against historical cohorts that received fresh HPC.
A retrospective chart review was conducted on all adult patients who received a peripheral blood alloHSCT in British Columbia, Canada between June 2017 and November 2021. Baseline characteristics, Kaplan-Meier (KM) overall survival (OS), engraftment, and incidences of acute and chronic graft versus host disease were compared between patients who received cryo-HPCs and fresh HPCs. Univariable analysis followed by multivariable analysis was performed using a backward stepwise selection procedure to generate predictors of OS, cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and primary and secondary graft failure.
Three hundred eighty-three patients were included in the analysis, with cryo-HPC representing 40%. Median viability was higher in the fresh-HPC group at 99.2% (IQR 98.3-99.5) versus cryo-HPCs at 97.0% (96.0, 98.6) (P < 0.01). The 12-month actuarial survivals were 77% in the fresh HPC and 75% in the cryo-HPC groups (P = 0.21). There were no differences between cryo-HPCs and fresh HPCs on univariable analysis of OS, CIR, or NRM. There was a shorter median time to platelet engraftment in patients receiving fresh HPC at 17 days (IQR 16, 20) versus cryo-HPC at 21 days (IQR 18, 29), P < 0.001. There was a shorter median time to neutrophil engraftment in the fresh HPC group at 17 days (IQR 14, 20) versus 20 days (17, 23), P < 0.001. Cryo-HPC accounted for 5 out of 6 cases of primary graft failure (P = 0.04), and 3 out of five cases of secondary graft failure (P = 0.39). There were no significant differences in acute GVHD between the fresh HPC and cryo-HPC groups (P = 0.34). The incidence of moderate or severe chronic GVHD was 32% in the fresh-HPC group and 17% in the cryo-HPC group (P < 0.001). In multivariable analysis, cryopreservation did not emerge as an independent predictor of OS, CIR, NRM, primary GF or secondary GF. However, viability <90% on arrival at our center was a significant predictor of OS (HR 5.3, 2.3-12.3, P < 0.01), primary graft failure (OR 36.3, 5.4-210.2, P < 0.01), and secondary graft failure (OR 18.4, 1.7-121.1, P < 0.01).
Patients who received cryo-HPCs had similar OS and relapse rates to those who received fresh-HPCs but typically took 2-3 days longer to achieve engraftment of platelets or neutrophils and were associated increased primary graft failure. However, after accounting for multiple variables, cryopreservation was no longer a significant predictor of survival or engraftment while viability <90% emerged as an important predictor of OS, primary graft failure, and secondary graft failure. If confirmed, this suggests that viability on arrival at the infusion center may be a good quality control indicator used to identify HPC products that may warrant recollection if the risk of graft failure is sufficiently increased.
异基因造血干细胞移植（alloHSCT）是治疗急性白血病和侵袭性淋巴瘤等血液系统恶性肿瘤的主要手段。从历史上看，由于担心冷冻保存过程中干细胞活力和数量的损失，新鲜造血祖细胞（HPC）产品比冷冻保存的产品（cryo - HPC）更受青睐。
我们旨在分析在COVID - 19大流行期间接受cryo - HPC的患者的结局，并将其与接受新鲜HPC的历史队列进行比较。
对2017年6月至2021年11月在加拿大不列颠哥伦比亚省接受外周血alloHSCT的所有成年患者进行回顾性图表审查。比较接受cryo - HPC和新鲜HPC的患者的基线特征、Kaplan - Meier（KM）总生存期（OS）、植入情况以及急性和慢性移植物抗宿主病的发生率。使用向后逐步选择程序进行单变量分析，然后进行多变量分析，以生成OS、复发累积发生率（CIR）、非复发死亡率（NRM）以及原发性和继发性移植物失败的预测因子。
383例患者纳入分析，其中cryo - HPC占40%。新鲜HPC组的中位活力较高，为99.2%（IQR 98.3 - 99.5），而cryo - HPC为97.0%（96.0，98.6）（P < 0.01）。新鲜HPC组和cryo - HPC组的12个月精算生存率分别为77%和75%（P = 0.21）。在OS、CIR或NRM的单变量分析中，cryo - HPC和新鲜HPC之间没有差异。接受新鲜HPC的患者血小板植入的中位时间较短，为17天（IQR 16，20），而cryo - HPC为21天（IQR 18，29），P < 0.001。新鲜HPC组中性粒细胞植入中位时间较短，为17天（IQR 14，20），而cryo - HPC组为20天（17，23），P < 0.001。6例原发性移植物失败中有5例为cryo - HPC（P = 0.04），5例继发性移植物失败中有3例为cryo - HPC（P = 0.39）。新鲜HPC组和cryo - HPC组之间急性移植物抗宿主病无显著差异（P = 0.34）。新鲜HPC组中度或重度慢性移植物抗宿主病的发生率为32%，cryo - HPC组为17%（P < 0.001）。在多变量分析中，冷冻保存未成为OS、CIR、NRM、原发性移植物失败或继发性移植物失败的独立预测因子。然而，到达我们中心时活力<90%是OS（HR 5.3，2.3 - 12.3，P < 0.01）、原发性移植物失败（OR 36.3，5.4 - 210.2，P < 0.01）和继发性移植物失败（OR 18.4，1.7 - 121.1，P < 0.01）的显著预测因子。
接受cryo - HPC的患者与接受新鲜HPC的患者的OS和复发率相似，但血小板或中性粒细胞植入通常要多花2 - 3天时间，且原发性移植物失败发生率增加。然而，在考虑多个变量后，冷冻保存不再是生存或植入的显著预测因子，而活力<9'0%成为OS、原发性移植物失败和继发性移植物失败的重要预测因子。如果得到证实，这表明到达输注中心时的活力可能是一个良好的质量控制指标，用于识别如果移植物失败风险充分增加可能需要重新采集的HPC产品。
