Impact of cryopreservation and transit times of allogeneic grafts on hematopoietic and immune reconstitution

Abstract

We sought to evaluate the impact of cryopreservation of unrelated donor peripheral blood stem cell (PBSC) grafts on engraftment, chimerism, and immune reconstitution in the context of the Covid-19 pandemic. We reviewed stem cell product characteristics and clinical outcomes in 101 patients receiving cryopreserved PBSCs from unrelated donors (URD) between January 1, 2019, and December 31, 2020, compared with 203 patients receiving fresh URD PBSCs. We observed no differences in 6-month overall survival, progression free survival, or non-relapse mortality. Patients receiving cryopreserved PBSCs had delayed platelet engraftment and impaired reconstitution of white blood cells and T cell subsets at Day 30. Thirty-four percent of patients receiving cryopreserved grafts had CD3 chimerism <50% at Day 30 after transplantation, compared with 14% of patients receiving fresh PBSCs (p=0.0002). At day 100, this difference persisted (CD3+ chimerism <50%: 17% of cryopreserved cohort vs 6% of fresh cohort, p=0.016). Additionally, greater product age at infusion is associated with an increase in graft failure, independent of cryopreservation. Receipt of grafts >48 hours old at time of cryopreservation or infusion significantly increased the risk of graft failure (sHR =4.57 (95% CI 1.71-12.3), p=0.0025). Our data indicate that cryopreservation is associated with similar overall short-term clinical outcomes compared to fresh PBSC. However, patients must be monitored closely for increased risk of other potentially adverse outcomes including graft failure and poor immune recovery, particularly for grafts with older overall age at infusion. Longer term follow-up is needed to determine impact on relapse and survival.

Assessing deviations for HPCs obtained during COVID‐19 (ADHOC): Evaluating impact of the COVID‐19 pandemic on cellular therapy products and processes, the BEST collaborative study

“…Logistic challenges were one of the drivers in the consideration to cryopreserve donations, due to the uncertain timings of deliveries dependent on airplanes and trains subject to delays or cancellations. Reassuringly, we did not see significant differences in the average times from collection to delivery, although others have reported increased times for international transfers 12 . There was not an evident shift to local collections over the relatively brief window of the survey period, and the WMDA report for 2020 noted only a small decrease in the proportion of donations not crossing national borders 20 .…”

Neither COVID-19, nor cryopreservation, prevented allogeneic product infusion: A report from the National Marrow Donor Program

“…Recent papers have emphasized the importance of transit time. In a recent study at Dana Farber Cancer Institute, researchers looked at outcomes of 101 recipients who received cryopreserved grafts and found that grafts >48 h old at the time of cryopreservation or infusion significantly increased risk of graft failure (hazard ratio = 4.57; 95% confidence interval, 1.71–12.3; p = .0025) ( 8 ). However, the travel restrictions may occasionally result in products delivery exceeding the 72-h limit.…”

Impact of Cryopreservation and Freeze-Thawing on Therapeutic Properties of Mesenchymal Stromal/Stem Cells and Other Common Cellular Therapeutics

“…Although HSPC grafts can be used fresh, modern routines often rely on cryobanking of BM, CB and PB grafts [ 50 – 54 ]. Particularly, CB and PB grafts are often stored cryobanked until clinical use [ 51 , 55 – 57 ]. Experience during the COVID-19 pandemic suggests that even in the well-established HSCT setting, cryopreservation and increased transit times can detrimentally affect immune reconstitution [ 57 , 58 ].…”