Allogeneic transplant procurement in the times of COVID-19: Quality report from the central European cryopreservation site

Abstract

Background Because of limitations of transportation imposed by the COVID-19 pandemic, current recommendation calls for cryopreservation of allogeneic stem cell transplants before patient conditioning. A single cell therapy laboratory was selected to function as the central cryopreservation hub for all European registry donor transplants intended for the Australian-Pacific region. We examined properties of these transplants to ascertain how quality is maintained. Methods We analyzed 100 pandemic-related allogeneic mobilized blood-derived stem cell apheresis products generated at 30 collection sites throughout Europe, shipped to and cryopreserved at our center between April and November of 2020. Products were shipped in the cool, subsequently frozen with DMSO as cryoprotectant. Irrespective of origin, all products were frozen within the prescribed shelf-life of 72 h. Results Prior to cryopreservation, viable stem cell and leukocyte count according to the collection site and our reference laboratory were highly concordant (r2 = 0.96 and 0.93, respectively) and viability was > 90% in all instances. Median nominal post-thaw recovery of viable CD34+ cells was 42%. Weakly associated with poorer CD34+ cell recovery was higher leukocyte concentration, but not time lag between apheresis or addition of cryopreservant, respectively, and start of freezing. The correlation between pre- and post-thaw CD34+ cell dose was high (r2 = 0.85), hence predictable. Neutrophil and platelet engraftment were prompt with no evidence of dose dependency within the range of administered cell doses (1.31–15.56 × 106 CD34+ cells/kg). Conclusions General cryopreservation of allogeneic stem cell transplants is feasible. While more than half of the CD34+ cell content is lost, the remaining stem cells ensure timely engraftment.

Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report

“…9 Wiercinska and colleagues showed that median post-thaw recovery of viable CD34+ cells was 42% compared to viability > 90% prior to cryopreservation of HSC products. 15 Although in our center cell viability and CD34 + cell content is not routinely measured after thawing of cryopreserved grafts we were able to evaluate these parameters by flow cytometry in available samples from the cryopreserved grafts and compare them to prospectively freshly collected allogeneic graft samples. Importantly, we did not observe decrease in the absolute counts of CD34 + cells and HSC and only a slight decrease in viability, which was consistent among the cryopreserved samples.…”

Cryopreserved versus fresh peripheral blood allogeneic stem cell transplantation outcomes in patients receiving post-transplant cyclophosphamide for graft-versus-host prophylaxis during the COVID-19 pandemic: a single center experience

“…Cryopreservation of hematopoietic progenitor cells (HPCs) in autologous and cord blood transplantation is a common practice. On the other hand, fresh allograft infusion is standard in allogeneic hematopoietic stem cell transplantation (allo-HSCT) [1].…”

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

“…Fadeyi et al 15 observed that TNC viabilities were lower in cryopreserved/thawed grafts than in fresh (74% vs. 99%), engraftment times were similar when equivalent CD34 doses were infused. We did not request post‐thaw CD34 + cell recoveries since they are not routinely measured, but other studies indicate that they are highly variable with medians of 42%, 16 71%, 17 76% 18 and 87% 19 . Therefore, the dose of viable CD34 + cells received by patients is likely to be lower with cryopreserved grafts and may be at least partially responsible for the delays to engraftment.…”