Hot Topic: Cryopreservation of HPCs During a Pandemic

October 19, 2021

During the 2021 Annual Meeting Hot Topic session “Cryopreservation of HPCs During a Pandemic,” attendees received an update on current trends in using cryopreservation to support hematopoietic cell transplant (HCT) during the pandemic. A donor registry’s experience in providing centralized cryopreservation services was detailed and a brief review given of recent studies on the use of cryopreserved allogeneic grafts.

Jeff Wren, from the National Marrow Donor Program (NMDP)/Be The Match, explained that when the pandemic hit, it provided a lot of uncertainty for the industry. There was no confidence that products traveling from the collection site to the transplant center would make it. They were unsure if there would be a decline in the number of transplants taking place, and they wondered which patients would proceed with transplants and which would hold off until the pandemic got more stable.

“In conjunction with considerations from our international peers and stakeholders in the industry, we decided to do an unprecedented move and put out a cryopreservation mandate,” Wren explained. Going forward, all products they provided for transplants from their donors needed to be cryopreserved before a patient was admitted for transplant. This was a safety decision for the patients meant to address the uncertainty about their ability to get a product to where it needed to be.

The mandate lasted between March-August 2020 with limited exceptions due to uncertainties around donor travel and access to apheresis or collection centers; product delivery, which relied on commercial airlines; and which patients would proceed with transplant. Before the pandemic, 5-10% of the products they provided were cryopreserved before transplant. It was largely considered a last resort. During the mandate, they saw most of their products cryopreserved before transplant. Currently they are still seeing 67% of their adult donor products cryopreserved before transplant.

Wren noted that peripheral blood stem cell products (PBSCs) – the most common product they provide – are more highly cryopreserved because most transplant centers are accustomed to freezing PBSCs, plus these products have more than enough cells to support cell loss. They saw a quick increase in cryopreservation marrow in the first quarter of the pandemic, but it has since declined, likely because cryopreserving marrow is not only a less-common practice, it’s also a trickier product to freeze because there is less tolerance for cell loss.

The Be The Match BioBank Cryopreservation service is a new model for providing cryopreserved products to transplant centers. Traditionally Be The Match provided fresh products to the transplant center, where it was frozen and held until the patient was ready for transplant. With this new model, Be The Match actually keeps the product within the registry. The donor donates, the product is delivered to one of two cryopreservation labs, the lab holds onto the product and, when the patient is ready, the product ships. It gives donors more flexibility, therefore increasing their availability. It also ensures the availability of high-quality products before patient admission. The service has cryopreserved over 150 donor products to date.

David H. McKenna, MD, from the University of Minnesota, focused on a single-center experience providing cryopreservation services. His cell therapy lab, a molecular and cellular therapeutics facility, is a cryopreservation hub supporting a variety of activities. In 2020 the lab supported 185 hematopoietic progenitor cell transplants. This was down a bit from previous years, due in part to the pandemic. They support, at any given time, roughly 20 in-house Investigational New Drugs for a variety of cell types and support roughly 30 external trials.

Their process is to reserve a request for cryopreservation through Be The Match. From that point, much communication, document preparation and donor eligibility gauging ensues. They receive the product, which is shipped at 2-8 degrees C, and they process it within 72 hours of collection (usually between 24-36 hours).

To date they have primarily focused on peripheral blood. They do a volume reduction and add a cryosolution, the product is frozen in more than 2 cryobags using controlled-rate freezers, they do standard quality control testing both pre- and post-thaw and then it is shipped.

Stephen Spellman, from the National Marrow Donor Program (NMDP)/Be The Match, discussed transplant outcomes using cryopreserved grafts, mainly focusing on the pre-COVID era, and also covered some recent cryopreservation-related publications that have come out during the COVID era.

A recent publication from the Center for International Blood Marrow Transplant Research (CIBMTR) was a retrospective, observational study of the CIBMTR registry initiated prior to the pandemic. They wanted to understand the potential benefits of biobanking on related donor products. The intent was to look at the effect of a donor graft cryopreservation on allogeneic transplant using both bone marrow and peripheral blood stem cells in the related and unrelated donor settings. The study population was 1,883 patients with hematologic malignancies undergoing allogeneic transplant with cryopreserved grafts between 2013-18 who were matched to a set of fresh products selected from 5,514 controls. They matched at three controls per case.

The central findings of the study:

  • No significant impacts of cryopreservation were seen in bone marrow grafts.
  • Cryopreservation was associated with differences in platelet engraftment and graft-versus-host disease in the matched related donor PBSC cohort.
  • Cryopreservation may be a surrogate for other factors contributing to inferior survival in the unrelated donor PBSC cohort.

He reviewed two other studies in allogeneic transplant settings and two single-center reports focused on cryopreserved versus fresh grafts in the COVID era.

During the pandemic, CIBMTR compared overall survival and hematopoietic engraftment between US patients receiving cryopreserved unrelated donor allografts between March-August 2020 and patients receiving fresh unrelated donor allografts between March-August 2019. Preliminary results suggest there was no adverse impact of cryopreservation through 180 days post-transplant. There was a slight delay in neutrophil engraftment (18 vs 19 days for fresh vs cryopreserved grafts).

These are early outcomes that will continue to be monitored and updated. Further follow-up is required to better understand any long-term impacts.

The Q&A session that followed was busy and, during a moment of levity, McKenna laughed when asked if his facility used controlled freezes or just kept the products outside in the snowy Minnesota cold.