When compared with transplant outcomes with fresh allografts, cryopreserved hematopoietic cell grafts had a statistically similar overall survival (OS) at one year but did not perform quite as well in some other areas, according to findings published in Blood Advances.
Researchers used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) to assess outcomes for transplants performed with fresh allografts and those performed with cryopreserved grafts during the early part of the COVID-19 pandemic. The analysis encompassed more than 4,000 transplants in all, and the findings represent the most rigorous look yet at the outcomes for cryopreserved grafts.
“We think that under most circumstances, fresh grafts are preferred over cryopreserved, but the outcomes with cryopreservation are good enough to warrant use, depending on a patient’s circumstances – for instance, if there needs to be a delay for some clinical reason, or perhaps that the donor can only donate on a certain day,” said lead author Steven Devine, MD, of the National Marrow Donor Program (NMDP) and the CIBMTR.
The COVID-19 pandemic presented an opportunity to take a much-needed closer look at the use of cryopreserved grafts, Dr. Devine said.
“Prior to the pandemic, virtually all the data we had on the impact of cryopreservation outcomes were derived from observational registries or single-center data,” he said. “It was retrospective, and in those studies you don’t always know all the reasons that patients receive cryopreserved products. Those data are not collected prospectively, so there are a lot of potential confounders.”
As the pandemic unfolded, the delivery of fresh allografts was not guaranteed, and the NMDP began to require that grafts be cryopreserved. Pandemic-related transportation issues could have delayed the arrival of grafts, and scheduled donations could have been scuttled if the donor came down with COVID, Dr. Devine said. The researchers looked at a six-month period – March to August 2020 – when about 95% of hematopoietic cell grafts used in transplantations were cryopreserved. Those outcomes were compared with fresh graft outcomes in the same six-month period in 2019.
The analysis included 1,543 cryopreserved grafts and 2,499 fresh grafts for patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndromes, lymphoma, and other blood cancers.
Researchers did not find a statistically significant difference in one-year OS between the groups (p=0.09). They did find that one-year disease-free survival was lower in the cryopreserved group, with a hazard ratio of 1.18 (p=0.006). They also found that the risk of primary graft failure was higher in the cryopreserved group, with an odds ratio of 1.48 (p=0.01).
Acute graft versus host disease (GVHD) was no different between the groups, but the risk of chronic GVHD was lower in the cryopreservation group.
Researchers also found that the risk of relapse at one year after hematopoietic cell transplant was higher in the cryopreservation group, with a hazard ratio of 1.21 (p=0.01).
Cryopreserved grafts don’t do quite as well as fresh grafts in some outcomes, Dr. Devine said, likely because of the effects of the cryopreservation process that includes dimethyl sulfoxide and the effects related to the process of freezing cells and then thawing them.
“Some of the cells die during the freeze-thaw process,” Dr. Devine noted. “So, recovery and cell dose can be limited through cryopreservation.” Another limitation, at least in theory, he explained, is that the function of immune cells from the cryopreserved grafts can be inhibited.
Still, the findings show that cryopreservation is an option when necessary. “If it makes the difference between transplant and no transplant, then cryopreservation is good enough,” Dr. Devine said.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Devine SM, Bo-Subait S, Kuxhausen, M, et al. Clinical impact of cryopreservation of allogeneic hematopoietic cell grafts during the onset of the COVID-19 pandemic [published online ahead of print, 2023 Apr 10]. Blood Adv. doi: 10.1182/bloodadvances.2023009786.