For patients undergoing allogeneic hematopoietic cell transplantation (alloHCT), freezing unrelated donor peripheral blood stem cells (PBSCs) prior to infusion in the recipient did not impair overall survival (OS) or relapse, according to study results published in Blood Advances. Patients who received frozen PBSCs had a lower incidence of chronic graft-versus-host disease (cGVHD) compared to patients who received fresh PBSCs.
“If these findings can be replicated in larger studies, it could shift practice toward regularly freezing stem cells rather than giving them fresh,” said lead author Katie Maurer, MD, PhD, of Dana-Farber Cancer Institute and Harvard School of Public Health in Boston. “This would allow greater flexibility in timing of transplant for some patients, since the collection of cells from the donor could be temporally decoupled from the cells immediately being given to the patient. It also raises the possibility that regular freezing of stem cells could be an effective and straightforward way to reduce cGVHD in patients.”
During the COVID-19 pandemic, it became necessary to freeze stem cells for alloHCT, explained senior author Sarah Nikiforow, MD, PhD, of Dana-Farber Cancer Institute. This is because the cells had to be collected and transported in a safe and timely manner while trying to ensure that air travel delays or COVID-19 infection in the donor or recipient would not delay the transplant.
“Our study looked at clinical outcomes of patients receiving these frozen stem cells compared to patients who received their stem cells fresh,” Dr. Nikiforow said. “We initially were concerned that freezing the cells might impair the stem and other immune cells’ engraftment and result in worse outcomes for patients, including higher disease relapse or mortality rates.”
But that was not the case. Researchers analyzed all adult patients who underwent first alloHCT with unrelated donor PBSCs at the Dana-Farber Cancer Institute between January 1, 2019, and July 31, 2021. Of 387 patients, 136 received cryopreserved PBSCs and 251 received fresh PBSCs. The clinical outcomes of interest included OS, progression-free survival (PFS), non-relapse mortality (NRM), relapse, acute GVHD (aGVHD), and cGVHD. The median follow-up time among survivors was 23.1 months (range = 12-40.9 months).
At two years post-transplantation, no difference was seen among patients who received cryopreserved versus fresh PBSCs for OS (60% vs. 65%; p=0.64) or PFS (55% vs. 58%; p=0.4). Relapse (34% vs. 29%; p=0.28), NRM (11% vs. 12%; p=0.74), and graft failure (5.1% vs. 2%; p=0.18) were comparable between the groups. Eight patients died of COVID-19, five of whom had received fresh PBSCs.
Further, T-cell chimerism was not different between patients who received cryopreserved and fresh PBSCs at one year, and the incidence of grade 2-4 and grade 3-4 aGVHD did not differ between the groups at six months (25% vs. 20%; p=0.36, and 12% vs. 8%; p=0.35). Moreover, the two-year incidence of any grade of cGVHD and moderate or severe cGVHD was lower in patients who received cryopreserved versus fresh PBSCs (any grade: 39% vs. 57%; p=0.00066, moderate/severe: 18% vs. 31%; p=0.00065). This significance was limited to patients who received a tacrolimus plus methotrexate and/or sirolimus GVHD prophylaxis regimen (any grade: 42% vs. 61%; p=0.0008, moderate/severe: 21% vs. 36%; p=0.0025) versus those receiving post-transplant cyclophosphamide (any grade: 29% vs. 29%; p=0.81, moderate/severe: 4.2% vs. 9.3%; p=0.28).
No difference in cGVHD was found based on the duration of cryopreservation (median = 262.7 hours, range = 48.4-2,855.7 hours).
The findings also raise “the question of how exactly the freezing process is leading to lower cGVHD,” Dr. Maurer said. “This will need to be carefully analyzed in follow-up studies, where we compare whether specific cell types are lost or altered by the freezing process, which could help us better understand the mechanisms by which cGVHD develops and could lead to better therapies for preventing GVHD in the future.”
Any conflicts of interest declared by the authors can be found in the original article.
Katie Robinson is a medical writer based in New York.
Reference
Maurer K, Kim HT, Garrity HM, et al. Lower incidence of chronic GVHD observed after transplantation with cryopreserved unrelated allogeneic stem cells [published online, 2023 Jan 3]. Blood Adv. doi: 10.1182/bloodadvances.2022009231.
