Clinical impact of cryopreservation of allogeneic hematopoietic cell grafts during the onset of the COVID-19 pandemic

Abstract

At the onset of the COVID-19 pandemic, the National Marrow Donor Program mandated the cryopreservation of hematopoietic cell grafts from volunteer unrelated donors due to numerous patient and donor safety concerns and logistical hurdles. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) outcomes database, we report the impact of cryopreservation on overall survival (OS) and other outcomes within one year following hematopoietic cell transplantation (HCT). We analyzed 1,543 recipients of cryopreserved allografts receiving HCT at US centers during the first 6-months of the pandemic and compared them to 2,499 recipients of fresh allografts during the same 6-month period in 2019. On multivariable regression analysis, we observed no difference in OS (HR, 1.12; 95% CI: 0.98-1.28; P=0.09), non-relapse mortality (HR, 1.01; 95% CI: 0.84-1.22; P=0.89), graft-versus-host disease (GVHD), or GVHD-free, relapse-free survival (HR 1.03; 95% CI 0.93-1.14; P=0.58) in recipients of cryopreserved versus fresh allografts. Disease-free survival (DFS) was lower in the cryopreserved group (HR, 1.18; 95% CI: 1.05-1.33; P=0.006) due to a higher risk of relapse (HR, 1.21; 95% CI: 1.04-1.41; P=0.01). Primary graft failure was higher with cryopreservation (OR 1.48; 95% CI: 1.10-2.00; P=0.01) and the risk of chronic GVHD was lower (HR, 0.65; 95% CI: 0.50-0.84; P=0.001). In conclusion, while there was no negative impact of cryopreservation on OS, relapse was higher and DFS was lower. Fresh grafts are recommended as the pandemic related logistical hurdles resolve. Cryopreservation should be considered an option for patients when fresh grafts are not feasible.

Pros and Cons of Cryopreserving Allogeneic Stem Cell Products

“…In total, 1739 references were identified on 15 January 2024. In the end, 29 papers were included [ 54 , 55 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ] ( Figure 1 ).…”

“…The authors concluded that PBSC cryopreservation is a reasonable and safe option [ 109 ]. Finally, using the CIBMTR database, Devine et al reported the impact of cryopreservation on OS and other outcomes at 1 year after transplant [ 110 ]. A total of 1543 recipients of cryopreserved allografts transplanted at US centers during the first 6 months of the pandemic were compared with 2499 recipients of fresh allografts transplanted during a 6-month period in 2019.…”

“…The risk of primary graft failure was higher in the cryopreserved group, and the probability of platelet recovery by day 100+ was lower. Finally, patients receiving cryopreserved grafts had a higher risk of moderate-to-severe chronic GvHD and relapse at 1 year than those in the group with fresh grafts (HR, 1.21; 95% CI, 1.04–1.41; p = 0.01) [ 110 ].…”

“…The evidence that cryopreservation can affect the hematopoietic recovery is reported by several authors, including most recent sizeable studies [ 54 , 88 , 91 , 92 , 93 , 100 , 101 , 104 , 107 , 108 , 109 , 110 ]. Despite this effect being modest in most cases ( Figure 2 ), some studies (including those performed in the pre-COVID-19 period) clearly reported an increased graft failure rate with cryopreserved products, namely if using PBSC grafts [ 54 , 87 , 90 ].…”

“…Notably, in studies of Parody et al [ 89 ] and Maurer et al [ 54 ], no or a few patients received PTCy, respectively, a drug which prevents aGvHD by favoring the selection of the T-reg subset [ 54 ]. On the contrary, in the setting of cGvHD, several studies found that severity and incidence may be reduced with cryopreserved grafts even in patients receiving PTCy [ 91 , 100 , 110 ], whereas this effect has also been observed when GvHD prophylaxis is carried out with other agents [ 93 , 95 ]. In the only study reporting an increased incidence of cGvHD with cryo-grafts, this observation could have been biased by the higher rate of in vivo T cell depletion in the fresh graft group [ 99 ].…”