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

Abstract

Background/objective Cryopreservation of grafts is not common practice in allogeneic hematopoietic stem cell transplant (HSCT) recipients. However, our center had to use cryopreserved cells for allogeneic HSCT during the COVID-19 pandemic to avoid delays in transplantation due to uncertainty regarding patient and donor exposures. Study designWe retrospectively evaluated post-transplant engraftment and survival outcomes of adult patients who received cryopreserved versus fresh allografts during the COVID-19 pandemic. Results Fifty-five patients with hematologic malignancies received either cryopreserved (n = 34) or fresh (n = 21) allogeneic HSCT using peripheral blood stem cells between January 2020 and December 2020. At a median follow-up time of 15 months, cryopreserved allograft recipients had significantly lower overall survival (OS) (p = 0.02). They also experienced significantly delayed neutrophil (p = 0.01) and platelet engraftments (p < 0.0001), as well as higher red blood cell transfusiondependence after day + 60 (67.6% vs. 28.6%; p = 0.01). Significantly more cryopreserved allograft recipients received donor lymphocyte infusion than fresh allograft recipients (35.3% vs. 4.8%, p = 0.01). Neither relapse-free survival nor non-relapse mortality differed significantly between the two groups. Conclusion Cryopreservation of allografts in combination with post-transplant cyclophosphamide may negatively affect engraftment and OS outcomes in HSCT recipients.

Pros and Cons of Cryopreserving Allogeneic Stem Cell Products

“…Therefore, the authors concluded that the inferior outcomes of cryopreserved transplants were possibly due to the combination of ATG and PTCy impacting the differential tolerance to cryopreservation of various components of the grafts [ 100 ]. Similar findings were reported by Guo et al in a single center study involving 34 patients receiving cryopreserved PBSC transplant and 31 controls [ 101 ]. Conversely, various single-institution studies found no differences between cryo- and fresh grafts in unrelated donor transplants [ 102 , 103 , 104 , 105 , 106 ].…”

“…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 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 ].…”

“…It is likely that the impaired immune reconstitution could account for this effect [ 54 ]. Finally, a group of studies heterogeneous for period, sample size, and patient populations suggest a cumulative detrimental effect of cryopreservation on OS [ 90 , 92 , 100 , 101 , 107 ]. Nevertheless, further studies with a longer follow-up and larger sample size are necessary to confirm this finding.…”

“… Days to neutrophil and platelet recovery [ 86 , 88 , 89 , 91 , 92 , 93 , 94 , 95 , 96 , 98 , 99 , 101 , 102 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 ]. Data are given as median and range, median and 95% confidence interval a , or median and interquartile range b .…”