ABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo- HSCT) has traditionally involves administering fresh peripheral blood or bone marrow stem cells. At onset of the COVID-19 pandemic in March 2020, the National Marrow Donor Program (NDMP) mandated cryopreservation of all unrelated peripheral blood stem cell (PBSC) products to prevent interruptions in transplant plans by donor COVID-19 infection after recipient's start of conditioning chemotherapy. Since the lifting of this mandate, many centers have continued to cryopreserve grafts prior to initiation of conditioning, but the longer-term clinical outcomes of this practice including chronic graft versus host disease (cGVHD) rates of patients receiving cryopreserved stem cells have not been previously well described. Prior work has raised concern for a deleterious effect of cryopreservation on overall survival and non-relapse mortality (PMID: 33865804). However, heterogeneity in the patient population and reason for cryopreservation suggest that further study is needed to assess these outcomes. Here we report our single-institution experience of clinical outcomes using cryopreserved versus fresh URD PBSCs for allo-HSCT. We examined long-term outcomes in 387 patients who received unrelated donor (URD) PBSCs (136 cryopreserved, 251 fresh) between January 1, 2019 and July 31, 2021. The cohorts had similar baseline characteristics including donor/recipient age/sex, disease, conditioning regimen/intensity, and GVHD prophylaxis regimens. Two-year OS, PFS, relapse, NRM, and acute GVHD rates were not different between recipients of fresh versus cryopreserved PBSCs. Strikingly, 2-year incidence of cGVHD (28% vs 52%, p=0.00001) and moderate/severe cGVHD (9% vs 24%, p=0.00016) was substantially lower in recipients of cryopreserved PBSCs compared to fresh, respectively (Figure 1). This difference was only noted in patients receiving a GVHD prophylaxis regimen without post-transplantation cyclophosphamide (PTCY) (no PTCY 2-year cGVHD incidence cryopreserved vs fresh: 29% vs 57%, p=0.000016), moderate/severe cGVHD 16% vs 34%, p=0.0006) (Figure 2). For patients receiving a PTCY-containing GVHD prophylaxis regimen, there was no difference in cGVHD incidence (cGVHD cryopreserved vs fresh: 24% vs 27%, p=0.56, moderate/severe cGVHD 7% vs 9.3%, p=0.3, Figure 3). (Figure Presented) (Figure Presented) (Figure Presented) While survival and relapse rates are not different, cryopreservation is associated with a marked reduction in cGVHD rates in the setting of non-PTCy based GVHD prophylaxis. Larger multicenter or registry analyses are needed to confirm these observations and may prompt a re-assessment of the role of cryopreservation of stem cell products in clinical practice. If confirmed, it will be critical to understand the immunologic consequences of cryopreservation and how they might influence the clinical impact on chronic GVHDCopyright © 2023 American Society for Transplantation and Cellular Therapy