Transplantation of allogeneic cryopreserved hematopoietic cell grafts during the Covid‐19 pandemic: A National Marrow Donor Program perspective

Logistical challenges imposed by the SARS-CoV-2 pandemic (Covid-19) have forced a massive shift toward the use of cryopreservation of hematopoietic stem cell (HSC) grafts from both related and unrelated donors, in order to ensure patients have a graft available on the day of transplantation. Although cryopreservation has been used as a standard for autologous and umbilical cord blood transplantation and is supported by a large body of clinical and technical literature, prior to the pandemic there was surprisingly little data beyond single center or small multi-center reports, with which to assure clinicians that cryopreservation of allogeneic grafts would not adversely impact critical post-transplant outcomes. These includes hematopoietic engraftment, graft vs host disease (GVHD), relapse, immune reconstitution, and overall survival. The Center for International Blood and Marrow Transplant Research (CIBMTR) has recently contributed important retrospective analyses suggesting cryopreservation should be avoided in patients with severe aplastic anemia due to high rates of graft failure but otherwise was not associated with adverse consequences in other settings, such as those that incorporate post-transplant cyclophosphamide (PTCy) to prevent GVHD. Another report from the CIBMTR in a large cohort of patients receiving more conventional GVHD prophylaxis is currently under review and should be available shortly. In this issue of American Journal of Hematology, a report by Alotaibi and colleagues from Princess Margaret Cancer Centre on the impact of planned cryopreservation on post-transplantation outcomes in a relatively large patient cohort at a single center adds important information to this literature and provides some reassurance to clinicians trying to decide in uncertain times whether to order a fresh vs a cryopreserved product. They evaluated the effect of cryopreservation of grafts on allogeneic transplant outcomes using related, unrelated and haploidentical donors collected following G-CSF mobilization to obtain peripheral blood stem cell (PBSC) for patients with a variety of hematological malignancies. Fresh grafts were received by 648 (68%) patients, 310 (32%) received cryopreserved. There was no difference between fresh vs cryopreserved grafts in neutrophil engraftment, platelet engraftment, graft failure, grade II-IV acute GVHD, or overall survival. The incidence of moderate/severe chronic GVHD was higher in the recipients of cryopreserved grafts. The authors interpreted these findings to suggest that cryopreservation was a safe option for allogeneic HCT, a conclusion based on these results with which I generally agree, but with some caveats. For instance, this study was limited to recipients of PBSC grafts and the vast majority of donors were HLA-matched relatives. The report does not provide a lot of data on cryopreservation of unrelated donor (URD) products or product transit time. The results were obtained at a single center and cryopreservation was planned well in advance and was a common practice at this particular center. Whether these results are extrapolatable to other centers using different standards of care is not entirely clear. How can these new data from Princess Margaret as well as recent CIBMTR retrospective analyses of cryopreservation impact be put into context? Viewing these data through the lens of my role as Chief Medical Officer at the National Marrow Donor Program (NMDP), none of the data can be considered definitive. However, this is the best we have to date and I do think they provide some important guidance for clinical decision making. When the NMDP made the decision in March of 2020 first to strongly recommend and then to require cryopreservation with limited exceptions, we knew we were making that decision with less than perfect information. What we did know was that as an organization charged with the awesome responsibility of delivering potentially life-saving products for patients in need, we could not allow even a single patient to receive myeloablative conditioning without a graft to infuse on the day of planned transplantation. That would clearly be unacceptable given the potentially devastating consequences. Assuring patient safety had to be our number one priority. Given the myriad uncertainties surrounding air travel logistics and risks of donors becoming infected with SARS-CoV-2 and unavailable after a patient initiated conditioning, we had no choice but to require the donor products we delivered be scheduled to arrive at the transplant centers prior to initiation of conditioning. Received: 3 November 2020 Accepted: 5 November 2020