key: cord-0993246-so4b22lo authors: Schmidt, Alexander H.; Buk, Deborah; Platz, Alexander; van den Brink, Marcel R.M. title: Cryopreservation for all is no option in unrelated stem cell transplantation (Comment to: Dholaria B, et al. Securing the graft during pandemic: are we ready for cryopreservation for all? Biol Blood Marrow Transplant. 2020;26(7):e145-e146.) date: 2020-08-18 journal: Biol Blood Marrow Transplant DOI: 10.1016/j.bbmt.2020.08.011 sha: 5b7ba7d2037536b575a1d774d874c0403fa5dd03 doc_id: 993246 cord_uid: so4b22lo nan Dholaria et al. [1] discuss the implications of two recent studies [2, 3] analyzing the outcome of allogeneic hematopoietic stem cell transplantation with cryopreserved products. As the results are rather encouraging, with the exception of severe aplastic anemia, the authors raise the question if we are "ready for cryopreservation for all". The commentary largely overlooked the implications for unrelated donors and from the perspective of an unrelated stem cell donor registry, we would caution the transplant community and answer this question with "no". However, we do point out a path that may in the future allow the interests of unrelated donors and patients with their physicians to be better reconciled. DKMS is a leading stem cell donor registry with more than 10 million registered donors in 6 countries, including over 6.6 million donors in Germany [4] . According to our information, 18 of the 262 products were not transfused. Eight have been discarded in the meantime, and at least some of the remaining 10 products will probably not be transfused either, resulting in a non-transfusion rate between 3.1% and 6.9%. Cryopreservation of stem cell products was at times unavoidable during the COVID-19 pandemic due to border closures, passenger flight cancellations and other crisis-related uncertainties and in some cases remains a prudent approach. Accordingly, the number of cryopreserved stem cell products from DKMS Germany donors has strongly increased. Of the 2299 products collected between March 1, 2020 and July 31, 2020, 1629 (70.9%) were cryopreserved. Thirty-one (1.9%) of these products will definitely not be transfused, according to information received by August 3, 2020. Worsening of the patient's health status and discontent with product characteristics (e.g., cell count) are typical reasons for nontransfusion. For many other cases, we know that the originally planned transplant date has passed without the product being transfused, or we have no information at this time. Based on our experience with the cases already closed, we currently assume that between 5% and 10% of the cryopreserved products will eventually not be transfused. When a fresh stem cell product is being transplanted, the conditioning of the patient begins before the product is even collected. At the time the product arrives at the transplant center, a last-minute change in therapy would in most cases not be in the best interest of the patient. Cryopreservation changes the clinical scenario: the cryopreserved product once received at the transplant center before conditioning has begun is now a therapeutic option, but not more. Of course, every transplant physician should at all times constantly re-evaluate all therapeutic options. Iffor whatever reasonthe cryopreserved product of an unrelated donor no longer seems to be the best therapeutic option, it would of course be absurd to transfuse it anyway. Donor safety must not play a role in this decision either, because the fact whether the product is transfused or not does obviously not change the risks of a past stem cell donation. From the perspective of an unrelated stem cell donor, the situation is different. The donor undergoes apheresis after several days of stem cell mobilization or bone marrow harvest under general anesthesia in order to help a stranger. Both procedures are fundamentally safe, but not entirely without risks [5, 6] , and are time-consuming as well as associated with inconvenience for the donor. Therefore, each unused stem cell product from an unrelated donor poses an ethical problem, which should be avoided wherever possible. As stated above, at DKMS Germany we had up to 18 such cases in 5,603 collections (0.32%) in 2019. The COVID-19 crisis taught us that the number of non-transfused products will increase significantly with a "cryopreservation for all", which raises serious ethical questions regarding the use of unrelated donors. Even before the COVID-19 crisis, DKMS has begun to set up an adult unrelated donor stem cell bank (SCB), i.e., the adult donor equivalent of a cord blood bank. The main goal is to be able to provide cryopreserved stem cell products from adult unrelated donors with 100% availability within a few days in urgent cases. We plan to cryopreserve the first stem cell products before the end of this year. The DKMS SCB will only include PBSC from stem cell collections, which have been performed for a specific patient. Our goal is to minimize additional donor burden. The donor will not be given an additional dose of G-CSF, nor will there be a second day of apheresis. We will focus on young male donors with frequent HLA genotypes and on collections with favorable donor-patient weight ratio. The stem cell products will be made available via the usual channels (World Marrow Donor Association, national registries). To our knowledge, several other stem cell donor registries are considering similar projects. We believe that this approach has the potential to address the interests both of unrelated donors, who should not be exposed to the risks of stem cell donation for an ultimately non-transfused product, and of patients and their physicians, for whom sometimes the logistical advantages of a cryopreserved product take precedence. Securing the graft during pandemic: are we ready for cryopreservation for all? Graft cryopreservation does not impact overall survival after allogeneic hematopoietic cell transplantation using posttransplantation cyclophosphamide for graft-versus-host disease prophylaxis Hematopoietic cell transplantation with cryopreserved grafts for severe aplastic anemia Immunogenetics in stem cell donor registry work: the DKMS example (Part 1) Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation Retrospective analysis of 37,287 observation years after peripheral blood stem cell donation The authors declare no conflict of interest.