Handling of Allogeneic HPC Grafts in European Transplant Centers during the COVID-19 Pandemic - a Survey from the Infectious Diseases and Cellular Therapy & Immunobiology Working Parties of the EBMT

Background: For more than two years, the COVID-19 pandemic has had detrimental impact on medical practices. Because of its intrinsic complexity, the delivery of allogeneic hematopoietic cell transplantation (HCT) in this context represents an enormous challenge. Transplant centers have adapted promptly and developed strategies to enable safe HCT, by introducing significant changes in their procedures, e.g. through changes in donor types and an unprecedented use of cryopreservation for allogeneic hematopoietic progenitor cell (HPC) grafts.

Methods: To explore how centers modified their strategies in terms of donor selection and implementation of new procedures (e.g. SARS-CoV-2 test strategy, cryopreservation), a 14-item survey was developed by the Infectious Disease (IDWP) & Cellular Therapy & Immunobiology (CTIWP) working parties of the European Society for Blood and Marrow Transplantation (EBMT). The survey was sent to 509 EBMT-affiliated allogeneic HCT in Q2, 2011 and re-opened between January 31^st and March 18^th, 2022 to also cover changes during to the infection period with the Omicron variant.

Results: One hundred thirty-five of 509 (27%) centers from 31countries responded. Seventy-four percent of centers introduced COVID-19 mitigation measures for their donors (e.g. physical and social distancing) to minimize the risk of infection. Thirty-four percent of centers changed their donor search strategy, and favored recruitment of related haploidentical donors over unrelated donors (URD). In addition, 33% and 50% of centers searched for a backup donor in the related and URD settings, respectively. Only 10 (7.4 %) of centers resorted to cord blood (CB) as an alternative source to URD. Of these, four centers where pediatric centers and three, pediatric and adult transplant centers. Before COVID-19, only ten of 135 centers (7.4%) were routinely cryopreserving HPC products, whereas this percentage increased to 90% (122/135) during the pandemic. In details, 84/122 (69%) of centers cryopreserved both related and URD grafts, 34 (28%) only URD and 4 (3%) related grafts only. One hundred twenty centers responded during the re-opening of the survey to cover the situation during the Omicron wave. Of those, 78% were still considering graft cryopreservation, whereas 18/26 (70%) of centers not using cryopreservation during the Omicron wave used it before that period. In the majority of centers, changes in policies were introduced based on EBMT recommendations (88/117; 75%) and/or national guidelines (73/117; 62%). Bone marrow (BM) grafts were avoided by 52 (39%) centers (possibly because of the notorious low recovery percentage of cryopreserved BM progenitor cells). In the study period, a total of 4,443 related and 4,586 URD transplants have been reported. Of these transplants, 62% (n=2,748) related and 71% (n=3,254) of URD grafts have been cryopreserved pre-emptively and infused in the vast majority of cases. Sixty-four (2.3 %) related and hundred-eight (3.3 %) URD cryopreserved products have not been infused during the observation period. Release criteria for cryopreserved products in terms of COVID-19 were based on a negative SARS-CoV-2 test (not further specified) in 58/121 (48%), interview of the donor (medical history) in 4/121 (3%), and both in 38/121 (31%) of centers. Eighty-eight centers reported on their test strategy for related donors (multiple answers possible). A SARS-CoV-2 test was performed during check-up in 43% (38/88), before HPC mobilization in 63% (55/88) and before HPC collection in 41% (36/88) centers. Test strategies for URD were not covered by the survey.

Conclusions: These data are limited by the low number of respondents, but show a historical increase in cryopreservation of allogeneic HPC grafts during the first three waves of the SARS-CoV-2 pandemic, more in URD than in related donor grafts. The use of BM decreased, and CB grafts were not used as an alternative at most centers. A significant proportion of cryopreserved products (2.8%) were not infused. The reason for this is under investigation. The clinical impact of allogeneic cryopreserved HPCs has to be further analyzed in a larger cohort of patients.

Worel:Kite Gilead: Honoraria; Sanofi Genzyme: Honoraria, Other: research fund; Therakos Mallinckrodt: Honoraria; Novartis: Honoraria; Janssens: Honoraria. Ljungman:Blueprint Pharmacueticals: Other: DSMB member; MSD: Honoraria, Research Funding, Speakers Bureau; Octapharma: Other: DMC chair; AlloVir: Research Funding; AiCuris: Consultancy; Enanta Pharmaceuticals: Other: DMC member; Takeda: Other: Endpoint committee, Research Funding. Kuball:Novartis: Research Funding; GADETA: Current equity holder in private company, Patents & Royalties: on gdTCR engineering strategies and targets , Research Funding; Miltenyi Biotech: Patents & Royalties: novel CAR T and engineering isolation strategies, Research Funding. Averbuch:Takeda: Consultancy, Speakers Bureau; Pfizer: Consultancy; GSK: Speakers Bureau. De La Camara:Pierre Fabre: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Speakers Bureau; ATARA: Honoraria, Speakers Bureau; MODERNA: Honoraria, Speakers Bureau; ASTRAZENECA: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Honoraria, Speakers Bureau. Chabannon:GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Speakers Bureau; BMS/CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN PHARMACEUTICALS: Membership on an entity's Board of Directors or advisory committees; TERUMO BCT: Speakers Bureau; MILTENYI BIOTECH: Research Funding; FRESENIUS KABI: Research Funding; EBMT: Membership on an entity's Board of Directors or advisory committees; BELLICUM PHARMACEUTICALS: Membership on an entity's Board of Directors or advisory committees; SANOFI SA: Honoraria, Research Funding, Speakers Bureau.