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EBMT 2021 Annual Meeting - How to manage cell collection during COVID-19

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Cellular Therapy & Immunobiology Working Party (CTIWP)

CTD3 Cell Therapy Day: How to manage cell collection and processing during COVID 19

Monday, March 15, 14:30 - 16:00, Auditorium 4

The third session in this year’s Cell Therapy Day will analyse the unique challenges in cell collection thrown up by the COVID-19 pandemic.

The first talk, “Should we have a backup donor always?”, will be given by Dr Catherine Faucher of the Haematopoietic Stem Cell Department, Agence de la biomédecine, Paris, France.

She explains: “The COVID-19 pandemic affected the global HSC donor process through increase in donor unavailability, reduction in donor on-site staffing, new transport restrictions due to borders closure, lower numbers of flights and higher courier unavailability…In response, international HCT societies published guidelines mainly recommending cryopreservation of the graft before conditioning of the patient, and/or providing a backup donor.”

Dr Faucher reviewed the guidelines from EBMT, ASTCT, the Australia & New Zealand BMT Society, WBMT and WMDA for this presentation. Data on post-transplant results with cryopreserved allografts suggest significant delayed haematological reconstitution, and underlie the ethical concerns for donors in case the graft is not transplanted. Dr Faucher says: “In this presentation, I will discuss some real-life experiences, published in 2020 by transplant teams from Madrid, Rome and Seattle.”

She will highlight there is a need to clarify which type of backup donor is recommended depending on patient and transplant indication: some data suggest a trend for an increase in cord blood transplantation at the international level.

She concludes: “Cryopreservation of the graft before conditioning is largely recommended even though not always feasible. A backup donor is mandatory, in our view, when there is a mix of the following situations for a given patient: urgent transplant, indication for HCT with a fresh product, SAA diagnosis, and a donor at high risk of infection.”

The second talk will be given by Dr Jesús Fernández Sojo, Haematologist, Stem Cells and CAR-T, Cell therapy Unit Banc de Sang i Teixits (Blood and Tissue Bank), Barcelona, Spain. He will discuss ‘cryopreservation in case of unrelated donor’.

Banc de Sang i Teixits is the reference cell therapy laboratory of seven transplant centres with unrelated haematopoietic Stem Cell Transplantation (HSCT) programs. When the COVID-19 pandemic started in Spain (March 2020), cryopreservation of unrelated donor haematopoietic progenitor cell (HPC) was recommended by national and international organisations. A total of 47 HPC were cryopreserved during this time.

Dr Fernández Sojo explains: “A total of 32 cryopreserved HSCT from peripheral blood non-manipulated performed during COVID-19 pandemic were compared with 32 fresh HSCT in the period immediately prior to the pandemic. Clinical outcomes were assessed, including neutrophil/platelet/full donor chimerism and overall survival (OS), and no statistical differences were observed. One graft failure came up in the cryopreserved group but optimal quality control in the thawed bag was confirmed.”

Six (13%) of these cryopreserved HPC had not yet been transfused as of February 1, 2021. The median time from collection to infusion in the total cryopreserved HSCT performed during COVID-19 pandemic (41) was 21 days and in one case up to 175 days. Dr Fernández Sojo concludes: “In our experience, cryopreservation was a safe process to guarantee availability of unrelated donor HPC at the time of conditioning. No statistical difference regarding myeloid engraftment and OS were observed compared with fresh grafts. Grafts that are not transfused represent an ethical problem, so starting conditioning after 24-48 h from cryopreservation should be implemented.”

Dr Boris Calmels (Cell Therapy Centre, Institut Paoli-Calmettes, Marseille, France) will then present on ‘cyropreservation in case of related donor’, explaining: “Under normal conditions, the majority of allogeneic hematopoietic progenitor cell (HPC) grafts are freshly infused, while cryopreservation is restricted to exceptional conditions. However, since the beginning of the global COVID-19 pandemic, recommendations from professional societies were issued to cryopreserve allogeneic HPC grafts in order to minimise the risk of harvesting a SARS-CoV-2 positive donor as well as to exclude transport setbacks.”

At Dr Calmels institution, 57 allogeneic peripheral blood HPC grafts, 32 from related donors (RD) and 25 from unrelated donors (URD), were processed between March 2020 and January 2021. CD34+ cell doses pre-cryopreservation and after thawing/washing as well as CFU counts were similar between URD and RD HPC grafts, ruling out effects of long transit times on the quality of lineage-specific progenitor cells. Of the 61 cryopreserved HPC grafts, 4 RD grafts were not infused due to worsening of the patient’s health status, corroborating the ethical issue raised by cryopreservation.

He concludes: “Thus, cryopreservation of allogeneic HPC grafts is a reasonable option to ensure both safety of the collected HPC graft during the COVID-19 pandemic or anticipated challenges in relation to cell procurement or transportation. While CD34+ cell loss remains unavoidable, inter-individual variability can be mitigated by robust standardised and automated post-collection processing.”

In the final talk in this session, Dr Rafael de la Cámara, La Princesa Hospital, Madrid, Spain will discuss the role of SARS-CoV-2 testing for donors in the workup process.