A French single-center experience on allogeneic stem cell transplant cryopreservation during severe acute respiratory syndrome coronavirus 2 pandemic.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemo-resistant hematological malignancies. Because of transport restriction imposed by the coronavirus disease 2019 pandemic, regulatory bodies and societies recommended graft cryopreservation before recipient conditioning. However, the freezing and thawing processes, including washing steps, might impair CD34+ cell recovery and viability, thereby impacting the recipient engraftment. Over 1 year (between March 2020 and May 2021), we aimed to analyze the results of frozen/thawed peripheral blood stem cell allografts in terms of stem cell quality and clinical outcomes. METHODS: Transplant quality was evaluated by comparing total nucleated cells (TNCs), CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM)/kg numbers as well as TNC and CD34+ cell viabilities before and after thawing. Intrinsic biological parameters such as granulocyte, platelet and CD34+ cell concentrations were analyzed, as they might be responsible for a quality loss. The impact of the CD34+ cell richness of the graft on TNC and CD34 yields was evaluated by designing three groups of transplants based on their CD34 /kg value at collection: >8 × 10 6/kg, between 6 and 8 × 106/kg and <6 × 106/kg. The consequences of cryopreservation were compared in the fresh and thawed group by evaluating the main transplant outcomes. RESULTS: Over 1 year, 76 recipients were included in the study; 57 patients received a thawed and 19 patients a fresh allo-SCT. None received allo-SCT from a severe acute respiratory syndrome coronavirus 2-positive donor. The freezing of 57 transplants led to the storage of 309 bags, for a mean storage time (between freezing and thawing) of 14 days. For the fresh transplant group, only 41 bags were stored for potential future donor lymphocyte infusions. Regarding the graft characteristics at collection, median number of cryopreserved TNC and CD34+ cells/kg were greater than those for fresh infusions. After thawing, median yields were 74.0%, 69.0% and 48.0% for TNC, CD34+ cells and CFU-GM, respectively. The median TNC dose/kg obtained after thawing was 5.8 × 108, with a median viability of 76%. The median CD34+ cells/kg was 5 × 106, with a median viability of 87%. In the fresh transplant group, the median TNC/kg was 5.9 × 108/kg, and the median CD34+ cells/kg and CFU-GM/kg were 6 × 106/kg and 276.5 × 104/kg, respectively. Sixty-one percent of the thawed transplants were out of specifications regarding the CD34+ cells/ kg requested cell dose (6 × 106/kg) and 85% of them would have had this dose if their hematopoietic stem cell transplant had been infused fresh. Regarding fresh grafts, 15.8% contained less than 6 × 106 CD34+ cells /kg and came from peripheral blood stem cells that did not reach 6 × 106 CD34+ cells /kg at collection. Regarding the factor that impaired CD34 and TNC yield after thawing, no significant impact of the granulocyte count, the platelet count or the CD34+ cells concentration/µL was observed. However, grafts containing more than 8 × 10 6/kg at collection showed a significantly lower TNC and CD34 yield. CONCLUSIONS: Transplant outcomes (engraftment, graft-versus-host disease, infections, relapse or death) were not significantly different between the two groups.

Progression to a severe form of COVID-19 among patients with chronic respiratory diseases.

RATIONALE: Viral respiratory infections, including SARS-CoV-2 infection, can trigger respiratory symptoms among patients suffering from chronic respiratory diseases, leading to exacerbations and hospitalizations. Despite the tropism of SARS-CoV-2 into the respiratory tract, chronic respiratory diseases do not seem to be risk factors for severe forms of COVID-19. OBJECTIVES: To assess whether hospitalized patients for COVID-19 with chronic respiratory diseases were at lower risk of developing a severe form than other patients. METHODS: This French study included patients admitted to hospital in COVID-19 ward, suffering from a SARS-CoV-2 infection, diagnosed on RT-PCR or chest computed tomography associated with clinical symptoms, from March 15 to June 30, 2020. Ambulatory patients who were tested in the emergency department and patients with severe hypoxaemia requiring intensive care were not included. All data were collected from electronic medical records up to discharge of the patient. MAIN RESULTS: 617 patients were included: 125 with a chronic respiratory disease, mainly chronic obstructive pulmonary disease (45%) and asthma (30%). The percentage of patients scoring 6 or higher on the WHO Clinical Progression Scale during hospital stay was lower in patients with chronic respiratory disease compared to those without chronic respiratory disease (21.6% versus 31.3%, respectively, p = 0.03). Among patients with chronic respiratory disease, temperature above 38 °C on admission (OR 16.88 (95% CI 4.01-71.00)), lymphopenia (OR 5.08 (1.25-20.72)), CPAP therapy (OR 4.46 (1.04-19.17)) and age (OR 1.09 (1.02-1.16)) were associated with an increased risk to reach a score of 6 or above. CONCLUSIONS: Hospital admissions in COVID-19 ward of patients suffering from chronic respiratory diseases are at lower risk of developing a severe form of COVID- 19, especially in patients with chronic obstructive pulmonary disease or asthma. Prospective studies would confirm our results and allow to better organize the follow-up of these patients in a pandemic period.