Background Haematopoietic stem-cell transplantation (HSCT) recipients are considered at high risk of poor outcomes after COVID-19 on the basis of their immunosuppressed status, but data from large studies in HSCT recipients are lacking. This study describes the characteristics and outcomes of HSCT recipients after developing COVID-19.
MethodsIn response to the pandemic, the Center for International Blood and Marrow Transplant Research (CIBMTR) implemented a special form for COVID-19-related data capture on March 27, 2020. All patients-irrespective of age, diagnosis, donor type, graft source, or conditioning regimens-were included in the analysis with data cutoff of Aug 12, 2020. The main outcome was overall survival 30 days after a COVID-19 diagnosis. Overall survival probabilities were calculated using Kaplan-Meier estimator. Factors associated with mortality after COVID-19 diagnosis were examined using Cox proportional hazard models. Findings 318 HSCT recipients diagnosed with COVID-19 were reported to the CIBMTR. The median time from HSCT to COVID-19 diagnosis was 17 months (IQR 8-46) for allogeneic HSCT recipients and 23 months (8-51) for autologous HSCT recipients. The median follow-up of survivors was 21 days (IQR 8-41) for allogeneic HSCT recipients and 25 days (12-35) for autologous HSCT recipients. 34 (18%) of 184 allogeneic HSCT recipients were receiving immunosuppression within 6 months of COVID-19 diagnosis. Disease severity was mild in 155 (49%) of 318 patients, while severe disease requiring mechanical ventilation occurred in 45 (14%) of 318 patients-ie, 28 (15%) of 184 allogeneic HSCT recipients and 17 (13%) of 134 autologous HSCT recipients. At 30 days after the diagnosis of COVID-19, overall survival was 68% (95% CI 58-77) for recipients of allogeneic HSCT and 67% (55-78) for recipients of autologous HSCT. Age 50 years or older (hazard ratio 2•53, 95% CI 1•16-5•52; p=0•020); male sex (3•53; 1•44-8•67; p=0•006), and development of COVID-19 within 12 months of transplantation (2•67, 1•33-5•36; p=0•005) were associated with a higher risk of mortality among allogeneic HSCT recipients, and a disease indication of lymphoma was associated with a higher risk of mortality compared with plasma cell disorder or myeloma (2•41, [1•08-5•38]; p=0•033) in autologous HSCT recipients. Interpretation Recipients of autologous and allogeneic HSCT who develop COVID-19 have poor overall survival. These data emphasise the need for stringent surveillance and aggressive treatment measures in HSCT recipients who develop COVID-19.
CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.
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