Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation

• Published in: The Journal of clinical investigation 2020-12, Vol.130 (12), p.6656-6667
• Main Authors: Shah, Gunjan L, Dewolf, Susan, Lee, Yeon Joo, Tamari, Roni, Dahi, Parastoo B, Lavery, Jessica A, Ruiz, Josel, Devlin, Sean M, Cho, Christina, Peled, Jonathan U, Politikos, Ioannis, Scordo, Michael, Babady, N Esther, Jain, Tania, Vardhana, Santosha, Daniyan, Anthony, Sauter, Craig S, Barker, Juliet N, Giralt, Sergio A, Goss, Cheryl, Maslak, Peter, Hohl, Tobias M, Kamboj, Mini, Ramanathan, Lakshmi, van Den Brink, Marcel R M, Papadopoulos, Esperanza, Papanicolaou, Genovefa, Perales, Miguel-Angel
• Format: Article
• Language: English
• Subjects: Antigens; Autografts; Biomedical research; Cancer therapies; CD19 antigen; Chimeric antigen receptors; Coronaviruses; COVID-19; Graft-versus-host reaction; Immune reconstitution; Immunoglobulins; Laboratories; Lymphocytes; Lymphocytes T; Malignancy; Neutropenia; Neutrophils; Severe acute respiratory syndrome coronavirus 2; Stem cell transplantation; Transplantation; Transplants & implants
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI141777.

BACKGROUND. Understanding outcomes and immunologic characteristics of cellular therapy recipients with SARS-CoV-2 is critical to performing these potentially life-saving therapies in the COVID-19 era. In this study of recipients of allogeneic (Allo) and autologous (Auto) hematopoietic cell transplant and CD19-directed chimeric antigen receptor T cell (CAR T) therapy at Memorial Sloan Kettering Cancer Center, we aimed to identify clinical variables associated with COVID-19 severity and assess lymphocyte populations. METHODS. We retrospectively investigated patients diagnosed between March 15, 2020, and May 7, 2020. In a subset of patients, lymphocyte immunophenotyping, quantitative real-time PCR from nasopharyngeal swabs, and SARS-CoV-2 antibody status were available. RESULTS. We identified 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days; IQR, 354-1611 days). Overall survival at 30 days was 78%. Clinical variables significantly associated with the composite endpoint of nonrebreather or higher oxygen requirement and death (n events = 25 of 77) included number of comorbidities (HR 5.41, P = 0.004), infiltrates (HR 3.08, P = 0.032), and neutropenia (HR 1.15, P = 0.04). Worsening graft-versus-host disease was not identified among Allo recipients. Immune profiling revealed reductions and rapid recovery in lymphocyte populations across lymphocyte subsets. Antibody responses were seen in a subset of patients. CONCLUSION. In this series of Allo, Auto, and CAR T recipients, we report overall favorable clinical outcomes for patients with COVID-19 without active malignancy and provide preliminary insights into the lymphocyte populations that are key for the antiviral response and immune reconstitution. FUNDING. NIH grant P01 CA23766 and NIH/National Cancer Institute grant P30 CA008748.