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Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation.
J Clin Invest. 2020 12 01; 130(12):6656-6667.JCI

Abstract

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.CONCLUSIONIn 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.FUNDINGNIH grant P01 CA23766 and NIH/National Cancer Institute grant P30 CA008748.

Authors+Show Affiliations

Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.Department of Medicine, Weill Cornell Medical College, New York, New York, USA. Infectious Disease Service, Department of Medicine.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Department of Epidemiology and Biostatistics.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.Department of Epidemiology and Biostatistics.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Clinical Microbiology Service, Department of Laboratory Medicine.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.Department of Medicine, Weill Cornell Medical College, New York, New York, USA. Lymphoma Service and.Department of Medicine, Weill Cornell Medical College, New York, New York, USA. Leukemia Service, Department of Medicine; and.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Transfusion Medicine Service.Cellular Immunology Laboratory, and.Department of Medicine, Weill Cornell Medical College, New York, New York, USA. Infectious Disease Service, Department of Medicine.Department of Medicine, Weill Cornell Medical College, New York, New York, USA. Infectious Disease Service, Department of Medicine.Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.Department of Medicine, Weill Cornell Medical College, New York, New York, USA. Infectious Disease Service, Department of Medicine.Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Department of Medicine, Weill Cornell Medical College, New York, New York, USA.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32897885

Citation

Shah, Gunjan L., et al. "Favorable Outcomes of COVID-19 in Recipients of Hematopoietic Cell Transplantation." The Journal of Clinical Investigation, vol. 130, no. 12, 2020, pp. 6656-6667.
Shah GL, DeWolf S, Lee YJ, et al. Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation. J Clin Invest. 2020;130(12):6656-6667.
Shah, G. L., DeWolf, S., Lee, Y. J., Tamari, R., Dahi, P. B., Lavery, J. A., Ruiz, J., Devlin, S. M., Cho, C., Peled, J. U., Politikos, I., Scordo, M., Babady, N. E., Jain, T., Vardhana, S., Daniyan, A., Sauter, C. S., Barker, J. N., Giralt, S. A., ... Perales, M. A. (2020). Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation. The Journal of Clinical Investigation, 130(12), 6656-6667. https://doi.org/10.1172/JCI141777
Shah GL, et al. Favorable Outcomes of COVID-19 in Recipients of Hematopoietic Cell Transplantation. J Clin Invest. 2020 12 1;130(12):6656-6667. PubMed PMID: 32897885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation. AU - Shah,Gunjan L, AU - DeWolf,Susan, AU - Lee,Yeon Joo, AU - Tamari,Roni, AU - Dahi,Parastoo B, AU - Lavery,Jessica A, AU - Ruiz,Josel, AU - Devlin,Sean M, AU - Cho,Christina, AU - Peled,Jonathan U, AU - Politikos,Ioannis, AU - Scordo,Michael, AU - Babady,N Esther, AU - Jain,Tania, AU - Vardhana,Santosha, AU - Daniyan,Anthony, AU - Sauter,Craig S, AU - Barker,Juliet N, AU - Giralt,Sergio A, AU - Goss,Cheryl, AU - Maslak,Peter, AU - Hohl,Tobias M, AU - Kamboj,Mini, AU - Ramanathan,Lakshmi, AU - van den Brink,Marcel Rm, AU - Papadopoulos,Esperanza, AU - Papanicolaou,Genovefa, AU - Perales,Miguel-Angel, PY - 2020/06/29/received PY - 2020/09/02/accepted PY - 2020/9/9/pubmed PY - 2020/12/15/medline PY - 2020/9/8/entrez KW - COVID-19 KW - Stem cell transplantation KW - T cells KW - Transplantation SP - 6656 EP - 6667 JF - The Journal of clinical investigation JO - J Clin Invest VL - 130 IS - 12 N2 - BACKGROUNDUnderstanding 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.METHODSWe 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.RESULTSWe 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.CONCLUSIONIn 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.FUNDINGNIH grant P01 CA23766 and NIH/National Cancer Institute grant P30 CA008748. SN - 1558-8238 UR - https://www.unboundmedicine.com/medline/citation/32897885/Favorable_outcomes_of_COVID_19_in_recipients_of_hematopoietic_cell_transplantation_ L2 - https://doi.org/10.1172/JCI141777 DB - PRIME DP - Unbound Medicine ER -