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Clinical Trial
. 2020 Dec 1;130(12):6656-6667.
doi: 10.1172/JCI141777.

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

Gunjan L Shah  1   2 , Susan DeWolf  1 , Yeon Joo Lee  2   3 , Roni Tamari  1   2 , Parastoo B Dahi  1   2 , Jessica A Lavery  4 , Josel Ruiz  1 , Sean M Devlin  4 , Christina Cho  1   2 , Jonathan U Peled  1   2 , Ioannis Politikos  1   2 , Michael Scordo  1   2 , N Esther Babady  5 , Tania Jain  1 , Santosha Vardhana  2   6 , Anthony Daniyan  2   7 , Craig S Sauter  1   2 , Juliet N Barker  1   2 , Sergio A Giralt  1   2 , Cheryl Goss  8 , Peter Maslak  9 , Tobias M Hohl  2   3 , Mini Kamboj  2   3 , Lakshmi Ramanathan  10 , Marcel Rm van den Brink  1   2 , Esperanza Papadopoulos  1   2 , Genovefa Papanicolaou  2   3 , Miguel-Angel Perales  1   2
Affiliations
Clinical Trial

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

Gunjan L Shah et al. J Clin Invest. .

Abstract

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.

Keywords: COVID-19; Stem cell transplantation; T cells; Transplantation.

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Conflict of interest statement

Conflict of interest: GLS reports research funding from Janssen and Amgen. YJL receives support for conducting industry-sponsored trials from Astellas Pharma and Ansun BioPharma. PBD served on an advisory board for Kite, a Gilead company. JUP reports research funding, intellectual property fees, and travel reimbursement from Seres Therapeutics and consulting fees from DaVolterra. IP reports research funding from Merck and serves on a Data and Safety Monitoring Board for ExCellThera. MS has served as a paid consultant for McKinsey & Company, Angiocrine Bioscience Inc., and Omeros Corporation. He reports research funding from Angiocrine Bioscience Inc. He has served on an ad hoc advisory board for Kite, a Gilead company. TJ reports consultancy honoraria from Takeda Oncology and has served on an advisory board for CareDx. SV reports personal fees from Immunai and personal fees from ADC Therapeutics; in addition, SV has a pending patent (PCT/US19/27610). CSS has served as a paid consultant on advisory boards for Juno Therapeutics; Sanofi-Genzyme; Spectrum Pharmaceuticals; Novartis, Genmab; Precision Biosciences; Kite, a Gilead company; Celgene; Gamida Cell; and GlaxoSmithKline. He reports research funding from Juno Therapeutics, Celgene, Precision Biosciences, and Sanofi-Genzyme. JNB reports research funding from Angiocrine Bioscience, Gamida Cell, and Merck. SAG has consulted for and received research funding from Amgen, Actinium, Celgene, Johnson & Johnson, Bristol-Myers Squibb, Sanofi, Pfizer, and Takeda and has received research funding from Miltenyi Biotec. SAG has consulted for Jazz Pharmaceuticals; GlaxoSmithKline; Novartis; Kite, a Gilead company; and Spectrum Pharmaceuticals. TMH has participated in scientific advisory boards for Merck and Partner Therapeutics. MRMVDB has received research support from Seres Therapeutics; has consulted, received honorarium from, or participated in advisory boards for Seres Therapeutics, Forty-Seven Inc., Magenta, Juno Therapeutics, Rheos, WindMIL Therapeutics, Novartis, Evelo, Jazz Pharmaceuticals, Therakos, Amgen, Magenta Therapeutics, Merck, Acute Leukemia Forum, and DKMS Medical Council (board); has IP licensing with Seres Therapeutics and Juno Therapeutics; and stock options from Smart Immune. MAP has served on advisory boards for MolMed, NexImmune, Medigene, and Servier; has received honoraria and served on advisory boards for Abbvie, Bellicum, Bristol-Meyers Squibb, Nektar Therapeutics, Novartis, Omeros, and Takeda; has consulted for and received honoraria from Merck; and has received research funding from Incyte, Miltenyi Biotec, Kite, a Gilead company.

Figures

Figure 1
Figure 1. Comorbidities at COVID-19 diagnosis.
Seventy-seven patients (Allo n = 35, Auto n = 37, CAR T n = 5). COPD, chronic obstructive pulmonary disease; HTN, hypertension; CHF, congestive heart failure; DM, diabetes mellitus; CKD, chronic kidney disease.
Figure 2
Figure 2. Monitoring patients with SARS-CoV-2 over time.
Cycle threshold data over time for patients with 2 or more PCR swabs (n = 31). All negative values were given a value of 40 (Ct ≥ 40 = negative test at MSKCC, indicated with open circle). Red asterisks indicate that the patient is deceased.
Figure 3
Figure 3. Outcomes and disease severity.
(A) Highest level of supplemental oxygen given by disease status. (B) COVID-19 disease severity by hematologic malignancy status. Seventy-seven patients (Allo, n = 35; Auto, n = 37; CAR T, n = 5). Severity of COVID-19 was defined as mild (no hospitalization required), moderate (hospitalization required), or severe (intensive care unit [ICU] required or goals of care changed to comfort care rather than escalation to the ICU).
Figure 4
Figure 4. COVID-19 status at last contact.
Seventy-seven patients (Allo, n = 35; Auto, n = 37; CAR T, n = 5). COVID-19 was defined as resolved at the end of clinical symptoms.
Figure 5
Figure 5. Overall survival by cell therapy type.
Seventy-seven patients (Allo, n = 35; Auto, n = 37; CAR T, n = 5).
Figure 6
Figure 6. Immune subsets in patients positive for SARS-CoV-2 after BMT.
(A) Absolute lymphocyte subsets in patients positive for SARS-CoV-2 compared with subsets from pre–COVID-19 time point within 1 year of infection (n = 12). (B) Absolute lymphocyte subsets within 2 years after transplant in 8 patients positive for SARS-CoV-2 who had received BMT (purple or blue symbols) compared with available data from historical controls (gray points, patients receiving unmodified peripheral blood stem cell [PBSC] allogeneic transplant at MSKCC, collected prior to the COVID-19 pandemic). Orange lines indicate Loess curve of historical controls.
Figure 7
Figure 7. Tracking lymphocyte subsets over time before, during, and in recovery from a COVID-19 infection.
Allo recipient who received a haploidentical transplant for acute myeloid leukemia. Available COVID-19 PCR data with cycle threshold (Ct) and antibody status included.
See this image and copyright information in PMC

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