Cellular Therapy During COVID-19: Lessons Learned and Preparing for Subsequent Waves

Nawas, Mariam T.; Shah, Gunjan L.; Feldman, Darren R.; Ruiz, Josel D.; Robilotti, Elizabeth; Aslam, Anoshé; Dundas, Mary L.; Kamboj, Mini; Barker, Juliet N.; Cho, Christina; Chung, David J.; Dahi, Parastoo B.; Giralt, Sergío; Gyurkocza, Boglarka; Lahoud, Oscar; Landau, Heather; Lin, Richard J.; Mailankody, Sham; Palomba, M. Lia; Papadopoulos, Esperanza B.; Politikos, Ioannis; Ponce, Doris M.; Sauter, Craig S.; Shaffer, Brian C.; Scordo, Michael; Brink, Marcel R.M. van den; Perales, Miguel-Ángel; Tamari, Roni

doi:10.1016/j.jtct.2021.02.011

Cited by 13 publications

(11 citation statements)

References 15 publications

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“…Later, a multicenter data from the Center of International Blood and Marrow Transplant Research (CIBMTR) reported that 27% of allogeneic hematopoietic cell transplantation (allo-HCT) recipients and 20% of autologous hematopoietic cell transplantation (auto-HCT) recipients with COVID-19 manifested moderate severity illness, while severe disease was reported in 15% and 13%, respectively, with an overall mortality of 21% (6). Our group has also reported the negative indirect effects of the pandemic on patients undergoing cellular therapies from delays in treatment leading to progression of disease and mortality (7). Effective immunization is vital for protecting cellular therapy recipients from COVID-19 and to mitigate spreading of the pandemic.…”

Section: Introductionmentioning

confidence: 74%

Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy

Tamari

Politikos

Knorr

et al. 2021

Blood Cancer Discovery

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Cellular therapies including allogeneic and autologous hematopoietic cell transplant (allo-HCT, auto-HCT) and chimeric antigen receptor T cell therapy (CAR T) render patients severely immunocompromised for extended periods post-therapy, and data on responses to COVID-19 vaccines are limited. We analyzed anti-SARS-CoV-2 spike IgG antibody (spike Ab) titers and neutralizing Ab among 217 recipients of cellular treatments (allo-HCT, n=149, auto HCT n=61, and CAR T n=7). At 3 months after vaccination, 188 patients (87%) had positive spike Ab levels and 139 (77%) had positive neutralization activity, compared to 100% for both in 54 concurrent healthy controls. Time from cellular therapy to vaccination and immune recovery post-cellular therapy were associated with response. Vaccination against COVID-19 is an important component of post-cellular therapy care, and predictors of quantitative and qualitative response are critical in informing clinical decisions about optimal timing of vaccines and the requirement for booster doses.

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Section: Introductionmentioning

confidence: 74%

Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy

Tamari

Politikos

Knorr

et al. 2021

Blood Cancer Discovery

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“…Our study adds to growing body of knowledge regarding COVID-19 and its impact on clinical outcomes of a distinctly vulnerable clinical population of HCT recipients. We previously showed that the COVID-19 pandemic caused substantial delays in HCT and that these delays resulted in inferior outcomes in a select group of patients and that patients who developed COVID-19 after HCT had varied clinical outcomes 7 , 8 , 9 . In the current cohort of patients with previous COVID-19 infections autologous and allogeneic HCTs were feasible and safe; no recurrent COVID-19 infection was observed.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic Cell Transplantation is Feasible in Patients with Prior COVID-19 Infection

Shah

Dahi

Ponce

et al. 2022

Transplantation and Cellular Therapy

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Background There are limited data on outcomes of patients with prior Coronavirus disease 2019 (COVID-19) who proceeded to autologous or allogeneic hematopoietic cell transplantation (HCT). It is unknown whether these patients are more susceptible to poor outcomes and recurrence of COVID-19. Objective We report a retrospective analysis of outcomes of 15 consecutive patients with hematologic malignancies who experienced COVID-19 and subsequently underwent autologous (n=8) or allogeneic (n=7) HCT between 6/17/20 and 2/17/21. The reported cohort included patients with asymptomatic past infections or symptomatic COVID-19 disease. Methods Data were obtained from chart review. Descriptive statistics were used to summarize patient characteristics. Results Among eight patients who underwent autologous HCT, four had a diagnosis of multiple myeloma while the rest had a diagnosis of non-Hodgkin's lymphoma. Four of the eight patients did not test positive for anti-SARS- CoV-2 IgG antibody at any point during their course. The remaining four patients had detectable anti-SARS-CoV-2 IgG antibodies prior to autologous HCT but only two of these patients remained anti-SARS-CoV-2 IgG antibody-positive at their last follow-up. One patient died from progression of disease. Seven patients with prior COVID-19 underwent allogeneic HCT for acute lymphoblastic leukemia (n=3); acute myeloid leukemia (n=1); chronic myeloid leukemia in lymphoid blast crisis (n=1); myelodysplastic syndrome (n=1); and myelofibrosis (n=1). Three of the seven patients tested positive for anti-SARS- CoV-2 IgG antibodies following the initial COVID-19 diagnosis; however, only one of these patients retained anti-SARS- CoV-2 IgG antibody following allogeneic stem cell transplantation. One patient died of infections (fungal and Pneumocystis jirovecii pneumonia) occurring in the context of ongoing treatment for GVHD. None of the 15 patients developed recurrence of COVID-19 infection. Conclusions Based on our experience, autologous and allogeneic HCT can be safely performed in select patients with previous COVID-19 infection.

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“…Transplant and cellular therapy centers worldwide have been challenged with the pandemic because of the high susceptibility to opportunistic and community-acquired infections and their complications in this unique subset of patients 12 , 13 , 14 . Nonetheless, in certain clinical scenarios, postponing transplantation or cellular therapy can negatively affect the prognosis of the malignancy [ 15 , 16 ]. Therefore, even though health systems are overwhelmed with COVID-19 patients and despite the increased risk of complications with cellular therapies, HCT and CAR-T therapy have continued to be performed around the globe [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

Mushtaq

Shahzad

Chaudhary

et al. 2021

Transplantation and Cellular Therapy

103

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Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020, and has caused more than 600,000 deaths in the United States at the time of this report. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have a higher risk of mortality with COVID-19 owing to profound immune dysregulation. In this study, we investigated the impact of SARS-CoV-2 in HCT/CAR-T therapy recipients. This single-center prospective study included all (n = 58) adult HCT/CAR-T recipients who were diagnosed with COVID-19 at the University of Kansas Medical Center between March 2020 and May 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (IBM, Armonk, NY). Bivariate analyses, using the chi-square and t-test, and logistic regression analyses were conducted. The study included 58 HCT/CAR-T patients who acquired SARS-CoV-2 infection, including recipients of allogeneic HCT (n = 32), autologous HCT (n = 23), and CAR-T therapy (n = 3). The median patient age was 58 years (range, 24 to 77 years), and 64% were males. The median time from HCT/CAR-T therapy to SARS-CoV-2 infection was 17.7 months (range, 0.2 to 201.9 months), and 22% of the patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T therapy. The primary hematologic disorders were plasma cell (36%), myeloid (38%), and lymphoid (26%) malignancies. Myeloablative conditioning was performed in 62% of patients. Donors were autologous (45%), matched sibling (15%), matched unrelated (21%), and haploidentical (19%). Prior history of grade II-IV acute graft-versus-host disease (GVHD), active GVHD, and current immunosuppressive therapy (IST) was noted in 22%, 31%, and 36% of patients, respectively. Concurrent infections were observed in 19%. Lymphopenia ( P = .049) and high serum ferritin concentration ( P = .020) were associated with mortality. COVID-19 severity was mild in 50% of the patients, moderate in 22%, and severe in 28%. Clinical findings included pneumonia or abnormal chest imaging (in 50%), hypoxia (28%), intensive care unit admission (19%), and mechanical ventilation (10%). Therapies included remdesivir (in 41%), convalescent plasma (35%), dexamethasone (22%), monoclonal antibodies (19%), and tocilizumab (3%). The median duration of viral shedding (positive SARS-CoV-2 PCR) was 7.7 weeks (range, 2 to 18.7 weeks), and 2 patients had a persistent infection for >5 months post-CAR-T therapy. After a median follow-up of 6.1 months (range, 0.5-13.6 months), the mortality rate was 16% in all patients and 28% in allogeneic HCT recipients. Among 9 patients who died, the median survival after SARS-CoV-2 infection was 23 days (range, 14 to 140 days). In survivors with moderate-severe COVID-19, the median time to recovery was 4.2 weeks (range, 1.1 to 24.7 weeks). Among allogeneic HCT...

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Cellular Therapy During COVID-19: Lessons Learned and Preparing for Subsequent Waves

Cited by 13 publications

References 15 publications

Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy

Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy

Hematopoietic Cell Transplantation is Feasible in Patients with Prior COVID-19 Infection

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

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