Cargando…

Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease

Hematopoietic stem cell transplantation (HSCT) is being increasingly used as a curative approach for sickle cell disease (SCD). With the risk of graft-versus-host disease (GVHD), especially in the human leukocyte antigen−mismatched donors, intense immunosuppression is required leading to an increase...

Descripción completa

Detalles Bibliográficos
Autores principales: Kinoshita, Hannah, Mandava, Mamatha, Jensen-Wachspress, Mariah, Lang, Haili, Joy, Elisabeth, Tanna, Jay, McCann, Chase D., O’Brien, Samuel, Burnett, Sianna, Shibli, Abeer, Hoq, Fahmida, Bhatia, Monica, Hanley, Patrick J., Dávila Saldaña, Blachy, Mahadeo, Kris M., Bollard, Catherine M., Keller, Michael D., Abraham, Allistair
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196792/
https://www.ncbi.nlm.nih.gov/pubmed/36516084
http://dx.doi.org/10.1182/bloodadvances.2022008219
_version_ 1785044420323704832
author Kinoshita, Hannah
Mandava, Mamatha
Jensen-Wachspress, Mariah
Lang, Haili
Joy, Elisabeth
Tanna, Jay
McCann, Chase D.
O’Brien, Samuel
Burnett, Sianna
Shibli, Abeer
Hoq, Fahmida
Bhatia, Monica
Hanley, Patrick J.
Dávila Saldaña, Blachy
Mahadeo, Kris M.
Bollard, Catherine M.
Keller, Michael D.
Abraham, Allistair
author_facet Kinoshita, Hannah
Mandava, Mamatha
Jensen-Wachspress, Mariah
Lang, Haili
Joy, Elisabeth
Tanna, Jay
McCann, Chase D.
O’Brien, Samuel
Burnett, Sianna
Shibli, Abeer
Hoq, Fahmida
Bhatia, Monica
Hanley, Patrick J.
Dávila Saldaña, Blachy
Mahadeo, Kris M.
Bollard, Catherine M.
Keller, Michael D.
Abraham, Allistair
author_sort Kinoshita, Hannah
collection PubMed
description Hematopoietic stem cell transplantation (HSCT) is being increasingly used as a curative approach for sickle cell disease (SCD). With the risk of graft-versus-host disease (GVHD), especially in the human leukocyte antigen−mismatched donors, intense immunosuppression is required leading to an increased risk of viral infection. Post-HSCT, adoptive transfer of virus-specific T-cell (VST) therapies have not been well-studied in patients with SCD. Here, we report the outcomes of patients with SCD at a single-center who received VSTs after transplant to prevent or treat viral infections. Thirteen patients who received HSCT from human leukocyte antigen-matched (n = 9) or -mismatched (n = 4) donors for SCD were treated with a total of 15 VST products for the treatment or prophylaxis of multiple viruses (cytomegalovirus, Epstein-Barr virus, adenovirus, BK virus, human herpes virus 6 +/− human parainfluenza virus 3). Of the patients evaluated, 46.2% (n = 6)) received VSTs as treatment for viral infection. Eighty percent of patients with active viremia (n = 4/5) achieved remission of at least 1 target virus. Seven additional patients (53.8%) received VSTs prophylactically and 6 of 7 (85.7%) remained virus-free after infusion. No immediate infusion-related toxicities occurred, and severe de novo acute GVHD occurred in only 2 (15.4%) patients. Given the good safety profile, high-rate of clinical responses and sustained remissions when administered with standard antiviral treatments, the routine use of VSTs after HSCT as prophylaxis or treatment may improve the overall safety of transplant for patients with SCD.
format Online
Article
Text
id pubmed-10196792
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher The American Society of Hematology
record_format MEDLINE/PubMed
spelling pubmed-101967922023-05-20 Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease Kinoshita, Hannah Mandava, Mamatha Jensen-Wachspress, Mariah Lang, Haili Joy, Elisabeth Tanna, Jay McCann, Chase D. O’Brien, Samuel Burnett, Sianna Shibli, Abeer Hoq, Fahmida Bhatia, Monica Hanley, Patrick J. Dávila Saldaña, Blachy Mahadeo, Kris M. Bollard, Catherine M. Keller, Michael D. Abraham, Allistair Blood Adv Immunobiology and Immunotherapy Hematopoietic stem cell transplantation (HSCT) is being increasingly used as a curative approach for sickle cell disease (SCD). With the risk of graft-versus-host disease (GVHD), especially in the human leukocyte antigen−mismatched donors, intense immunosuppression is required leading to an increased risk of viral infection. Post-HSCT, adoptive transfer of virus-specific T-cell (VST) therapies have not been well-studied in patients with SCD. Here, we report the outcomes of patients with SCD at a single-center who received VSTs after transplant to prevent or treat viral infections. Thirteen patients who received HSCT from human leukocyte antigen-matched (n = 9) or -mismatched (n = 4) donors for SCD were treated with a total of 15 VST products for the treatment or prophylaxis of multiple viruses (cytomegalovirus, Epstein-Barr virus, adenovirus, BK virus, human herpes virus 6 +/− human parainfluenza virus 3). Of the patients evaluated, 46.2% (n = 6)) received VSTs as treatment for viral infection. Eighty percent of patients with active viremia (n = 4/5) achieved remission of at least 1 target virus. Seven additional patients (53.8%) received VSTs prophylactically and 6 of 7 (85.7%) remained virus-free after infusion. No immediate infusion-related toxicities occurred, and severe de novo acute GVHD occurred in only 2 (15.4%) patients. Given the good safety profile, high-rate of clinical responses and sustained remissions when administered with standard antiviral treatments, the routine use of VSTs after HSCT as prophylaxis or treatment may improve the overall safety of transplant for patients with SCD. The American Society of Hematology 2022-12-15 /pmc/articles/PMC10196792/ /pubmed/36516084 http://dx.doi.org/10.1182/bloodadvances.2022008219 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Immunobiology and Immunotherapy
Kinoshita, Hannah
Mandava, Mamatha
Jensen-Wachspress, Mariah
Lang, Haili
Joy, Elisabeth
Tanna, Jay
McCann, Chase D.
O’Brien, Samuel
Burnett, Sianna
Shibli, Abeer
Hoq, Fahmida
Bhatia, Monica
Hanley, Patrick J.
Dávila Saldaña, Blachy
Mahadeo, Kris M.
Bollard, Catherine M.
Keller, Michael D.
Abraham, Allistair
Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease
title Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease
title_full Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease
title_fullStr Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease
title_full_unstemmed Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease
title_short Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease
title_sort outcomes following posttransplant virus-specific t-cell therapy in patients with sickle cell disease
topic Immunobiology and Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196792/
https://www.ncbi.nlm.nih.gov/pubmed/36516084
http://dx.doi.org/10.1182/bloodadvances.2022008219
work_keys_str_mv AT kinoshitahannah outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT mandavamamatha outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT jensenwachspressmariah outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT langhaili outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT joyelisabeth outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT tannajay outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT mccannchased outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT obriensamuel outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT burnettsianna outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT shibliabeer outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT hoqfahmida outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT bhatiamonica outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT hanleypatrickj outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT davilasaldanablachy outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT mahadeokrism outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT bollardcatherinem outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT kellermichaeld outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease
AT abrahamallistair outcomesfollowingposttransplantvirusspecifictcelltherapyinpatientswithsicklecelldisease