Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity

Abstract Background Despite routine post‐transplant viral monitoring and pre‐emptive therapy, viral infections remain a major cause of allogeneic hematopoietic cell transplantation‐related morbidity and mortality. Objective We here aimed to prospectively assess the kinetics and the magnitude of cyto...

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Main Authors: Anastasia Papadopoulou, Kiriakos Koukoulias, Maria Alvanou, Vassilios K. Papadopoulos, Zoe Bousiou, Vasiliki Kalaitzidou, Fotini S. Kika, Apostolia Papalexandri, Despina Mallouri, Ioannis Batsis, Ioanna Sakellari, Achilles Anagnostopoulos, Evangelia Yannaki
Format: Article
Language:English
Published: Wiley 2021-08-01
Series:eJHaem
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Online Access:https://doi.org/10.1002/jha2.175
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author Anastasia Papadopoulou
Kiriakos Koukoulias
Maria Alvanou
Vassilios K. Papadopoulos
Zoe Bousiou
Vasiliki Kalaitzidou
Fotini S. Kika
Apostolia Papalexandri
Despina Mallouri
Ioannis Batsis
Ioanna Sakellari
Achilles Anagnostopoulos
Evangelia Yannaki
author_facet Anastasia Papadopoulou
Kiriakos Koukoulias
Maria Alvanou
Vassilios K. Papadopoulos
Zoe Bousiou
Vasiliki Kalaitzidou
Fotini S. Kika
Apostolia Papalexandri
Despina Mallouri
Ioannis Batsis
Ioanna Sakellari
Achilles Anagnostopoulos
Evangelia Yannaki
author_sort Anastasia Papadopoulou
collection DOAJ
description Abstract Background Despite routine post‐transplant viral monitoring and pre‐emptive therapy, viral infections remain a major cause of allogeneic hematopoietic cell transplantation‐related morbidity and mortality. Objective We here aimed to prospectively assess the kinetics and the magnitude of cytomegalovirus‐(CMV), Epstein Barr virus‐(EBV), and BK virus‐(BKV)‐specific T cell responses post‐transplant and evaluate their role in guiding therapeutic decisions by patient risk‐stratification. Study design The tri‐virus‐specific immune recovery was assessed by Elispot, in 50 consecutively transplanted patients, on days +20, +30, +60, +100, +150, +200 post‐transplant and in case of reactivation, weekly for 1 month. Results The great majority of the patients experienced at least one reactivation, while over 40% of them developed multiple reactivations from more than one of the tested viruses, especially those transplanted from matched or mismatched unrelated donors. The early reconstitution of virus‐specific immunity (day +20), favorably correlated with transplant outcomes. Εxpanding levels of CMV‐, EBV‐, and BKV‐specific T cells (VSTs) post‐reactivation coincided with decreasing viral load and control of infection. Certain cut‐offs of absolute VST numbers or net VST cell expansion post‐reactivation were determined, above which, patients with CMV or BKV reactivation had >90% probability of complete response (CR). Conclusion Immune monitoring of virus‐specific T‐cell reconstitution post‐transplant may allow risk‐stratification of virus reactivating patients and enable patient‐tailored treatment. The identification of individuals with high probability of CR will minimize unnecessary overtreatment and drug‐associated toxicity while allowing candidates for pre‐emptive intervention with adoptive transfer of VSTs to be appropriately selected.
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spelling doaj.art-8a80793674994034a868137d8f533acc2023-08-21T14:10:34ZengWileyeJHaem2688-61462021-08-012342843910.1002/jha2.175Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunityAnastasia Papadopoulou0Kiriakos Koukoulias1Maria Alvanou2Vassilios K. Papadopoulos3Zoe Bousiou4Vasiliki Kalaitzidou5Fotini S. Kika6Apostolia Papalexandri7Despina Mallouri8Ioannis Batsis9Ioanna Sakellari10Achilles Anagnostopoulos11Evangelia Yannaki12Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceBlood Bank Department General Hospital of Pella‐Giannitsa Giannitsa GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceHematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki GreeceAbstract Background Despite routine post‐transplant viral monitoring and pre‐emptive therapy, viral infections remain a major cause of allogeneic hematopoietic cell transplantation‐related morbidity and mortality. Objective We here aimed to prospectively assess the kinetics and the magnitude of cytomegalovirus‐(CMV), Epstein Barr virus‐(EBV), and BK virus‐(BKV)‐specific T cell responses post‐transplant and evaluate their role in guiding therapeutic decisions by patient risk‐stratification. Study design The tri‐virus‐specific immune recovery was assessed by Elispot, in 50 consecutively transplanted patients, on days +20, +30, +60, +100, +150, +200 post‐transplant and in case of reactivation, weekly for 1 month. Results The great majority of the patients experienced at least one reactivation, while over 40% of them developed multiple reactivations from more than one of the tested viruses, especially those transplanted from matched or mismatched unrelated donors. The early reconstitution of virus‐specific immunity (day +20), favorably correlated with transplant outcomes. Εxpanding levels of CMV‐, EBV‐, and BKV‐specific T cells (VSTs) post‐reactivation coincided with decreasing viral load and control of infection. Certain cut‐offs of absolute VST numbers or net VST cell expansion post‐reactivation were determined, above which, patients with CMV or BKV reactivation had >90% probability of complete response (CR). Conclusion Immune monitoring of virus‐specific T‐cell reconstitution post‐transplant may allow risk‐stratification of virus reactivating patients and enable patient‐tailored treatment. The identification of individuals with high probability of CR will minimize unnecessary overtreatment and drug‐associated toxicity while allowing candidates for pre‐emptive intervention with adoptive transfer of VSTs to be appropriately selected.https://doi.org/10.1002/jha2.175allogeneic hematopoietic cell transplantationantithymocyte globulingraft versus host diseasepost‐transplant infectionsvirus‐specific T‐cells
spellingShingle Anastasia Papadopoulou
Kiriakos Koukoulias
Maria Alvanou
Vassilios K. Papadopoulos
Zoe Bousiou
Vasiliki Kalaitzidou
Fotini S. Kika
Apostolia Papalexandri
Despina Mallouri
Ioannis Batsis
Ioanna Sakellari
Achilles Anagnostopoulos
Evangelia Yannaki
Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
eJHaem
allogeneic hematopoietic cell transplantation
antithymocyte globulin
graft versus host disease
post‐transplant infections
virus‐specific T‐cells
title Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
title_full Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
title_fullStr Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
title_full_unstemmed Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
title_short Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
title_sort patient risk stratification and tailored clinical management of post transplant cmv ebv and bkv infections by monitoring virus specific t cell immunity
topic allogeneic hematopoietic cell transplantation
antithymocyte globulin
graft versus host disease
post‐transplant infections
virus‐specific T‐cells
url https://doi.org/10.1002/jha2.175
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