Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
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
Affiliations
Anastasia Papadopoulou
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Kiriakos Koukoulias
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Maria Alvanou
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Vassilios K. Papadopoulos
Blood Bank Department General Hospital of Pella‐Giannitsa Giannitsa Greece
Zoe Bousiou
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Vasiliki Kalaitzidou
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Fotini S. Kika
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Apostolia Papalexandri
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Despina Mallouri
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Ioannis Batsis
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Ioanna Sakellari
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Achilles Anagnostopoulos
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
Evangelia Yannaki
Hematology Department‐Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center “George Papanikolaou” Hospital Thessaloniki Greece
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.
