Viral specific T cell therapy in kidney transplant recipients - A single-center experience.


Journal

Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688

Informations de publication

Date de publication:
01 Nov 2023
Historique:
revised: 14 09 2023
received: 07 06 2023
accepted: 06 10 2023
medline: 1 11 2023
pubmed: 1 11 2023
entrez: 1 11 2023
Statut: aheadofprint

Résumé

Viral infections such as adenovirus (ADV), BK virus (BKV), and cytomegalovirus (CMV) after kidney transplantation negatively impact outcomes in transplant recipients despite advancements in screening and antiviral therapy. We describe our experience of using the virus-specific T cell therapy (VSTs) in kidney transplant recipients (KTR) at our transplant center. This is a retrospective, single center review of KTR with ADV, BKV and CMV infections between June 2021 and December 2022. These patients received third party VSTs as part of the management of infections. The immunosuppression, details of infection and outcome data were obtained from electronic medical records. Two cases of ADV infection resolved after one infusion of VSTs. The response rate of BKV and CMV infection was not as robust with close to 50% reduction in median viral load after VSTs. Out of 23 patients, two patients developed chronic allograft nephropathy from membranoproliferative glomerulonephritis and acute rejection. Patients that are resistant to antivirals or who have worsening viremia despite conventional management may benefit from VSTs therapy to treat underlying viral infection. Additional studies are needed to ascertain efficacy and short- and long-term risks secondary to VSTs.

Sections du résumé

BACKGROUND BACKGROUND
Viral infections such as adenovirus (ADV), BK virus (BKV), and cytomegalovirus (CMV) after kidney transplantation negatively impact outcomes in transplant recipients despite advancements in screening and antiviral therapy. We describe our experience of using the virus-specific T cell therapy (VSTs) in kidney transplant recipients (KTR) at our transplant center.
METHODS METHODS
This is a retrospective, single center review of KTR with ADV, BKV and CMV infections between June 2021 and December 2022. These patients received third party VSTs as part of the management of infections. The immunosuppression, details of infection and outcome data were obtained from electronic medical records.
RESULTS RESULTS
Two cases of ADV infection resolved after one infusion of VSTs. The response rate of BKV and CMV infection was not as robust with close to 50% reduction in median viral load after VSTs. Out of 23 patients, two patients developed chronic allograft nephropathy from membranoproliferative glomerulonephritis and acute rejection.
CONCLUSION CONCLUSIONS
Patients that are resistant to antivirals or who have worsening viremia despite conventional management may benefit from VSTs therapy to treat underlying viral infection. Additional studies are needed to ascertain efficacy and short- and long-term risks secondary to VSTs.

Identifiants

pubmed: 37910558
doi: 10.1111/tid.14179
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e14179

Informations de copyright

© 2023 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.

Références

Parajuli S, Jorgenson M, Meyers RO, Djamali A, Galipeau J. Role of virus-specific T Cell therapy for cytomegalovirus and BK infections in kidney transplant recipients. Kidney360. 2021;2(5):905-915. Published 2021 Mar 26. doi:10.34067/KID.0001572021
Florescu DF, Schaenman JM, AST Infectious Diseases Community of Practice. Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13527. doi:10.1111/ctr.13527
Ison MG, Hayden RT. Adenovirus. Microbiol Spectr. 2016;4(4): doi:10.1128/microbiolspec.DMIH2-0020-2015
Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients - Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9): e13512. doi:10.1111/ctr.13512
Purighalla R, Shapiro R, McCauley J, Randhawa P. BK virus infection in a kidney allograft diagnosed by needle biopsy. Am J Kidney Dis. 1995;26(4):671-673. doi:10.1016/0272-6386(95)90608-8
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(Suppl 3): S1-S155. doi:10.1111/j.1600-6143.2009.02834.x
Nankivell BJ, Renthawa J, Sharma RN, Kable K, O'Connell PJ, Chapman JR. BK virus nephropathy: Histological evolution by sequential pathology. Am J Transplant. 2017;17(8):2065-2077. doi:10.1111/ajt.14292
Drachenberg CB, Papadimitriou JC, Chaudhry MR, et al. Histological evolution of BK virus associated nephropathy: Importance of integrating clinical and pathological findings. Am J Transplant 2017. doi:10.1111/ajt.14314
Tzannou I, Papadopoulou A, Naik S, et al. Off-the-shelf virus-specific T cells to treat BK virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr Virus, and adenovirus infections after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2017;35(31):3547-3557. doi:10.1200/JCO.2017.73.0655
Nelson AS, Heyenbruch D, Rubinstein JD, et al. Virus-specific T-cell therapy to treat BK polyomavirus infection in bone marrow and solid organ transplant recipients. Blood Adv. 2020;4(22):5745-5754. doi:10.1182/bloodadvances.2020003073
Feuchtinger T, Opherk K, Bethge WA, et al. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116(20):4360-4367. doi:10.1182/blood-2010-01-262089
Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome [published correction appears in Blood. 2015 Aug 20;126(8):1048. Dosage error in article text] [published correction appears in Blood. 2016 Sep 15;128(11):1533]. Blood. 2014;124(2):188-195. doi:10.1182/blood-2014-05-552729
Rubinstein JD, Zhu X, Leemhuis T, et al. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Blood Adv. 2021;5(17):3309-3321. doi:10.1182/bloodadvances.2021004456
Sester M, Leboeuf C, Schmidt T, Hirsch HH. The “ABC” of virus-specific T cell immunity in solid organ transplantation. Am J Transplant. 2016;16(6):1697-1706. doi:10.1111/ajt.13684
Sester M, Sester U, Alarcon Salvador S, et al. Age-related decrease in adenovirus-specific T cell responses. J Infect Dis. 2002;185(10):1379-1387. doi:10.1086/340502
Manuel O, Husain S, Kumar D, et al. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013;56(6):817-824. doi:10.1093/cid/cis993

Auteurs

Manish Anand (M)

Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Jake Nysather (J)

Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Gregory McGraw (G)

Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Senu Apewokin (S)

Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Ruby Khoury (R)

Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.

Michael S Grimley (MS)

Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.

Shalini Bumb (S)

Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Amit Govil (A)

Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Classifications MeSH