HHV8 and Solid Organ Transplantation

Screening for HHV8 Infection in Solid Organ Transplantation Donors, Candidates and Recipients

Solid organ transplant candidates will undergo serological screening for HHV8 at time of listing and transplantation.

In the event of a recipient/donor mismatch R-/D+ or in the presence of a seropositive recipient (R+), blood levels of HHV8 DNA will be monitored together with specific IGRA for HHV8.

Study Overview

• Status: Recruiting
• Conditions: Castleman Disease; Kaposi Sarcoma; Liver Transplant; Complications; Lung Transplant; Complications; Kidney Transplant; Complications; HHV8; HHV8 Infection; HHV8-Related Malignant Neoplasm
• Intervention / Treatment: Diagnostic test: Diagnostic test for HHV8 exposure

Detailed Description

Patients on the waiting list for solid organ transplantation will undergo serological screening for HHV8 (lytic and latent antigens) in the pre-transplant phase, both at time of listing and then at the time of transplantation; if seropositivity is found, further investigations will be performed, i.e. blood levels of HHV8 DNA and specific Elispot for HHV8.

As for donors, serological testing for HHV8 (lytic and latent antigens) will be performed.

AFTER SOLID ORGAN TRANSPLANTATION

• Patients found HHV8 seropositive in the pretransplant phase (R +), being at risk of HHV8 reactivation, will be monitored monthly in terms of viremia (HHV8 DNA) and specific IGRA for HHV8 for the first 6 months after transplantation and subsequently every 3 months up to 12 months post transplant.
• In case of patients who were found HHV8 seronegative at time of transplantation, donor serology will be evaluated. In case of R-/D+ mismatch, SOT recipients will receive the same monitoring of R + patients (blood levels of HHV8 DNA and specific IGRA for HHV8 monthly for the first 6 months and then every 3 months up to 12 months after transplantation).
• With reference to lung transplant patients, in cases of R + or R- / D +, HHV8 DNA will also be searched on the BAL obtained during surveillance bronchoscopies (usually at 3, 6 and 12 months after transplantation).

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Valeria Rossetti, MD; Phone Number: 0039 2 55033782; Email: valeria.rossetti@policlinico.mi.it
• Study Contact Backup: Name: Letizia Corinna Morlacchi, MD; Phone Number: 0039 2 55033782; Email: letizia.morlacchi@policlinico.mi.it

Study Locations

• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
    • Contact: Valeria Rossetti, MD; Phone Number: 00393395605478; Email: valeria.rossetti@policlinico.mi.it
    • Contact: Letizia Corinna Morlacchi, MD; Phone Number: 00393338158766; Email: letizia.morlacchi@policlinico.mi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

We will include all the donors being used for transplantation purposes at our centre and the respective recipients.

Description

SOT DONORS:

Inclusion Criteria:

• all donors used for transplantation purposes (kidney, liver, lung), including living donors in case of kidney transplantation

Exclusion Criteria:

• None

SOT CANDIDATES RECIPIENTS:

Inclusion Criteria:

• All patients listed for solid organ transplantation (lung, liver and kidney)

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SOT Donors; Solid organ transplantation donors	Diagnostic test: Diagnostic test for HHV8 exposure; Venipuncture for blood sampling
LuTx candidates and recipients; Lung transplant candidates and recipients	Diagnostic test: Diagnostic test for HHV8 exposure; Venipuncture for blood sampling
LTx candidates and recipients; Liver transplant candidates and recipients	Diagnostic test: Diagnostic test for HHV8 exposure; Venipuncture for blood sampling
KTx candidates and recipients; Kidney transplant candidates and recipients	Diagnostic test: Diagnostic test for HHV8 exposure; Venipuncture for blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of HHV8 seropositivity among SOT donors and recipients	Incidence of HHV8 seropositivity among solid organ transplantations donors, candidates and recipients	2021-2024
Incidence of HHV8 mismatch between SOT donors and recipients	Incidence of HHV8 mismatch between solid organ transplantations donors and recipients	2021-2024

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of HHV8 related disease after solid organ transplantation	Incidence of HHV8 related disease after solid organ transplantation	2021-2025

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Publications and helpful links

General Publications

• Tzannou I, Papadopoulou A, Naik S, Leung K, Martinez CA, Ramos CA, Carrum G, Sasa G, Lulla P, Watanabe A, Kuvalekar M, Gee AP, Wu MF, Liu H, Grilley BJ, Krance RA, Gottschalk S, Brenner MK, Rooney CM, Heslop HE, Leen AM, Omer B. 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 Nov 1;35(31):3547-3557. doi: 10.1200/JCO.2017.73.0655. Epub 2017 Aug 7.
• Polizzotto MN, Uldrick TS, Wyvill KM, Aleman K, Marshall V, Wang V, Whitby D, Pittaluga S, Jaffe ES, Millo C, Tosato G, Little RF, Steinberg SM, Sereti I, Yarchoan R. Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS). Clin Infect Dis. 2016 Mar 15;62(6):730-738. doi: 10.1093/cid/civ996. Epub 2015 Dec 12. Erratum In: Clin Infect Dis. 2018 Mar 5;66(6):985.
• Chiereghin A, Barozzi P, Petrisli E, Piccirilli G, Gabrielli L, Riva G, Potenza L, Cappelli G, De Ruvo N, Libri I, Maggiore U, Morelli MC, Potena L, Todeschini P, Gibertoni D, Labanti M, Sangiorgi G, La Manna G, Pinna AD, Luppi M, Lazzarotto T. Multicenter Prospective Study for Laboratory Diagnosis of HHV8 Infection in Solid Organ Donors and Transplant Recipients and Evaluation of the Clinical Impact After Transplantation. Transplantation. 2017 Aug;101(8):1935-1944. doi: 10.1097/TP.0000000000001740.
• Pietrosi G, Vizzini G, Pipitone L, Di Martino G, Minervini MI, Lo Iacono G, Conaldi PG, Grossi P, Lamonaca V, Galatioto L, Gruttadauria S, Gridelli B. Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study. Am J Transplant. 2011 Dec;11(12):2715-23. doi: 10.1111/j.1600-6143.2011.03769.x. Epub 2011 Oct 3.
• Riva G, Luppi M, Barozzi P, Forghieri F, Potenza L. How I treat HHV8/KSHV-related diseases in posttransplant patients. Blood. 2012 Nov 15;120(20):4150-9. doi: 10.1182/blood-2012-04-421412. Epub 2012 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Lung transplant; Kidney transplant; Kaposi Sarcoma; Liver transplant; Castleman Disease; Solid organ transplant; HHV8
• Additional Relevant MeSH Terms: Virus Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; DNA Virus Infections; Herpesviridae Infections; Neoplasms, Vascular Tissue; Neoplasms; Sarcoma; Infections; Castleman Disease; Sarcoma, Kaposi
• Other Study ID Numbers: S_OTTO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No