Impact of the Lack of CMV-Specific CD8+ T Cell Response in CMV-Seropositive Donors in CMV Reactivation After Hematopoietic Stem Cells Transplant in CMV-Seropositive Recipients

Study Overview
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Brief Summary
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Donor and recipient CMV-serostatus is one of the risk factor for CMV infection in solid organ transplantation. Recipients with IgG positive anti-CMV are classified as low-risk patients since it is considered that patients also have specific cellular immunity against CMV. However, investigators group has published that around 25% of solid organ transplant candidates lack CMV-specific CD8+ T-cell response (humoral/cellular mismatch) and they are at a higher risk of CMV replication after transplantation. The main goal of this study is to analyze the impact of the humoral/cellular mismatch in hematopoietic stem cell transplantation (HSCT) CMV-seropositive donors on the CMV reactivation after HSCT in CMVseropositive recipients. Investigators will study not only the incidence of CMV reactivation but also the severity (duration and peak viral load), CMV disease and survival. CMV-seropositive patients who receive a HSCT (bone marrow or peripheral blood) from related donors will be consecutively recruited from Reina Sofía Hospital (Córdoba) and Marqués de Valdecilla Hospital (Santander). Patients will be monitored during 12 months after HSCT. CMV-specific CD8+ T-cell response will be determined in their donors, using QuantiFERON-CMV assay, to know the frequency of humoral/cellular mismatch. Innate and adaptive immune reconstitution will be assessed by flow cytometry and experimental QuantiFERON Monitor assay. CMV-specific CD8+ T-cell reconstitution will be determined using QuantiFERON-CMV assay.

Official Title
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Impact of the Lack of CMV-Specific CD8+ T Cell Response in CMV-Seropositive Donors in CMV Reactivation After Hematopoietic Stem Cells Transplant in CMV-Seropositive Recipients

Conditions
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Cytomegalovirus Infection, HSCT

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CMV Seropositive patients who receive a HSCT (Bone marrow or peripheral) blood from related donors >14 years old signed Inform consent form Exclusion Criteria: 1. HIV, HCV, HBV Infection

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the incidence and severity of CMV reactivation in CMV-seropositive patients whose stem cells come from CMV seropositive donors lacking CMV-specific CD8+ T-Cell response [D+(T-)/R+] in comparison with D+(T+)/R+ and D-/R+ patients | To determine the incidence and severity of CMV reactivation in CMV-seropositive patients whose stem cells come from CMV seropositive donors lacking CMV-specific CD8+ T-Cell response [D+(T-)/R+] in comparison with D+(T+)/R+ and D-/R+ patients | During the 6 months after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To analyze the frequency of CMV-seropositive stem cells donors lacking CMV-specific CD8+ T-Cell response [D+(T-)] | To analyze the frequency of CMV-seropositive stem cells donors lacking CMV-specific CD8+ T-Cell response [D+(T-)] | 3 years | 
| Innate and adaptive immune reconstitution: Units (percentage and absolute number) | To analyze the differences in the innate, adaptive as well as CMV-specific immune reconstitution between D+(T-)/R+ vs D-/R+ and D+(T+)/R+ patients | 3 years | 
| To evaluate the incidence of CMV disease as well as the type and severity of the disease in D+(T-)/R+ vs D-/R+ and D+(T+)/R+ patients | To evaluate the incidence of CMV disease as well as the type and severity of the disease in D+(T-)/R+ vs D-/R+ and D+(T+)/R+ patients | 3 years | 
| CMV-specific immune reconstitution: Units (Percentage respect to CD8+ T cells) and interferon-gamma production (IU/mL). | To test the differences in mortality/survival between the three groups | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cells transplantation, Cytomegalovirus infection, CMV-Specific Immune response, Immune reconstitution, Humoral/Cellular mismatch, Interferon-gamma