Prospective Survey of CMV, Herpesviruses Infections and Diseases in Allo-HSCT

Study Overview
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Brief Summary
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Prospective observational study of epidemiological surveillance, multicenter, non-profit, spontaneous, Italian with objective to describe the incidence of CMV infections and diseases in adult and pediatric patients undergoing allo-HSCT during the first 6 months from transplant. This study will evaluate approximately 1500 subjects (with competitive enrolment) from GITMO investigational centers.

Detailed Description
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This is a prospective observational study of epidemiological surveillance, multicenter, non-profit, spontaneous, italian on patients submitted to allogeneic haematopoietic stem cell transplantation organized under the auspices of the Gruppo Italiano Trapianti di Midollo Osseo that involves the principal Centres active in transplantation of any kind of hematopoietic stem cells in Italy. Allogeneic haematopoietic stem cell transplantation patients continue to be one of the highest risk categories for developing viral infections. Cytomegalovirus infection is the leading viral cause of morbidity and mortality and HHV6 and EBV are other major causes of complications in transplant. The risk of these infections is directly related to the type of transplant. A better and continuous monitoring of Cytomegalovirus and other herpesviruses complication in this setting would contribute to a better knowledge of the evolving epidemiology and would lead to a better use of diagnostic strategies and of preventive and therapeutic measures. This study is aimed to identify epidemiological characteristics of allogeneic haematopoietic stem cell transplantation patients developing cytomegalovirus and other herpesviruses infections, risk factors, diagnostic peculiarities and factors that may guide to pre-emptive therapy versus prophylaxis strategies. Virological monitoring and health care resources utilization in Allogeneic haematopoietic stem cell transplantation recipients according to the different risk of viral infection will be also assessed. This prospective analysis will provide useful information for local clinicians to define tailored antiviral strategies in line with the change of transplantation procedures. All consecutive patients submitted to allogeneic haematopoietic stem cell transplantation will be prospectively monitored for Cytomegalovirus Cytomegalovirus, Herpesvirus human 6 and Virus Epstein-Barr infections and diseases during the six months from transplant, because most of viral infections and diseases occur within this period after transplant. Risk factors, incidence and prognostic factors of each viral infection and disease, as well as diagnostic and therapeutic strategies employed in the various transplant centers, will be evaluated in the overall population and in subpopulations according to different transplant characteristics. The incidence of these infections and diseases will be also collected and described according to the different types of transplant and underlying disease conditions. The Secondary Objectives are: To assess the factors that may affect the incidence and the prognosis of allogeneic haematopoietic stem cell transplantation infections and diseases, as well as of Herpesvirus human 6 and Virus Epstein-Barr infections and related diseases To assess the impact of allogeneic haematopoietic stem cell transplantation infections and diseases on the overall and attributable mortality at 12 months from the transplant To describe the virological diagnostic strategies of allogeneic haematopoietic stem cell transplantation, Herpesvirus human 6 and Virus Epstein-Barr infections and the allogeneic haematopoietic stem cell transplantation specific immunological reconstitution tests used in the various centres To describe the antiviral strategies employed in the various centers and in the various subpopulations of transplant patients with focus on use of antiviral drugs in prophylaxis and therapy and use of allogeneic haematopoietic stem cell transplantation -specific intravenous IVIG in prophylaxis and therapy To evaluate the impact of a local strategy about use of antiviral drugs and allogeneic haematopoietic stem cell transplantation -specific IVIG in prophylaxis and therapy on the epidemiological findings, the clinical evolution of the allogeneic haematopoietic stem cell transplantation infections and diseases and on the Health Care Resources utilization (diagnostic procedures, pharmaco-utilization, hospitalization, outpatient visits). A web system data entry will be used for this study. Data will be stored using specific e-CRFs designed by GITMO committee and includes mainly descriptive variables. Data Center will perform extensive consistency checks and issue electronic Query Forms in case of inconsistent data. Follow-up period for the evaluation of survival will be from the date of transplant until 12 months post-transplant or death. However, patients may not have 12 months follow up and if the patients are not having 12 months of observation due to lost to follow up and not due to mortality, these patients characteristics will be compared with the rest of the patients in order to ascertain there is no bias or estimate the bias. The study will be conducted according to the principles of Good Clinical Practice, the current Italian and European laws and regulations, in agreement with the declaration of Helsinki. The protocol has been written and the study will be conducted according to The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Harmonized Tripartite Guideline for Good Clinical Practice, issued by the European Union. The responsible Local Ethical Committee approval must be obtained before starting the trial. A copy of the patient informed consent form must be submitted to the appropriate authority or committee, together with the protocol for written approval. Written approval of the protocol and informed consent by the responsible and appropriate authority or committee must be obtained prior to recruitment of patients to the study.

Official Title
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A Prospective, Multicenter Survey of Cytomegalovirus (CMV) and Other Herpesviruses Infections and Diseases in Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT) Recipients.

Conditions
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Hematologic Diseases, Stem Cell Transplant Complications, Cytomegalovirus Viremia, Herpesvirus Infection

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prospective observational study of epidemiological surveillance, multicenter, non-profit, spontaneous, Italian with objective to describe the incidence of CMV infections and diseases in adult and pediatric patients undergoing allo-HSCT during the first 6 months from transplant. This study will evaluate approximately 1500 subjects, with competitive enrolment from GITMO investigational centers. Exclusion Criteria: Absence of consent Written information
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with hematological disease<br>Adult and children allogenic Hematopoietic stem cell transplantation recipients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytomegalovirus infection | incidence of Cytomegalovirus after allogeneic haematopoietic stem cell transplantation | 6 months from transplant | 
| Cytomegalovirus disease | incidence of Cytomegalovirus after allogeneic haematopoietic stem cell transplantation | 6 months from transplant | 
| Herpesvirus human 6 infection | incidence of human 6 infection after allogeneic haematopoietic stem cell transplantation | 6 months from transplant | 
| Herpesvirus human 6 disease | incidence of human 6 disease after allogeneic haematopoietic stem cell transplantation | 6 months from transplant | 
| Virus Epstein-Barr infection | incidence of Virus Epstein-Barr infections after allogeneic haematopoietic stem cell transplantation | 6 months from transplant | 
| Virus Epstein-Barr disease | incidence of Virus Epstein-Barr disease after allogeneic haematopoietic stem cell transplantation | 6 months from transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis | These outcome measures will be assessed at 1 year from transplant | 
| Disease Free Survival (DFS) | DFS is defined as the probability of being alive free of disease at any point in time. | These outcome measures will be assessed at 1 year from transplant | 
| Transplant Related Mortality (TRM) | TRM was defined as death due to any transplantation-related cause other than disease | These outcome measures will be assessed at 1 year from transplant | 
| Relapse risk (RR) | RR or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. | These outcome measures will be assessed at 1 year from transplant | 
| Acute Graft-versus-Host Disease | cumulative incidence of acute GvHD (grade II-IV) | These outcome measures will be assessed at 100 days from transplant | 
| chronic graft-versus-host disease | cumulative incidence and severity of chronic graft-versus-host disease | These outcome measures will be assessed at 1 year from transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haematopoietic transplantation, CMV, Herpesviruses