Transfusion-related Epstein-Barr Virus (EBV) Infection Among Allogeneic Stem Cell Transplant Pediatric Recipients: a Multicenter Prospective Cohort Study (TREASuRE Study)
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 324
- 试验地点
- 3
- 主要终点
- Measure of the risk of EBV infection in HSCT pediatric recipients from blood products transfusions (red blood cells, platelets, plasma) by EBV PCR and serology testing
研究概览
简要总结
In many countries, numerous steps are taken to minimize the risk of infection from transfused blood products. Typically, blood banking organisations will screen for an array of infectious pathogens as part of their quality control protocol. While transmission of these tested agents via transfusion has become exceedingly rare, the risk of transfusion-transmitted infections for which testing is not currently performed continues to be a concern. Among these untested infectious agents is Epstein-Barr virus (EBV, also known as human herpesvirus-4). Most notably, infection with this virus in transplant recipients can give rise to a malignant disorder called post-transplant lymphoproliferative disease (PTLD), a life-threatening complication which is due to the uncontrolled expansion of EBV-infected cells. It is also associated with other complications such as hepatitis, hemophagocytic syndrome, etc. in transplant population. It is recognised that EBV infection can occurred in transfused immune suppressed graft recipients but the origin of the viral infection is still a matter of debate. It is a known fact that the EBV already present in the recipient's blood can undergo reactivation due to immune suppression. However, because it is known to occur more frequently in patients who are EBV-seronegative at the time of transplant, it is also accepted that primary infection contracted via an infected graft can be a source of virus. The question we are seeking to answer is whether immune suppressed graft recipients can acquire primary EBV infection via transfusion of blood products. EBV is present in the blood of most adults and cases of EBV transfusion-related infection have been reported. Transplant populations are generally transfused with very large volumes of blood products and our recent pilot study supports the possibility that transfusion-related EBV infection can be transmitted to pediatric hematopoietic stem cell (HSCT) recipients (Trottier et al, 2012). The aim of this study is to analyse the risk of EBV transmission through blood product transfusion in pediatric allogeneic HSCT patients.
详细描述
All patients will be recruited approximately 1 month before transplantation (before pre-transplant conditioning chemotherapy and pre-surgery evaluation) and followed-up to 1 year post-transplantation. Thus, each subject will be followed-up for a 13-month period. At entry, a questionnaire will document socio-demographic data and pre-transplant clinical indicators such as age, gender, primary diagnosis, previous chemotherapy, previous transfusion, etc. During follow-up, case report forms (CRF) will allow prospective reporting of all variables pertaining to EBV serology, transplantation, blood product transfusion and EBV complication.
EBV PCR and serology testing:
This study is observational and will use the results of EBV PCR and EBV serology allowing our objectives to be achieved with considerable cost reduction. Time zero is when the patient receives his graft. Some tests are done before time zero (pre-transplant array of test including EBV serology). After time zero, in all sites, there is a follow-up treatment protocol including EBV PCR testing. Pre-transplant sera from recipients and donors are tested by standard methods for mmunoglobulin G (IgG) antibodies to the EBV capsid antigen (VCA), IgG antibodies to EBV early antigens (EA) and anticomplement antibodies to the EBV nuclear antigens (EBNA). EBV DNA testing is performed by quantitative polymerase chain reaction (PCR). Each centre has an established threshold value for determining viral load. In order to properly interpret the patients' viral load data from each participating center, all will be required to fill out a site report form (SRF) to describe their testing method for EBV PCR and EBV serology.
Pre-transplant measurement of EBV antibodies:
Serology testing, including EBV seroprevalence, is always done in all participating sites during the pre-transplant evaluation (before conditioning chemotherapy) in both donors and recipients. Serology testing is the test that is used to confirm the presence of the virus in the blood. For grafts provided by external sites, donor blood samples are always available and will allow for serology testing at the laboratory center where the transplantation is performed. Serology testing will not be done on cord-blood donor as it is virtually always negative for EBV. Donors and recipients will be classified according to their pre-transplant serology status as: 1) having past infection (VCA and EBNA IgG titers > 10), 2) having recent infection or being immune suppressed (VCA IgG titers > 10 and EBNA IgG titers < 10), 3) having reactivated infection (VCA, EBNA and EA IgG titers > 10), or 4) being naïve (no serological sign of prior infection).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients receiving allogeneic HSCT (marrow, cord-blood, and peripheral blood stem cells)
- •age below 21 years
- •first HSCT
排除标准
- 未提供
结局指标
主要结局
Measure of the risk of EBV infection in HSCT pediatric recipients from blood products transfusions (red blood cells, platelets, plasma) by EBV PCR and serology testing
时间窗: 1 month before transplantation to 1 year post-transplantation
EBV PCR and serology testing every 1-2 weeks until hospital discharge and at follow-up visit thereafter.
次要结局
- Incidence of post-transplant EBV infection in allogeneic HSCT pediatric recipients stratified according to the EBV serostatus of the patient and the EBV status of the graft(1 month before transplantation to 1 year post-transplantation)
- Incidence of "high or increasing viral load EBV infection and PTLD" in allogeneic HSCT pediatric recipients stratified according to the EBV serostatus of the patient and the EBV status of the graft(1 month before transplantation to 1 year post-transplantation)
- Description of other complications related to EBV infection in this transplant population(1 month before transplantation to 1 year post-transplantation)
研究者
Helen Trottier
Associate Professor
St. Justine's Hospital