Study duration :
Total study duration: 37 months Duration of recruitment: 24 months Duration of participation for each patient: 13 months
Inclusion criteria:
Retrospective study: Patient who underwent HSCT, in Saint-Antoine hospital, between 2010-2015, treated by rituximab for high level EBV-DNAemia (above 3.3 log copies/mL).
Prospective study: Patients who underwent HSCT, in Saint-Antoine hospital and la Pitié-Salpêtrière, in 2016-2017, treated by rituximab for high level EBV-DNAemia (above 10 000c/mL), And/or having post-transplant lymphoproliferative diseases(PTLD) Concerned population Allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients with a high Epstein-Barr virus (EBV) viral load
Study endpoints:
Primary endpoint (linked to the primary objective) Respective percentages of latent versus replicative EBV profiles, defined by the methylation level of specific sites of EBV genome, in a cohort of HSCT patients with a high EBV viral load (above 3.3 log copies/ml) before the initiation of treatment per rituximab. A methylation index will be calculated from the respective differences of the "Cycle thresholds" of the methyl-qPCR performed on patients blood samples Secondary endpoints (linked to the secondary objectives)
1. Characteristics of the patients according to the EBV q-PCR results
2. Patients' outcome according to the EBV profile defined by the methyl-qPCR :
* Response to Rituximab infusion (EBV DNA-emia \< 3.3 log copies/mL) after a maximum of 4 infusions)
* Disease-free survival (DFS) at 12 months defined as survival without relapse
* Overall survival (OS) at 12 months
* Relapse incidence (RI) at 12 months
* Non-relapse mortality (NRM) at 12 months
* Number of post-HSCT infections within 12 months
Statistical Analysis :
1. Comparison between characteristics of latent and lytic genomes will be performed using parametric (Student t-test) or non-parametric (Mann Whitney test) when appropriate for continuous variables, Chi-Square test for qualitative variables.
Multivariate analysis for determination of risk factors associated with "lytic EBV" profiles will be performed using logistic regression.
2. Correlation between "latent versus lytic EBV" profiles" and response to rituximab infusion will be performed using logistic regression including in the model all other factors potentially associated to the response to rituximab. OS and DFS will be estimated by using the Kaplan-Meier method. Cumulative incidences of RI and NRM will be calculated from the date of inclusion to the date of relapse or death in remission, respectively, with the other event being the competing risk. Death or progression will be considered as a competing events for estimating the incidence of acute GVHD. Multivariate analyses for survival endpoints will be performed using the Cox proportional hazards model. The type I error rate is fixed at 0.05 for determination of factors associated with time to event outcomes. All statistical analyses will be performed with R software packages (R Foundation for Statistical Computing, Vienna, Austria)
