Management of Post-Transplant Lymphoproliferative Disorders in the Real Life: The French Attitude Between 2010 and 2013
Authors: Boussen Inès , Algrin Caroline , Rossignol Julien , Durot Eric , Guenounou Sarah , Bonnet Antoine , Delage Jeremy , Gyan Emmanuel , Bijou Fontanet , Milpied Noel , Chauchet Adrien , Tempescul Adrien , Damaj Gandhi , Jaccard Arnaud , Cornillon Jerome , Ifrah Norbert , Leblond Veronique , Choquet Sylvain 
Published: October 2019

Abstract
Introduction
Post-transplant lymphoproliferative disorders (PTLD) are a rare but severe complication occurring after organ transplantation as a result of immunosuppressive therapy (IST). Until recently, there was no consensus regarding best treatment practice. In 2006, a phase 2 trial using a monotherapy with rituximab showed an overall response rate of 44%, with a complete response (CR) rate of 28%. In 2012, the PTLD-1 international multicenter trial evaluating rituximab followed by CHOP chemotherapy proved an efficacy of 90% and an overall survival of 6.6 years in PTLD treatment.
K-virogref is a French national expert network created in 2011 to structure and improve the management of viro-induced cancers, occurring in adult after transplantation, including PTLD.
Within this network, an epidemiological observational study has been set up in September 2013. The aim of our study was to analyze the management of PTLD in France before the creation of the national database of K-virogref.
Patients and methods
We included solid organ or allogeneic stem cell recipients, aged 18 years and above, with a histologically proven PTLD, diagnosed between January 2010 and September 2013 in 19 French hematology departments. We collected from clinical charts data regarding transplant characteristics, PTLD presentation, first-line treatment and outcomes.
Results
The study population consisted of 94 patients, 67% were men and median age was 53 years (ranging 18 - 81 years). The majority of patients received kidney transplantation (54%), followed in almost equal proportion by heart (13%), liver (13%) and allogeneic stem cell transplantation (10%). Most of the time (80% of patients), PTLD occurred more than one year after organ transplantation with a median delay of 7.8 years. Histologically, mainly monomorphic PTLD were observed with 66% of diffuse large B cell lymphoma and PTLD was EBV associated in 54%. At the time of diagnosis, 80% were classified as stage IV according to Ann Arbor. The median follow-up time was 28.3 months (ranging 0.2 - 78 months).
As far as treatment is concerned, modification of IST was performed in 68% of patients but response was rarely evaluable because a specific treatment was often started at the same time. Surprisingly, first line treatment consisted in rituximab alone or rituximab followed by CHOP chemotherapy in only 32% of the patients. Among these patients, the overall response rate was 81% with 55% of CR. Most patients (56%) received chemotherapy (n=11) or immunochemotherapy (n=46) without previous rituximab therapy. For these patients the overall response rate was 71% with a CR rate of 53%. At 1 and 3 years of follow-up, the relapse-free rates were 56% (95% confidence interval (CI) 46% - 68%) and 47% (95% CI 37% - 60%), respectively. Overall, 49% of patients died during follow-up of which 37% due to infectious complications and 32% due to PTLD progression.
Conclusion
This is one of the largest cohort study of PTLD in the literature, providing an overview of epidemiological features, treatments and outcomes of this rare disease. The lag between the management of PTLD and literature data emphasizes the usefulness of a national expert network such as K-virogref in order to generalize a less toxic and more powerful attitude.

Disclosures
Leblond: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Choquet:Celgene: Consultancy; Janssen: Consultancy.