Christine Wildermann, Germany
University Medical Center Ulm Department of Pediatrics and Adolescent MedicinePresenter of 1 Presentation
SUCCESSFUL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN A PATIENT WITH RECURRENT EBV-INDUCED LYMPHOPROLIFERATION DUE TO A HOMOZYGOUS MISSENSE MUTATION IN 4-1BB
Abstract
Background and Aims
We report on a male patient with a history of recurrent generalized Epstein Barr virus (EBV) positive lymphoproliferation starting with the diagnosis of EBV-positive Hodgkin lymphoma at the age of 4 years. He was born as 2nd child to consanguineous arabic parents. His older brother is healthy. On arrival at our institution with nine years of age he presented with a generalized EBV-positive diffuse large B-cell lymphoma (DLBCL). In a previously initiated “whole exome sequencing” approach a homozygous mutation in TNFRS9 encoding 4-1BB or CD137 had been detected (Alosaimi et al., JACI 2019). 4-1BB is a costimulatory molecule expressed on activated T cells and upon ligation induces a signaling cascade that results in T cell proliferation, cytokine secretion and enhanced effector function.
Methods
According to the immunohistology of the DLBCL we initiated a therapy consisting of daratumumab (anti-CD38 mAb), bortezomib (proteasome inhibitor), dexamethasone and rituximab (anti-CD20 mAb) to achieve clinical and radiological regression of his lymphoma, followed by an allogenic hematopoietic stem cell transplantation (HSCT) from a 10/10 matched unrelated donor, after conditioning with Busulfan (targeted AUC 80mg/l*h), Fludarabine, Thiotepa and Alemtuzumab.
Results
He is currently well and in an excellent clinical condition 4 months after HSCT with complete donor chimerism and clinical remission of the lymphoma.
Conclusions
Patients with a history of recurrent EBV-positive lymphoma on the basis of a primary immunodeficiency caused by mutations in TNFRS9 should be considered for HSCT for permanent cure of the disease.