Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines

Abstract

E pstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virusspecific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged. Management of Epstein-Barr Virus infections

Lymphocyte subset at time of Epstein‐Barr viremia post‐allogeneic hematopoietic stem cell transplantation in children may predict development of post‐transplant lymphoproliferative disease: CD8:CD20 ratio as a sensitive predictor

“…Proven PTLD diagnosis was based on the previously published WHO criteria . Probable PTLD was diagnosed based on the presence of the following: significant EBV viremia together with significant lymphadenopathy, hepatosplenomegaly, or other end‐organ manifestations without tissue diagnosis, in the absence of other documented causes …”

“…Quantitative reduction in CD3 + and CD4 + T cells and qualitative impairment of CD8 + T cells have been reported to increase risk of development of PTLD . Moreover, utilizing both CD3 + T‐cell number and EBV viral load to trigger preemptive rituximab therapy was shown to be an effective strategy .…”

Immunotherapy for transplantation-associated viral infections

“…Despite these measures, up to one-third of patients with clinically apparent PTLD will succumb to uncontrolled disease, such that cellular therapeutic options are of great clinical relevance (68).…”

Role of PET‐CT in management of posttransplant lymphoproliferative disorder

“…Recently, the 6th European Conference on Infections in Leukemia (ECIL‐6) presented guidelines on management of PTLD after stem cell transplantation . PET‐CT imaging was assessed to have a key role during the diagnostic workup and clinical staging, both for children and adults.…”