Invasive pulmonary Successful treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disease with central nervous system involvement following allogeneic haematopoietic stem cell transplantation –a case study

Abstract

Post-transplant lymphoproliferative disease (PTLD) is a rare but severe form of Epstein-Barr virus (EBV)-driven complication that develops in patients after haematopoietic stem cell transplantation. In rare cases it manifests as primary central nervous system (CNS) involvement, which is thought to be the most unfavourable localisation with respect to outcome. Disease confined to the CNS is much more challenging than systemic PTLD, and one of the contributing factors is the limited drug penetration across the blood-brain barrier. We describe the case of a 29-year-old woman who was successfully treated for PTLD with CNS involvement. The patient was diagnosed with T-cell lymphoblastic lymphoma and underwent the procedure of haematopoietic stem cell transplantation from an unrelated donor. Two months after transplantation she manifested severe headache and progressive mental deterioration accompanied by enlargement of the lymph nodes. Magnetic resonance imaging (MRI) scan revealed segmental, asymmetrical thickening of the meninges. Based on the clinical picture and the laboratory findings diagnosis of PTLD was made. The patient was effectively treated with reduction of immunosuppressive therapy and intravenous rituximab. Initially started intrathecal chemotherapy was stopped due to iatrogenic complications. We conclude that in this case the involvement of meninges in the course of the lymphoproliferative process might have compromised the blood-brain barrier. This factor probably improved rituximab's penetration to CNS, contributing to our patient's recovery.

Epstein-Barr Virus-Related Post-Transplantation Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation

“…In a retrospective analysis of 84 patients with primary CNS PTLDs, most of the cases (83%) occurred late (>1 year posttransplantation) and were EBV-positive (>90%), with median PFS and OS at 8 months and 17 months, respectively [69]. Treatment strategies include RI [2,72], chemotherapy (eg, highdose methotrexate or high-dose cytarabine) [2] with or without rituximab [73], i.v. or intrathecal rituximab [6,14,72], EBV-CTLs [46,62], and radiation [1].…”

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

“…To date, no standard therapy has been accepted. Possible therapeutic options include: (i) chemotherapy±rit-uximab in line with primary CNS lymphoma protocols based on high dose methotrexate and/or cytarabine 82 or hydroxyurea; 83 (ii) monotherapy with rituximab, either systemic 3,84 or intrathecal; 85 (iii) T-cell therapy with EBVspecific CTLs; 63,68 (iv) radiotherapy. Response to therapy.…”

Epstein-Barr Virus–related Posttransplant Lymphoproliferative Disorder in Children

“…Both after solid organ transplantation or HSCT procedures, CNS-PTLD is associated with significantly inferior survival in comparison to non-CNS-PTLD. 15 Radiotherapy alone has a significant enhancing effect on the survival of CNS-PTLD patients. 16 The diagnosis of PTLD represented a challenge and may arise in different anatomic sites.…”