Journal Article

Response to Rituximab-Based Therapy and Risk Factor Analysis in Epstein Barr Virus—Related Lymphoproliferative Disorder After Hematopoietic Stem Cell Transplant in Children and Adults: A Study From the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

Donnelly, J. Peter, Sica, Simona, Matthes, Susanne, de la Camara, Rafael, Fagioli, Franca, Hoek, Jennifer, Tomaszewska, Agnieszka, Hubacek, Petr, Kalwak, Krzysztof, Omar, Hamdy, Gil, Lidia, Styczynski, Jan, Migliavacca, Maddalena, Ljungman, Per, van Biezen, Anja, van der Velden, Walter, Theunissen, Koen, Tridello, Gloria, Diaz, Miguel A., Halkes, Constantijn, Faraci, Maura, Iacobelli, Simona, Martino, Rodrigo, Nozzoli, Chiara, Cesaro, Simone, Balduzzi, Adriana, Einsele, Hermann

2013

Overview

Background. The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)—related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting. Methods. A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease. Results. One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extra-lymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0–1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival. Conclusions. More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.

• Publisher: Oxford University Press
• Subject: Adolescent / Adult / Aged / Antibodies, Monoclonal, Murine-Derived - therapeutic use / ARTICLES AND COMMENTARIES / Biological and medical sciences / Blood / Blood diseases / Child / Child, Preschool / Clinical outcomes / DNA, Viral - blood / Drug therapy / Epstein Barr virus infections / Epstein-Barr virus / Epstein-Barr Virus Infections - drug therapy / Epstein-Barr Virus Infections - epidemiology / Epstein-Barr Virus Infections - surgery / Epstein-Barr Virus Infections - virology / Europe - epidemiology / Factor analysis / Graft vs host disease / Health outcomes / Hematologic and hematopoietic diseases / Hematology / Hematopoietic Stem Cell Transplantation / Herpesvirus 4, Human - isolation & purification / Humans / Immunologic Factors - therapeutic use / Immunomodulators / Immunosuppression / Infant / Infectious diseases / Kaplan-Meier Estimate / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Lymphoproliferative disorders / Lymphoproliferative Disorders - drug therapy / Lymphoproliferative Disorders - epidemiology / Lymphoproliferative Disorders - surgery / Lymphoproliferative Disorders - virology / Medical sciences / Middle Aged / Mortality / Multivariate analysis / Pharmacology. Drug treatments / Predisposing factors / Prescription drugs / Prognosis / Retrospective Studies / Risk Factors / Rituximab / Stem cells / Transplantation / Viral diseases / Viral Load