title: Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment.
abstract: Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD.
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: angela.chiereghin@gmail.com.
authors.forename: Angela
authors.initials: A
authors.lastname: Chiereghin
authors.affiliation: Department of Specialised, Experimental, and Diagnostic Medicine, Hematopathology Section, St. Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: clarabertuzzi@gmail.com.
authors.forename: Clara
authors.initials: C
authors.lastname: Bertuzzi
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: giulia.piccirilli@yahoo.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Piccirilli
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: liliana.gabrielli@aosp.bo.it.
authors.forename: Liliana
authors.initials: L
authors.lastname: Gabrielli
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: diegosquarzoni@yahoo.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Squarzoni
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: turellogabriele@gmail.com.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Turello
authors.affiliation: Institute of Hematology and Medical Oncology, "L. and A. Seràgnoli", St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: ferioli.martina@alice.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Ferioli
authors.affiliation: Institute of Hematology and Medical Oncology, "L. and A. Seràgnoli", St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: sessamariarosaria@gmail.com.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Sessa
authors.affiliation: Institute of Hematology and Medical Oncology, "L. and A. Seràgnoli", St. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: francesca.bonifazi@unibo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonifazi
authors.affiliation: Department of Specialised, Experimental, and Diagnostic Medicine, Operative Unit of Nuclear Medicine, St. Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: luciaironic@hotmail.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Zanoni
authors.affiliation: Department of Specialised, Experimental, and Diagnostic Medicine, Hematopathology Section, St. Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: elena.sabattini@aosp.bo.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Sabattini
authors.affiliation: Department of Specialised, Experimental, and Diagnostic Medicine, Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: tiziana.lazzarotto@unibo.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lazzarotto
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000097:blood; D042241:Early Diagnosis; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy; D006084:Graft Rejection / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D008297:Male; D015166:Monitoring, Immunologic; D000069283:Rituximab / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D004279:DNA, Viral; D000069283:Rituximab
keywords: Allogeneic bone marrow transplant; Anti-CD20 monoclonal antibody (rituximab); EBV DNA load; EBV-PTLD; EBV-specific T-cell responses