title: EBV-negative aggressive B-cell lymphomas of donor origin after allogeneic hematopoietic stem cell transplantation: a report of three cases.
abstract: Post-transplant lymphoproliferative disorders (PTLD) develop as a consequence of iatrogenic immunosuppression, and the majority is associated with EBV. PTLD after allogeneic hematopoietic stem cell transplantation (allo-HCT) are rare. Most cases are donor-derived, reflecting immune reconstitution by malignant transformed donor cells, and are EBV-positive. We report three unusual cases of aggressive EBV-negative PTLD of monomorphic type after allo-HCT. All cases were of donor origin and arose with long latency, 4-12 years after HCT. The patients had a history of severe graft-versus-host disease (GVHD) resulting in prolonged immunosuppression before the diagnosis of lymphoma. In one case, the temporal evolution of the malignant clone was analyzed by clone-specific PCR targeting the immunoglobulin heavy chain rearrangement. A tumor-specific product was already detected 3 years before lymphoma development. This indicates that chronic antigenic stimulation and reduced immune surveillance, may promote the outgrowth of premalignant donor-derived clones after acquisition of additional genetic alterations.
authors.affiliation: a Institute of Pathology and Neuropathology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany ;
authors.forename: Birgit
authors.initials: B
authors.lastname: Federmann
authors.affiliation: a Institute of Pathology and Neuropathology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany ;
authors.forename: Irina
authors.initials: I
authors.lastname: Bonzheim
authors.affiliation: a Institute of Pathology and Neuropathology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany ;
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.affiliation: a Institute of Pathology and Neuropathology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany ;
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martínez
authors.affiliation: a Institute of Pathology and Neuropathology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany ;
authors.forename: Barbara
authors.initials: B
authors.lastname: Mankel
authors.affiliation: b Department of Internal Medicine Hematology and Oncology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany.
authors.forename: Wichard
authors.initials: W
authors.lastname: Vogel
authors.affiliation: b Department of Internal Medicine Hematology and Oncology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Faul
authors.affiliation: b Department of Internal Medicine Hematology and Oncology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bethge
authors.affiliation: a Institute of Pathology and Neuropathology , University Hospital and Comprehensive Cancer Center Tuebingen, University of Tuebingen , Tuebingen , Germany ;
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D001706:Biopsy; D060965:Clonal Evolution / Q000235:genetics; D003131:Combined Modality Therapy; D003952:Diagnostic Imaging; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: Clinical results; lymphoma and Hodgkin disease; manipulation of the immune response