title: Effect of Irradiation on Incidence of Post-Transplant Lymphoproliferative Disorder after Hematopoietic Cell Transplantation in Miniature Swine.
abstract: Post-transplant lymphoproliferative disease (PTLD) is a major complication of clinical organ and cell transplantation. Conditioning and immunosuppressive regimens that significantly impair T cell immunity, including depleting antibodies and calcineurin inhibitors, increase the risk of PTLD after transplantation. Swine PTLD has been shown to closely resemble human PTLD in morphology, histology, and viral-driven reactivation of B cells. Previously, we reported high incidences of PTLD after hematopoietic cell transplantation (HCT) in miniature swine recipients conditioned with thymic irradiation (TI) in addition to T cell depletion and cyclosporine A monotherapy after transplantation. Replacement of TI with 100 cGy of total body irradiation resulted in similar numbers of B cells early post-transplantation, greater numbers of T cells at day 0, and markedly decreased incidence of PTLD, suggesting that a threshold number of T cells may be necessary to prevent subsequent B cell proliferation and development of overt PTLD. Results from this large cohort of animals provide insight into the important effect of irradiation and T cell immunity on the incidence of PTLD after HCT and reinforce the pig model as a valuable tool for the study of PTLD and HCT.
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; University of Central Florida College of Medicine, Orlando, Florida.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Matar
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Aarti R
authors.initials: AR
authors.lastname: Patil
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Musa
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hanekamp
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Christene A
authors.initials: CA
authors.lastname: Huang
authors.affiliation: Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts; Columbia Center for Translational Immunology, Columbia University, New York, New York. Electronic address: rduranst@gmail.com.
authors.forename: Raimon
authors.initials: R
authors.lastname: Duran-Struuck
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology / Q000662:veterinary; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D011558:Herpesvirus 1, Suid / Q000472:pathogenicity; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015182:Lymphatic Irradiation / Q000009:adverse effects* / Q000379:methods; D008212:Lymphocyte Depletion / Q000009:adverse effects; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000517:prevention & control* / Q000662:veterinary; D013552:Swine; D013553:Swine Diseases / Q000209:etiology / Q000517:prevention & control / Q000821:virology; D013556:Swine, Miniature / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000528:radiation effects; D013950:Thymus Gland / Q000528:radiation effects*; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014412:Tumor Virus Infections / Q000662:veterinary; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase
keywords: Hematopoietic cell transplantation; Post-transplant lymphoproliferative disease