title: Choice of immunosuppression influences cytomegalovirus DNAemia in cynomolgus monkey (Macaca fascicularis) islet allograft recipients.
abstract: This retrospective study reviews the results of our experience with the occurrence of CMV DNAemia in islet cell transplanted cynomolgus monkeys subjected to different immunosuppressive protocols, including induction treatment with thymoglobulin (TMG), with a combination of thymoglobulin and fludarabine (FLUD), with cyclophosphamide, or with daclizumab. CMV DNA in the peripheral blood (CMV DNAemia) of 47 monkeys was quantified by real-time PCR on a weekly to biweekly basis. As compared to other immunosuppressive regimens, and in association with greater decreases in WBC, lymphocyte, CD3+CD4+, and CD3+CD8+ lymphocyte counts, frequent CMV DNAemia occurred earlier (within the first month posttransplant), and was of greater severity and duration in recipients of TMG ± FLUD. Treatment of recipients with alternative induction agents that resulted in less dramatic reductions in WBC and lymphocyte counts, however, resulted in occurrence of CMV DNAemia after postoperative day 60. The frequency, average intensity, duration, and area under the curve (AUC) for CMV DNAemia in animals receiving TMG ± FLUD were 75-100%, 4.02 ± 1.75 copies/ng DNA, 23.0 ± 5.3 days, and 367.0 ± 121.1 days × copies/ng DNA, respectively; corresponding values in animals receiving other treatments (0-44%, 0.19 ± 0.10 copies/ng DNA, 0.5 ± 0.3 days, and 75.4 ± 40.2 days × copies/ng DNA, respectively) were significantly different. The value of WBC, T and B cells at the nadir of cell depletion greatly affects the occurrence of CMV DNAemia. No animals developed CMV DNAemia within the next 3 weeks when the lowest value of WBC, lymphocyte, CD3+, CD3+CD4+, CD3+CD8+, or CD20+ cells was above 4500, 1800, 300, 200, 150, or 300 cells/μl, respectively. Oral valganciclovir prophylaxis did not completely prevent the appearance of CMV DNAemia.
authors.affiliation: Diabetes Research Institute, University of Miami School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA. dhan@med.miami.edu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Han
authors.forename: Dora M
authors.initials: DM
authors.lastname: Berman
authors.forename: Melissa
authors.initials: M
authors.lastname: Willman
authors.forename: Peter
authors.initials: P
authors.lastname: Buchwald
authors.forename: Daniel
authors.initials: D
authors.lastname: Rothen
authors.forename: Norman M
authors.initials: NM
authors.lastname: Kenyon
authors.forename: Norma S
authors.initials: NS
authors.lastname: Kenyon
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics* / Q000276:immunology; D004279:DNA, Viral / Q000097:blood*; D000077561:Daclizumab; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008252:Macaca fascicularis; D009942:Organometallic Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D012189:Retrospective Studies; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology; D014184:Transplantation, Homologous / Q000276:immunology*; D000077562:Valganciclovir; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018712:Analgesics, Non-Narcotic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C061972:samarium Sm-153 lexidronam; D000077561:Daclizumab; C512542:thymoglobulin; D014740:Vidarabine; D000077562:Valganciclovir; C024352:fludarabine; D015774:Ganciclovir; D020123:Sirolimus; D016559:Tacrolimus