Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft Recipients
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 fludarab...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2010-12-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368910X513973 |
| _version_ | 1818962300647768064 |
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| author | Dongmei Han Ph.D. Dora M. Berman Melissa Willman Peter Buchwald Daniel Rothen Norman M. Kenyon Norma S. Kenyon |
| author_facet | Dongmei Han Ph.D. Dora M. Berman Melissa Willman Peter Buchwald Daniel Rothen Norman M. Kenyon Norma S. Kenyon |
| author_sort | Dongmei Han Ph.D. |
| collection | DOAJ |
| description | 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 x 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 x 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. |
| first_indexed | 2024-12-20T12:27:08Z |
| format | Article |
| id | doaj.art-add83bf4c66244a0b313c52ab8e43478 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-20T12:27:08Z |
| publishDate | 2010-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-add83bf4c66244a0b313c52ab8e434782022-12-21T19:40:51ZengSAGE PublishingCell Transplantation0963-68971555-38922010-12-011910.3727/096368910X513973Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft RecipientsDongmei Han Ph.D.0Dora M. Berman1Melissa Willman2Peter Buchwald3Daniel Rothen4Norman M. Kenyon5Norma S. Kenyon6 Diabetes Research Institute, University of Miami School of Medicine, Miami, FL, USA Department of Surgery, University of Miami School of Medicine, Miami, FL, USA Diabetes Research Institute, University of Miami School of Medicine, Miami, FL, USA Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL, USA Division of Veterinary Resources, University of Miami School of Medicine, Miami, FL, USA Diabetes Research Institute, University of Miami School of Medicine, Miami, FL, USA Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL, USAThis 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 x 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 x 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.https://doi.org/10.3727/096368910X513973 |
| spellingShingle | Dongmei Han Ph.D. Dora M. Berman Melissa Willman Peter Buchwald Daniel Rothen Norman M. Kenyon Norma S. Kenyon Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft Recipients Cell Transplantation |
| title | Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft Recipients |
| title_full | Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft Recipients |
| title_fullStr | Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft Recipients |
| title_full_unstemmed | Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft Recipients |
| title_short | Choice of Immunosuppression Influences Cytomegalovirus DNAemia in Cynomolgus Monkey () Islet Allograft Recipients |
| title_sort | choice of immunosuppression influences cytomegalovirus dnaemia in cynomolgus monkey islet allograft recipients |
| url | https://doi.org/10.3727/096368910X513973 |
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