Choice of immunosuppression influences cytomegalovirus DNAemia in cynomolgus monkey (Macaca fascicularis) islet allograft recipients

Dongmei Han, Dora Berman-Weinberg, Melissa Willman, Peter Buchwald, Daniel E Rothen, Norman M. Kenyon, Norma S Kenyon

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 post-transplant), 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.

Original languageEnglish
Pages (from-to)1547-1561
Number of pages15
JournalCell Transplantation
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2010

Fingerprint

Macaca fascicularis
Cytomegalovirus
Lymphocytes
Immunosuppression
Allografts
DNA
Animals
Lymphocyte Count
Immunosuppressive Agents
Transplants
Islets of Langerhans
Cyclophosphamide
Area Under Curve
Haplorhini
Real-Time Polymerase Chain Reaction
Blood
B-Lymphocytes
Therapeutics
Retrospective Studies
Cells

Keywords

  • Cytomegalovirus
  • Immunosuppression
  • Infection
  • Nonhuman primates
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Choice of immunosuppression influences cytomegalovirus DNAemia in cynomolgus monkey (Macaca fascicularis) islet allograft recipients. / Han, Dongmei; Berman-Weinberg, Dora; Willman, Melissa; Buchwald, Peter; Rothen, Daniel E; Kenyon, Norman M.; Kenyon, Norma S.

In: Cell Transplantation, Vol. 19, No. 12, 01.12.2010, p. 1547-1561.

Research output: Contribution to journalArticle

@article{5d0710e6efc6468c95a8305860f5a33e,
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 post-transplant), 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.",
keywords = "Cytomegalovirus, Immunosuppression, Infection, Nonhuman primates, Transplantation",
author = "Dongmei Han and Dora Berman-Weinberg and Melissa Willman and Peter Buchwald and Rothen, {Daniel E} and Kenyon, {Norman M.} and Kenyon, {Norma S}",
year = "2010",
month = "12",
day = "1",
doi = "10.3727/096368910X513973",
language = "English",
volume = "19",
pages = "1547--1561",
journal = "Cell Transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "12",

}

TY - JOUR

T1 - Choice of immunosuppression influences cytomegalovirus DNAemia in cynomolgus monkey (Macaca fascicularis) islet allograft recipients

AU - Han, Dongmei

AU - Berman-Weinberg, Dora

AU - Willman, Melissa

AU - Buchwald, Peter

AU - Rothen, Daniel E

AU - Kenyon, Norman M.

AU - Kenyon, Norma S

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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 post-transplant), 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.

AB - 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 post-transplant), 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.

KW - Cytomegalovirus

KW - Immunosuppression

KW - Infection

KW - Nonhuman primates

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=79951821946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951821946&partnerID=8YFLogxK

U2 - 10.3727/096368910X513973

DO - 10.3727/096368910X513973

M3 - Article

C2 - 20587138

AN - SCOPUS:79951821946

VL - 19

SP - 1547

EP - 1561

JO - Cell Transplantation

JF - Cell Transplantation

SN - 0963-6897

IS - 12

ER -