Intravenous pulse administration of cyclophosphamide is an effective and safe treatment for sensitized cardiac allograft recipients

Silviu Itescu, Elizabeth Burke, Katherine Lietz, Ranjit John, Donna Mancini, Robert E. Michler, Eric Rose, Mehmet Oz, Niloo Edwards

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Background - The proportion of cardiac transplant recipients with preexisting sensitization to HLA alloantigens has been increasing. Sensitization prolongs duration to obtaining a donor and predicts poorer long-term allograft survival because of increased risk of cellular rejections, We investigated the effect of cyclophosphamide pulse therapy in sensitized cardiac allograft recipients. Methods and Results - Pretransplant and posttransplant outcomes were compared between 88 cardiac allograft recipients at risk for sensitization and 26 sensitized recipients treated with intravenous cyclophosphamide pulse therapy together with intravenous immune globulin before transplant and as part of a cyclosporine-based triple immunosuppressive regimen after transplant. Preformed IgG anti-HLA antibodies predicted longer duration to transplantation, earlier cellular rejection, and 2.7-fold higher cumulative rejection frequency (P=0.002). Before transplant, cyclophosphamide reduced waiting time and mortality to levels in nonsensitized patients. After transplant, cyclophosphamide prevented induction of IgG anti-HLA class II antibodies and interleukin-2 receptor-positive T-cell outgrowth from biopsy sites (both P<0.01), prolonged the rejection-free interval (P=0.009), and reduced cumulative rejections to levels in nonsensitized patients (P=0.003). By multivariable analysis, the risk of rejection was 3.7-fold higher in patients treated with mycophenolate mofetil than patients treated with cyclophosphamide (P=0.019). There were no differences in infectious or other significant complications. Conclusions - Immunosuppression corporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized cardiac transplant recipients. When used after transplantation as part of triple immunosuppression, cyclophosphamide is superior to mycophenolate mofetil in reducing rejection. The mechanism may involve prevention of diversification of the recipient immune response to donor HLA class II molecules.

Original languageEnglish (US)
Pages (from-to)1214-1219
Number of pages6
JournalCirculation
Volume105
Issue number10
DOIs
StatePublished - Mar 12 2002
Externally publishedYes

Fingerprint

Intravenous Administration
Cyclophosphamide
Allografts
Mycophenolic Acid
Transplants
Transplantation
Immunosuppression
Therapeutics
Tissue Donors
Isoantigens
Immunoglobulin Isotypes
Interleukin-2 Receptors
Intravenous Immunoglobulins
Immunosuppressive Agents
Cyclosporine
Anti-Idiotypic Antibodies
Immunoglobulin G
T-Lymphocytes
Biopsy
Mortality

Keywords

  • Antigens
  • Cells
  • Grafting
  • Rejection
  • Transplantation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Intravenous pulse administration of cyclophosphamide is an effective and safe treatment for sensitized cardiac allograft recipients. / Itescu, Silviu; Burke, Elizabeth; Lietz, Katherine; John, Ranjit; Mancini, Donna; Michler, Robert E.; Rose, Eric; Oz, Mehmet; Edwards, Niloo.

In: Circulation, Vol. 105, No. 10, 12.03.2002, p. 1214-1219.

Research output: Contribution to journalArticle

Itescu, Silviu ; Burke, Elizabeth ; Lietz, Katherine ; John, Ranjit ; Mancini, Donna ; Michler, Robert E. ; Rose, Eric ; Oz, Mehmet ; Edwards, Niloo. / Intravenous pulse administration of cyclophosphamide is an effective and safe treatment for sensitized cardiac allograft recipients. In: Circulation. 2002 ; Vol. 105, No. 10. pp. 1214-1219.
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T1 - Intravenous pulse administration of cyclophosphamide is an effective and safe treatment for sensitized cardiac allograft recipients

AU - Itescu, Silviu

AU - Burke, Elizabeth

AU - Lietz, Katherine

AU - John, Ranjit

AU - Mancini, Donna

AU - Michler, Robert E.

AU - Rose, Eric

AU - Oz, Mehmet

AU - Edwards, Niloo

PY - 2002/3/12

Y1 - 2002/3/12

N2 - Background - The proportion of cardiac transplant recipients with preexisting sensitization to HLA alloantigens has been increasing. Sensitization prolongs duration to obtaining a donor and predicts poorer long-term allograft survival because of increased risk of cellular rejections, We investigated the effect of cyclophosphamide pulse therapy in sensitized cardiac allograft recipients. Methods and Results - Pretransplant and posttransplant outcomes were compared between 88 cardiac allograft recipients at risk for sensitization and 26 sensitized recipients treated with intravenous cyclophosphamide pulse therapy together with intravenous immune globulin before transplant and as part of a cyclosporine-based triple immunosuppressive regimen after transplant. Preformed IgG anti-HLA antibodies predicted longer duration to transplantation, earlier cellular rejection, and 2.7-fold higher cumulative rejection frequency (P=0.002). Before transplant, cyclophosphamide reduced waiting time and mortality to levels in nonsensitized patients. After transplant, cyclophosphamide prevented induction of IgG anti-HLA class II antibodies and interleukin-2 receptor-positive T-cell outgrowth from biopsy sites (both P<0.01), prolonged the rejection-free interval (P=0.009), and reduced cumulative rejections to levels in nonsensitized patients (P=0.003). By multivariable analysis, the risk of rejection was 3.7-fold higher in patients treated with mycophenolate mofetil than patients treated with cyclophosphamide (P=0.019). There were no differences in infectious or other significant complications. Conclusions - Immunosuppression corporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized cardiac transplant recipients. When used after transplantation as part of triple immunosuppression, cyclophosphamide is superior to mycophenolate mofetil in reducing rejection. The mechanism may involve prevention of diversification of the recipient immune response to donor HLA class II molecules.

AB - Background - The proportion of cardiac transplant recipients with preexisting sensitization to HLA alloantigens has been increasing. Sensitization prolongs duration to obtaining a donor and predicts poorer long-term allograft survival because of increased risk of cellular rejections, We investigated the effect of cyclophosphamide pulse therapy in sensitized cardiac allograft recipients. Methods and Results - Pretransplant and posttransplant outcomes were compared between 88 cardiac allograft recipients at risk for sensitization and 26 sensitized recipients treated with intravenous cyclophosphamide pulse therapy together with intravenous immune globulin before transplant and as part of a cyclosporine-based triple immunosuppressive regimen after transplant. Preformed IgG anti-HLA antibodies predicted longer duration to transplantation, earlier cellular rejection, and 2.7-fold higher cumulative rejection frequency (P=0.002). Before transplant, cyclophosphamide reduced waiting time and mortality to levels in nonsensitized patients. After transplant, cyclophosphamide prevented induction of IgG anti-HLA class II antibodies and interleukin-2 receptor-positive T-cell outgrowth from biopsy sites (both P<0.01), prolonged the rejection-free interval (P=0.009), and reduced cumulative rejections to levels in nonsensitized patients (P=0.003). By multivariable analysis, the risk of rejection was 3.7-fold higher in patients treated with mycophenolate mofetil than patients treated with cyclophosphamide (P=0.019). There were no differences in infectious or other significant complications. Conclusions - Immunosuppression corporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized cardiac transplant recipients. When used after transplantation as part of triple immunosuppression, cyclophosphamide is superior to mycophenolate mofetil in reducing rejection. The mechanism may involve prevention of diversification of the recipient immune response to donor HLA class II molecules.

KW - Antigens

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KW - Grafting

KW - Rejection

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