Six-year clinical effect of donor bone marrow infusions in renal transplant patients

Gaetano Ciancio, Joshua Miller, Rolando O. Garcia-Morales, Manuel Carreno, George W Burke, David Roth, Warren Kupin, Andreas G. Tzakis, Camillo Ricordi, Anne Rosen, Laphalle Fuller, Violet Esquenazi

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Background. To date, several single, and multicenter clinical trials have attempted to induce specific immunological unresponsiveness using donor bone marrow cell infusions to augment solid organ transplantation, but the outcomes have not been definitive. Methods. Between September 1994 and May 1998, 63 cadaver (CAD) renal transplant recipients of either one or two postoperative donor bone marrow cell (DBMC) infusions were prospectively compared with 219 non-infused controls given equivalent immunosuppression. There was at least a 1 HLA DR antigen match present between donors and recipients. The iramunosuppressive regimen included a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. A total 7.01 × 10 1.9 × 108 (SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=42) or one half of that dose on day 4 (n=21) postoperatively. Clinical follow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also performed of humoral immunity and quantitative cellular chimerism. Results. There is clear-cut equivalence in immunosuppressive dosaging and in the other major demographic variables in both groups. However, only 2/63 DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed chronic rejection in the controls (P=<0.01). In both groups, mortality was not associated with rejection. The actuarial graft survival at 6.3 years in the CAD DBMC group was 84.3% compared with 72.2% in the control group (not statistically significant). However, if death with a functioning graft was excluded, graft survival was 94.1% in the DBMC group and 79.8% in the controls (P=0.039). Forty patients in the control group continue to have deteriorating renal function (increasing serum creatinine concentrations to 2 mg/dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold in yearly sequential measurements between 1 and 4 years postoperatively averaging 1.3±0.36% (SE) most recently. This has not occurred in the controls. Conclusions. There now appears to be more solid long-term evidence, in kidney transplant recipients prospectively receiving DBMC infusions, of an improvement in long-term graft survival, and of the degree of chimerism positively correlating with the absence of graft loss.

Original languageEnglish
Pages (from-to)827-835
Number of pages9
JournalTransplantation
Volume71
Issue number7
StatePublished - Apr 15 2001

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Bone Marrow Cells
Bone Marrow
Tissue Donors
Transplants
Kidney
Chimerism
Graft Survival
Cadaver
Mycophenolic Acid
Muromonab-CD3
Control Groups
Methylprednisolone
Tacrolimus
Organ Transplantation
HLA-DR Antigens
Immunosuppressive Agents
Humoral Immunity
Immunosuppression
Multicenter Studies
Creatinine

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Ciancio, G., Miller, J., Garcia-Morales, R. O., Carreno, M., Burke, G. W., Roth, D., ... Esquenazi, V. (2001). Six-year clinical effect of donor bone marrow infusions in renal transplant patients. Transplantation, 71(7), 827-835.

Six-year clinical effect of donor bone marrow infusions in renal transplant patients. / Ciancio, Gaetano; Miller, Joshua; Garcia-Morales, Rolando O.; Carreno, Manuel; Burke, George W; Roth, David; Kupin, Warren; Tzakis, Andreas G.; Ricordi, Camillo; Rosen, Anne; Fuller, Laphalle; Esquenazi, Violet.

In: Transplantation, Vol. 71, No. 7, 15.04.2001, p. 827-835.

Research output: Contribution to journalArticle

Ciancio, G, Miller, J, Garcia-Morales, RO, Carreno, M, Burke, GW, Roth, D, Kupin, W, Tzakis, AG, Ricordi, C, Rosen, A, Fuller, L & Esquenazi, V 2001, 'Six-year clinical effect of donor bone marrow infusions in renal transplant patients', Transplantation, vol. 71, no. 7, pp. 827-835.
Ciancio, Gaetano ; Miller, Joshua ; Garcia-Morales, Rolando O. ; Carreno, Manuel ; Burke, George W ; Roth, David ; Kupin, Warren ; Tzakis, Andreas G. ; Ricordi, Camillo ; Rosen, Anne ; Fuller, Laphalle ; Esquenazi, Violet. / Six-year clinical effect of donor bone marrow infusions in renal transplant patients. In: Transplantation. 2001 ; Vol. 71, No. 7. pp. 827-835.
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abstract = "Background. To date, several single, and multicenter clinical trials have attempted to induce specific immunological unresponsiveness using donor bone marrow cell infusions to augment solid organ transplantation, but the outcomes have not been definitive. Methods. Between September 1994 and May 1998, 63 cadaver (CAD) renal transplant recipients of either one or two postoperative donor bone marrow cell (DBMC) infusions were prospectively compared with 219 non-infused controls given equivalent immunosuppression. There was at least a 1 HLA DR antigen match present between donors and recipients. The iramunosuppressive regimen included a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. A total 7.01 × 108± 1.9 × 108 (SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=42) or one half of that dose on day 4 (n=21) postoperatively. Clinical follow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also performed of humoral immunity and quantitative cellular chimerism. Results. There is clear-cut equivalence in immunosuppressive dosaging and in the other major demographic variables in both groups. However, only 2/63 DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed chronic rejection in the controls (P=<0.01). In both groups, mortality was not associated with rejection. The actuarial graft survival at 6.3 years in the CAD DBMC group was 84.3{\%} compared with 72.2{\%} in the control group (not statistically significant). However, if death with a functioning graft was excluded, graft survival was 94.1{\%} in the DBMC group and 79.8{\%} in the controls (P=0.039). Forty patients in the control group continue to have deteriorating renal function (increasing serum creatinine concentrations to 2 mg/dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold in yearly sequential measurements between 1 and 4 years postoperatively averaging 1.3±0.36{\%} (SE) most recently. This has not occurred in the controls. Conclusions. There now appears to be more solid long-term evidence, in kidney transplant recipients prospectively receiving DBMC infusions, of an improvement in long-term graft survival, and of the degree of chimerism positively correlating with the absence of graft loss.",
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AU - Ciancio, Gaetano

AU - Miller, Joshua

AU - Garcia-Morales, Rolando O.

AU - Carreno, Manuel

AU - Burke, George W

AU - Roth, David

AU - Kupin, Warren

AU - Tzakis, Andreas G.

AU - Ricordi, Camillo

AU - Rosen, Anne

AU - Fuller, Laphalle

AU - Esquenazi, Violet

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N2 - Background. To date, several single, and multicenter clinical trials have attempted to induce specific immunological unresponsiveness using donor bone marrow cell infusions to augment solid organ transplantation, but the outcomes have not been definitive. Methods. Between September 1994 and May 1998, 63 cadaver (CAD) renal transplant recipients of either one or two postoperative donor bone marrow cell (DBMC) infusions were prospectively compared with 219 non-infused controls given equivalent immunosuppression. There was at least a 1 HLA DR antigen match present between donors and recipients. The iramunosuppressive regimen included a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. A total 7.01 × 108± 1.9 × 108 (SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=42) or one half of that dose on day 4 (n=21) postoperatively. Clinical follow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also performed of humoral immunity and quantitative cellular chimerism. Results. There is clear-cut equivalence in immunosuppressive dosaging and in the other major demographic variables in both groups. However, only 2/63 DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed chronic rejection in the controls (P=<0.01). In both groups, mortality was not associated with rejection. The actuarial graft survival at 6.3 years in the CAD DBMC group was 84.3% compared with 72.2% in the control group (not statistically significant). However, if death with a functioning graft was excluded, graft survival was 94.1% in the DBMC group and 79.8% in the controls (P=0.039). Forty patients in the control group continue to have deteriorating renal function (increasing serum creatinine concentrations to 2 mg/dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold in yearly sequential measurements between 1 and 4 years postoperatively averaging 1.3±0.36% (SE) most recently. This has not occurred in the controls. Conclusions. There now appears to be more solid long-term evidence, in kidney transplant recipients prospectively receiving DBMC infusions, of an improvement in long-term graft survival, and of the degree of chimerism positively correlating with the absence of graft loss.

AB - Background. To date, several single, and multicenter clinical trials have attempted to induce specific immunological unresponsiveness using donor bone marrow cell infusions to augment solid organ transplantation, but the outcomes have not been definitive. Methods. Between September 1994 and May 1998, 63 cadaver (CAD) renal transplant recipients of either one or two postoperative donor bone marrow cell (DBMC) infusions were prospectively compared with 219 non-infused controls given equivalent immunosuppression. There was at least a 1 HLA DR antigen match present between donors and recipients. The iramunosuppressive regimen included a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. A total 7.01 × 108± 1.9 × 108 (SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=42) or one half of that dose on day 4 (n=21) postoperatively. Clinical follow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also performed of humoral immunity and quantitative cellular chimerism. Results. There is clear-cut equivalence in immunosuppressive dosaging and in the other major demographic variables in both groups. However, only 2/63 DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed chronic rejection in the controls (P=<0.01). In both groups, mortality was not associated with rejection. The actuarial graft survival at 6.3 years in the CAD DBMC group was 84.3% compared with 72.2% in the control group (not statistically significant). However, if death with a functioning graft was excluded, graft survival was 94.1% in the DBMC group and 79.8% in the controls (P=0.039). Forty patients in the control group continue to have deteriorating renal function (increasing serum creatinine concentrations to 2 mg/dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold in yearly sequential measurements between 1 and 4 years postoperatively averaging 1.3±0.36% (SE) most recently. This has not occurred in the controls. Conclusions. There now appears to be more solid long-term evidence, in kidney transplant recipients prospectively receiving DBMC infusions, of an improvement in long-term graft survival, and of the degree of chimerism positively correlating with the absence of graft loss.

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