A randomized pilot study of donor stem cell infusion in living-related kidney transplant recipients receiving alemtuzumab

Gaetano Ciancio, Junichiro Sageshima, Edip Akpinar, Jeffrey Gaynor, Linda J Chen, Alberto Zarak, Lois Hanson, Lissett Tueros, Giselle Guerra, Adela D Mattiazzi, Warren Kupin, David Roth, Camillo Ricordi, George W Burke

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9 Citations (Scopus)

Abstract

BACKGROUND: Transplant tolerance would remove the need for maintenance immunosuppression while improving survival and quality of life. METHODS: A prospective, randomized pilot study was undertaken to assess the safety and efficacy of donor stem cell infusion (DSCI) in living-related kidney transplant recipients treated with alemtuzumab (C1H) induction and tacrolimus and mycophenolate maintenance with switch to sirolimus and weaning over 2 years. RESULTS: Four patients received DSCI; five patients were controls. Graft failure occurred in two patients in the DSCI arm. Recurrence of glomerular disease occurred in two DSCI recipients, leading to graft loss in one. Biopsy-proven acute rejection episodes occurred in three patients (two in the DSCI vs. one in the control). One DSCI patient, with recurrence, subsequently developed antibody-mediated rejection leading to graft failure. In the remaining two DSCI patients, weaning was attempted but was not successful. All (4 of 4) DSCI patients had biopsy-proven chronic allograft injury and/or recurrence. CONCLUSION: DSCI with C1H induction and a steroid-free maintenance regimen in a small group of patients failed to induce tolerance, with suboptimal patient and graft survival. The results do not justify extension of this particular trial and underscore the importance of patient selection, specifically avoidance of patients with glomerulopathies whose recurrence may obscure potential benefit.

Original languageEnglish
Pages (from-to)800-806
Number of pages7
JournalTransplantation
Volume96
Issue number9
DOIs
StatePublished - Nov 15 2013

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Stem Cells
Tissue Donors
Kidney
Transplants
Recurrence
Maintenance
Weaning
Transplant Recipients
alemtuzumab
Biopsy
Tacrolimus
Graft Survival
Sirolimus
Immunosuppression
Patient Selection
Allografts
Arm
Steroids
Quality of Life
Safety

Keywords

  • Alemtuzumab
  • Allograft tolerance
  • Donor-derived hematopoietic stem cells
  • Living-related kidney transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

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title = "A randomized pilot study of donor stem cell infusion in living-related kidney transplant recipients receiving alemtuzumab",
abstract = "BACKGROUND: Transplant tolerance would remove the need for maintenance immunosuppression while improving survival and quality of life. METHODS: A prospective, randomized pilot study was undertaken to assess the safety and efficacy of donor stem cell infusion (DSCI) in living-related kidney transplant recipients treated with alemtuzumab (C1H) induction and tacrolimus and mycophenolate maintenance with switch to sirolimus and weaning over 2 years. RESULTS: Four patients received DSCI; five patients were controls. Graft failure occurred in two patients in the DSCI arm. Recurrence of glomerular disease occurred in two DSCI recipients, leading to graft loss in one. Biopsy-proven acute rejection episodes occurred in three patients (two in the DSCI vs. one in the control). One DSCI patient, with recurrence, subsequently developed antibody-mediated rejection leading to graft failure. In the remaining two DSCI patients, weaning was attempted but was not successful. All (4 of 4) DSCI patients had biopsy-proven chronic allograft injury and/or recurrence. CONCLUSION: DSCI with C1H induction and a steroid-free maintenance regimen in a small group of patients failed to induce tolerance, with suboptimal patient and graft survival. The results do not justify extension of this particular trial and underscore the importance of patient selection, specifically avoidance of patients with glomerulopathies whose recurrence may obscure potential benefit.",
keywords = "Alemtuzumab, Allograft tolerance, Donor-derived hematopoietic stem cells, Living-related kidney transplantation",
author = "Gaetano Ciancio and Junichiro Sageshima and Edip Akpinar and Jeffrey Gaynor and Chen, {Linda J} and Alberto Zarak and Lois Hanson and Lissett Tueros and Giselle Guerra and Mattiazzi, {Adela D} and Warren Kupin and David Roth and Camillo Ricordi and Burke, {George W}",
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T1 - A randomized pilot study of donor stem cell infusion in living-related kidney transplant recipients receiving alemtuzumab

AU - Ciancio, Gaetano

AU - Sageshima, Junichiro

AU - Akpinar, Edip

AU - Gaynor, Jeffrey

AU - Chen, Linda J

AU - Zarak, Alberto

AU - Hanson, Lois

AU - Tueros, Lissett

AU - Guerra, Giselle

AU - Mattiazzi, Adela D

AU - Kupin, Warren

AU - Roth, David

AU - Ricordi, Camillo

AU - Burke, George W

PY - 2013/11/15

Y1 - 2013/11/15

N2 - BACKGROUND: Transplant tolerance would remove the need for maintenance immunosuppression while improving survival and quality of life. METHODS: A prospective, randomized pilot study was undertaken to assess the safety and efficacy of donor stem cell infusion (DSCI) in living-related kidney transplant recipients treated with alemtuzumab (C1H) induction and tacrolimus and mycophenolate maintenance with switch to sirolimus and weaning over 2 years. RESULTS: Four patients received DSCI; five patients were controls. Graft failure occurred in two patients in the DSCI arm. Recurrence of glomerular disease occurred in two DSCI recipients, leading to graft loss in one. Biopsy-proven acute rejection episodes occurred in three patients (two in the DSCI vs. one in the control). One DSCI patient, with recurrence, subsequently developed antibody-mediated rejection leading to graft failure. In the remaining two DSCI patients, weaning was attempted but was not successful. All (4 of 4) DSCI patients had biopsy-proven chronic allograft injury and/or recurrence. CONCLUSION: DSCI with C1H induction and a steroid-free maintenance regimen in a small group of patients failed to induce tolerance, with suboptimal patient and graft survival. The results do not justify extension of this particular trial and underscore the importance of patient selection, specifically avoidance of patients with glomerulopathies whose recurrence may obscure potential benefit.

AB - BACKGROUND: Transplant tolerance would remove the need for maintenance immunosuppression while improving survival and quality of life. METHODS: A prospective, randomized pilot study was undertaken to assess the safety and efficacy of donor stem cell infusion (DSCI) in living-related kidney transplant recipients treated with alemtuzumab (C1H) induction and tacrolimus and mycophenolate maintenance with switch to sirolimus and weaning over 2 years. RESULTS: Four patients received DSCI; five patients were controls. Graft failure occurred in two patients in the DSCI arm. Recurrence of glomerular disease occurred in two DSCI recipients, leading to graft loss in one. Biopsy-proven acute rejection episodes occurred in three patients (two in the DSCI vs. one in the control). One DSCI patient, with recurrence, subsequently developed antibody-mediated rejection leading to graft failure. In the remaining two DSCI patients, weaning was attempted but was not successful. All (4 of 4) DSCI patients had biopsy-proven chronic allograft injury and/or recurrence. CONCLUSION: DSCI with C1H induction and a steroid-free maintenance regimen in a small group of patients failed to induce tolerance, with suboptimal patient and graft survival. The results do not justify extension of this particular trial and underscore the importance of patient selection, specifically avoidance of patients with glomerulopathies whose recurrence may obscure potential benefit.

KW - Alemtuzumab

KW - Allograft tolerance

KW - Donor-derived hematopoietic stem cells

KW - Living-related kidney transplantation

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SN - 0041-1337

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