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.
RCT Entities:
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 DSCIpatient, with recurrence, subsequently developed antibody-mediated rejection leading to graft failure. In the remaining two DSCIpatients, weaning was attempted but was not successful. All (4 of 4) DSCIpatients 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.
Authors: J M Mathew; M Carreno; L Fuller; C Ricordi; N Kenyon; A G Tzakis; J Miller; V Esquenazi Journal: Transplantation Date: 1999-10-27 Impact factor: 4.939
Authors: Maria T Millan; Judith A Shizuru; Petra Hoffmann; Sussan Dejbakhsh-Jones; John D Scandling; F Carl Grumet; Jane C Tan; Oscar Salvatierra; Richard T Hoppe; Samuel Strober Journal: Transplantation Date: 2002-05-15 Impact factor: 4.939
Authors: G Ciancio; J Miller; R O Garcia-Morales; M Carreno; G W Burke; D Roth; W Kupin; A G Tzakis; C Ricordi; A Rosen; L Fuller; V Esquenazi Journal: Transplantation Date: 2001-04-15 Impact factor: 4.939
Authors: Allan D Kirk; Douglas A Hale; Roslyn B Mannon; David E Kleiner; Steven C Hoffmann; Robert L Kampen; Linda K Cendales; Douglas K Tadaki; David M Harlan; S John Swanson Journal: Transplantation Date: 2003-07-15 Impact factor: 4.939
Authors: Gaetano Ciancio; George W Burke; Jeffrey J Gaynor; Adela Mattiazzi; Ramin Roohipour; Manuel R Carreno; David Roth; Phillip Ruiz; Warren Kupin; Anne Rosen; Violet Esquenazi; Andreas G Tzakis; Joshua Miller Journal: Transplantation Date: 2004-08-15 Impact factor: 4.939
Authors: Stuart J Knechtle; John D Pirsch; John H Fechner; Bryan N Becker; Andreas Friedl; Robert B Colvin; Lauralynn K Lebeck; L Thomas Chin; Yolanda T Becker; Jon S Odorico; Anthony M D'Alessandro; Munci Kalayoglu; Majed M Hamawy; Huaizhong Hu; Debra D Bloom; Hans W Sollinger Journal: Am J Transplant Date: 2003-06 Impact factor: 8.086
Authors: W H Barber; J A Mankin; D A Laskow; M H Deierhoi; B A Julian; J J Curtis; A G Diethelm Journal: Transplantation Date: 1991-01 Impact factor: 4.939
Authors: Gaetano Ciancio; George W Burke; Rolando Garcia-Morales; Kiliana Suzart; Anne Rosen; Camillo Ricordi; Norma S Kenyon; James M Mathew; Andreas G Tzakis; Violet Esquenazi; Joshua Miller Journal: Transplantation Date: 2002-08-27 Impact factor: 4.939
Authors: Ron Shapiro; Mark L Jordan; Amit Basu; Velma Scantlebury; Santosh Potdar; Henkie P Tan; Edward A Gray; Parmjeet S Randhawa; Noriko Murase; Adriana Zeevi; Anthony J Demetris; Jennifer Woodward; Amadeo Marcos; John J Fung; Thomas E Starzl Journal: Ann Surg Date: 2003-10 Impact factor: 12.969
Authors: A D Kirk; A Guasch; H Xu; J Cheeseman; S I Mead; A Ghali; A K Mehta; D Wu; H Gebel; R Bray; J Horan; L S Kean; C P Larsen; T C Pearson Journal: Am J Transplant Date: 2014-03-31 Impact factor: 8.086
Authors: Christian Morath; Anita Schmitt; Florian Kälble; Martin Zeier; Michael Schmitt; Flavius Sandra-Petrescu; Gerhard Opelz; Peter Terness; Matthias Schaier; Christian Kleist Journal: Pediatr Nephrol Date: 2017-02-23 Impact factor: 3.714
Authors: Rainer Oberbauer; Matthias Edinger; Gabriela Berlakovich; Peter Kalhs; Nina Worel; Georg Heinze; Michael Wolzt; Thomas Lion; Thomas Wekerle Journal: Front Med (Lausanne) Date: 2021-01-27