Five-year clinical effects of donor bone marrow cells infusions in kidney allograft recipients: improved graft function and higher graft survival

Chimerism. 2013 Jul-Sep;4(3):87-94. doi: 10.4161/chim.24719. Epub 2013 May 31.

Abstract

Augmentation of microchimerism in solid organ transplant recipients by donor bone marrow cells (DBMC) infusion may promote immune hyporesponsiveness and consequently improve long-term allograft survival. Between March 2005 and July 2007, outcomes for 20 living unrelated donor (LURD) primary kidney recipients with concurrent DBMC infusion (an average of 2.19 ± 1.13 x 10⁹ donor cells consisting of 2.66 ± 1.70 x 10⁷ CD34⁺ cells) were prospectively compared with 20 non-infused control allograft recipients given similar conventional immunosuppressive regimens. With five years of clinical follow up, a total of 11 cases experienced rejection episodes (3 DBMI patients vs. 8 controls, p = 0.15). One DBMC-infused patient experienced chronic rejection vs. two episodes (1 biopsy-confirmed) in the control patients. Actuarial and death-censored 5-y graft survival was significantly higher in infused patients compared with controls (p = 0.01 and p = 0.03, respectively). Long-term graft survival was significantly associated with pre-transplant anti-HLA antibodies (p = 0.01), slightly with peripheral microchimerism (p = 0.09) and CD4⁺CD25⁺FoxP3⁺ T cells (p = 0.09). Immunosuppressant dosing was lower in infused patients than controls, particularly for mycophenolate mofetil (p = 0.001). The current findings as well as our previous reports on these patients indicates clinical improvement in long-term graft survival of renal transplant patients resulting from low-dose DBMC infusion given without induction therapy.

Keywords: donor bone marrow infusion; kidney allograft; microchimerism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts / physiology*
  • Bone Marrow Transplantation*
  • Case-Control Studies
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / immunology*
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Kidney Transplantation*
  • Prospective Studies
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / immunology
  • Transplantation Chimera / immunology
  • Treatment Outcome
  • Unrelated Donors

Substances

  • IL10 protein, human
  • Transforming Growth Factor beta1
  • Interleukin-10