Hong Kong Journal of Nephrology
Volume 7, Issue 1 , Pages 27-33, April 2005

Classical Tolerance Induction in Renal Transplantation — A Study of 11 Patients

  • Hargovind L. Trivedi

      Affiliations

    • Corresponding Author InformationAddress correspondence and reprint requests to: Professor Hargovind L. Trivedi, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Civil Hospital Campus, Asarwa, Ahmedabad 380-016, Gujarat, India. Fax: (+91) 79-2268-5454
    • ,
  • Javed M. Vakil
  • Aruna V. Vanikar

      Affiliations

    • Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India
    • ,
  • Pranjal R. Modi

      Affiliations

    • Department of Urology and Transplantation Surgery, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India
    • ,
  • Veena R. Shah

      Affiliations

    • Department of Anesthesiology and Critical Care, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India
    • ,
  • Sajni I. Khemchandani

      Affiliations

    • Department of Urology and Transplantation Surgery, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India
    • ,
  • Varsha B. Trivedi

      Affiliations

    • Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India
    • ,
  • Rashmi D. Patel

      Affiliations

    • Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India

Department of Nephrology and Clinical Transplantation, Institute of Kidney Diseases & Research Centre and Institute of Transplantation Sciences, Ahmedabad, India

Article Outline

Background

Transplantation biology has accumulated evidence of persistent mixed lymphohematopoietic chimerism (MLHC) after allogeneic hematopoietic stem cell (HSC) grafting, resulting in donor-specific tolerance to alloantigens in solid organ transplantation. We aimed to design a safe, non-toxic, non-myeloablative, high-dose allogeneic HSC transplantation (HSCT) protocol to achieve grafting with persistent low-level MLHC-associated, donor-specific tolerance across major histocompatibility complex barriers in our living related donor (LRD) renal allograft recipients.

Methods

HSC infusion into the portal, marrow and systemic circulation was performed in 11 LRD renal allograft recipients. All patients underwent a tolerance induction protocol (TIP), but two patients also had HSC infusion (n = 1) or donor renal tissue inoculation (n = 1) into the recipient thymus. All patients received low-dose immunosuppressive therapy for a mean of 1 year post-transplantation. Such therapy was discontinued for the following reasons: poor compliance; drug toxicity; and low-level chimerism, as tested across gendermismatched donors by a fluorescent in situ hybridization technique.

Results

All patients had prope tolerance with early, stable allograft function without any episodes of rejection, infection, or graft versus host disease. MLHC could be tested in seven patients, all of whom showed persistent MLHC (average 0.54%) in peripheral blood. All patients had stable allograft function for a mean of 32.6 months after the withdrawal of immunosuppressive therapy, and all had a normal clinical profile as tested by laboratory parameters.

Conclusion

Of 483 patients who underwent TIP using HSCT, weaning of immunosuppressive therapy was implemented in 165 (34.2%), and 11 patients developed successful MLHC-associated donor-specific tolerance.

Key words:  donor-specific transplantation tolerance , hematopoietic stem cell transplantation , mixed lymphohematopoietic chimerism , renal transplantation , tolerance induction protocol

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Trivedi HL , Shah VR , Shah PR , Darji P , Sane A , Vanikar A , et al.   High dose DBMC associated tolerance in live-related renal allograft recipients . Transplant Proc . 2000;32:2001–2002
  2. Trivedi HL , Shah VR , Shah PR , Sane AS , Vanikar AV , Trivedi VB , et al.   Megadose approach to DBMC infusion-induced allograft hyporesponsiveness in living-related renal allograft recipients . Transplant Proc . 2001;33:71–76
  3. Trivedi HL , Shah VR , Vanikar AV , Gera D , Shah PR , Trivedi VB , et al.   High-dose peripheral blood stem cell infusion: a strategy to induce donor-specific hyporesponsiveness to allografts in pediatric renal transplant recipients . Pediatr Transplant . 2002;6:63–68
  4. Trivedi H , Vanikar A , Shah V , Mehta A , Shah S , Shah T , et al.   Mega dose unfractionated donor bone marrow-derived cell infusion in thymus and periphery - an integrated clinical approach for tolerance in living related renal allografts . Transplant Proc . 2003;35:203–206
  5. Billingham RE , Brent L , Medawar PB . 'Actively acquired tolerance' of foreign cells . Nature . 1953;172:603–606
  6. Guzzetta PC , Sundt TM , Suzuki T , Mixon A , Rosengard BR , Sachs DH . Induction of kidney transplantation tolerance across major histocompatibility complex barriers by bone marrow transplantation in miniature swine . Transplantation . 1991;51:862–866
  7. Smith CV , Nakajima K , Mixon A , Guzzetta PC , Rosengard BR , Fishbein JM , et al.   Successful induction of long-term specific tolerance to fully allogeneic renal allografts in miniature swine . Transplantation . 1992;53:438–444
  8. Kawai T , Cosimi AB , Colvin RB , Powelson J , Eason J , Kozlowski T , et al.   Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys . Transplantation . 1995;59:256–262
  9. Kimikawa M , Sachs DH , Colvin RB , Bartholomew A , Kawai T , Cosimi AB . Modifications of the conditioning regimen for achieving mixed chimerism and donor-specific tolerance in cynomolgus monkeys . Transplantation . 1997;64:709–716
  10. Starzl TE , Zinkernagel RM . Transplantation tolerance from a historical perspective . Nat Rev Immunol . 2001;1:233–239
  11. Garcia-Morales R , Esquenazi K , Zucker K , Gomez CI , Fuller L , Carreno M , et al.   An assessment of the effects of cadaver donor bone marrow on kidney allograft recipient blood cell chimerism by a novel technique combining PCR and flow cytometry . Transplantation . 1996;62:1149–1160
  12. Garcia-Morales R , Carreno M , Mathew J , Zucker K , Cirocco R , Ciancio G , et al.   The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients . J Clin Invest . 1997;99:1118–1129
  13. Rugeles MT , Aitouche A , Zeevi A , Fung JJ , Watkins SC , Starzl TE , et al.   Evidence for the presence of multilineage chimerism and progenitors of donor dendritic cells in the peripheral blood of bone marrow-augmented organ transplant recipients . Transplantation . 1997;64:735–741
  14. Garcia-Morales R , Carreno M , Mathew J , Cirocco R , Zucker K , Ciancio G , et al.   Continuous observations on the regulatory effects of donor-specific bone marrow cell infusions and chimerism in kidney transplant recipients . Transplantation . 1998;65:956–965
  15. Sayegh MH , Fine NA , Smith JL , Rennke HG , Milford EL , Tilney NL . Immunologic tolerance to renal allografts after bone marrow transplants from the same donors . Ann Int Med . 1991;114:954–955
  16. Spitzer TR , Delmonico F , Tolkoff-Rubin N , McAfee S , Sackstein R , Saidman S , et al.   Combined histocompatibility leucocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism . Transplantation . 1999;68:480–484

PII: S1561-5413(09)60177-0

doi:10.1016/S1561-5413(09)60177-0

Hong Kong Journal of Nephrology
Volume 7, Issue 1 , Pages 27-33, April 2005

Article Tools