IN PURSUIT OF THE ULTIMATE- TRANSPLANTATION TOLERANCE!

Allograft transplantation requires lifelong immunosuppressive drugs to prevent rejection. The use of such drugs is associated with significant morbidity and mortality, apart from being expensive. The only answer is induction of “donor- specific transplantation tolerance” where the patient can live almost a normal life with normal functioning transplanted organ without immunosuppressive drugs

We started in search of this Utopian dream of transplantation tolerance in 1998 with small doses of pre-transplantation donor-specific transfusions in our live-related renal allograft recipients. By 2010 we have more than 1500 kidney transplant recipients transplanted under continuously improving Ahmedabad transplantation induction protocol (ATIP) who have done well with minimum immunosuppression (5/10 mg Prednione ± MMF or CsA/ Tacrolimus in low dose). Our 1 year patient/ graft survival is approximately 97%, 5 year survival approximately 80% and 10 year survival is approximately 65%). These transplants are across HLA barriers from living related donors! .

The steps used in our protocol (ATIP) are:

• Clonal stimulation with stem cell cocktail (hematopoietic stem cells from BM, PBSC, MSC from donor adipose tissue)- administered in portal circulation through omental vein, periphery and thymus[in certain cases])
• Clonal deletion with Bortezomib, methylpredniosne, r-ATG, Rituximab
• Chimerism and T-reg cell associated tolerance
• Kidney transplantation with minimal/ no conventional immunosuppression

It takes about 3 weeks to complete tolerance induction protocol and transplantation is carried out after achieving favorable immune response in the form of negative LCM-CDCC, flow cross-match for T and B-cells and single antigen (SA) test for donor specific antibodies (DSA) using luminex platform which was set-up by Prof. Paul Terasaki, the inventor of tissue typing (LA, US) who is our research collaborator. Regular monitoring with MLR and DSA is done at 3 monthly intervals to monitor the status of antibodies and T-cell activity.

Post-transplant immunosuppression regime varies from no drugs to low dose drugs as under:- Cyclosporin, 2-3 mg/kg BW/ day in the first month with the aim of maintaining trough levels around 150-180 ng/ml initially and tapered thereafter.

• MMF, 360 mg twice a day
• Prednisone, 5-10 mg/day

We have the largest cohort of 29 patients who are living a normal life without immunosuppression over an average follow-up of 2.5 years.

All transplantations are done across the MHC barrier, again the most revolutionizing concept in the field of transplantation. This research has made transplantation as a financially viable life saving option for the masses of developing countries, and has rendered an almost normal life to patients who had no other option than to endure all sufferings related to organ failure or routine transplantation offered as a salvage therapy.

The protocol is safe, with no graft versus host disease and zero mortality.

STEM CELLS FOR DM

We have treated about 25 patients suffering from type1 DM in the age range 12-54 years and 2patients with type 2 DM of age 36 and 54 years with insulin-making stem cells. Over a mean follow-up of 2.5 years these patients have sustained results of reduced insulin requirement to about 50% of original requirement after single cycle of stem cells.