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2013 - CTS 2013 Congress


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Oral Communications 12

26.2 - Pre-Transplant Infusion Of Donor Stem Cells Protects The Graft From Antibody Mediated Immune Injury- Single Centre Experience In Living Donor Renal Transplantation

Presenter: Aruna, Vanikar, AHMEDABAD, India
Authors: Aruna Vanikar1,2, Hargovind Trivedi1,2, Shruti Dave1,2, Himanshu Patel1,2, Vivek Kute1,2, Manoj Gumber1,2, Pankaj Shah1,2

Pre-Transplant Infusion Of Donor Stem Cells Protects The Graft From Antibody Mediated Immune Injury- Single Centre Experience In Living Donor Renal Transplantation

Aruna Vanikar1,2, Hargovind Trivedi1,2, Shruti Dave1,2, Himanshu Patel1,2, Vivek Kute1,2, Manoj Gumber1,2, Pankaj Shah1,2

1Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute Of Kidney Diseases & Research Centre (IKDRC)- Dr. H.L. Trivedi Institute Of Transplantation Sciences (ITS), AHMEDABAD, India; 2Department of Nephrology and Transplantation Medicine, G. R. Doshi and K. M. Mehta Institute Of Kidney Diseases & Research Centre (IKDRC)- Dr. H.L. Trivedi Institute Of Transplantation Sciences (ITS), AHMEDABAD, India

 

Introduction: Transplantation is a well-accepted therapeutic modalityfor end organ failure. However it has limitations of requirement of life-long immunosuppression to prevent rejection of the grafted organ in spite of which rejection is not fully controlled. Over and above, it increases morbidity and mortality due to infections/ malignancies associated with immunosuppressive medications. Stem cells (SC) are known to have immunomodulatory role in organ transplantation. We report a cohort of living donor renal transplant patients who were subjected to pre-transplant stem cell infusion (SCI) under non-myeloablative conditioning with an aim of minimizing immunosuppression with minimum/ no immune injury.
Material and methods: Totally 138 patients with mean age 32 years and mean HLA-match 2.6, were subjected to pre-transplant SCI  consisting of donor peripheral blood stem cells, hematopoietic stem cells (HSC) from cultured bone marrow; and donor adipose tissue-derived mesenchymal stem cells (ad-MSC) in a subset of patients, under principal nonmyeloablative conditioning of irradiation to delete stimulated T and B-cell clones and to create space in marrow for grafting of SC. Transplantation was carried out with favourable cross-match under calcineurin inhibitor based low dose immunosuppression with mycofenolate and prednisone. Post-transplant immune monitoring included serum creatinine (SCr) with routine hematology, biochemical parameters and peripheral blood lymphohematopoietic chimerism by fluorescent in-situ hybridization in subset of patients with gender-mismatched donors. Immunosuppression minimization was performed with stable graft function, and normal protocol biopsies in patients who gave their consent. Their peripheral T-regulatory cells (pTregs) [CD4+CD25highCD127low/neg] were measured by flow-cytometry and HLA antibodies by luminex assay. Rescue immunosuppression was started with rise of SCr / biopsy-proven rejection.
Results: Mean quantum of SC infused was 273 ml, with mean CD34+ 2.02 x 106/kg body-weight (KgBW), mean CD45-/90+ 4.3 x 104 /kgBW and CD45-/73+ 0.7 x 104/kgBW. There were no untoward effects of SCI/ conditioning. All patients had stable graft function; however there was presence of donor-specific antibodies (DSA) in one set of patients and absence of DSA in other set. Chimerism was not observed consistently. Hence they were further subdivided into 2 groups based on presence/ absence of DSA; group-1consisted of  90 patients (81 males, 9 females) with mean age 31.8 years, mean  HLA-match, 2.41and presence of DSA, and group-2 of 48 patients (46 males, 2 females) with mean age 32.5 years, mean  HLA-match, 2.93 had absence of DSA.
Over a mean follow-up of 6.3 years, mean SCr (mg/dL) was 1.43 in group-1; and 1.4 in group-2 over a mean follow-up of 6.06 years. Totally 36.7% patients in group-1 vs. 56.3% in group-2 were on low dose steroid monotherapy and others were on mycofenolate sodium, 360 mg BD. Out of 51 protocol biopsies in group-1, 90.2% were unremarkable and out of 26 protocol biopsies in group-2, 76.9% were unremarkable. Mean pTregs were 3.3% in group-1 and 3.5% in group-2. There was no patient/ graft loss in either group.   
Conclusion:SC help in achieving stable renal allograft function with minimization of immunosuppression in spite of presence of DSA. We believe that SCI has protected the graft from immune injury.


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