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Molecular level HLA mismatches in UNOS mandatory share kidney transplants
7
Abstracts
6.1
DIFFERENTIAL EFFECTS OF REPEATED HLA MISMATCHES IN RENAL TRANSPLANTATION: HLA CLASS II MISMATCHES ARE DETRIMENTAL HLA CLASS I ARE NOT. LI.N. Doxiadis, P. de Lange, J. D'Amaro, J. de Meester, G.M.Th. Schreuder, and F.H.J. Claas, Department of Immunohaematology and Bloodbank, Eurotransplant, University Hospital Leiden, The Netherlands In Eurotransplant, a multinational organ exchange organisation, the survival of primary renal allografts is 81%,71% and 63% at 1, 3, and 5 years respectively. The results of regrafts are significantly lower (74%, 63% and 53% for the same periods. The difference may therefore reflect immunisation of the patient not depicted by the cross match prior to regrafting. We addressed the question whether repeated HLA mismatches (MM) influence the outcome of the second transplant. We selected from the Eurotransplant data base all regrafts: 4596 HLAA,B MM (N=461 repeated and N=4135 not repeated), and 1467 HLA-DR MM (N=126 repeated and N=1341 not repeated). We based our MM definition on the HLA "broad" specificities. Overall graft survival of repeated HLA-A,B MM were 68%, 58%, and 51 % at 1, 3, and 5 years (ns.), and for the repeated HLA-DR MM 58%,48% and 44% at 1, 3, and 5 years respectively (Peorr < 0.01). A subdivision of the latter group into those who lost their primary graft in the first six months post transplantation and those who lost their graft thereafter, showed, that for the first group the results were 51%, 21% and 20% while for the second 67% 60% and 54% at 1, 3, and 5 years. We conclude that repeated HLA-A,B MM do not seem to harm a reg raft. Repeated HLA-DR MM harm the regraft especially if the first transplant was lost within six months post transplantation. Therefore, repeated HLA-DR MM should not be transplanted if the first graft was lost within the first six months.
6.1
MOLECULAR LEVEL HLA MISMATCHES IN UNOS MANDATORY SHARE KIDNEY TRANSPLANTS. DJ Cook, L Roeske, EE Hodge, TC Li, LL Klingman, D Goldfarb, S Flechner, VW Dennis and AC Novick. Transplant Center, The Cleveland Clinic Foundation, Cleveland Ohio. The outcome of kidney transplants resulting from the UNOS mandatory share program have been shown to be superior to transplants involving a lesser degree of match. We have reviewed 50 UNOS mandatory share transplants performed at our institution since 1989 for HLA mismatching. HLA-A, B, Cw, DR and DQ typings were obtained by serology at the time of transplant, and high level (SSO) DNA results were obtained for HLADRBl, DQBl and DPBl. By locus there was one case with HLA-A mismatches (MM), 2 cases with B MM's, 15 cases with C MM's, 20 cases with DRBI MM's, 14 cases with DQBl MM's and 35 cases with DPBl MM's. When all 6 loci were considered, only 7 cases (15%) involved no mismatches, with as many as 6 total mismatches being identified. When compared to a group of38 cadaver transplant recipients for whom DNA results were available, outcome was superior in the mandatory share transplants. One year actuarial survival for the matched transplants was 93.6% vs 75.8% for the controls (p=0.003, 10grank). Rejection free one year survival was 85% in the mandatory share transplants vs 57.5% in the control group (p=0.02). None of the seven patients with no detectable HLA mismatches either lost their grafts or had a rejection episode. In summary, we found that while HLA mismatches were identified in the majority of these mandatory share transplants, we did not find an association with graft loss or rejection. It seems that with current immunosuppressive practices, the degree of matching obtained through this UNOS program is adequate to ensure superior results. For the future, the subgroup without detectable mismatches might benefit from reducing or even eliminating immunosuppression.
Abstracts
6.1
DIFFERENTIAL EFFECTS OF REPEATED HLA MISMATCHES IN RENAL TRANSPLANTATION: HLA CLASS II MISMATCHES ARE DETRIMENTAL HLA CLASS I ARE NOT. LI.N. Doxiadis, P. de Lange, J. D'Amaro, J. de Meester, G.M.Th. Schreuder, and F.H.J. Claas, Department of Immunohaematology and Bloodbank, Eurotransplant, University Hospital Leiden, The Netherlands In Eurotransplant, a multinational organ exchange organisation, the survival of primary renal allografts is 81%,71% and 63% at 1, 3, and 5 years respectively. The results of regrafts are significantly lower (74%, 63% and 53% for the same periods. The difference may therefore reflect immunisation of the patient not depicted by the cross match prior to regrafting. We addressed the question whether repeated HLA mismatches (MM) influence the outcome of the second transplant. We selected from the Eurotransplant data base all regrafts: 4596 HLAA,B MM (N=461 repeated and N=4135 not repeated), and 1467 HLA-DR MM (N=126 repeated and N=1341 not repeated). We based our MM definition on the HLA "broad" specificities. Overall graft survival of repeated HLA-A,B MM were 68%, 58%, and 51 % at 1, 3, and 5 years (ns.), and for the repeated HLA-DR MM 58%,48% and 44% at 1, 3, and 5 years respectively (Peorr < 0.01). A subdivision of the latter group into those who lost their primary graft in the first six months post transplantation and those who lost their graft thereafter, showed, that for the first group the results were 51%, 21% and 20% while for the second 67% 60% and 54% at 1, 3, and 5 years. We conclude that repeated HLA-A,B MM do not seem to harm a reg raft. Repeated HLA-DR MM harm the regraft especially if the first transplant was lost within six months post transplantation. Therefore, repeated HLA-DR MM should not be transplanted if the first graft was lost within the first six months.
6.1
MOLECULAR LEVEL HLA MISMATCHES IN UNOS MANDATORY SHARE KIDNEY TRANSPLANTS. DJ Cook, L Roeske, EE Hodge, TC Li, LL Klingman, D Goldfarb, S Flechner, VW Dennis and AC Novick. Transplant Center, The Cleveland Clinic Foundation, Cleveland Ohio. The outcome of kidney transplants resulting from the UNOS mandatory share program have been shown to be superior to transplants involving a lesser degree of match. We have reviewed 50 UNOS mandatory share transplants performed at our institution since 1989 for HLA mismatching. HLA-A, B, Cw, DR and DQ typings were obtained by serology at the time of transplant, and high level (SSO) DNA results were obtained for HLADRBl, DQBl and DPBl. By locus there was one case with HLA-A mismatches (MM), 2 cases with B MM's, 15 cases with C MM's, 20 cases with DRBI MM's, 14 cases with DQBl MM's and 35 cases with DPBl MM's. When all 6 loci were considered, only 7 cases (15%) involved no mismatches, with as many as 6 total mismatches being identified. When compared to a group of38 cadaver transplant recipients for whom DNA results were available, outcome was superior in the mandatory share transplants. One year actuarial survival for the matched transplants was 93.6% vs 75.8% for the controls (p=0.003, 10grank). Rejection free one year survival was 85% in the mandatory share transplants vs 57.5% in the control group (p=0.02). None of the seven patients with no detectable HLA mismatches either lost their grafts or had a rejection episode. In summary, we found that while HLA mismatches were identified in the majority of these mandatory share transplants, we did not find an association with graft loss or rejection. It seems that with current immunosuppressive practices, the degree of matching obtained through this UNOS program is adequate to ensure superior results. For the future, the subgroup without detectable mismatches might benefit from reducing or even eliminating immunosuppression.