- Email: [email protected]
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Abstracts / Human Immunology 73 (2012) 49–167
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GVHD IN MVT AND SMALL INTESTINAL TRANPLANTATION HSCT AS SAVAGE THERAPY. Deborah Cova, Alexandra Amador, Jennifer Garcia, Akin Tekin, David Levi, Genaro Selvaggi, Seigo Nishida, Andrea Tzakis, Phillip Ruiz. Surgery, University of Miami, Miami, FL, USA. Aim: Graft-versus-host disease (GVHD) after solid organ transplantation is a rare but fatal complication. The highest 5% to 10% reported after small intestine transplantation. The combination of chronic host immune suppression, minimal leukocyte antigen (HLA) matching and an inflammacion is capable of activating donor effector T cells all creating an environment for proliferation of donor alloreactive effector T cells resulting in acute GVHD. Purpose of this study is to propose therapeutic help in patients that underwent small bowel transplantation with GVHD no order therapeutic alternative with a fatal outcome. Methods: Five patients that underwent multivisceral and insolated intestinal transplantation, these patients had no CPRA or DSA, induction immunosupression with ATG, Solumedrol and maintenance with Prograf and Medrol. GVHD was determined by clinical,pathological and Chimerism correlation. Chimerism was determined by SBT in CD3+. Donor/recipient allelic ratios were calculated simultaneous with absolute lymphocyte counts (ALC). Small bowel biopsy was assessed for rejection and GVHD. Results: One adult and one pediatric patient underwent multivisceral transplantation develop GVHD. Donor T-cell Chimerism was detected as early as postoperative day 16 this donor T-cell Chimerism ranged from 0% to 93.6%; simultaneous CD4/CD8 ratio varied from 0. 1 to 1.3. Histopathological finding were seen at their native colon in these patients. Conclusions: Graft-versus-host disease is a rare but potentially lethal complication after solid organ transplantation with a very high reported mortality of 75% to 100% in the adult and 20 to 30% in pediatric population after isolated small bowel transplantation. In this study, these patients respond with ATG for the rejection but with no recover of their Bone Marrow we propose for this patient’s savage therapy with HSCT, saving the cells prior transplant and offering in cases of no recovery to avoid fatal complications of the serious infections.
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HLA MISMATCHES PROMOTE CLASS-SPECIFIC ANTI-DONOR ANTIBODY FORMATION IN RENAL TRANSPLANT PATIENTS. Danielle Ladie, Kristina Krecko, Robert Scott, Mary Waybill, Harold Yang, Seth Narins. Transplant Surgery, PinnacleHealth, Harrisburg, PA, USA. Aim: Antibody formation against human leukocyte antigens (HLA) is associated with graft dysfunction and loss in renal transplant recipients. We have previously shown that recipients with positive leukocyte antibody panel (LABB) tests demonstrate significantly more HLA mismatches with their donors, as compared to patients with negative LABB. Antibody production against donor-specific HLA (DSA) is not observed de novo in non-sensitized patients. It is not currently known if a relationship exists between HLA mismatches and specificity of antibodies produced after transplant. Methods: This is a retrospective analysis of 49 renal transplant patients with positive LABB between October 2010 and January 2011. HLA of recipients and their donors were compared for mismatches at A,B,DR, and DQ loci. LABB results were reviewed for class and donor HLA specificity of observed antibody production. Four patients were excluded due to insufficient HLA documentation or previous sensitization with non-DSA only (n = 45). Percent accuracy was calculated for Class I and II HLA mismatches and DSA, and chi-square test was utilized to determine significance of agreement. Results: [Table 0] 44/45 patients (97.8%) demonstrated Class I mismatches, and 42/45 (93.3%) demonstrated Class II mismatches. Among patients with Class I mismatches, 13/44 (28.9%) generated Class I antibody. Among patients with Class II mismatches, 18/42 (40%) generated Class II antibody. All antibody was class specific for the HLA mismatch identified (100% accuracy), and Class II HLA mismatches trended towards higher agreement with DSA production (47% vs 31%; p = 0.1301). Conclusions: Antibody production after transplantation is donor and class-specific, and is directed against mismatched HLA loci. Increased numbers of HLA mismatches may result in increased vulnerability to posttransplant antibody formation and antibody-mediated graft injury. Yang: Novartis: Grant Research; Speakers Bureau; Astellas: Grant Research.
Class I DSA No Class I Mismatch No Yes
1 31
Class II DSA Yes 0 13
Class II Mismatch No Yes
No
Yes
3 24
0 18
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105
GVHD IN MVT AND SMALL INTESTINAL TRANPLANTATION HSCT AS SAVAGE THERAPY. Deborah Cova, Alexandra Amador, Jennifer Garcia, Akin Tekin, David Levi, Genaro Selvaggi, Seigo Nishida, Andrea Tzakis, Phillip Ruiz. Surgery, University of Miami, Miami, FL, USA. Aim: Graft-versus-host disease (GVHD) after solid organ transplantation is a rare but fatal complication. The highest 5% to 10% reported after small intestine transplantation. The combination of chronic host immune suppression, minimal leukocyte antigen (HLA) matching and an inflammacion is capable of activating donor effector T cells all creating an environment for proliferation of donor alloreactive effector T cells resulting in acute GVHD. Purpose of this study is to propose therapeutic help in patients that underwent small bowel transplantation with GVHD no order therapeutic alternative with a fatal outcome. Methods: Five patients that underwent multivisceral and insolated intestinal transplantation, these patients had no CPRA or DSA, induction immunosupression with ATG, Solumedrol and maintenance with Prograf and Medrol. GVHD was determined by clinical,pathological and Chimerism correlation. Chimerism was determined by SBT in CD3+. Donor/recipient allelic ratios were calculated simultaneous with absolute lymphocyte counts (ALC). Small bowel biopsy was assessed for rejection and GVHD. Results: One adult and one pediatric patient underwent multivisceral transplantation develop GVHD. Donor T-cell Chimerism was detected as early as postoperative day 16 this donor T-cell Chimerism ranged from 0% to 93.6%; simultaneous CD4/CD8 ratio varied from 0. 1 to 1.3. Histopathological finding were seen at their native colon in these patients. Conclusions: Graft-versus-host disease is a rare but potentially lethal complication after solid organ transplantation with a very high reported mortality of 75% to 100% in the adult and 20 to 30% in pediatric population after isolated small bowel transplantation. In this study, these patients respond with ATG for the rejection but with no recover of their Bone Marrow we propose for this patient’s savage therapy with HSCT, saving the cells prior transplant and offering in cases of no recovery to avoid fatal complications of the serious infections.
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HLA MISMATCHES PROMOTE CLASS-SPECIFIC ANTI-DONOR ANTIBODY FORMATION IN RENAL TRANSPLANT PATIENTS. Danielle Ladie, Kristina Krecko, Robert Scott, Mary Waybill, Harold Yang, Seth Narins. Transplant Surgery, PinnacleHealth, Harrisburg, PA, USA. Aim: Antibody formation against human leukocyte antigens (HLA) is associated with graft dysfunction and loss in renal transplant recipients. We have previously shown that recipients with positive leukocyte antibody panel (LABB) tests demonstrate significantly more HLA mismatches with their donors, as compared to patients with negative LABB. Antibody production against donor-specific HLA (DSA) is not observed de novo in non-sensitized patients. It is not currently known if a relationship exists between HLA mismatches and specificity of antibodies produced after transplant. Methods: This is a retrospective analysis of 49 renal transplant patients with positive LABB between October 2010 and January 2011. HLA of recipients and their donors were compared for mismatches at A,B,DR, and DQ loci. LABB results were reviewed for class and donor HLA specificity of observed antibody production. Four patients were excluded due to insufficient HLA documentation or previous sensitization with non-DSA only (n = 45). Percent accuracy was calculated for Class I and II HLA mismatches and DSA, and chi-square test was utilized to determine significance of agreement. Results: [Table 0] 44/45 patients (97.8%) demonstrated Class I mismatches, and 42/45 (93.3%) demonstrated Class II mismatches. Among patients with Class I mismatches, 13/44 (28.9%) generated Class I antibody. Among patients with Class II mismatches, 18/42 (40%) generated Class II antibody. All antibody was class specific for the HLA mismatch identified (100% accuracy), and Class II HLA mismatches trended towards higher agreement with DSA production (47% vs 31%; p = 0.1301). Conclusions: Antibody production after transplantation is donor and class-specific, and is directed against mismatched HLA loci. Increased numbers of HLA mismatches may result in increased vulnerability to posttransplant antibody formation and antibody-mediated graft injury. Yang: Novartis: Grant Research; Speakers Bureau; Astellas: Grant Research.
Class I DSA No Class I Mismatch No Yes
1 31
Class II DSA Yes 0 13
Class II Mismatch No Yes
No
Yes
3 24
0 18