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C1q Testing in Pediatric Heart Transplant Recipients at Risk for Antibody Mediated Rejection
Abstracts S123 to the heart failure death/RT group with a median of 1081 pg/ml (range 2075258 pg/ml) (p= 0.013). Conclusion: Sudden death occurred in 24% of CAV associated patient or organ deaths. The SD patients were more likely to have normal hemodynamics and a lower BNP. Normal hemodynamics may not be reassuring in the setting of CAV. 3( 21) Antithymocyte Globulin But Not Basiliximab Is Beneficial After Infant Heart Transplantation - Analysis of the UNOS Database B. Coleman , A. Phillips, J. Mirocha, J. Patel, F. Arabia, J. Kobashigawa. Cedars- Sinai Heart Institute, Los Angeles, CA. Purpose: Disparities in pediatric heart transplant (HTx) outcomes comparing African American (AA) to Caucasian American (CA) recipients are known. The role of induction therapy in the AA infant population has not been established. Furthermore, it is not known whether all induction therapy medications confer the same post transplant outcomes. We explored the impact of Antithymocyte globulin (ATG), Basiliximab (Bas) and no induction on HTx outcomes in AA and CA infants, using the UNOS database. Methods: 979 (222 AA; 757 CA) infant HTx recipients (age 0 to 2 years) transplanted between 5/1999 to 3/2011 were included in this study. Three groups were analyzed and stratified by race; patients who received ATG (84 AA; 322 CA), Bas (22 AA; 49 CA) induction therapy or no induction therapy (116 AA; 386 CA). Cox proportional hazards models were used to assess factors related to 10-year survival, hazard ratios and 95% confidence intervals (CI). Ten-year survival was estimated by the Kaplan-Meier method. Survival was compared across induction types by the Log-Rank test. Results: AA infants who received ATG but not Bas had improved survival at 10 years compared to no induction (p = 0.010, HR 0.50 95% CI 0.30-0.86, Log-Rank). No survival benefit was found for CA infants who received ATG or Bas compared to no induction (overall Log-Rank P = 0.72). Conclusion: In infant HTx, AA recipients had improved 10-year survival with ATG compared with no induction therapy. CA infant recipients demonstrated no benefit from use of either ATG or Bas. Prospective randomized trials are needed to confirm these observations.
3( 22) C1q Testing in Pediatric Heart Transplant Recipients at Risk for Antibody Mediated Rejection E. Albers ,1 R. Boucek,1 M. Kemna,1 S. Law,1 P. Warner,2 Y. Law.1 1Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA; 2Puget Sound Blood Center, Seattle, WA. Purpose: Antibody mediated rejection (AMR) is an important cause of morbidity and mortality after pediatric heart transplant. Donor-specific antibodies (DSA) against human leukocyte antigens (HLA) have been associated with AMR. Not all DSA, however, result in clinical rejection. Testing for complement-fixing (C1q) DSA may help identify patients at higher risk for AMR. Methods: A single center retrospective review was conducted to identify patients with at least 1 DSA or history of AMR. Samples with the maximum single locus DSA MFI (if no history of AMR) or at diagnosis of AMR were retrospectively tested for C1q DSA. All DSA were considered positive if MFI > 5000. Comparisons were made with respect to AMR and graft survival. Results: Of 38 patients who met inclusion criteria, 17 (44.7%) had 21 episodes of AMR. Of 42 cases with either positive DSA or AMR, 38 samples were available for C1q testing. Of these, 20 had C1q DSA: 11 with AMR vs. 9 with no AMR (p = 0.321, positive predictive value [PPV] = 55%). Thirtyseven (88.1%) had DSA to Class II HLA (16 C1q), while only 11 (26.2%) had DSA to Class I HLA (5 C1q). AMR was associated with the presence of Class I DSA (p = 0.014, PPV 82%) and Class I C1q DSA (p= 0.016, PPV 100%). Twenty-one (50%) had DSA to > 1 HLA locus of either Class (6 C1q), of which 15 (5 C1q) had AMR (p = 0.005, PPV 71%; C1q: p = 0.075, PPV 83%). Over a median follow-up period of 42 months, 4 patients died and 1 required re-transplant (graft survival 92% at 5yrs, 86% at 10yrs). When considering either a history of AMR, C1q DSA, the presence of Class I DSA, or the presence of > 1 DSA locus, only the presence of > 1 DSA locus was associated with decreased graft survival (p = 0.044). Conclusion: AMR occurred in fewer than 50% of patients in this cohort with positive DSA. A positive C1q test alone was not predictive of AMR, but in certain cases increased the PPV of DSA testing. Most patients had DSA to Class II HLA, but only the presence of DSA to Class I HLA was associated with AMR. The presence of DSA to > 1 HLA locus was not only associated with AMR, it was also associated with decreased graft survival. 3( 23) How Does Donor Specific Antibody Relate to Biopsy-diagnosed Antibody-mediated Rejection after Pediatric Heart Transplantation? A. Ware ,1 G. Snow,2 E. Hammond,3 D.V. Miller,3 J. Stehlik,4 A.G. Kfoury,3 A. Eckhauser,4 D. Eckels,5 M. Everitt.4 1University of Utah, Salt Lake City, UT; 2Intermountain Medical Center, Salt Lake City, UT; 3Intermountain Medical Center/UTAH Cardiac Transplant Program, Salt Lake City, UT; 4University of Utah/UTAH Cardiac Transplant Program, Salt Lake City, UT; 5Pathology, University of Utah, Salt Lake City, UT. Purpose: Antibody-mediated rejection (AMR) is a major cause of mortality after heart transplant (HT). Both biopsy grading of pathologic AMR (pAMR) and assessment for circulating donor specific antibodies (DSA) are recommended for post HT monitoring. However, the relationship between pAMR grade and DSA has not been reported in children after HT. This is the aim of our analysis. Methods: The UTAH Cardiac Transplant database was queried for all children ≤ 21 yrs of age that had testing for DSA within 3 days of EMB. Solid phase immunoassay was used to determine the presence of DSA with positivity defined as antibody specificity to donor HLA at mean fluorescent intensity ≥ 2000. The relationship of DSA (class I, class II, or both) to pAMR grade was assessed using the Mantel-Haenzel chi-squared test. Results: Of 70 HT recipients followed between 2009 and 2013, 28 (40%) had ≥ 1 test positive for DSA. Those with detectable DSA vs. without any DSA were more likely to have a diagnosis of congenital heart disease (CHD) (75% vs. 43%, p= 0.01), more likely to be sensitized (non-donor HLA antibody) pre-HT (46% vs. 10%, p< 0.001), and more commonly received antilymphocyte induction (50% vs. 12%, p< 0.001). Of the 28 with DSA, 4 (14%) had pre-HT DSA with a positive crossmatch at HT. There were 258 EMB with a paired DSA test. Of 56 pAMR1 (h or i) episodes, 57% had DSA. For pAMR2, 27/28 (96%) had DSA. Of 5 pAMR3 episodes, all had DSA. Among 169 EMB negative for AMR, 62 (37%) had circulating DSA.
3( 22) C1q Testing in Pediatric Heart Transplant Recipients at Risk for Antibody Mediated Rejection E. Albers ,1 R. Boucek,1 M. Kemna,1 S. Law,1 P. Warner,2 Y. Law.1 1Pediatric Cardiology, Seattle Children’s Hospital, Seattle, WA; 2Puget Sound Blood Center, Seattle, WA. Purpose: Antibody mediated rejection (AMR) is an important cause of morbidity and mortality after pediatric heart transplant. Donor-specific antibodies (DSA) against human leukocyte antigens (HLA) have been associated with AMR. Not all DSA, however, result in clinical rejection. Testing for complement-fixing (C1q) DSA may help identify patients at higher risk for AMR. Methods: A single center retrospective review was conducted to identify patients with at least 1 DSA or history of AMR. Samples with the maximum single locus DSA MFI (if no history of AMR) or at diagnosis of AMR were retrospectively tested for C1q DSA. All DSA were considered positive if MFI > 5000. Comparisons were made with respect to AMR and graft survival. Results: Of 38 patients who met inclusion criteria, 17 (44.7%) had 21 episodes of AMR. Of 42 cases with either positive DSA or AMR, 38 samples were available for C1q testing. Of these, 20 had C1q DSA: 11 with AMR vs. 9 with no AMR (p = 0.321, positive predictive value [PPV] = 55%). Thirtyseven (88.1%) had DSA to Class II HLA (16 C1q), while only 11 (26.2%) had DSA to Class I HLA (5 C1q). AMR was associated with the presence of Class I DSA (p = 0.014, PPV 82%) and Class I C1q DSA (p= 0.016, PPV 100%). Twenty-one (50%) had DSA to > 1 HLA locus of either Class (6 C1q), of which 15 (5 C1q) had AMR (p = 0.005, PPV 71%; C1q: p = 0.075, PPV 83%). Over a median follow-up period of 42 months, 4 patients died and 1 required re-transplant (graft survival 92% at 5yrs, 86% at 10yrs). When considering either a history of AMR, C1q DSA, the presence of Class I DSA, or the presence of > 1 DSA locus, only the presence of > 1 DSA locus was associated with decreased graft survival (p = 0.044). Conclusion: AMR occurred in fewer than 50% of patients in this cohort with positive DSA. A positive C1q test alone was not predictive of AMR, but in certain cases increased the PPV of DSA testing. Most patients had DSA to Class II HLA, but only the presence of DSA to Class I HLA was associated with AMR. The presence of DSA to > 1 HLA locus was not only associated with AMR, it was also associated with decreased graft survival. 3( 23) How Does Donor Specific Antibody Relate to Biopsy-diagnosed Antibody-mediated Rejection after Pediatric Heart Transplantation? A. Ware ,1 G. Snow,2 E. Hammond,3 D.V. Miller,3 J. Stehlik,4 A.G. Kfoury,3 A. Eckhauser,4 D. Eckels,5 M. Everitt.4 1University of Utah, Salt Lake City, UT; 2Intermountain Medical Center, Salt Lake City, UT; 3Intermountain Medical Center/UTAH Cardiac Transplant Program, Salt Lake City, UT; 4University of Utah/UTAH Cardiac Transplant Program, Salt Lake City, UT; 5Pathology, University of Utah, Salt Lake City, UT. Purpose: Antibody-mediated rejection (AMR) is a major cause of mortality after heart transplant (HT). Both biopsy grading of pathologic AMR (pAMR) and assessment for circulating donor specific antibodies (DSA) are recommended for post HT monitoring. However, the relationship between pAMR grade and DSA has not been reported in children after HT. This is the aim of our analysis. Methods: The UTAH Cardiac Transplant database was queried for all children ≤ 21 yrs of age that had testing for DSA within 3 days of EMB. Solid phase immunoassay was used to determine the presence of DSA with positivity defined as antibody specificity to donor HLA at mean fluorescent intensity ≥ 2000. The relationship of DSA (class I, class II, or both) to pAMR grade was assessed using the Mantel-Haenzel chi-squared test. Results: Of 70 HT recipients followed between 2009 and 2013, 28 (40%) had ≥ 1 test positive for DSA. Those with detectable DSA vs. without any DSA were more likely to have a diagnosis of congenital heart disease (CHD) (75% vs. 43%, p= 0.01), more likely to be sensitized (non-donor HLA antibody) pre-HT (46% vs. 10%, p< 0.001), and more commonly received antilymphocyte induction (50% vs. 12%, p< 0.001). Of the 28 with DSA, 4 (14%) had pre-HT DSA with a positive crossmatch at HT. There were 258 EMB with a paired DSA test. Of 56 pAMR1 (h or i) episodes, 57% had DSA. For pAMR2, 27/28 (96%) had DSA. Of 5 pAMR3 episodes, all had DSA. Among 169 EMB negative for AMR, 62 (37%) had circulating DSA.