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HLA Allosensitization in ECMO as a Bridge to Lung Transplantation
S170
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
patients undergoing LTx at a single centre between 1/8/08 and 30/10/ 11. All patients underwent prospective T- and B-cell crossmatches (XM) prior to LTx. Outcome variables analyzed included acute cellular and antibody-mediated rejection, BOS and survival. Results: Pre-LTx class I and class II anti-HLA antibodies were present in 73/155 (47%) and 25/155 (16%) patients, respectively, but did not predict a positive T- or B-cell XM which was weekly positive in 1/158 and 25/158 patients, respectively. Class I and II donor-specific antibodies (DSA) were present pre-LTx in 27/157 (17%) and 9/157 (6%) patients, respectively. The presence pre-LTx of class I anti-HLA antibodies (OR 10, p¼0.01) and HLA-Cw DSA (OR 5.6, p¼0.01) predicted for AMR. In a univariate analysis BOS (HR 8.1, po0.001), AMR (HR 4.2, p¼0.01) and pre-LTx class anti-HLA antibodies (HR 2.2, p¼0.5) were associated with early mortality. Conclusions: Sensitization to non-specific and donor-specific class I HLA whilst on the lung transplant waiting list is associated with poor post-LTX outcomes. Solid phase assays provide prognostic information beyond that provided by a negative prospective XM. 451 Tacrolimus Level Variability Is a Novel Measure Associated with Increased Acute Rejection in Lung Transplant (LTx) Recipients C.Y. Chiang,1 H.G. Schneider,1 B. Levvey,2 L. Mitchell,2 G.I. Snell.2 1 Pathology, Alfred Hospital, Prahran, VIC, Australia; 2Lung Transplant Service, Alfred Hospital, Prahran, VIC, Australia. Purpose: Tacrolimus blood level variability post LTx can be due to non-adherence, intercurrent illness, concommitant medications or poor absorption. The last factor is important in cystic fibrosis recipients with exocrine pancreatic insufficiency. We hypothesize that high variability in tacrolimus level is a risk factor in early acute rejection. Methods and Materials: Data was collected for consecutive LTx performed over a 16 month period. Transbronchial biopsy took place routinely on week 1, 2, 4, month 2, 3, 6, 9, and 12. Acute rejection is defined as 4ISHLT Grade 2 on biopsy, absence of rejection is defined as grade 0 or 1. Standard deviation (SD), mean and the total number of tacrolimus requested were separated into time intervals post LTx. The SD of early rejectors (o3 months post LTx) was compared to SD of non-rejectors using cox regression analysis. Results: Of 108 LTx recipients, 9 were excluded (tacrolimus cessation, death unrelated to rejection, or lack of biopsy data). Ten of 14 acute rejections occurred within 90 days post LTx (mean ¼ 28.6 ⫾19.1 days). For each 1 unit increase in SD in the day 8-90 post LTx period, the risk of rejection increased by 23% (H.R.¼ 1.23, C.I ¼ 1.04-1.46). The mean tacrolimus level was higher in the rejectors compared to non-rejectors during day 8-30 (12.0 vs 10.4 mcg/L, p ¼0.01). When the pre-rejection tacrolimus levels were compared to levels in non-rejectors in the follow-up period, variability remained higher in the rejection group (H.R.¼ 1.44, C.I.¼1.18 – 1.76). The mean tacrolimus level prerejection did not predict rejection (H.R.¼ 0.824, C.I. ¼ 0.55-1.250). There was a higher proportion of cystic fibrosis patients in the rejection group compared to the non-rejection group (p ¼ 0.01). Conclusions: Tacrolimus variability is a risk factor for early acute LTx rejection. The higher proportion of cystic fibrosis lung recipient in the rejection group suggests poor tacrolimus absorption might contribute to this variability. 452 HLA Allosensitization in ECMO as a Bridge to Lung Transplantation S. Zeltzer,1 R. Fadul,2 M. Askar,3,4 C. Lane,2 P. Garcha,2 O. Akindipe,2 A. Tang,6 J. Schold,6 K. McCurry,3,5 G. Petterson,3,5 D.P. Mason,3,5 S. Murthy,3,5 D. Johnston,3 M. Budev.1,3,5 1Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland; 2 Respiratory Institute, Cleveland Clinic, Cleveland; 3Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH; 4Allogen Laboratories, Cleveland Clinic, Cleveland, OH; 5Transplantation Cener, Cleveland Clinic, Cleveland, OH; 6Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH.
Purpose: Use of extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation (BTT) has raised concerns ECMO support leads to the development of serum antibodies due to multiple blood transfusions. We examined the development of HLA sensitization in a cohort of lung transplant (LT) recipients where ECMO BTT was employed. Methods and Materials: A retrospective chart review of all LT recipients with ECMO BTT from 2006-2012 was conducted. Data collected included demographics, Luminex, blood product utilization and posttransplant outcomes. HLA sensitization was defined as PRA410% in either HLA type I or II while highly sensitized was PRA490%. Results: 21 patients (12 males) were identified as BTT to LT on ECMO, median ECMO duration of 7.0 days (range:0-38 days). 6 patients (35%) were sensitized prior to ECMO, mean PRA HLA type I 36%⫾22.7 and type II 27%⫾2.2. No significant change from baseline PRA was noted, mean difference for HLA type I of 4.3⫾11.9 (p¼0.19) or type II of 2.9⫾7.7 (p¼0.16). During ECMO BTT, 1 sensitized patient became highly sensitized (HLA type I 94%) who received 47 PRBCs. The second highest PRBC usage (31) during BTT resulted in new sensitization (HLA type I 31%). Patients received on average of 14.0⫾2.7 (range:0-49) during ECMO BTT, which was not associated with the mean difference between baseline-ECMO for HLA type I (p¼0.52) or type II (p¼0.06). All patients were successfully transplanted, 8 received induction therapy, with no evidence of hyperacute rejection.
PRBCs Received during ECMO BTT Patient
Days on ECMO
PRBCs Received
D Sensitization Status
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
10 3 13 10 1 4 7 2 38 1 8 5 17 4 3 12 1 4 22 20 15
27 21 15 49 2 9 18 4 31 0 15 11 11 3 7 15 0 0 23 27 5
No No Yes Yes No Yes Yes No Yes No Yes No No No No Yes No No No No No
PRBCs-packed red blood cell units
Conclusions: HLA sensitization does occur rarely in ECMO BTT and may be associated with large amounts of PRBCs received during ECMO BTT. Although sensitization may occur, successful transplantation is possible without evidence of hyperacute rejection. 453 Antibody Directed Therapy after Lung Transplant A.L. Gray,1 Z. Wang,1 N. Patel,1 J.M. Reynolds,1 R.D. Davis,2 S.M. Palmer,1 L.D. Snyder.1 1Medicine, Duke University Medical Center, Durham, NC; 2Surgery, Duke University Medical Center, Durham, NC.
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
patients undergoing LTx at a single centre between 1/8/08 and 30/10/ 11. All patients underwent prospective T- and B-cell crossmatches (XM) prior to LTx. Outcome variables analyzed included acute cellular and antibody-mediated rejection, BOS and survival. Results: Pre-LTx class I and class II anti-HLA antibodies were present in 73/155 (47%) and 25/155 (16%) patients, respectively, but did not predict a positive T- or B-cell XM which was weekly positive in 1/158 and 25/158 patients, respectively. Class I and II donor-specific antibodies (DSA) were present pre-LTx in 27/157 (17%) and 9/157 (6%) patients, respectively. The presence pre-LTx of class I anti-HLA antibodies (OR 10, p¼0.01) and HLA-Cw DSA (OR 5.6, p¼0.01) predicted for AMR. In a univariate analysis BOS (HR 8.1, po0.001), AMR (HR 4.2, p¼0.01) and pre-LTx class anti-HLA antibodies (HR 2.2, p¼0.5) were associated with early mortality. Conclusions: Sensitization to non-specific and donor-specific class I HLA whilst on the lung transplant waiting list is associated with poor post-LTX outcomes. Solid phase assays provide prognostic information beyond that provided by a negative prospective XM. 451 Tacrolimus Level Variability Is a Novel Measure Associated with Increased Acute Rejection in Lung Transplant (LTx) Recipients C.Y. Chiang,1 H.G. Schneider,1 B. Levvey,2 L. Mitchell,2 G.I. Snell.2 1 Pathology, Alfred Hospital, Prahran, VIC, Australia; 2Lung Transplant Service, Alfred Hospital, Prahran, VIC, Australia. Purpose: Tacrolimus blood level variability post LTx can be due to non-adherence, intercurrent illness, concommitant medications or poor absorption. The last factor is important in cystic fibrosis recipients with exocrine pancreatic insufficiency. We hypothesize that high variability in tacrolimus level is a risk factor in early acute rejection. Methods and Materials: Data was collected for consecutive LTx performed over a 16 month period. Transbronchial biopsy took place routinely on week 1, 2, 4, month 2, 3, 6, 9, and 12. Acute rejection is defined as 4ISHLT Grade 2 on biopsy, absence of rejection is defined as grade 0 or 1. Standard deviation (SD), mean and the total number of tacrolimus requested were separated into time intervals post LTx. The SD of early rejectors (o3 months post LTx) was compared to SD of non-rejectors using cox regression analysis. Results: Of 108 LTx recipients, 9 were excluded (tacrolimus cessation, death unrelated to rejection, or lack of biopsy data). Ten of 14 acute rejections occurred within 90 days post LTx (mean ¼ 28.6 ⫾19.1 days). For each 1 unit increase in SD in the day 8-90 post LTx period, the risk of rejection increased by 23% (H.R.¼ 1.23, C.I ¼ 1.04-1.46). The mean tacrolimus level was higher in the rejectors compared to non-rejectors during day 8-30 (12.0 vs 10.4 mcg/L, p ¼0.01). When the pre-rejection tacrolimus levels were compared to levels in non-rejectors in the follow-up period, variability remained higher in the rejection group (H.R.¼ 1.44, C.I.¼1.18 – 1.76). The mean tacrolimus level prerejection did not predict rejection (H.R.¼ 0.824, C.I. ¼ 0.55-1.250). There was a higher proportion of cystic fibrosis patients in the rejection group compared to the non-rejection group (p ¼ 0.01). Conclusions: Tacrolimus variability is a risk factor for early acute LTx rejection. The higher proportion of cystic fibrosis lung recipient in the rejection group suggests poor tacrolimus absorption might contribute to this variability. 452 HLA Allosensitization in ECMO as a Bridge to Lung Transplantation S. Zeltzer,1 R. Fadul,2 M. Askar,3,4 C. Lane,2 P. Garcha,2 O. Akindipe,2 A. Tang,6 J. Schold,6 K. McCurry,3,5 G. Petterson,3,5 D.P. Mason,3,5 S. Murthy,3,5 D. Johnston,3 M. Budev.1,3,5 1Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland; 2 Respiratory Institute, Cleveland Clinic, Cleveland; 3Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH; 4Allogen Laboratories, Cleveland Clinic, Cleveland, OH; 5Transplantation Cener, Cleveland Clinic, Cleveland, OH; 6Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH.
Purpose: Use of extracorporeal membrane oxygenation (ECMO) as a bridge to transplantation (BTT) has raised concerns ECMO support leads to the development of serum antibodies due to multiple blood transfusions. We examined the development of HLA sensitization in a cohort of lung transplant (LT) recipients where ECMO BTT was employed. Methods and Materials: A retrospective chart review of all LT recipients with ECMO BTT from 2006-2012 was conducted. Data collected included demographics, Luminex, blood product utilization and posttransplant outcomes. HLA sensitization was defined as PRA410% in either HLA type I or II while highly sensitized was PRA490%. Results: 21 patients (12 males) were identified as BTT to LT on ECMO, median ECMO duration of 7.0 days (range:0-38 days). 6 patients (35%) were sensitized prior to ECMO, mean PRA HLA type I 36%⫾22.7 and type II 27%⫾2.2. No significant change from baseline PRA was noted, mean difference for HLA type I of 4.3⫾11.9 (p¼0.19) or type II of 2.9⫾7.7 (p¼0.16). During ECMO BTT, 1 sensitized patient became highly sensitized (HLA type I 94%) who received 47 PRBCs. The second highest PRBC usage (31) during BTT resulted in new sensitization (HLA type I 31%). Patients received on average of 14.0⫾2.7 (range:0-49) during ECMO BTT, which was not associated with the mean difference between baseline-ECMO for HLA type I (p¼0.52) or type II (p¼0.06). All patients were successfully transplanted, 8 received induction therapy, with no evidence of hyperacute rejection.
PRBCs Received during ECMO BTT Patient
Days on ECMO
PRBCs Received
D Sensitization Status
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
10 3 13 10 1 4 7 2 38 1 8 5 17 4 3 12 1 4 22 20 15
27 21 15 49 2 9 18 4 31 0 15 11 11 3 7 15 0 0 23 27 5
No No Yes Yes No Yes Yes No Yes No Yes No No No No Yes No No No No No
PRBCs-packed red blood cell units
Conclusions: HLA sensitization does occur rarely in ECMO BTT and may be associated with large amounts of PRBCs received during ECMO BTT. Although sensitization may occur, successful transplantation is possible without evidence of hyperacute rejection. 453 Antibody Directed Therapy after Lung Transplant A.L. Gray,1 Z. Wang,1 N. Patel,1 J.M. Reynolds,1 R.D. Davis,2 S.M. Palmer,1 L.D. Snyder.1 1Medicine, Duke University Medical Center, Durham, NC; 2Surgery, Duke University Medical Center, Durham, NC.