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recipient (-) EBV mismatch leads to a high incidence of post-transplant lymphoproliferative disorder in pediatric lung transplant recipients
The Journal of Heart and Lung Transplantation Volume 26, Number 2S
Results: Transplant patients had higher body mass index (BMI 22.9⫾5.9, 19.8⫾3.7 and 18.5⫾3.0 in TX, Fontan and healthy groups, p⫽0.01) and baseline HR (107⫾11, 88⫾14 and 90⫾17 beats/min, p⬍0.001) compared to control groups. Both TX and Fontan patients had similar degree of chronotropic impairment (peak HR 158⫾19 (76⫾9%predicted), 164⫾17 (79⫾8%predicted) and 196⫾10 beats/min (95⫾5% predicted) in TX, Fontan and healthy groups). However, exercise duration was significantly lower in TX patients (9.1⫾2.0, 10.7⫾2.5 and 14.4⫾ 2.3 min, p⫽0.01). HR recovery was markedly slower in TX patients compared to control groups at both 1 minute (5⫾7 beats (3⫾4%), 23⫾10 beats (15⫾7%) and 39⫾15 beats (20⫾7%), p⬍0.001) and 3 minutes (20⫾13 beats (13⫾8%), 50⫾15 beats (30⫾9%) and 80⫾15 beats (41⫾7%), p⬍0.001) following peak exercise. In multivariable linear regression models, patient group and BMI were predictors of HR recovery at 1 and 3 minutes; exercise duration was not. Conclusions: Heart rate recovery following maximal exercise is markedly slower in children one-year following heart transplant compared to age-matched controls. Whether chronotropic response and HR recovery improve with time due to autonomic re-innervation is unknown and requires serial studies in these patients. 514 DONOR (ⴙ)/RECIPIENT (-) EBV MISMATCH LEADS TO A HIGH INCIDENCE OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN PEDIATRIC LUNG TRANSPLANT RECIPIENTS O. Elidemir,1 M.G. Schecter,1 E.D. McKenzie,2 J.S. Heinle,2 G.B. Mallory,1 1Pediatric Pulmonology, Baylor College of Medicine, Houston, TX; 2Congenital Heart Surgery, Baylor College of Medicine, Houston, TX Purpose: To investigate the relationship between donor and recipient serological status for EBV, primary diagnosis leading to lung transplantation and risk of post-transplant lymphoproliferative disorder (PTLD) in pediatric lung transplant recipients. Methods and Materials: Retrospective chart review of a single center experience. Patients were excluded if they died within 90 days of transplantation or were less than 3 months post-transplant at the time of analysis. Results: Between 2002 and 2006, a total of 49 bilateral lung transplants were performed, 34 met the inclusion criteria. PTLD developed in seven patients giving an overall incidence of 21%. 16 patients (33%) were EBV (-) and received lungs from EBV(⫹) donors. Eleven of these 16 patients were eligible for analysis. Five of these 11 (45%) developed PTLD. One of the 17 EBV (⫹) recipients who received EBV (⫹) lungs and one of the 4 EBV (-) recipients who received EBV (-) lungs developed PTLD, (6% and 25%, respectively). Neither of the 2 EBV (⫹) recipients who received EBV (-) lungs developed PTLD. Primary diagnosis leading to lung transplantation was cystic fibrosis (CF) in 67%, pulmonary hypertension in 15%, interstitial lung disease (including surfactant protein abnormalities) in 15% and bronchiolitis obliterans in 3%. Incidence of PTLD was higher in lung transplant recipients with CF than non-CF recipients, 19% vs. 6%, respectively (p⬍0.05). Conclusions: Risk of PTLD is significantly elevated in EBV (-) pediatric lung transplant recipients if they receive EBV (⫹) grafts. In addition, risk of PTLD is higher in CF lung transplant recipients when compared to patients undergoing lung transplantation for other reasons. Based on our findings, we recommend matching EBV status in pediatric lung transplant recipients and donors. If their primary diagnosis is CF, the importance of matching EBV status is of greater importance to decrease the risk of PTLD.
Abstracts
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515 OUTCOMES OF FETAL, NEONATE AND INFANT CANDIDATES FOR HEART TRANSPLANTATION S.M. Pollock-BarZiv,1 B.W. McCrindle,1 L.J. West,2 M. VanderVliet,1 A.I. Dipchand,1 1Cardiology, Hospital for Sick Children, Toronto, ON, Canada; 2Heart Transplantation Research, University of Alberta, Edmonton, AB, Canada Purpose: Heart transplantation (HTx) in infancy is now accepted therapy but long-term outcome data is lacking. Neonates (⬍1 month) and infants (1-12 months) have unique developmental issues differentiating them from older children. We sought to assess outcomes of infant patients (pts) wait-listed for HTx over the past 16 yrs. Methods and Materials: Review of cardiac and HTx databases of fetal, neonate, and infant listings between 1990-07/ 2006 Results: A total of 269 pt listings and 185 HTx in169 pts. 117/269 listings were infants, (26 fetal/63 neonatal). Diagnoses (n⫽117): 91 congenital heart disease (CHD), 23 cardiomyopathy (CM), 2 LV tumor, 1 EFE. De novo HTx in 80/117 (68%) pts after median 21 d wait-listed (1-665 d): 22 were delisted [9 too sick; 9 surgical options; 4 improved]; 15 (13%) died on the wait-list. Of 80 HTx; 16 (20%) were neonates [1 EFE, 11 HLHS, 4 complex CHD]. Median age at HTx was 2.7 m (0.03-31 m). 35 (44%) ABO-incompatible grafts. Ten (12.5%) sensitized pre-HTx. ECMO pre-HTx in 11 (median 11 d (4-17 d); 4 died at median 2.3 mos post-Htx (0.4-8.4 mos); 7 survivors alive at median 4.9 y (0.5-10 y). Median ICU stay post-HTx 11d; 16 required ECMO post-HTx. Of 80 HTx recipients, 19 died; 13 deaths ⱕ3 mos post-HTx: aspiration (1), sepsis (4), primary graft failure (PGF) (5), accelerated CAD (1), antibody mediated rej (AMR, 1), pulmonary hypertension (1). Five late deaths (⬎3 mos): CAD (2), PTLD (1); Inf/MOF (1), PGF post HTx2 (1). Actuarial survival at 1, 5, 10 yrs was 80%, 75%, 69%. Thirty-two pts (40%) had Rej ⱖ grade 2 R [median time to first 2 R: 2 m (0.2-26 m). 5/10 sensitized pts had mild-mod AMR at median 1 m post-HTx (0.25-1 m). Nine pts (7.5%) developed PTLD at median time post-HTx; T-cell (2), B-cell (6), unknown (1); 1 died. Eight pts (10%) developed CAD at median 2.8 y post-Tx (0.5-5.4 y). Eight pts were reTx: 4 early for PGF; 4 late for CAD. Mild to mod renal dysfunction in ⬃45% within 1 y of HTx. Conclusions: Infant HTx recipients have good intermediate and long term outcomes, with low rates of rejection, CAD, PTLD and reasonable long term survival. 516 USE OF ENDOMYOCARDIAL BIOPSY FOR REJECTION SURVEILLANCE IN PEDIATRIC HEART TRANSPLANT PATIENTS D.A. Dodd,1 J. Burger,1 1Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN Purpose: Endomyocardial biopsy was developed early in the history of heart transplantation to monitor for cellular rejection. While it has relatively low risk in the adult population, some have supported the use of echocardiogram and other non-invasive methods to monitor for rejection in the pediatric population, especially in infants. Also, in the present era cellular rejection is less common, consequently changing the risk/benefit ratio for surveillance biopsies. The purpose of this study was to determine the frequency of surveillance biopsies in infant and adolescent heart recipients at pediatric centers in the US in the present era. Methods and Materials: Questionnaires were emailed to members of the Pediatric Heart Transplant Study Group (2004 roster). The three questions were: how many surveillance biopsies are performed for infants in the first year; how many for adolescents during the first year;
Results: Transplant patients had higher body mass index (BMI 22.9⫾5.9, 19.8⫾3.7 and 18.5⫾3.0 in TX, Fontan and healthy groups, p⫽0.01) and baseline HR (107⫾11, 88⫾14 and 90⫾17 beats/min, p⬍0.001) compared to control groups. Both TX and Fontan patients had similar degree of chronotropic impairment (peak HR 158⫾19 (76⫾9%predicted), 164⫾17 (79⫾8%predicted) and 196⫾10 beats/min (95⫾5% predicted) in TX, Fontan and healthy groups). However, exercise duration was significantly lower in TX patients (9.1⫾2.0, 10.7⫾2.5 and 14.4⫾ 2.3 min, p⫽0.01). HR recovery was markedly slower in TX patients compared to control groups at both 1 minute (5⫾7 beats (3⫾4%), 23⫾10 beats (15⫾7%) and 39⫾15 beats (20⫾7%), p⬍0.001) and 3 minutes (20⫾13 beats (13⫾8%), 50⫾15 beats (30⫾9%) and 80⫾15 beats (41⫾7%), p⬍0.001) following peak exercise. In multivariable linear regression models, patient group and BMI were predictors of HR recovery at 1 and 3 minutes; exercise duration was not. Conclusions: Heart rate recovery following maximal exercise is markedly slower in children one-year following heart transplant compared to age-matched controls. Whether chronotropic response and HR recovery improve with time due to autonomic re-innervation is unknown and requires serial studies in these patients. 514 DONOR (ⴙ)/RECIPIENT (-) EBV MISMATCH LEADS TO A HIGH INCIDENCE OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN PEDIATRIC LUNG TRANSPLANT RECIPIENTS O. Elidemir,1 M.G. Schecter,1 E.D. McKenzie,2 J.S. Heinle,2 G.B. Mallory,1 1Pediatric Pulmonology, Baylor College of Medicine, Houston, TX; 2Congenital Heart Surgery, Baylor College of Medicine, Houston, TX Purpose: To investigate the relationship between donor and recipient serological status for EBV, primary diagnosis leading to lung transplantation and risk of post-transplant lymphoproliferative disorder (PTLD) in pediatric lung transplant recipients. Methods and Materials: Retrospective chart review of a single center experience. Patients were excluded if they died within 90 days of transplantation or were less than 3 months post-transplant at the time of analysis. Results: Between 2002 and 2006, a total of 49 bilateral lung transplants were performed, 34 met the inclusion criteria. PTLD developed in seven patients giving an overall incidence of 21%. 16 patients (33%) were EBV (-) and received lungs from EBV(⫹) donors. Eleven of these 16 patients were eligible for analysis. Five of these 11 (45%) developed PTLD. One of the 17 EBV (⫹) recipients who received EBV (⫹) lungs and one of the 4 EBV (-) recipients who received EBV (-) lungs developed PTLD, (6% and 25%, respectively). Neither of the 2 EBV (⫹) recipients who received EBV (-) lungs developed PTLD. Primary diagnosis leading to lung transplantation was cystic fibrosis (CF) in 67%, pulmonary hypertension in 15%, interstitial lung disease (including surfactant protein abnormalities) in 15% and bronchiolitis obliterans in 3%. Incidence of PTLD was higher in lung transplant recipients with CF than non-CF recipients, 19% vs. 6%, respectively (p⬍0.05). Conclusions: Risk of PTLD is significantly elevated in EBV (-) pediatric lung transplant recipients if they receive EBV (⫹) grafts. In addition, risk of PTLD is higher in CF lung transplant recipients when compared to patients undergoing lung transplantation for other reasons. Based on our findings, we recommend matching EBV status in pediatric lung transplant recipients and donors. If their primary diagnosis is CF, the importance of matching EBV status is of greater importance to decrease the risk of PTLD.
Abstracts
S245
515 OUTCOMES OF FETAL, NEONATE AND INFANT CANDIDATES FOR HEART TRANSPLANTATION S.M. Pollock-BarZiv,1 B.W. McCrindle,1 L.J. West,2 M. VanderVliet,1 A.I. Dipchand,1 1Cardiology, Hospital for Sick Children, Toronto, ON, Canada; 2Heart Transplantation Research, University of Alberta, Edmonton, AB, Canada Purpose: Heart transplantation (HTx) in infancy is now accepted therapy but long-term outcome data is lacking. Neonates (⬍1 month) and infants (1-12 months) have unique developmental issues differentiating them from older children. We sought to assess outcomes of infant patients (pts) wait-listed for HTx over the past 16 yrs. Methods and Materials: Review of cardiac and HTx databases of fetal, neonate, and infant listings between 1990-07/ 2006 Results: A total of 269 pt listings and 185 HTx in169 pts. 117/269 listings were infants, (26 fetal/63 neonatal). Diagnoses (n⫽117): 91 congenital heart disease (CHD), 23 cardiomyopathy (CM), 2 LV tumor, 1 EFE. De novo HTx in 80/117 (68%) pts after median 21 d wait-listed (1-665 d): 22 were delisted [9 too sick; 9 surgical options; 4 improved]; 15 (13%) died on the wait-list. Of 80 HTx; 16 (20%) were neonates [1 EFE, 11 HLHS, 4 complex CHD]. Median age at HTx was 2.7 m (0.03-31 m). 35 (44%) ABO-incompatible grafts. Ten (12.5%) sensitized pre-HTx. ECMO pre-HTx in 11 (median 11 d (4-17 d); 4 died at median 2.3 mos post-Htx (0.4-8.4 mos); 7 survivors alive at median 4.9 y (0.5-10 y). Median ICU stay post-HTx 11d; 16 required ECMO post-HTx. Of 80 HTx recipients, 19 died; 13 deaths ⱕ3 mos post-HTx: aspiration (1), sepsis (4), primary graft failure (PGF) (5), accelerated CAD (1), antibody mediated rej (AMR, 1), pulmonary hypertension (1). Five late deaths (⬎3 mos): CAD (2), PTLD (1); Inf/MOF (1), PGF post HTx2 (1). Actuarial survival at 1, 5, 10 yrs was 80%, 75%, 69%. Thirty-two pts (40%) had Rej ⱖ grade 2 R [median time to first 2 R: 2 m (0.2-26 m). 5/10 sensitized pts had mild-mod AMR at median 1 m post-HTx (0.25-1 m). Nine pts (7.5%) developed PTLD at median time post-HTx; T-cell (2), B-cell (6), unknown (1); 1 died. Eight pts (10%) developed CAD at median 2.8 y post-Tx (0.5-5.4 y). Eight pts were reTx: 4 early for PGF; 4 late for CAD. Mild to mod renal dysfunction in ⬃45% within 1 y of HTx. Conclusions: Infant HTx recipients have good intermediate and long term outcomes, with low rates of rejection, CAD, PTLD and reasonable long term survival. 516 USE OF ENDOMYOCARDIAL BIOPSY FOR REJECTION SURVEILLANCE IN PEDIATRIC HEART TRANSPLANT PATIENTS D.A. Dodd,1 J. Burger,1 1Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN Purpose: Endomyocardial biopsy was developed early in the history of heart transplantation to monitor for cellular rejection. While it has relatively low risk in the adult population, some have supported the use of echocardiogram and other non-invasive methods to monitor for rejection in the pediatric population, especially in infants. Also, in the present era cellular rejection is less common, consequently changing the risk/benefit ratio for surveillance biopsies. The purpose of this study was to determine the frequency of surveillance biopsies in infant and adolescent heart recipients at pediatric centers in the US in the present era. Methods and Materials: Questionnaires were emailed to members of the Pediatric Heart Transplant Study Group (2004 roster). The three questions were: how many surveillance biopsies are performed for infants in the first year; how many for adolescents during the first year;