IPTA 8th Congress on Pediatric Transplantation March 28 – 31, 2015 San Francisco, CA, USA ABSTRACTS
CONCURRENT SESSION 1: HEART
Abstracts
All presenters are required to disclose relevant conflicts of interest. All such disclosures are published within the Abstract Book following each abstract. Any presenters who have nothing to disclose have been omitted from the disclosure listing.
Concurrent Session 1: Heart
norms in our province. There are significant amounts of missing data in this retrospective review and given the importance of these psychosocial milestones, a prospective trial is warranted.
Abstract # OR1
DOES DONOR-RECIPIENT WEIGHT MISMATCH ADVERSELY AFFECT THE OUTCOMES IN PEDIATRIC ORTHOTOPIC HEART TRANSPLANTATION? D. Absi, A. Bertolotti, M. Peradejordi, L. Favaloro, J. Trentadue, R. Favaloro, Favaloro’s Foundation, Buenos Aires, Argentina.
Abstract # OR3
CONVERSION TO EVEROLIMUS IN PEDIATRIC HEART TRANSPLANT PATIENTS C. Castleberry, B. Taylor, A. Hohlbein, J. Jefferies, A. Lorts, C. Chin, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Purpose: The aim of this study was to show the effect of heart transplant donor-recipient weight oversizing on mortality and mid-term control of systemic blood pressure. Methods: From 1994 to 2014 inclusive, 28 patients undergoing orthotopic heart transplantation at our centre were retrospectively analyzed. Donorrecipient body weight ratio (DRWr) was analyzed with respect to development of hypertension, cephaleas, seizures and its impact on mortality. Categorical data were shown as frequencies/percentages and continuous data as means with standard deviation (SD). Cox method analysis was used to demonstrate variables associated with mortality. Non-parametric comparisons were made using the Spearman’s rank correlation test. Fisher’s exact test and the chi-square analysis were used to compare continuous and categorical variables, respectively. Actuarial survival and freedom from hypertension were estimated with the Kaplan-Meier method and the log-rank test. Results: Median follow-up was 5.17 years. The median receptor age was 10.5 years (0,3 to 17 ys). Twenty six patients presented dilated myocardiopathy and eleven (39%) pretransplant mechanical circulatory support. A total of 15 patients (53,5%) received an oversized donor (DRWr >1.5). Mean hospital stay was 25,8 days (± 24,7). Postoperative hypertension correlated with seizures (p=0,012), cephaleas (p=0,031), gender mismatch (p=0,017) but not with oversizing (p=0,2). There was no association between patients in whom the DRWr was 1,5 or greater and either midterm mortality (p = 0.6) or hypertension (p= 0.44). On survival analysis, there was no a higher mortality among those with the oversized donor (log-rank p = 0.65). Hospital mortality was 14,2% and overall post-transplant survival was 85%, 72% and 66% at 1,5 and 10 years respectively. Conclusion: The shortage of donor hearts, increasing demand, and constraint of financial or medical resources require optimal organ utilization. Our current policy involves accepting a maximum donor-recipient weight ratio of 2 in an era when marginal donors are increasingly sought. These findings cautiously justify this policy.
Purpose: Everolimus, a hydroxyethyl derivative of sirolimus, inhibits the mTOR receptor and suppresses T and B cell activation. It has been used as maintenance immunosuppression in solid organ transplantation, but use in pediatrics is limited. We aim to describe the use of everolimus in a pediatric heart transplant population. Methods: Data from patients converted to everolimus were collected retrospectively at baseline, then every 6 months after conversion. Comparisons were made to determine the impact of immunosuppression conversion. Results: Twelve patients [17% male, median age 12 years (range 3-20)] were converted to everolimus. Median dose at conversion was 3mg/day (range 1-4mg/day) with median target level of 4-8ng/ml (minimum target 2-8ng/ml and maximum target 4-10ng/ml). All patients concomitantly received a calcineurin inhibitor (10 tacrolimus, 2 cyclosporine). Everolimus was discontinued on two patients, only one believed to be drug related (significant rash). There was only 1 episode of rejection (grade 3A) in 23 biopsy samples after conversion. One year post-conversion, there was an increase in GFR by cystatin C from 67.70 ml/min/1.73m2 to 127.16 ml/ min/1.73m2 (p-value=0.0152, Figure 1). There was no difference in other measured parameters (Figure 2). There was also no change in ISHLT coronary artery disease grade or intravascular ultrasound scores 1 year after conversion (p=0.78 and 0.42, respectively). Conclusion: Pediatric heart transplant patients can be successfully transitioned to everolimus with no significant increase in rate of rejection. Renal function improves; but further studies are needed to determine longterm benefits including impact on coronary artery disease.
Abstract # OR2
AN EXPLORATORY STUDY EXAMINING PSYCHOSOCIAL OUTCOMES IN ADOLESCENTS WITH A HEART TRANSPLANT A. Aujnarain, M. Kaufman, A. Dipchand, I. Chen, The Hospital for Sick Children, Toronto, ON, Canada. Purpose: Planning of developmentally appropriate services and resources for adolescents who have had heart transplants requires data on important psychosocial milestones and high risk behaviors. To meet this purpose, baseline information was collected for adolescent heart transplant patients to determine whether a prospective trial is warranted to be able to modify services in our institution. Methods: A retrospective database review of adolescents with heart transplants born between 1983 and 2000 was performed and 92 charts were extracted. Data was collected on educational attainment, job status, bullying, alcohol and drug use, sexual activity and mood on a 1-10 scale for each clinic visit. Yes or no answers were assigned binary numbers, and unknown values were not included in the analysis. If no 10-point scale value was provided, it was assigned 5 as neutral/okay, 3 if sad and 8 if happy. Prevalence of each outcome measure was calculated. Results: The preliminary results demonstrated that the study population were not in the appropriate grade for their age, most often behind by one year. There were fewer adolescents who reported drinking or substance use than the Ontario norm. Furthermore, the study population were less likely to be sexual active compared to national norms. Every patient who reported their mood had at least one visit falling 3000) B63 B27 B38 B60 B61 B41 Class B45 B47 B49 I B50 B51 B52 B53 B55 B56 B58 B59 B73 B81 B82
Purpose: The purpose of this study was to examine renal function over time in a cohort of pediatric heart transplant recipients and assess risk factors for deterioration. Methods: All patients who underwent cardiac transplantation between 2001 and 2013 and who had at least one GFR measurement by nuclear medicine scintigraphy after transplantation (initially done at 6 months post-transplantation and annually thereafter) were included in this study. Changes in GFR over time were modeled in linear regression model adjusted for repeated measures. Freedom from moderate (60-89 ml/min/1.73m2), severe (30-59 ml/min/1.73m2), and end-stage (1000. Epitope spreading was evident with SAB testing for total IgG. Interestingly, when assessed for C1Q-binding IgG, the only reactivities were the mismatched homograft antigens and closely related antigens, which still produced a cPRA=96%(Table 1). Much of the sensitization was due to the patient’s unique HLA type which lacked public class I epitopes; Aw4, and class II; DR51/52/53, DQ1,DQ3, related to being homozygous for less common class II HLA types(Figure 1). Conclusion: The patient is currently on the waitlist and is unlikely to find a compatible donor. This case highlights the significant impact of HLA mismatches in homograft implants, particularly in patients with unique HLA types. It also provides insight into the properties of HLA abs formed in the absence of immunosuppression, as evidenced by the differences in SAB testing for total IgG versus C1Q-binding IgG
68
Mismatch: A2 A29 B44 B57 Others: B45 B58 65
100
A3 A11 A36 A66 B7 B8 B42 B54 B67 Cw7
Mismatch: DR7, DR53, DQ2 DQ9 DQA02 DP11 UNACDPA02 CEPTABLE Others: DR1 ANTIGENS DR9 DR10 HLA (MFI>3000) DR12 DR14 Class DR17 DR52 II DQ5 DQ6 DQ7 DQ8 DQA03 DP15
Abstract # OR5
cPRA cPRA cPRA COM- SAB (C1Q) cPRA COMBINED BINED
100
100
A43
Mismatch: DR7 DR53 DQ2 DQ9 Others: DR9 DR12 DQ7 DQ8
DR52
96
92
CONCURRENT SESSION 1: KIDNEY/IMMUNOSUPPRESSION
Matching criteria were age at Tx, living-related donation, preemptive Tx and gender. Clinical outcome and side effects were evaluated over 4 years. Results: Patient and graft survival were 100% and 98.5% in the EVR group and 100% and 100% in controls. The median eGFR in the EVR group at 1 to 4 years posttransplant was 62, 61, 58 and 65 ml/min/1.73 m2 as compared to 70, 68, 63 and 63 in controls (n.s.). Acute rejection (BANFF ≥ Ia) in the 1st year posttransplant was diagnosed in 6% (EVR) vs. 13% (controls) (P=0.23). Steroids were withdrawn in 83% and 38% of the children within the 1st year. EVR was not discontinued in any patient, while MMF was permanently stopped in 18% of the controls. Donor-specific antibodies were found in 11% vs. 33% (P=0.03) with the diagnosis of chronic antibody-mediated rejection in 3% and 2%. One child in both groups developed EBV-associated PTLD that was successfully treated with rituximab. CMV infections were diagnosed in 3% vs. 5%, BKV infections in 3% vs. 3%. The rate of unscheduled hospitalizations during 4 years posttransplant was 3.4 per patient in the EVR group and 2.7 in controls (n.s.). Growth was comparable (height SDS -0.73/1.05 and -0.74/-0.94, 2 and 4 years after Tx) in EVR patients and controls. Conclusion: This case-control study suggests that a treatment regimen consisting of basiliximab, low-dose CsA, EVR, and withdrawal of steroids yields comparable mid-term results as a standard regimen with CNI and MMF.
Abstract # OR6
CORTICOSTEROID-FREE KIDNEY TRANSPLANTATION IMPROVES GROWTH: LONG-TERM FOLLOW-UP OF THE TWIST RANDOMIZED CONTROLLED TRIAL R. Grenda, The Children’s Memorial Health Institute, Warsaw, Poland; S. Douglas, N. Webb, Royal Manchester Children’s Hospital, Manchester, United Kingdom; A. Rajai, Department of Medical Statistics Central Manchester University Hospitals, Manchester, United Kingdom; S. Roberts, Royal Manchester Children’s Hospital,, Machester, United Kingdom; S. Marks, Great Ormond Street Hospital, London, United Kingdom; A. Watson, Nottingham University Hospitals, Nottingham, United Kingdom; M. Fitzpatrick, Leeds General Infirmary, Leeds, United Kingdom; K. Vondrak, University Hospital Motol, Prague, Czech Republic; H. Maxwell, Royal Hospital for Sick Children, Glasgow, United Kingdom; J. Jaray, Semmelweis University of Medicine, Budapest, Hungary; R. Van Damme-Lombaerts, Universitair Ziekenhuis KU, Leuven, Belgium; D. Milford, Birmingham Children’s Hospital, Birmingham, United Kingdom; N. Godefroid, Université Catholique de Louvain Medical School, Bruxelles, Belgium; P. Cochat, Hopital Femme Mere Enfant, Lyon, France; M. Ognjanovic, Royal Victoria Infirmary, Newcastle, United Kingdom; L. Murer, Azienda Ospedaliera di Padova, Padova, Italy; M. McCulloch, Red Cross Children’s Hospital, Cape Town, South Africa; B. Toenshoff, University Children’s Hospital, Heidelberg, Germany; N. Webb, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Abstract # OR8
PUBERTAL DEVELOPMENT AFTER PEDIATRIC K I D N E Y T R A N S P L A N TAT I O N : C O M PA R I S O N BETWEEN EVEROLIMUS-BASED AND CONVENTIONAL IMMUNOSUPPRESSION L. Pape, T. Ahlenstiel-Grunow, J. Förster, Hannover Medical School, Hannover, Germany; A. Zapf, University of Göttingen, Göttigen, Germany; M. Mynarek, University of Hamburg, Hamburg, Germany. Purpose: mTOR inhibitors (mTORi) have been discussed to eventually influence pubertal development after pediatric kidney transplantation (KTx). This is the first trial to compare pubertal development in children with and without mTORi-treatment. Methods: Data of 108 children (66m), mean age at Tx of 7 (SD 4) years, have been evaluated, mean observation time of 7 (SD 4) years. 67 patients were treated with mTORi (40m). 41 patients were treated with CNI and Mycophenolate Mofetil without mTORi (26m). Steroid therapy was administered a mean of 5 (SD 4) years after Tx and then stopped. Data on the clinical signs of puberty (Tanner stages), serum levels of reproductive hormones, medication, and graft function were analyzed. Results: The mean age at the onset of puberty was 12 years (SD 2) as compared to 13 (SD 2) years in males with and without mTORi. Mean age at menarche was 12 years (SD 2) in both groups and of spermarche 13 (SD 2) vs. 14 (SD 2) in children with and without mTORi. A delayed onset of puberty (> 2 SD) compared to healthy population data was recognized in 0/1 male and 0/0 female with and without mTORi. Elevated LH and/or FSH levels were found in 0/3 girls (age of first diagnosis 10 yrs.) and 8/4 boys with mTORi/ without mTORi. Androstendion levels were decreased in 6/4 girls and 4/4 boys with and without mTORi. DHEAS levels were decreased in 10/7 girls and 14/7 with and without mTORi. Testosterone was decreased in 9/6 boys with and without mTORi and Oestradiol in 3/2 girls. In the Fischer-exact test no differences were found between mTORi- and non-mTORi-group (p>0.05). Conclusion: There were no significant differences in pubertal development and reproductive hormones between children treated with and without mTORi after KTx resulting in a normal pubertal and sex hormone status in most of the patients.
Purpose: This 2-year follow-up of RCT TWIST study (Am J Trans 2010) aimed to determine whether improved growth persisted in the longer term. Methods: Data on growth, graft outcomes and AEs were collected at 1-year (113 patients) and 2-years (106 patients). The primary outcome was change in height SDS from baseline. Secondary outcomes : incidence of AR, patient and graft survival, change in BMI, kidney function and incidence of hypertension, dyslipidaemia, obesity, abnormal glucose metabolism, malignancy and infection. Longitudinal growth calculated as delta height SDS, was analysed using a mixed model repeated measures model. Results: CW subjects grew better at one-year (p=0.001). At two-years, growth remained numerically better in CW subjects ( p=0.06), and significantly better in pre-pubertal subjects (p=0.004). Freedom from biopsy-proven acute rejection at two years post-transplant were CW 82.3% and CC 88.1% (p=0.3). There was no significant difference between the two groups in patient or graft survival, rejection rate, eGFR, blood pressure, lipid profile, BMI, malignancy or other AEs. Conclusion: Early CW effectively and safely improves growth up to two years post-transplant, particularly in pre-pubertal children.
Abstract # OR7
LONG-TERM EFFICACY AND SAFETY OF AN EVR- VS. AN MMF-BASED REGIMEN AFTER PEDIATRIC KIDNEY TRANSPLANTATION: A CASE-CONTROL STUDY WITHIN THE CERTAIN REGISTRY L. Brunkhorst, T. AhlenstielGrunow, L. Pape, Hannover Medical School, Hannover, Germany; B. Höcker, K. Kruppka, B. Toenshoff, University Children’s Hospital, Heidelberg, Germany; M. Bald, Department of Pediatric Nephrology, Olgahospital, Stutt, Germany. Purpose: Only short-term trials using everolimus (EVR) in children after kidney transplantation have been published. Hereby we present 4 year data on low-dose ciclosporin A (CsA), EVR and steroid elimination 8-10 months post-transplant compared to matched pairs of patients treated with a standard immunosuppressive regimen consisting of a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF) and steroids. Methods: 35 children (median age 10.7±5.6 yr.) received basiliximab induction, CsA and prednisolone after kidney transplantation between the years 2004 -2010. EVR (1.6 mg/m2 per day) was added 2 weeks posttransplant combined with CsA (target trough level 40-70 µg/L). These patients were 1:2 matched to 70 patients (median age 9.8±5.4 yr.) from the CERTAIN Registry who were transplanted in the same period. 12 patients received CsA + MMF, 63 received tacrolimus + MMF ± basiliximab (n=5).
69
Abstracts
Concurrent Session 1: Kidney/Immunosuppression
CONCURRENT SESSION 1: LIVER
and agreed to continue the study as planned. Baseline characteristics of 32 patients included in safety analysis are presented here. 18 (56.3%) patients were female, 28 (87.5%) Caucasian; with a median (range) weight of 29.7 kg (10.0-64.6); height, 142.0 cm (77.5-176.5); and BMI, 16.9 kg/m2 (12.6-22.2). The median (range) age of pRTxRs was 11.0 years (2.0-17.0) with 8 (25%) patients in range of 1-
CONCURRENT SESSION 1: HEART
Abstracts
All presenters are required to disclose relevant conflicts of interest. All such disclosures are published within the Abstract Book following each abstract. Any presenters who have nothing to disclose have been omitted from the disclosure listing.
Concurrent Session 1: Heart
norms in our province. There are significant amounts of missing data in this retrospective review and given the importance of these psychosocial milestones, a prospective trial is warranted.
Abstract # OR1
DOES DONOR-RECIPIENT WEIGHT MISMATCH ADVERSELY AFFECT THE OUTCOMES IN PEDIATRIC ORTHOTOPIC HEART TRANSPLANTATION? D. Absi, A. Bertolotti, M. Peradejordi, L. Favaloro, J. Trentadue, R. Favaloro, Favaloro’s Foundation, Buenos Aires, Argentina.
Abstract # OR3
CONVERSION TO EVEROLIMUS IN PEDIATRIC HEART TRANSPLANT PATIENTS C. Castleberry, B. Taylor, A. Hohlbein, J. Jefferies, A. Lorts, C. Chin, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Purpose: The aim of this study was to show the effect of heart transplant donor-recipient weight oversizing on mortality and mid-term control of systemic blood pressure. Methods: From 1994 to 2014 inclusive, 28 patients undergoing orthotopic heart transplantation at our centre were retrospectively analyzed. Donorrecipient body weight ratio (DRWr) was analyzed with respect to development of hypertension, cephaleas, seizures and its impact on mortality. Categorical data were shown as frequencies/percentages and continuous data as means with standard deviation (SD). Cox method analysis was used to demonstrate variables associated with mortality. Non-parametric comparisons were made using the Spearman’s rank correlation test. Fisher’s exact test and the chi-square analysis were used to compare continuous and categorical variables, respectively. Actuarial survival and freedom from hypertension were estimated with the Kaplan-Meier method and the log-rank test. Results: Median follow-up was 5.17 years. The median receptor age was 10.5 years (0,3 to 17 ys). Twenty six patients presented dilated myocardiopathy and eleven (39%) pretransplant mechanical circulatory support. A total of 15 patients (53,5%) received an oversized donor (DRWr >1.5). Mean hospital stay was 25,8 days (± 24,7). Postoperative hypertension correlated with seizures (p=0,012), cephaleas (p=0,031), gender mismatch (p=0,017) but not with oversizing (p=0,2). There was no association between patients in whom the DRWr was 1,5 or greater and either midterm mortality (p = 0.6) or hypertension (p= 0.44). On survival analysis, there was no a higher mortality among those with the oversized donor (log-rank p = 0.65). Hospital mortality was 14,2% and overall post-transplant survival was 85%, 72% and 66% at 1,5 and 10 years respectively. Conclusion: The shortage of donor hearts, increasing demand, and constraint of financial or medical resources require optimal organ utilization. Our current policy involves accepting a maximum donor-recipient weight ratio of 2 in an era when marginal donors are increasingly sought. These findings cautiously justify this policy.
Purpose: Everolimus, a hydroxyethyl derivative of sirolimus, inhibits the mTOR receptor and suppresses T and B cell activation. It has been used as maintenance immunosuppression in solid organ transplantation, but use in pediatrics is limited. We aim to describe the use of everolimus in a pediatric heart transplant population. Methods: Data from patients converted to everolimus were collected retrospectively at baseline, then every 6 months after conversion. Comparisons were made to determine the impact of immunosuppression conversion. Results: Twelve patients [17% male, median age 12 years (range 3-20)] were converted to everolimus. Median dose at conversion was 3mg/day (range 1-4mg/day) with median target level of 4-8ng/ml (minimum target 2-8ng/ml and maximum target 4-10ng/ml). All patients concomitantly received a calcineurin inhibitor (10 tacrolimus, 2 cyclosporine). Everolimus was discontinued on two patients, only one believed to be drug related (significant rash). There was only 1 episode of rejection (grade 3A) in 23 biopsy samples after conversion. One year post-conversion, there was an increase in GFR by cystatin C from 67.70 ml/min/1.73m2 to 127.16 ml/ min/1.73m2 (p-value=0.0152, Figure 1). There was no difference in other measured parameters (Figure 2). There was also no change in ISHLT coronary artery disease grade or intravascular ultrasound scores 1 year after conversion (p=0.78 and 0.42, respectively). Conclusion: Pediatric heart transplant patients can be successfully transitioned to everolimus with no significant increase in rate of rejection. Renal function improves; but further studies are needed to determine longterm benefits including impact on coronary artery disease.
Abstract # OR2
AN EXPLORATORY STUDY EXAMINING PSYCHOSOCIAL OUTCOMES IN ADOLESCENTS WITH A HEART TRANSPLANT A. Aujnarain, M. Kaufman, A. Dipchand, I. Chen, The Hospital for Sick Children, Toronto, ON, Canada. Purpose: Planning of developmentally appropriate services and resources for adolescents who have had heart transplants requires data on important psychosocial milestones and high risk behaviors. To meet this purpose, baseline information was collected for adolescent heart transplant patients to determine whether a prospective trial is warranted to be able to modify services in our institution. Methods: A retrospective database review of adolescents with heart transplants born between 1983 and 2000 was performed and 92 charts were extracted. Data was collected on educational attainment, job status, bullying, alcohol and drug use, sexual activity and mood on a 1-10 scale for each clinic visit. Yes or no answers were assigned binary numbers, and unknown values were not included in the analysis. If no 10-point scale value was provided, it was assigned 5 as neutral/okay, 3 if sad and 8 if happy. Prevalence of each outcome measure was calculated. Results: The preliminary results demonstrated that the study population were not in the appropriate grade for their age, most often behind by one year. There were fewer adolescents who reported drinking or substance use than the Ontario norm. Furthermore, the study population were less likely to be sexual active compared to national norms. Every patient who reported their mood had at least one visit falling 3000) B63 B27 B38 B60 B61 B41 Class B45 B47 B49 I B50 B51 B52 B53 B55 B56 B58 B59 B73 B81 B82
Purpose: The purpose of this study was to examine renal function over time in a cohort of pediatric heart transplant recipients and assess risk factors for deterioration. Methods: All patients who underwent cardiac transplantation between 2001 and 2013 and who had at least one GFR measurement by nuclear medicine scintigraphy after transplantation (initially done at 6 months post-transplantation and annually thereafter) were included in this study. Changes in GFR over time were modeled in linear regression model adjusted for repeated measures. Freedom from moderate (60-89 ml/min/1.73m2), severe (30-59 ml/min/1.73m2), and end-stage (1000. Epitope spreading was evident with SAB testing for total IgG. Interestingly, when assessed for C1Q-binding IgG, the only reactivities were the mismatched homograft antigens and closely related antigens, which still produced a cPRA=96%(Table 1). Much of the sensitization was due to the patient’s unique HLA type which lacked public class I epitopes; Aw4, and class II; DR51/52/53, DQ1,DQ3, related to being homozygous for less common class II HLA types(Figure 1). Conclusion: The patient is currently on the waitlist and is unlikely to find a compatible donor. This case highlights the significant impact of HLA mismatches in homograft implants, particularly in patients with unique HLA types. It also provides insight into the properties of HLA abs formed in the absence of immunosuppression, as evidenced by the differences in SAB testing for total IgG versus C1Q-binding IgG
68
Mismatch: A2 A29 B44 B57 Others: B45 B58 65
100
A3 A11 A36 A66 B7 B8 B42 B54 B67 Cw7
Mismatch: DR7, DR53, DQ2 DQ9 DQA02 DP11 UNACDPA02 CEPTABLE Others: DR1 ANTIGENS DR9 DR10 HLA (MFI>3000) DR12 DR14 Class DR17 DR52 II DQ5 DQ6 DQ7 DQ8 DQA03 DP15
Abstract # OR5
cPRA cPRA cPRA COM- SAB (C1Q) cPRA COMBINED BINED
100
100
A43
Mismatch: DR7 DR53 DQ2 DQ9 Others: DR9 DR12 DQ7 DQ8
DR52
96
92
CONCURRENT SESSION 1: KIDNEY/IMMUNOSUPPRESSION
Matching criteria were age at Tx, living-related donation, preemptive Tx and gender. Clinical outcome and side effects were evaluated over 4 years. Results: Patient and graft survival were 100% and 98.5% in the EVR group and 100% and 100% in controls. The median eGFR in the EVR group at 1 to 4 years posttransplant was 62, 61, 58 and 65 ml/min/1.73 m2 as compared to 70, 68, 63 and 63 in controls (n.s.). Acute rejection (BANFF ≥ Ia) in the 1st year posttransplant was diagnosed in 6% (EVR) vs. 13% (controls) (P=0.23). Steroids were withdrawn in 83% and 38% of the children within the 1st year. EVR was not discontinued in any patient, while MMF was permanently stopped in 18% of the controls. Donor-specific antibodies were found in 11% vs. 33% (P=0.03) with the diagnosis of chronic antibody-mediated rejection in 3% and 2%. One child in both groups developed EBV-associated PTLD that was successfully treated with rituximab. CMV infections were diagnosed in 3% vs. 5%, BKV infections in 3% vs. 3%. The rate of unscheduled hospitalizations during 4 years posttransplant was 3.4 per patient in the EVR group and 2.7 in controls (n.s.). Growth was comparable (height SDS -0.73/1.05 and -0.74/-0.94, 2 and 4 years after Tx) in EVR patients and controls. Conclusion: This case-control study suggests that a treatment regimen consisting of basiliximab, low-dose CsA, EVR, and withdrawal of steroids yields comparable mid-term results as a standard regimen with CNI and MMF.
Abstract # OR6
CORTICOSTEROID-FREE KIDNEY TRANSPLANTATION IMPROVES GROWTH: LONG-TERM FOLLOW-UP OF THE TWIST RANDOMIZED CONTROLLED TRIAL R. Grenda, The Children’s Memorial Health Institute, Warsaw, Poland; S. Douglas, N. Webb, Royal Manchester Children’s Hospital, Manchester, United Kingdom; A. Rajai, Department of Medical Statistics Central Manchester University Hospitals, Manchester, United Kingdom; S. Roberts, Royal Manchester Children’s Hospital,, Machester, United Kingdom; S. Marks, Great Ormond Street Hospital, London, United Kingdom; A. Watson, Nottingham University Hospitals, Nottingham, United Kingdom; M. Fitzpatrick, Leeds General Infirmary, Leeds, United Kingdom; K. Vondrak, University Hospital Motol, Prague, Czech Republic; H. Maxwell, Royal Hospital for Sick Children, Glasgow, United Kingdom; J. Jaray, Semmelweis University of Medicine, Budapest, Hungary; R. Van Damme-Lombaerts, Universitair Ziekenhuis KU, Leuven, Belgium; D. Milford, Birmingham Children’s Hospital, Birmingham, United Kingdom; N. Godefroid, Université Catholique de Louvain Medical School, Bruxelles, Belgium; P. Cochat, Hopital Femme Mere Enfant, Lyon, France; M. Ognjanovic, Royal Victoria Infirmary, Newcastle, United Kingdom; L. Murer, Azienda Ospedaliera di Padova, Padova, Italy; M. McCulloch, Red Cross Children’s Hospital, Cape Town, South Africa; B. Toenshoff, University Children’s Hospital, Heidelberg, Germany; N. Webb, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Abstract # OR8
PUBERTAL DEVELOPMENT AFTER PEDIATRIC K I D N E Y T R A N S P L A N TAT I O N : C O M PA R I S O N BETWEEN EVEROLIMUS-BASED AND CONVENTIONAL IMMUNOSUPPRESSION L. Pape, T. Ahlenstiel-Grunow, J. Förster, Hannover Medical School, Hannover, Germany; A. Zapf, University of Göttingen, Göttigen, Germany; M. Mynarek, University of Hamburg, Hamburg, Germany. Purpose: mTOR inhibitors (mTORi) have been discussed to eventually influence pubertal development after pediatric kidney transplantation (KTx). This is the first trial to compare pubertal development in children with and without mTORi-treatment. Methods: Data of 108 children (66m), mean age at Tx of 7 (SD 4) years, have been evaluated, mean observation time of 7 (SD 4) years. 67 patients were treated with mTORi (40m). 41 patients were treated with CNI and Mycophenolate Mofetil without mTORi (26m). Steroid therapy was administered a mean of 5 (SD 4) years after Tx and then stopped. Data on the clinical signs of puberty (Tanner stages), serum levels of reproductive hormones, medication, and graft function were analyzed. Results: The mean age at the onset of puberty was 12 years (SD 2) as compared to 13 (SD 2) years in males with and without mTORi. Mean age at menarche was 12 years (SD 2) in both groups and of spermarche 13 (SD 2) vs. 14 (SD 2) in children with and without mTORi. A delayed onset of puberty (> 2 SD) compared to healthy population data was recognized in 0/1 male and 0/0 female with and without mTORi. Elevated LH and/or FSH levels were found in 0/3 girls (age of first diagnosis 10 yrs.) and 8/4 boys with mTORi/ without mTORi. Androstendion levels were decreased in 6/4 girls and 4/4 boys with and without mTORi. DHEAS levels were decreased in 10/7 girls and 14/7 with and without mTORi. Testosterone was decreased in 9/6 boys with and without mTORi and Oestradiol in 3/2 girls. In the Fischer-exact test no differences were found between mTORi- and non-mTORi-group (p>0.05). Conclusion: There were no significant differences in pubertal development and reproductive hormones between children treated with and without mTORi after KTx resulting in a normal pubertal and sex hormone status in most of the patients.
Purpose: This 2-year follow-up of RCT TWIST study (Am J Trans 2010) aimed to determine whether improved growth persisted in the longer term. Methods: Data on growth, graft outcomes and AEs were collected at 1-year (113 patients) and 2-years (106 patients). The primary outcome was change in height SDS from baseline. Secondary outcomes : incidence of AR, patient and graft survival, change in BMI, kidney function and incidence of hypertension, dyslipidaemia, obesity, abnormal glucose metabolism, malignancy and infection. Longitudinal growth calculated as delta height SDS, was analysed using a mixed model repeated measures model. Results: CW subjects grew better at one-year (p=0.001). At two-years, growth remained numerically better in CW subjects ( p=0.06), and significantly better in pre-pubertal subjects (p=0.004). Freedom from biopsy-proven acute rejection at two years post-transplant were CW 82.3% and CC 88.1% (p=0.3). There was no significant difference between the two groups in patient or graft survival, rejection rate, eGFR, blood pressure, lipid profile, BMI, malignancy or other AEs. Conclusion: Early CW effectively and safely improves growth up to two years post-transplant, particularly in pre-pubertal children.
Abstract # OR7
LONG-TERM EFFICACY AND SAFETY OF AN EVR- VS. AN MMF-BASED REGIMEN AFTER PEDIATRIC KIDNEY TRANSPLANTATION: A CASE-CONTROL STUDY WITHIN THE CERTAIN REGISTRY L. Brunkhorst, T. AhlenstielGrunow, L. Pape, Hannover Medical School, Hannover, Germany; B. Höcker, K. Kruppka, B. Toenshoff, University Children’s Hospital, Heidelberg, Germany; M. Bald, Department of Pediatric Nephrology, Olgahospital, Stutt, Germany. Purpose: Only short-term trials using everolimus (EVR) in children after kidney transplantation have been published. Hereby we present 4 year data on low-dose ciclosporin A (CsA), EVR and steroid elimination 8-10 months post-transplant compared to matched pairs of patients treated with a standard immunosuppressive regimen consisting of a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF) and steroids. Methods: 35 children (median age 10.7±5.6 yr.) received basiliximab induction, CsA and prednisolone after kidney transplantation between the years 2004 -2010. EVR (1.6 mg/m2 per day) was added 2 weeks posttransplant combined with CsA (target trough level 40-70 µg/L). These patients were 1:2 matched to 70 patients (median age 9.8±5.4 yr.) from the CERTAIN Registry who were transplanted in the same period. 12 patients received CsA + MMF, 63 received tacrolimus + MMF ± basiliximab (n=5).
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Abstracts
Concurrent Session 1: Kidney/Immunosuppression
CONCURRENT SESSION 1: LIVER
and agreed to continue the study as planned. Baseline characteristics of 32 patients included in safety analysis are presented here. 18 (56.3%) patients were female, 28 (87.5%) Caucasian; with a median (range) weight of 29.7 kg (10.0-64.6); height, 142.0 cm (77.5-176.5); and BMI, 16.9 kg/m2 (12.6-22.2). The median (range) age of pRTxRs was 11.0 years (2.0-17.0) with 8 (25%) patients in range of 1-
