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Basiliximab in critically ill children undergoing heart transplantation: initial data
The Journal of Heart and Lung Transplantation Volume 23, Number 2S
month, 91% at 6 months, and 91% at 1 year following infection. The major risk factor for CMV was D⫹/R- (p ⬍ 0.0001). Among all other D/R combinations, the freedom from CMV infection ranged from 90 –98% at 6 months. In all D/R combinations (including D⫹/R-), there was no significant reduction in CMV infection with any form of prophylaxis. Conclusions: CMV infection is infrequent except in CMV negative recipients with CMV positive donors. Death from CMV infection is uncommon. There does not appear to be a demonstrable benefit of any type of CMV prophylaxis in our study. 251 BASILIXIMAB IN CRITICALLY ILL CHILDREN UNDERGOING HEART TRANSPLANTATION: INITIAL DATA K.A. Ford,1 C.M. Cale,2 P.G. Rees,3 M.J. Elliott,3 M. Burch,3 1 Pharmacy Department, Great Ormond Street Hospital for Children, London, United Kingdom; 2Immunology Department, Great Ormond Street Hospital for Children, London, United Kingdom; 3Cardiology Department, Great Ormond Street Hospital for Children, London, United Kingdom Rationale: More children are coming to heart transplantation (HTx) on extracoporeal membrane oxygenation (ECMO), or inotropic support and/or renal impairment. The use of basiliximab, a chimaeric monoclonal antibody against CD25 (IL2Ralpha) has not been previously reported in critically ill paediatric heart transplant patients. Basiliximab has potential advantages in the management of patients with renal impairment. Patients: Basiliximab was given to 29 patients (median age: 7.8y; 0.4-16y) on ECMO, with renal impairment or on intravenous inotropes preceeding transplantation. Children normally received two doses on day 0 and day 4 post-transplant. Calcineurin inhibitor (CI) was given in low dose or withheld altogether in patients with renal impairment. Flow cytometry was used to monitor CD25. Results: At transplantation, 12 patients were on ciclosporin, the remaining 17 were on tacrolimus. All but 3 patients had subtherapeutic levels of CI in the first post-operative week. There were 21 patients who had more than 2 consecutive doses of CI cancelled in the first week (median consecutive cancelled doses: 8; 3-40doses). There were 64 surveillance biopsies and 3 episodes of severe acute rejection in the first 6 months. In all children, serum creatinine had returned to within normal limits for age by 1 month post-tx. Infections rates were low and acceptable. CD25 was undetectable at first assessment, and in all but two patients (on ECMO) thereafter. There were no adverse effects. Conclusion: Basiliximab can be used safely in critically ill children undergoing HTx. In children with pre- or post- operative renal dysfunction, basiliximab provided adequate immunosuppression to allow delay of CI for up to 40 consecutive doses without increase risk of rejection. These preliminary results are encouraging yet need confirmation in a large prospective trial. 252 ASSOCIATION OF GROWTH HORMONE THERAPY WITH THE DEVELOPMENT OF BRONCHIOLITIS OBLITERANS SYNDROME IN PEDIATRIC LUNG TRANSPLANT RECIPIENTS S.C. Sweet,1 M.T. de la Morena,1 P.M. Schuler,1 C.B. Huddleston,2 E.N. Mendeloff,2 1Department of Pediatrics, Washington University, St. Louis, MO; 2Department of Cardiothoracic Surgery, Washington University, St. Louis, MO Background: Many pediatric lung transplant recipients suffer from somatic growth failure. The majority have growth failure prior to transplant due to chronic respiratory failure and factors related to
Abstracts
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underlying disease. The use of corticosteroids is felt to be the primary post-transplant factor. However, some patients fail to improve their somatic growth when steroids are weaned during the first year after transplant. In these instances growth hormone (GH) has been considered. Studies of GH use in renal transplant have raised questions about its contribution to chronic rejection of the transplanted kidney. Therefore, we reviewed our experience with GH administration to determine the impact of GH on development of bronchiolitis obliterans syndrome (BOS). Methods: Computerized records of patients who underwent lung transplantation at St. Louis Children’s Hospital between June 1990 and July 2003 were reviewed. Of 236 recipeints, nine received GH after transplant. Outcomes in this group of patients were compared to 71 patients of similar age and diagnosis who underwent lung transplant during the same period. Results: Of the nine patients who received GH, eight developed BOS subsequent to beginning GH therapy. The ninth patient was well at last follow-up at our center 2 years ago. Compared to the group of patients with similar age at transplant and pre-transplant diagnosis, patients who received GH were more likely to develop BOS (RR 8.7, p ⫽ 0.03, Fisher’s Exact Test). In contrast, Kaplan-Meier analysis of the freedom from BOS in the GH population compared to control was not significantly different. There was no difference in Kaplan-Meier graft survival between the two groups. Conclusions: Patients who received GH treatment following lung transplant had a higher incidence of OB compared to a control cohort. Survival and freedom from BOS was not different. Analysis of a larger group of patients is necessary to clarify these findings. However, based on this analysis, we recommend that GH be used cautiously in pediatric lung transplant recipients. 253 RENAL INSUFFICIENCY IS ASSOCIATED WITH EARLY MORTALITY IN PEDIATRIC LUNG RE-TRANSPLANTATION M.T. de la Morena,1 S.C. Sweet,1 K. Schechtman,3 P.M. Schuler,1 E.N. Mendeloff,2 C.B. Huddleston,2 1Pediatrics, Washington University School of Medicine, St. Louis, MO; 2Cardio-Thoracic Surgery, Washington University School of Medicine, St. Louis, MO; 3 Biostatistics, Washington University School of Medicine, St. Louis, MO Introduction: Early survival is lower in patients undergoing lung re-transplantation. We sought to identify risk factors associated with mortality in pediatric patients that receive a second lung transplant. Material and Methods: We reviewed the charts of all pediatric patients undergoing bilateral lung transplantation (BLT) between June of 1990 through November 2002. Demographic, physiologic, operative and outcome data were collected and categorized as variables prior to transplant, at time of transplant and post-transplantation. Data corresponding to a first transplant in those patients receiving a second transplant were excluded to avoid bias. Results: 203 transplants were performed: 175 patients (pts) received 1st transplant (Txp); 28 pts received a 2nd Txp; median follow up was 667days. Both cadaveric BLT and living donor lobar transplants (LDLT) were included. A higher proportion of patients received LDLT as a second transplant (p ⫽-0.002). No statistical difference were noted for gender, primary diagnosis, infectious colonization, mechanical ventilation at time of transplant, height and weight z-scores, need for re-operation, bypass time, rejection episodes in first year, development of bronchiolitis obliterans or post transplant lymphoproliferative disease for either transplant. The differences in survival between 1st and 2nd Txp is accounted for by mortality during the first year (p ⬍ 0.01). Donor CMV status and operative bleeding were predictors of mortality for both 1st and 2nd Txp (p ⬍ 0.05). However,
month, 91% at 6 months, and 91% at 1 year following infection. The major risk factor for CMV was D⫹/R- (p ⬍ 0.0001). Among all other D/R combinations, the freedom from CMV infection ranged from 90 –98% at 6 months. In all D/R combinations (including D⫹/R-), there was no significant reduction in CMV infection with any form of prophylaxis. Conclusions: CMV infection is infrequent except in CMV negative recipients with CMV positive donors. Death from CMV infection is uncommon. There does not appear to be a demonstrable benefit of any type of CMV prophylaxis in our study. 251 BASILIXIMAB IN CRITICALLY ILL CHILDREN UNDERGOING HEART TRANSPLANTATION: INITIAL DATA K.A. Ford,1 C.M. Cale,2 P.G. Rees,3 M.J. Elliott,3 M. Burch,3 1 Pharmacy Department, Great Ormond Street Hospital for Children, London, United Kingdom; 2Immunology Department, Great Ormond Street Hospital for Children, London, United Kingdom; 3Cardiology Department, Great Ormond Street Hospital for Children, London, United Kingdom Rationale: More children are coming to heart transplantation (HTx) on extracoporeal membrane oxygenation (ECMO), or inotropic support and/or renal impairment. The use of basiliximab, a chimaeric monoclonal antibody against CD25 (IL2Ralpha) has not been previously reported in critically ill paediatric heart transplant patients. Basiliximab has potential advantages in the management of patients with renal impairment. Patients: Basiliximab was given to 29 patients (median age: 7.8y; 0.4-16y) on ECMO, with renal impairment or on intravenous inotropes preceeding transplantation. Children normally received two doses on day 0 and day 4 post-transplant. Calcineurin inhibitor (CI) was given in low dose or withheld altogether in patients with renal impairment. Flow cytometry was used to monitor CD25. Results: At transplantation, 12 patients were on ciclosporin, the remaining 17 were on tacrolimus. All but 3 patients had subtherapeutic levels of CI in the first post-operative week. There were 21 patients who had more than 2 consecutive doses of CI cancelled in the first week (median consecutive cancelled doses: 8; 3-40doses). There were 64 surveillance biopsies and 3 episodes of severe acute rejection in the first 6 months. In all children, serum creatinine had returned to within normal limits for age by 1 month post-tx. Infections rates were low and acceptable. CD25 was undetectable at first assessment, and in all but two patients (on ECMO) thereafter. There were no adverse effects. Conclusion: Basiliximab can be used safely in critically ill children undergoing HTx. In children with pre- or post- operative renal dysfunction, basiliximab provided adequate immunosuppression to allow delay of CI for up to 40 consecutive doses without increase risk of rejection. These preliminary results are encouraging yet need confirmation in a large prospective trial. 252 ASSOCIATION OF GROWTH HORMONE THERAPY WITH THE DEVELOPMENT OF BRONCHIOLITIS OBLITERANS SYNDROME IN PEDIATRIC LUNG TRANSPLANT RECIPIENTS S.C. Sweet,1 M.T. de la Morena,1 P.M. Schuler,1 C.B. Huddleston,2 E.N. Mendeloff,2 1Department of Pediatrics, Washington University, St. Louis, MO; 2Department of Cardiothoracic Surgery, Washington University, St. Louis, MO Background: Many pediatric lung transplant recipients suffer from somatic growth failure. The majority have growth failure prior to transplant due to chronic respiratory failure and factors related to
Abstracts
S127
underlying disease. The use of corticosteroids is felt to be the primary post-transplant factor. However, some patients fail to improve their somatic growth when steroids are weaned during the first year after transplant. In these instances growth hormone (GH) has been considered. Studies of GH use in renal transplant have raised questions about its contribution to chronic rejection of the transplanted kidney. Therefore, we reviewed our experience with GH administration to determine the impact of GH on development of bronchiolitis obliterans syndrome (BOS). Methods: Computerized records of patients who underwent lung transplantation at St. Louis Children’s Hospital between June 1990 and July 2003 were reviewed. Of 236 recipeints, nine received GH after transplant. Outcomes in this group of patients were compared to 71 patients of similar age and diagnosis who underwent lung transplant during the same period. Results: Of the nine patients who received GH, eight developed BOS subsequent to beginning GH therapy. The ninth patient was well at last follow-up at our center 2 years ago. Compared to the group of patients with similar age at transplant and pre-transplant diagnosis, patients who received GH were more likely to develop BOS (RR 8.7, p ⫽ 0.03, Fisher’s Exact Test). In contrast, Kaplan-Meier analysis of the freedom from BOS in the GH population compared to control was not significantly different. There was no difference in Kaplan-Meier graft survival between the two groups. Conclusions: Patients who received GH treatment following lung transplant had a higher incidence of OB compared to a control cohort. Survival and freedom from BOS was not different. Analysis of a larger group of patients is necessary to clarify these findings. However, based on this analysis, we recommend that GH be used cautiously in pediatric lung transplant recipients. 253 RENAL INSUFFICIENCY IS ASSOCIATED WITH EARLY MORTALITY IN PEDIATRIC LUNG RE-TRANSPLANTATION M.T. de la Morena,1 S.C. Sweet,1 K. Schechtman,3 P.M. Schuler,1 E.N. Mendeloff,2 C.B. Huddleston,2 1Pediatrics, Washington University School of Medicine, St. Louis, MO; 2Cardio-Thoracic Surgery, Washington University School of Medicine, St. Louis, MO; 3 Biostatistics, Washington University School of Medicine, St. Louis, MO Introduction: Early survival is lower in patients undergoing lung re-transplantation. We sought to identify risk factors associated with mortality in pediatric patients that receive a second lung transplant. Material and Methods: We reviewed the charts of all pediatric patients undergoing bilateral lung transplantation (BLT) between June of 1990 through November 2002. Demographic, physiologic, operative and outcome data were collected and categorized as variables prior to transplant, at time of transplant and post-transplantation. Data corresponding to a first transplant in those patients receiving a second transplant were excluded to avoid bias. Results: 203 transplants were performed: 175 patients (pts) received 1st transplant (Txp); 28 pts received a 2nd Txp; median follow up was 667days. Both cadaveric BLT and living donor lobar transplants (LDLT) were included. A higher proportion of patients received LDLT as a second transplant (p ⫽-0.002). No statistical difference were noted for gender, primary diagnosis, infectious colonization, mechanical ventilation at time of transplant, height and weight z-scores, need for re-operation, bypass time, rejection episodes in first year, development of bronchiolitis obliterans or post transplant lymphoproliferative disease for either transplant. The differences in survival between 1st and 2nd Txp is accounted for by mortality during the first year (p ⬍ 0.01). Donor CMV status and operative bleeding were predictors of mortality for both 1st and 2nd Txp (p ⬍ 0.05). However,