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Cardiac Allograft Vasculopathy in Young Adults Who Underwent Heart Transplant in Childhood - A Serial Intravascular Ultrasound Study
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The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
9( 23) Total Lymphoid Irradiation to Successfully Treat Refractory Rejection in Pediatric Heart Transplant Recipients L.E. Hernandez , P.A. Kofflin, R.K. Ameduri. Department of Pediatrics, University of Minnesota, Minneapolis, MN. Purpose: Total lymphoid irradiation (TLI) is used to treat acute recurrent heart transplant (HTx) rejection, especially in those not responding to the usual therapies. We evaluate the role of TLI in the management of refractory rejection in a single center review. Methods: We performed a retrospective review of pediatric HTx recipients who underwent TLI for refractory rejection at our center. Indication for HTx; cross-match results; rejection history, conventional treatment received, TLI dose and treatment course, rejection and graft failure after the TLI and TLI side effects were reviewed. Results: The reason for HTx was failed congenital heart disease palliation in 3 patients and cardiomyopathy in 1 patient. T and B cell cross-match was negative in all patients. Patient 1 and 2 developed severe antibody mediated rejection; patient 3 and 4 had a combination of cellular and antibody mediated rejection. All patients were treated aggressively with multiple rounds of conventional therapy including intravenous steroids, plasmapheresis, thymoglobulin, and in more recent cases rituximab, before TLI. TLI therapy duration ranged from 4 to 10 treatments, and occurred over a period as short as 4 days or as long as 5 weeks. Patient 1 just completed therapy but is clinically improved with improving graft function. No patients had recurrence of rejection following TLI therapy. Patients 2 and patient 4 did undergo retransplantation due to coronary artery vasculopathy (re-transplant 5 years and 7 years after TLI, respectively), however neither had rejection in their second HTx. Only nausea and mild neutropenia was observed in the four patients with no evidence of severe infection, lymphoproliferative disorder or mortality during long term follow up. Conclusion: TLI was an effective treatment for recurrent and refractory rejection in our pediatric HTx recipients, helping during the acute episode and also decreasing the incidence of recurrent rejection. Although 2 patients did require re-transplant, this was likely related to damage to the HTx graft from the recurrent rejection, but it is encouraging that these recipients did not experience rejection in their second Htx. Previous reports suggest that TLI increases the risk for serious infection or lymphoproliferative disease, however these were not observed in our patients. 9( 24) Cardiac Allograft Vasculopathy in Young Adults Who Underwent Heart Transplant in Childhood - A Serial Intravascular Ultrasound Study M.A. Kuhn ,1 L.N. Stoletniy,2 M.G. Stevenson,2 B.M. Gordon,1 A.J. Razzouk,3 R.E. Chinnock.1 1Pediatrics, Loma Linda Univ, Loma Linda, CA; 2Cardiology, Loma Linda Univ, Loma Linda, CA; 3Cardiothoracic Surgery, Loma Linda Univ, Loma Linda, CA. Purpose: Care for pediatric heart transplant recipients can be difficult as they transition to adult providers. We evaluated pediatric heart transplant recipients for cardiac allograft vasculopathy (CAV) with serial intravascular ultrasound (IVUS) exams as they entered adulthood. Methods: We retrospectively reviewed young adult patients who underwent pediatric heart transplant at our institution and have been followed by our pediatric and adult programs. During childhood, serial IVUS of the left anterior descending artery was routinely performed as part of the annual evaluation. A repeat IVUS was performed as adults with each patient having an IVUS at age 12/13 (Pre-Teen), age 17/18 (Late Teen) and age 19/up (Adult). IVUS measurements included maximal intimal thickness (MIT) and intimal index (II) and was graded using Stanford classification (SC). Each patient’s IVUS was compared to their other studies to evaluate for progression. The patients were further divided into 2 groups: those transplanted as neonates (less than 1 month of age) and older patients (greater than 1 month of age). MIT, II and the presence of severe intimal thickening (SC 4) were compared between the two groups. Results are given as mean +/- SD. Statistics used: Student’s t-test and chi-square analysis. A P-value of 0.05 was considered significant. Results: To date, 46 pts have been evaluated. Mean age at last IVUS was 21.6 ± 2 years with a mean transplant age of 18 ± 5 years. MIT increased significantly from Pre-Teen to Late Teen (0.16 ± 0.07 mm vs. 0.28 ±0.17
mm, p< 0.001), and to Adult (0.16 ± 0.07 mm vs. 0.45 ± 0.34 mm, p < 0.001). II did not significantly increase from Pre-Teen to Late Teen but did increase significantly from Late Teen to Adult (0.12 ± 0.07 vs. 0.17 ± 0.09, p < 0.001). When the Neonatal group was compared to the Older group, there no difference in MIT, II or SC 4 at the Pre-Teen and Late Teen stages. There was significantly higher MIT (0.34 ± 20 vs. 0.59 ± 0.42, P = 0.025), II (0.14 ± 0.05 vs. 0.21 ± 0.11 P = 0.018) and number patients with SC 4 (2/26 vs. 8/20 P= 0.013) in the Older group at the Adult study. Conclusion: CAV continues to progress in pediatric heart transplant patients into adult life. Neonatal heart transplant recipients appear to develop less CAV compared to older patients, although the mechanism remains unclear. Further evaluation of this population is important as they age. 9( 25) Incidence and Outcomes of Acute Kidney Injury Following Lung Transplantation in Pediatric Population: Retrospective Review M. Gazzaneo ,1 A. Akcan-Arikan,1 O. Papadias,1 R. Abelt,2 E. Melicoff,1 S. Kim,1 N. Crews,1 G. Mallory.1 1Pediactric Pulmonary Transplantation, Texas Childrens Hospital, Houston, TX; 2Pediactric Pulmonary, Texas Childrens Hospital, Houston, TX. Purpose: Acute Kidney Injury (AKI) is a common complication following lung transplantation (LTx). Our aim was to describe the incidence, factors and outcomes associated with acute kidney injury in the immediate post operative period after lung transplantation. Methods: This study retrospectively evaluated data on 38 patients who underwent lung transplantation at Texas Children’s Hospital between 2012 and 2014. The primary outcome was AKI, defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, in the first 7 post operative days. Secondary outcomes included hospital length of stay, -, utilization of renal replacement therapy (RRT). and renal recovery. Results: Of 38 patients who received lung transplant, AKI occurred in 27 (71%) with severity classified as Stage I in 70.3 % (n= 19), Stage II in 22.2% (n= 6) and Stage III 7.4% (n= 2) within the first 7 days after transplantation. 57.8% (n= 11) of patients in Stage I, 33.3% (n= 2) in Stage II, and 100% (n= 2) in Stage III AKI recovered within 7 days post transplant. Five (13.15%) patients with AKI received RRT via peritoneal dialysis, and no patients received extracorporeal renal support. Of patients with AKI, all (n= 27) had longer CPB time (> 360 min) compared to patients with no AKI (< 312 min); 96.2% (n= 26) had elevated tacrolimus levels (> 15 ng/ml), and 70.3% (n= 19) had longer hospital length of stay (> 2 weeks). Conclusion: AKI was common following lung transplantation and was associated with longer hospital stay. Longer CPB time and high tacrolimus serum levels were risk factors. Only 55% recovered renal function within 7 days after lung transplant. There is a closely knit association between surgical and treatment factors and AKI in pediatric patients after lung transplantation. Further recovery of the renal function should be closely monitored as these patients remain at high risk for chronic kidney disease development due to continuous exposure to nephrotoxic medications. 9( 26) Adenovirus Infection After Pediatric Lung Transplantation: A Pediatric Center Experience and Development of a Clinical Practice Guideline N. Crews , M. Ebenbichler, S. Kim, S. Nicholas, E. Melicoff, M. Gazzaneo, G. Mallory. Pediactric Pulmonary Transplantation, Texas Childrens Hospital, Houston, TX. Purpose: Adenovirus (Ad) infection among lung transplant (LTx) patients results in substantial morbidity and mortality. Children < 5 yrs of age are at highest risk. The incidence, morbidity and mortality associated with Ad disease in pediatric LTx patients < 5 yrs of age and the potential impact of a clinical practice guideline were examined. Methods: Retrospective chart review October 2002 to May 2014. Results: Of 163 pediatric LTx performed at Texas Children’s Hospital, 26 were in patients < 5 yrs old. Among these, 6 (23%) had Ad disease defined as symptoms associated with Ad identification in nasal wash or bronchoalveolar lavage (BAL), and viremia. Most (83%) were children < 3 years old. Time of initial diagnosis ranged from 3 weeks to 2 months post-LTx, with 50% < 4 weeks and 50% between 4 and 8 weeks post-LTx. Five patients (83%) received IV cidofovir (minimum of 1 dose). One patient is now 9 yrs post-LTx
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
9( 23) Total Lymphoid Irradiation to Successfully Treat Refractory Rejection in Pediatric Heart Transplant Recipients L.E. Hernandez , P.A. Kofflin, R.K. Ameduri. Department of Pediatrics, University of Minnesota, Minneapolis, MN. Purpose: Total lymphoid irradiation (TLI) is used to treat acute recurrent heart transplant (HTx) rejection, especially in those not responding to the usual therapies. We evaluate the role of TLI in the management of refractory rejection in a single center review. Methods: We performed a retrospective review of pediatric HTx recipients who underwent TLI for refractory rejection at our center. Indication for HTx; cross-match results; rejection history, conventional treatment received, TLI dose and treatment course, rejection and graft failure after the TLI and TLI side effects were reviewed. Results: The reason for HTx was failed congenital heart disease palliation in 3 patients and cardiomyopathy in 1 patient. T and B cell cross-match was negative in all patients. Patient 1 and 2 developed severe antibody mediated rejection; patient 3 and 4 had a combination of cellular and antibody mediated rejection. All patients were treated aggressively with multiple rounds of conventional therapy including intravenous steroids, plasmapheresis, thymoglobulin, and in more recent cases rituximab, before TLI. TLI therapy duration ranged from 4 to 10 treatments, and occurred over a period as short as 4 days or as long as 5 weeks. Patient 1 just completed therapy but is clinically improved with improving graft function. No patients had recurrence of rejection following TLI therapy. Patients 2 and patient 4 did undergo retransplantation due to coronary artery vasculopathy (re-transplant 5 years and 7 years after TLI, respectively), however neither had rejection in their second HTx. Only nausea and mild neutropenia was observed in the four patients with no evidence of severe infection, lymphoproliferative disorder or mortality during long term follow up. Conclusion: TLI was an effective treatment for recurrent and refractory rejection in our pediatric HTx recipients, helping during the acute episode and also decreasing the incidence of recurrent rejection. Although 2 patients did require re-transplant, this was likely related to damage to the HTx graft from the recurrent rejection, but it is encouraging that these recipients did not experience rejection in their second Htx. Previous reports suggest that TLI increases the risk for serious infection or lymphoproliferative disease, however these were not observed in our patients. 9( 24) Cardiac Allograft Vasculopathy in Young Adults Who Underwent Heart Transplant in Childhood - A Serial Intravascular Ultrasound Study M.A. Kuhn ,1 L.N. Stoletniy,2 M.G. Stevenson,2 B.M. Gordon,1 A.J. Razzouk,3 R.E. Chinnock.1 1Pediatrics, Loma Linda Univ, Loma Linda, CA; 2Cardiology, Loma Linda Univ, Loma Linda, CA; 3Cardiothoracic Surgery, Loma Linda Univ, Loma Linda, CA. Purpose: Care for pediatric heart transplant recipients can be difficult as they transition to adult providers. We evaluated pediatric heart transplant recipients for cardiac allograft vasculopathy (CAV) with serial intravascular ultrasound (IVUS) exams as they entered adulthood. Methods: We retrospectively reviewed young adult patients who underwent pediatric heart transplant at our institution and have been followed by our pediatric and adult programs. During childhood, serial IVUS of the left anterior descending artery was routinely performed as part of the annual evaluation. A repeat IVUS was performed as adults with each patient having an IVUS at age 12/13 (Pre-Teen), age 17/18 (Late Teen) and age 19/up (Adult). IVUS measurements included maximal intimal thickness (MIT) and intimal index (II) and was graded using Stanford classification (SC). Each patient’s IVUS was compared to their other studies to evaluate for progression. The patients were further divided into 2 groups: those transplanted as neonates (less than 1 month of age) and older patients (greater than 1 month of age). MIT, II and the presence of severe intimal thickening (SC 4) were compared between the two groups. Results are given as mean +/- SD. Statistics used: Student’s t-test and chi-square analysis. A P-value of 0.05 was considered significant. Results: To date, 46 pts have been evaluated. Mean age at last IVUS was 21.6 ± 2 years with a mean transplant age of 18 ± 5 years. MIT increased significantly from Pre-Teen to Late Teen (0.16 ± 0.07 mm vs. 0.28 ±0.17
mm, p< 0.001), and to Adult (0.16 ± 0.07 mm vs. 0.45 ± 0.34 mm, p < 0.001). II did not significantly increase from Pre-Teen to Late Teen but did increase significantly from Late Teen to Adult (0.12 ± 0.07 vs. 0.17 ± 0.09, p < 0.001). When the Neonatal group was compared to the Older group, there no difference in MIT, II or SC 4 at the Pre-Teen and Late Teen stages. There was significantly higher MIT (0.34 ± 20 vs. 0.59 ± 0.42, P = 0.025), II (0.14 ± 0.05 vs. 0.21 ± 0.11 P = 0.018) and number patients with SC 4 (2/26 vs. 8/20 P= 0.013) in the Older group at the Adult study. Conclusion: CAV continues to progress in pediatric heart transplant patients into adult life. Neonatal heart transplant recipients appear to develop less CAV compared to older patients, although the mechanism remains unclear. Further evaluation of this population is important as they age. 9( 25) Incidence and Outcomes of Acute Kidney Injury Following Lung Transplantation in Pediatric Population: Retrospective Review M. Gazzaneo ,1 A. Akcan-Arikan,1 O. Papadias,1 R. Abelt,2 E. Melicoff,1 S. Kim,1 N. Crews,1 G. Mallory.1 1Pediactric Pulmonary Transplantation, Texas Childrens Hospital, Houston, TX; 2Pediactric Pulmonary, Texas Childrens Hospital, Houston, TX. Purpose: Acute Kidney Injury (AKI) is a common complication following lung transplantation (LTx). Our aim was to describe the incidence, factors and outcomes associated with acute kidney injury in the immediate post operative period after lung transplantation. Methods: This study retrospectively evaluated data on 38 patients who underwent lung transplantation at Texas Children’s Hospital between 2012 and 2014. The primary outcome was AKI, defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, in the first 7 post operative days. Secondary outcomes included hospital length of stay, -, utilization of renal replacement therapy (RRT). and renal recovery. Results: Of 38 patients who received lung transplant, AKI occurred in 27 (71%) with severity classified as Stage I in 70.3 % (n= 19), Stage II in 22.2% (n= 6) and Stage III 7.4% (n= 2) within the first 7 days after transplantation. 57.8% (n= 11) of patients in Stage I, 33.3% (n= 2) in Stage II, and 100% (n= 2) in Stage III AKI recovered within 7 days post transplant. Five (13.15%) patients with AKI received RRT via peritoneal dialysis, and no patients received extracorporeal renal support. Of patients with AKI, all (n= 27) had longer CPB time (> 360 min) compared to patients with no AKI (< 312 min); 96.2% (n= 26) had elevated tacrolimus levels (> 15 ng/ml), and 70.3% (n= 19) had longer hospital length of stay (> 2 weeks). Conclusion: AKI was common following lung transplantation and was associated with longer hospital stay. Longer CPB time and high tacrolimus serum levels were risk factors. Only 55% recovered renal function within 7 days after lung transplant. There is a closely knit association between surgical and treatment factors and AKI in pediatric patients after lung transplantation. Further recovery of the renal function should be closely monitored as these patients remain at high risk for chronic kidney disease development due to continuous exposure to nephrotoxic medications. 9( 26) Adenovirus Infection After Pediatric Lung Transplantation: A Pediatric Center Experience and Development of a Clinical Practice Guideline N. Crews , M. Ebenbichler, S. Kim, S. Nicholas, E. Melicoff, M. Gazzaneo, G. Mallory. Pediactric Pulmonary Transplantation, Texas Childrens Hospital, Houston, TX. Purpose: Adenovirus (Ad) infection among lung transplant (LTx) patients results in substantial morbidity and mortality. Children < 5 yrs of age are at highest risk. The incidence, morbidity and mortality associated with Ad disease in pediatric LTx patients < 5 yrs of age and the potential impact of a clinical practice guideline were examined. Methods: Retrospective chart review October 2002 to May 2014. Results: Of 163 pediatric LTx performed at Texas Children’s Hospital, 26 were in patients < 5 yrs old. Among these, 6 (23%) had Ad disease defined as symptoms associated with Ad identification in nasal wash or bronchoalveolar lavage (BAL), and viremia. Most (83%) were children < 3 years old. Time of initial diagnosis ranged from 3 weeks to 2 months post-LTx, with 50% < 4 weeks and 50% between 4 and 8 weeks post-LTx. Five patients (83%) received IV cidofovir (minimum of 1 dose). One patient is now 9 yrs post-LTx