Lung and Heart–Lung Transplantation in Children and Adolescents: A Long-term Single-center Experience

doi:10.1016/j.healun.2008.12.012

The Journal of Heart and Lung Transplantation

Volume 28, Issue 3, March 2009, Pages 243-248

https://doi.org/10.1016/j.healun.2008.12.012 Get rights and content

Background

Pediatric lung transplantation (LTx) remains a challenge for a highly selected group of patients. The requirements for immunosuppressive therapy and the associated risks must be weighed against the long-term prognosis of this operation. Therefore, we retrospectively analyzed our experience after 53 lung and heart–lung transplantations (HLTx) in children.

Methods

All pediatric patients <18 years of age who underwent LTx (n = 37) and HLTx (n = 16) at our institution were included in this study. We analyzed indications for transplantation, survival rates and causes of death. Herein we assess pediatric-specific challenges in comparison to adults.

Results

Thirty-day mortality was 13.2%. Kaplan–Meier survival rates at 1, 3, 5 and 10 years were 69%, 64%, 44% and 39%, respectively. Main indications for transplantation were cystic fibrosis and congenital heart disease with Eisenmenger syndrome. Other diagnoses were retransplantation, primary pulmonary hypertension and pulmonary fibrosis. The main causes of death were infection and chronic graft failure. Reduced-size transplantation was performed in 42% of double-lung transplantation (DLTx) patients without negatively impacting survival. Six patients received pulmonary retransplantation, 1 of whom died early.

Conclusions

Pediatric transplantation is a feasible therapeutic option when undertaken by an experienced team. It should be offered to the small patient population suffering from end-stage pulmonary disease. The limited number of pediatric donor organs can be overcome by using reduced-size organs. However, the management of pediatric-specific complications and therapeutic requirements is essential for positive long-term results after LTx in these patients.

Section snippets

Patients

Between December 1987 and December 2007, a total of 1,002 LTx and HLTx were performed at Hannover Medical School, among them 53 procedures in 47 patients <18 years of age. Six patients received pulmonary retransplantation. Pediatric heart transplantations were excluded from this analysis.

Immunosuppression and Post-operative Management

Post-operative immunosuppression consisted of a triple maintenance therapy based on tacrolimus in combination with mycophenolate mofetil and steroids. Induction therapy was not administered. All patients were

Patient Population

Between December 1987 and December 2007, a total of 53 pediatric LTx and HLTx were performed at our institution. Of these, 31 (58.5%) were double-lung transplantations (DLTx), 6 (11.3%) were single-lung transplantations (SLTx) and 16 (30.2%) were HLTx. Twenty-nine (54.7%) patients were male and 24 (45.3%) female with a mean age of 14 ± 3.8 years (range 1 to 17 years). As shown in Figure 2, the majority of patients were adolescents rather than children. Mean height was 149 ± 22.8 cm and mean

General Considerations

In this study we have described our experience with LTx and HLTx in children and adolescents. As we have noted, the worldwide numbers of pediatric LTx and HLTx performed are low.1, 2 Indeed, a potential reason is that there is low prevalence of presenting indications for LTx in children. This, in addition to a general skepticism toward this therapeutic approach, has resulted in limited cases. According to a recently published analysis by Liou and colleagues,³ the outcome of LTx in children with

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Cited by (33)

Pediatric Lung Transplant Outcomes Based on Immunosuppressive Regimen at Discharge: Retrospective Cohort Study Using Real-World Evidence From the US Scientific Registry of Transplant Recipients
2023, Transplantation Proceedings
This retrospective analysis of the US Scientific Registry of Transplant Recipients was undertaken to obtain real-world evidence concerning the efficacy and safety of tacrolimus-based immunosuppression in pediatric lung transplant recipients to support a supplemental New Drug Application.
Overall, 725 pediatric recipients of a primary deceased-donor lung transplant between January 1, 1999, and December 31, 2017, were followed for up to 3 years post-transplant based on an immunosuppressive regimen at hospital discharge: immediate-release tacrolimus (TAC)+mycophenolate mofetil (MMF), TAC+azathioprine (AZA), cyclosporine (CsA)+MMF, or CsA+AZA. The primary outcome was the composite endpoint of graft failure or death (all-cause) at 1 year post-transplant, calculated by Kaplan–Meier analysis.
The use of TAC+MMF increased over time. During 2010 to 2017, 91.7% of pediatric lung transplant recipients were receiving TAC+MMF at the time of discharge. The proportion of recipients continuing their discharge regimen at 1 year post-transplant was 83.7% with TAC+MMF and 40.4% to 59.7% with the other regimens. Cumulative incidence of the composite endpoint of graft failure or death at 1 year post-transplant was 7.7% with TAC+MMF, 13.9% with TAC+AZA, 8.9% with CsA+MMF, and 9.1% with CsA+AZA. There was no significant difference in the risk of graft failure or death at 1 year post-transplant between groups from 1999 to 2005 (the only era when adequate numbers on each regimen allowed statistical comparison). No increase in hospitalization for infection or malignancy was seen with TAC+MMF.
The real-world evidence from the US database of transplant recipients supported the Food and Drug Administration's approval of tacrolimus-based maintenance immunosuppression in pediatric lung transplant recipients.
A multicentric evaluation of pediatric lung transplantation in Italy
2023, Journal of Thoracic and Cardiovascular Surgery
Citation Excerpt :
In particular, more than one half of patients who required postoperative tracheostomy were mechanically ventilated before transplantation, so we can assume that most of them arrived to transplant in compromised conditions with a possible exhaustion of muscular strength which may have resulted in unsuccessful weaning from postoperative MV. However, considering the whole pediatric population, the posttransplant results of our study are satisfactory; in particular, our 30-day mortality of 6% is lower than the 8.1% reported by the Vienna group,8 the 10% reported by the Paris group,7 and the 13.1% of the group of Hannover.5 The comparison of other short-term outcomes is, however, more difficult to make, as they are not reported by each study: the median duration of mechanical ventilation, ICU stay, and postoperative hospital stay is analyzed only by Schmid and colleagues6 with values of 24 hours, 4 days, and 40 days, respectively.
Pediatric lung transplantation is performed in highly experienced centers due to the peculiar population characteristics. The literature is limited and not representative of individual countries' differences. The purpose of this study was to analyze the Italian experience.
A multicentric retrospective analysis was performed on 110 pediatric patients (<18 years old) who underwent lung transplantation from 1992 to 2019 at 9 Italian centers. Heart–lung transplantations and lung retransplantations were excluded.
The population was composed of 44 male and 66 female patients, with a median age of 15 years. The most frequent indication was cystic fibrosis (83%). One quarter of patients were transplanted in an emergency setting. Median donors' Oto score and age were 1 and 15 years, respectively, with 43% of adult donors. In 17% of patients a graft reduction was performed. Postoperatively, the median duration of mechanical ventilation, intensive care unit, and in-hospital stay were 48 hours, 11 and 35 days, respectively. Thirty-day mortality was 6%, and 1-, 5-, and 10-year survival was 72%, 52%, and 33%, respectively. Risk factors for mortality were Oto score and recipients' body mass index.
The outcomes of pediatric lung transplantation in Italy are comparable with current literature. Particular attention should be paid to the Oto score and recipient body mass index. Conversely, adult donors and graft reductions can be safely used to expand the donor pool.
Full recovery of right ventricular systolic function in children undergoing bilateral lung transplantation for severe PAH
2022, Journal of Heart and Lung Transplantation
We investigated whether RV function recovers in children with pulmonary arterial hypertension (PAH) and RV failure undergoing lung transplantation (LuTx).
Prospective observational study of 15 consecutive children, 1.9 to 17.6 years old, with PAH undergoing bilateral LuTx. We performed advanced echocardiography (Echo) and cardiac magnetic resonance imaging (MRI), followed by conventional and strain analysis, pre- and ∼6 weeks post-LuTx.
After LuTx, RV/LV end-systolic diameter ratio (Echo), RV volumes and systolic RV function (RVEF 63 vs 30 %; p < 0.05) by MRI completely normalized, even in children with severe RV failure (RVEF < 40%). The echocardiographic end-systolic LV eccentricity index nearly normalized post-LuTx (1.0 vs 2.0, p < 0.0001) while RV hypertrophy regressed more slowly and was still evident. We found especially the end-systolic RV/LV ratios by Echo (diameter: 0.6 vs 2.6) or MRI (volumes: 0.8 vs 3.4) excellent diagnostic tools (p < 0.05): Together with RVEF by MRI, these ratios were superior to tricuspid annular plane systolic excursion (TAPSE; p = 0.4551) in assessing global systolic RV dysfunction. Moreover, children with severe PAH had reduced RV 2D longitudinal strain (Echo, MRI; p = 0.0450) and decreased RV 2D radial and circumferential strain (MRI; p = 0.0026 and p = 0.0036 respectively), all of which greatly improved following LuTx.
We demonstrate full recovery of RV systolic function in children within two months after LuTx for severe PAH, independently of the patients’ age, weight, and hemodynamic compromise preceding the LuTx. Even in end-stage pediatric PAH with poor RV function and low cardiac output, LuTx should be preferred over heart-lung transplantation.
Indications and outcome after lung transplantation in children under 12 years of age: A 16-year single center experience
2022, Journal of Heart and Lung Transplantation
Citation Excerpt :
Less cooperation for the maneuver, higher sensitivity for obstructive changes and independence from body size might be positive factors, but standardization and definitions for CLAD are lacking. In summary, a multidisciplinary team work, a careful donor and recipient selection, and the standardization of surgical and perioperative management strategies (the intraoperative use of ECMO instead of CPB whenever possible, the use of perioperative awake-ECMO, the prompt DSA detection and treatment, the aggressive weaning from the mechanical ventilation support) explain the survival improvement in our patients, in comparison to our previous experience and to the most recent ISHLT registry data.1,35 Of note, these results were achieved without performing any induction therapy, that, although still used in many pediatric lung transplant centers, was not associated with better survival or a lower ACR incidence.1
: Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children <12 years of age in comparison to adolescents (12-17 years old).
: Records of patients <18 years who underwent first lung transplantation between 01/2005 and 01/2021 were retrospectively reviewed, and compared between children <12 years old and adolescents. Median (IQR) follow-up was 51 (23-91) months.
Of the 117 patients underwent first lung transplantation at our institution, of whom 42 (35.8%) patients were <12 years and 75 (64.2%) ≥12 years old. Compared to adolescents, children were more often transplanted for interstitial lung disease (33.3% vs 12%, p = 0.005) and precapillary pulmonary hypertension (28.6% vs 12%, p = 0.025), and required more often intraoperative cardiopulmonary bypass (31% vs 14.7%, p = 0.036) and postoperative ECMO support (47.6% vs 13.3%, p < 0.001). Postoperatively, children required longer ventilation times (78 vs 18 hours, p = 0.009) and longer ICU stay (9.5 vs 3 days, p < 0.001) compared to their older counterparts. Primary graft dysfunction grade 3 at 72 hours (9.5% vs 9.3%, p = 0.999), in-hospital mortality (2.4% vs 6.7%, p = 0.418), graft survival (80% vs 62%, p = 0.479) and freedom from chronic lung allograft dysfunction (76% vs 59%, p = 0.41) at 8-year follow-up did not differ between groups.
: Lung transplantation in children under 12 years is challenging due to underlying medical conditions and operative complexity. Nevertheless, outcomes are comparable to those in older children.
The influence of retransplantation on survival for pediatric lung transplant recipients
2018, Journal of Thoracic and Cardiovascular Surgery
Citation Excerpt :
It reflects the standard of treatment during the most recent 13 years, whereas the early period owns more historic aspects. Especially the observed 5-year survival rate of 73.9% during the second period compares favorably to data from the registry (56.4% for the period 2008-2013), but also to results from other single centers (44% for 1987-2007 from Hannover, 61% for 1991-2009 from St Louis—only patients with idiopathic pulmonary artery hypertension included).5,6 This outcome was found to be even better than the outcome described for the adult population in the registry for a similar period of time (1 year, 82.7% and 5 years, 55.4% for the period 2005-2012).2
We reviewed our 25-year experience in pediatric lung transplantation with the aim to identify trends and influencing factors over time.
We reviewed our prospectively maintained database and analyzed all patients younger than age 18 years who underwent primary lung transplantation at Medical University of Vienna between 1990 and 2015.
Eighty-six consecutive patients were enrolled with a mean age of 12.9 ± 4.1 years at primary transplantation. The most frequent indication for primary transplantation was cystic fibrosis (64.0). Bilateral double-lung transplantation was performed in 84 patients (97.7%), including lobar transplantation in 35 patients (40.7%). sixty-eight patients (79.1%) underwent transplant on venoarterial extracorporeal membrane oxygenation and 7 patients (8.1%) utilized cardiopulmonary bypass. The 30-day and in-hospital mortality was 8.1% and 17.4%, respectively, and 1-, 5-, and 10-year overall survival (OS) was 79.0%, 67.5%, and 57.1%, respectively. A significant improvement of OS was observed during the second treatment period after 2003 with a 1-, 5-, and 10-year OS of 86.0%, 73.9%, and 73.9%, respectively (P < .01). Seventeen retransplantations were performed in 14 patients. Twelve patients (85.7%) underwent 15 late elective retransplantations for chronic lung allograft dysfunction resulting in a 1- and 5-year OS of 91.7% and 80.2%, respectively. In contrast, 2 patients (14.3%) who underwent acute retransplantation for primary graft failure died during the postoperative period.
Our outcomes for pediatric lung transplantation have improved over the past 25 years and have become comparable to those for adult transplantation. Elective re-transplantations for pediatric patients were performed successfully, and strongly influenced improved long-term OS.
Pediatric lung transplantation in Broussais-HEGP: A 23-year experience (1990-2013)
2014, Revue de Pneumologie Clinique
La transplantation pulmonaire pédiatrique (TP) reste une petite partie des TP effectuées dans le monde. La majorité de ces TP concerne les jeunes adolescents, les transplantations chez les nourrissons restant anecdotiques. Nous avons mené une étude rétrospective de TP chez les enfants et les adolescents dans un centre à Paris depuis le début des années 90 à 2013.
Les données de l’hôpital Broussais puis celles de l’HEGP ont été recueillies rétrospectivement de 1990 à 2013 : 380 TP ont été rapportées chez 368 patients, dont 111 TP réalisées chez des enfants de 5 à 18 ans (30 %).
Cent onze patients ont reçu 121 TP : 86 greffes bipulmonaires, 13 greffes combinées poumons-foie, 3 greffes monopulmonaires, 5 greffes cœur-poumons et 4 greffes combinées cœur-poumons-foie. Quatre-vingt-huit pour cent des patients étaient greffés pour mucoviscidose. L’âge médian était de 14 ans, le poids de 34 kg et la taille de 144 cm. L’âge médian des donneurs était de 27 ans, le poids de 60 kg et la taille de 167 cm. Les courbes de survie conditionnelle pour les enfants n’étaient pas différentes de celles des adultes : 72 % à un an, 42 % à 5 ans, 37 % à 10 ans et de 26 % à 15 ans. Il n’y avait pas de surmortalité précoce après transplantation. La survie selon la période de greffe était significativement plus élevée après l’année 2000 (53 % à 5 ans vs 32 %, p = 0,03).
La transplantation pulmonaire chez les enfants de moins de 18 ans a des résultats similaires à ceux des adultes.
Pediatric lung transplantations (LTx) remains a small part of LTx performed worldwide. The majority of these Tx concerns young adolescents, transplantations in infants being anecdotic. We conducted a retrospective study of LTx in children and adolescents in one center in Paris from the beginning of the 90's to 2013.
Data from Broussais then HEGP were collected retrospectively from 1990 to 2013: 380 LTx were reported in 368 patients including 111 LTx performed among children from 5 to 18 years of age (30%).
One hundred and eleven patients received 121 LTx: 86 bilateral LTx, 13 combined lung-liver, 3 monopulmonary, 5 heart-lung and 4 combined heart-lung-liver Tx. Eighty-eight percent of the patients had cystic fibrosis. Median age was 14 years, weight 34 kg and height 144 cm. Median age of donors was 27 years, weight 60 kg and height 167 cm. Conditional survival for children was not different than adults: 72% at one year, 42% at 5 years, 37% at 10 years and 26% at 15 years. There was not overall early mortality after transplantation. Era graft survival was significantly higher after year 2000 (53% at 5 years vs 32% P = 0.03).
Lung transplantation among children under 18 years have similar outcome to those of adult patients.

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Pediatric transplantationLung and Heart–Lung Transplantation in Children and Adolescents: A Long-term Single-center Experience

Background

Methods

Results

Conclusions

Section snippets

Patients

Immunosuppression and Post-operative Management

Patient Population

General Considerations

J Heart Lung Transplant

J Heart Lung Transplant

Lancet

Am J Transplant

J Thorac Cardiovasc Surg

Thorac Cardiovasc Surg

Pediatric transplantation
Lung and Heart–Lung Transplantation in Children and Adolescents: A Long-term Single-center Experience