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ABSTRACT: Therapeutic plasma exchange (TPE) is an increasingly utilized immunosuppressive adjunct for treatment of antibody-mediated rejection (AMR) following organ transplantation. TPE works through removal of donor-specific HLA antibodies (DSAs) in the recipient's plasma. However, there is no clear laboratory measure evaluating efficacy of removal of DSAs or predicting clinical outcome. We hypothesized that semi-quantitative DSA measurement by multiplex HLA antibody immunoassay may provide qualitative and quantitative data for DSA clearance and predict treatment efficacy. To evaluate this, we retrospectively investigated DSA concentrations and clinical outcome for 21 pediatric patients who received 31 cycles of TPE peri-operatively as an adjunct treatment for transplantation in the setting of a positive cytotoxic crossmatch (CXM) and in recipients with AMR following heart or lung transplantation. Immunoassay measurement of DSAs during 15/20 cycles correlated significantly with clinical outcome in the AMR treatment group (P = 0.02), demonstrating the utility of DSA measurement in predicting clinical outcome. In contrast, immunoassay correlated with clinical outcome in only 7/11 patients treated peri-operatively with TPE for CXM-positive transplantations (P = 0.58). Changes in mean fluorescence intensity (MFI) for the DSAs correlated better with clinical response than surrogate CXM titers in a subset of patients. We conclude that semi-quantitative measurement of DSAs by immunoassay can predict clinical response to TPE for treatment of AMR is more reliable than surrogate CXM titer, and should be used to guide TPE treatment of AMR. J. Clin. Apheresis, 2013. © 2013 Wiley Periodicals, Inc.
Journal of Clinical Apheresis 02/2013; · 1.93 Impact Factor
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ABSTRACT: Neonates who experience respiratory failure despite maximal ventilatory support have only extracorporeal membrane oxygenation as a rescue therapy, but it has very poor outcomes as a bridge to transplantation. A pumpless lung-assist device has been used in adults as a bridge to lung transplantation. An alternative membrane oxygenator, the Quadrox iD, is a suitable size for neonatal blood flow. Here we report the use of the Quadrox iD membrane oxygenator with central cannulation as a paracorporeal respiratory support therapy for a neonate with alveolar capillary dysplasia awaiting lung transplantation.
The Annals of thoracic surgery 02/2013; 95(2):692-4. · 3.74 Impact Factor
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ABSTRACT: BACKGROUND: Malnutrition is common in children undergoing lung transplantation, particularly among those with cystic fibrosis (CF). However, the effect of body habitus on outcome after pediatric lung transplantation is unknown. We studied body mass index (BMI) and its effect on outcome in pediatric lung transplantation. METHODS: The International Society for Heart and Lung Transplantation Registry on Pediatric Lung Transplantation was queried for primary pediatric lung transplant recipients (aged<18 years) between 1990 and 2008. BMI cohorts were defined according to International Obesity Task Force cutoffs: thinness grade 3, BMI<16 kg/m(2); thinness grade 2, 16 to<17 kg/m(2); thinness grade 1, 17 to<18.5 kg/m(2); normal, 18.5 to<25 kg/m(2); overweight, 25 to<30 kg/m(2); and obese,≥30 kg/m(2). Survival was compared among BMI cohorts within CF and non-CF recipient groups. RESULTS: Included were 897 recipients. The median age at transplantation was 14 years (interquartile, 11, 16 years) and 63% had CF. The incidence of thinness was 59% in CF vs 39% in non-CF patients (p<0.001). A significant proportion of CF patients were underweight, whereas more non-CF patients were obese. Cox regression showed neither underweight nor overweight CF recipients differed in survival compared with recipients of normal-weight recipients. Grade of thinness was not related to outcome after transplantation. For non-CF recipients, being overweight/obese increased risk of death compared with normal-weight recipients (hazard ratio, 2.05; 95% confidence interval, 1.28-3.26; p = 0.002). CONCLUSION: The incidence of underweight status amongst pediatric lung transplant recipients with CF is high. However, we did not find a significant negative effect of underweight body habitus on survival in CF children after lung transplantation. Overweight pediatric recipients appear to have poorer survival after transplant.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 11/2012; · 3.54 Impact Factor
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ABSTRACT: The natural history of idiopathic pulmonary arterial hypertension (IPAH) in patients of all ages is one of relentless progression. For those who fail medical therapy, lung transplantation remains the ultimate palliation. In the USA, IPAH is the second leading indication for lung transplantation in children and first for children 1 to 5 years of age. In this study, we report our 18-year experience with lung transplantation in children with IPAH.
We performed a retrospective chart review of children with IPAH listed for lung transplant at our center between 1991 and 2009. Our data reflect a total of 26 children ranging in age from 1.6 to 18.9 years. Nineteen were transplanted and 7 died while waiting (27%). The impact of a number of pre-transplant variables on survival was evaluated.
Median survival for those transplanted was 5.8 years, with 1- and 5-year survival rates of 95% and 61%, respectively. Survival was independent of pre-transplant considerations such as age, weight, need for intravenous (IV) inotropes, use of IV pulmonary vasodilators, year of transplant and severity of right-sided cardiac pressures. There was 1 hospital death. Compared with the transplanted group, children who died waiting had a significantly higher incidence of supra-systemic right heart pressures (p = 0.02) and hemoptysis (p = 0.01).
Our study is the largest to date to look at outcomes for lung transplantation in children with IPAH. Their median survival compares favorably with that of all pediatric lung transplant recipients, 5.8 years vs 4.5 years, respectively. We did not identify any pre-transplant variables that presaged a poorer outcome. Thus, survival seemed more related to factors that influence long-term outcomes in all transplant recipients such as rejection and infection. Lung transplantation remains a viable option for children with IPAH, especially for those with supra-systemic right heart pressures despite maximal medical therapy.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 05/2011; 30(10):1148-52. · 3.54 Impact Factor
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The Journal of thoracic and cardiovascular surgery 03/2011; 141(6):e48-50. · 3.41 Impact Factor
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ABSTRACT: Effectiveness of preoperative and postoperative extracorporeal membrane oxygenation support in pediatric lung transplantation was studied.
Institutional database of pediatric lung transplants from 1990 to 2008 was reviewed.
Three hundred forty-four patients underwent lung transplants in the study period. Thirty-three of 344 patients (9.6%) required perioperative extracorporeal membrane oxygenation support. Fifteen patients (median, age 1.3 years; range, 0.2-18 years) required 16 pretransplant extracorporeal membrane oxygenation runs. Indications were respiratory failure (8/16, 50%), severe pulmonary hypertension (5/16, 31%), and cardiopulmonary collapse (3/16, 19%). Four of these patients (27%) also required postoperative support. Six (40%) were weaned before lung transplant. Six (40%) survived to hospital discharge. Survival to discharge was higher among patients weaned before lung transplant (4/6, 66% vs 2/9, 22%). Twenty-two patients (median age, 9.4 years; range, 0.2-21 years) underwent 24 extracorporeal membrane oxygenation runs after lung transplant. Indications for postoperative support were primary graft dysfunction (18/24, 75%), pneumonia (4/24, 16%), and others (2/24, 9%). Median time between lung transplant and institution of extracorporeal membrane oxygenation was 32 hours (range, 0-1084 hours); median duration of support was 141 hours (range, 48-505 hours). Five of these patients (23%) survived to hospital discharge. Among nonsurvivors, causes of death were intractable respiratory failure (12/17, 70%) and infectious complications (4/17, 24%).
Need for perioperative extracorporeal membrane oxygenation support is associated with significant morbidity and mortality among pediatric patients receiving lung transplants. A subset of patients who can be weaned from support preoperatively have greater likelihood of survival.
The Journal of thoracic and cardiovascular surgery 08/2010; 140(2):427-32. · 3.41 Impact Factor
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Stuart C Sweet
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 07/2010; 29(7):756-8. · 3.54 Impact Factor
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Christian Benden,
Albert Faro,
Sarah Worley,
Susana Arrigain,
Paul Aurora,
Manfred Ballmann,
Debra Boyer,
Carol Conrad,
Irmgard Eichler,
Okan Elidemir,
Samuel Goldfarb,
George B Mallory,
Peter J Mogayzel,
Daiva Parakininkas,
Melinda Solomon,
Gary Visner, Stuart C Sweet,
Lara A Danziger-Isakov
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ABSTRACT: In adult lung transplantation, a single minimal AR episode is a significant predictor of BOS independent of other factors. However, the significance of single minimal AR episodes in children is unknown. A retrospective, multi-center analysis was performed to determine whether isolated single AR episodes are associated with an increased BOS risk in children. Risk factors for BOS, death, or re-transplantation, and a combined outcome of BOS, death, or re-transplantation were assessed. Original data included 577 patients (<21 yr of age). A total of 383 subjects were eligible for the study. Fifteen percent of patients developed BOS, and 13% of patients either died or underwent re-transplant within one-yr post-transplant. In the multivariable survival model for time to BOS, there was no significant risk to developing BOS after a single minimal AR (A1) episode (HR 1.7, 95% CI 0.64-4.8; p=0.28). Even after a second minimal AR episode, no significant risk for BOS was appreciated. However, a single episode of mild AR (A2) was associated with twice the risk of BOS within one-yr post-transplant. In this select cohort, a single minimal AR episode was not associated with an increased risk for BOS within one yr following lung transplantation, in contrast to previous reports in adults.
Pediatric Transplantation 06/2010; 14(4):534-9. · 1.48 Impact Factor
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Frederick R Adler,
Paul Aurora,
David H Barker,
Mark L Barr,
Laura S Blackwell,
Otto H Bosma,
Samuel Brown,
D R Cox,
Judy L Jensen,
Geoffrey Kurland, [......],
Sandy L Romero,
Helen Spencer, Stuart C Sweet,
Wim van der Bij,
J Vermeulen,
Erik A M Verschuuren,
Elianne J L E Vrijlandt,
William Walsh,
Marlyn S Woo,
Theodore G Liou
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ABSTRACT: Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions.
Proceedings of the American Thoracic Society 12/2009; 6(8):619-33.
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Stuart C Sweet
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ABSTRACT: In May 2005, a system was established to allocate deceased donor lungs to adolescents and adults in the United States based on models of waiting list mortality and one-yr transplant survival benefit. The goal of the new system is to reduce the mortality of patients awaiting lung transplant and maximize the survival benefit of lung transplantation. This article discusses the considerations given to pediatric candidates during the development of the LAS, early outcome observations with emphasis on pediatric candidates and finally, future changes and impact on pediatric lung transplantation.
Pediatric Transplantation 11/2009; 13(7):808-13. · 1.48 Impact Factor
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ABSTRACT: To determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared with control patients, and evaluate for genotype-phenotype correlations. Since its first description over 30 years ago, AWP has frequently been anecdotally associated with CF, but this association has not been confirmed in a rigorous prospective case-control study.
Blinded comparison.
The CF and dermatology clinics at St Louis Children's Hospital.
Forty-four individuals with CF from a CF clinic and 26 controls from a dermatology clinic. Intervention Participants were tested for AWP using 3 minutes of water immersion with room-temperature tap water. Main Outcome Measure The degree of AWP was scored from 0 (no wrinkling) to 4 (severe wrinkling) by 3 blinded physicians. For genotype-phenotype correlations, patients with CF were divided into those homozygous for the DeltaF508 mutation and those with other genotypes.
The mean AWP score of the CF group was significantly higher than the mean score of the control group (1.5 vs 0.6; P < .001). Patients with CF who were homozygous for the DeltaF508 mutation (n = 27) had significantly higher scores than patients with CF who were not homozygous for the DeltaF508 mutation (n = 17) (1.7 vs 1.1; P = .02). The 17 patients with CF who were not homozygous for the DeltaF508 mutation still had higher scores than the control group (1.1 vs 0.6; P = .03). There was no correlation between sweat chloride concentrations measured at the time of diagnosis and AWP score.
Our results confirm the association between AWP and CF. Among patients with CF, greater AWP occurs in those who are homozygous for the DeltaF508 mutation.
Archives of dermatology 11/2009; 145(11):1296-9. · 4.76 Impact Factor
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Kavitha Ranganathan,
Sarah Worley,
Marian G Michaels,
Susana Arrigan,
Paul Aurora,
Manfred Ballmann,
Debra Boyer,
Carol Conrad,
Irmgard Eichler,
Okan Elidemir,
Samuel Goldfarb,
George B Mallory,
Peter J Mogayzel,
Daiva Parakininkas,
Melinda Solomon,
Gary Visner, Stuart C Sweet,
Albert Faro,
Lara Danziger-Isakov
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ABSTRACT: Cytomegalovirus (CMV) has been associated with morbidity, including chronic allograft rejection, in transplant recipients. Data from adult centers suggests that CMV hyperimmune globulin (CMVIG) and ganciclovir together are superior in preventing CMV viremia than ganciclovir alone.
A retrospective review of pediatric lung transplant recipients at 14 sites in North America and Europe was conducted to evaluate the effect of adding cytomegalovirus immunoglobulin (CMVIG) prophylaxis to at least 3 weeks of intravenous ganciclovir therapy in pediatric lung transplant recipients. Data were recorded for the first year after transplantation. Associations between time to CMV and risk factors, including CMVIG use, were assessed by multivariable Cox proportional hazards models.
Of 599 patients whose records were reviewed, 329 received at least 3 weeks of ganciclovir, with 62 (19%) receiving CMVIG. CMVIG was administered more frequently with CMV donor-positive/recipient-negative serostatus (p < 0.05). In multivariable models, patients who did not receive CMVIG as part of their prophylaxis were 3 times more likely to develop CMV infection (hazard ratio, 3.4; 95% confidence interval, 1.2-9.5) independent of CMV serostatus. However, CMVIG administration was not associated with decreased risk of episodes of CMV disease. Receipt of CMVIG was not associated with decreased risks of post-transplant morbidities (acute rejection, respiratory viral infection or early bronchiolitis obliterans) or morbidity within the first year after pediatric lung transplantation.
The use of CMVIG in addition to antiviral prophylaxis in pediatric lung transplantation requires further evaluation.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 10/2009; 28(10):1050-6. · 3.54 Impact Factor
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ABSTRACT: Certain congenital heart lesions in children can lead to irreversible lung disease thus making lung transplantation a therapeutic option. We retrospectively analyzed our experience with lung transplantation in 32 children with three distinct underlying congenital heart defects: (1) Eisenmenger syndrome (EIS); (2) tetralogy of Fallot with pulmonary atresia (PA); and (3) pulmonary vein stenosis (PVS).
Pediatric patients <18 years of age with either EIS (n = 7), PA (n = 8) or PVS (n = 17), who underwent lung or heart-lung transplantation, were analyzed. We compared survival rates between the three groups. Pre- and peri-operative variables were also assessed for their effect on outcome.
Compared with EIS and PA patients, PVS patients were younger and sicker at the time of transplantation. All EIS and PA patients required either additional intracardiac repairs or a heart transplant at the time of lung transplantation. PA patients had the highest rate of major post-operative complications and in-hospital deaths. Median survival was comparable between EIS (6.1 years) and PVS (6.5 years) patients. Outcomes for PA patients were dramatically worse, with a median survival of only 0.12 year ( approximately 47 days). Needing additional intracardiac surgery or a heart transplant at the time of lung transplantation did not impact survival. The diagnosis of PA itself correlated with a worse outcome.
Outcomes in EIS and PVS patients undergoing lung transplantation compare favorably to that of all pediatric lung transplant recipients (median survival 4.3 years). For PA patients, their underlying pathology appears to make them high-risk candidates for lung transplantation. For the younger and acutely sicker PVS patients, lung transplantation is a viable therapeutic alternative.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2009; 28(11):1221-5. · 3.54 Impact Factor
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Stuart C Sweet
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ABSTRACT: Pediatric lung and heart-lung transplantation are viable therapeutic interventions for end stage pulmonary parenchymal or pulmonary vascular diseases. Issues specific to pediatrics include unique diagnoses and increased need for mechanical ventilation before transplant and increased complications related to infection both before and after transplant. Although outcomes for children as a group are similar to those for adults, young children often fare better, perhaps in part due to reduced incidence of acute and chronic rejection. As in other solid organs, long-term outcomes in adolescents are poor. Increased focus on improving adherence in this age group will be important. Similar to adults, bronchiolitis obliterans remains the major late complication. Uniform treatment protocols and multicenter pediatric studies will be required to ultimately overcome this pervasive problem and improve pediatric lung transplant outcomes.
Proceedings of the American Thoracic Society 02/2009; 6(1):122-7.
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New England Journal of Medicine 05/2008; 358(16):1754; author reply 1755. · 53.30 Impact Factor
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ABSTRACT: In their provocative paper, "Lung transplantation and survival in children with cystic fibrosis," Liou and colleagues state that "Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality of life benefit from lung transplantation." Unfortunately, that conclusion is not supportable. Liou's dataset introduced bias against transplantation by using covariates obtained well before the time of transplant (when predicted survival was good) and having a cohort with lower than expected post-transplant survival than reported elsewhere. The calculated hazard ratios are based on factors that may have changed between listing and transplant, and do not reflect true benefit on a patient by patient basis. The findings of the study are contrary to other studies using similar methods. Finally, recent changes in US lung transplant allocation policy may have made the study findings moot. In contrast to Liou's suggestion to perform an ethically and logistically challenging randomized trial to verify the benefit of lung transplantation, a research agenda is recommended for pediatric lung transplantation for cystic fibrosis that focuses on developing strategies to continually reassess and maximize quality of life and survival benefit.
Pediatric Transplantation 04/2008; 12(2):129-36. · 1.48 Impact Factor
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ABSTRACT: The need for evidence-based practice guidelines requires high quality, carefully controlled clinical research trials. This multidisciplinary conference attempted to: identify urgent clinical and research issues, identify obstacles to performing clinical trials, develop concepts for organ-specific and all-organ research and generate a report that would serve as a blueprint for future research initiatives. A few themes became evident. First, young children present a unique immunologic environment which may lead to tolerance, therefore, including young children in immunosuppression withdrawal and tolerance trials may increase the potential benefits of these studies. Second, adolescence poses significant barriers to successful transplantation. Non-adherence may be insufficient to explain poorer outcomes. More studies focused on identification and prevention of non-adherence, and the potential effects of puberty are required. Third, the relatively naive immune system of the child presents a unique opportunity to study primary infections and alloimmune responses. Finally, relatively small numbers of transplants performed in pediatric centers mandate multicenter collaboration. Investment in registries, tissue and DNA repositories will enhance productivity. The past decade has proven that outcomes after pediatric transplantation can be comparable to adults. The pediatric community now has the opportunity to design and complete studies that enhance outcomes for all transplant recipients.
Pediatric Transplantation 04/2008; 12(2):153-66. · 1.48 Impact Factor
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ABSTRACT: Simultaneous liver-lung transplantation is an infrequent but technically feasible procedure in patients with end-stage lung disease and advanced liver disease. We characterize the outcomes of pediatric patients who underwent this procedure at our institution.
We performed a retrospective, case-control study and reviewed the medical records of all patients referred to our transplant program from its inception. Seven patients were listed for simultaneous liver-lung transplant. The five patients who survived to transplant were matched to 13 controls who underwent isolated bilateral sequential lung transplant for underlying diagnosis, age at time of transplant, gender, and era of transplant. Outcome measures included patient and graft survival, occurrence of bronchiolitis obliterans (BO), and episodes of rejection.
Of the five study patients who underwent liver-lung transplant, one died of multiorgan failure 11 days after transplant compared with 9 of 13 controls who died. The median survival for the study patients was 89 months (range, 0-112 months) compared with the controls, who had a median survival of 34 months (range, 0-118 months). The remaining four patients had bronchiolitis obliterans syndrome scores of 0 compared with 5 of 13 control patients (P=0.02). The rate of acute rejection per 100 patient days was 0.012 for the study patients compared with 0.11 for the controls (P=0.025).
Simultaneous liver-lung transplantation is a technically feasible procedure with excellent long-term outcomes. The surviving study subjects remain free from bronchiolitis obliterans syndrome. These results suggest that the transplanted liver may bestow immunologic privilege to the lung allograft.
Transplantation 07/2007; 83(11):1435-9. · 4.00 Impact Factor
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ABSTRACT: Patients with cystic fibrosis (CF) who are listed for lung transplantation may require mechanical ventilatory support before transplant. Although CF is a risk factor for poor outcomes in adults, no data currently exist pertaining to pre-transplant ventilatory support in children with CF.
In a retrospective cohort study, we reviewed the medical records of 18 consecutive CF patients transplanted at St. Louis Children's Hospital (SLCH) who required mechanical ventilation before lung transplantation. Controls included patients transplanted at SLCH who were not mechanically ventilated before transplant and were matched for underlying diagnosis, gender, age, type of transplant (cadaveric vs living donor) and year of transplant.
Ventilated and non-ventilated patients were similar in their pre-transplant characteristics (weight, height and body mass index) and ischemic and bypass times. However, patients ventilated before transplantation had significantly worse immediate post-transplant outcomes, including early graft dysfunction (p = 0.012), prolonged mechanical ventilation (34.1 vs 5 days, p = 0.009), prolonged stay in the pediatric intensive care unit (35.4 vs 8.1 days, p = 0.01), longer time to hospital discharge (38.4 vs 21.3 days, p = 0.033), and worse 1-year mortality after transplant (221.6 vs 335.2 days, p = 0.021). Among ventilated patients, length of pre-transplant ventilation did not affect post-transplant outcomes (length of ventilation, p = 0.92; length of stay in the pediatric intensive care unit, p = 0.68; time to hospital discharge, p = 0.46; and 1-year mortality rate, p = 0.25).
This is the first report in pediatric patients with CF demonstrating that mechanical ventilation before lung transplant is a predictor of poor short-term outcomes, including 1-year-survival, after transplant. Length of pre-transplant ventilatory support does not appear to impact outcomes.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2007; 26(2):127-31. · 3.54 Impact Factor
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Stuart C Sweet
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ABSTRACT: Living donor lobar lung transplantation (LDLLT) was developed in order to mitigate the growing competition for deceased donor (DD) lungs and resultant increase in waiting list mortality. Because each of the two donor lobes serves as an entire lung for the recipient, donors who are taller than the recipient are preferred. Therefore LDLLT is particularly well suited for pediatric recipients for whom adults serve as donors. Although long-term outcomes after LDLLT reported by the Organ Procurement and Transplantation Network (OPTN) are worse compared with DD recipients, overall pediatric outcomes as well as single center reports from the most experienced programs are more promising. Particularly encouraging are the findings that bronchiolitis obliterans (OB) is less frequent or less severe in LDLLT recipients in comparison to DD recipients. Moreover, outcomes may be improved by careful selection of donors to ensure adequately sized donor lobes and minimization of infectious risks. Although no donor deaths have been reported, there is a moderate risk of significant short-term complications. Long-term follow-up has not been reported. The use of LDLLT has decreased in recent years, and the recent change by the OPTN to an urgency/benefit allocation system for DD lungs in patients 12 yr and older may further reduce the demand. Nonetheless, we anticipate that LDLLT will continue to be utilized in select circumstances, particularly in children under 12 where access to DD organs remains challenging.
Pediatric Transplantation 12/2006; 10(7):861-8. · 1.48 Impact Factor
