RESUMO
OBJECTIVE: To determine the frequency, predisposing factors, clinical presentation, and outcome of posttransplantation lymphoproliferative disorders (PTLDs) in pediatric thoracic organ transplant recipients. METHODS: Retrospective review of the medical records of all 120 children who survived longer than 1 month after thoracic organ transplantation at our center. RESULTS: PTLD was diagnosed in 14 patients (11.7%), including 7.7% of heart and 19.5% of heart-lung/lung recipients. Presentation of PTLD was variable, ranging from asymptomatic lung nodules on chest radiograph to diffuse multiorgan failure. Treatment with a reduction of immunosuppression and antiviral therapy resulted in resolution of PTLD in eight patients. Eight patients died. PTLD contributed to death in five. No patient seropositive for Epstein-Barr virus (EBV) before transplantation had PTLD. There was a significant association between primary EBV infection after transplantation and the presence of PTLD. CONCLUSIONS: PTLD occurs with greater frequency in pediatric thoracic organ transplant recipients than in the adult transplant population. Primary EBV infection after transplantation is the major risk factor for the development of PTLD. Patients in whom primary EBV infection develops after transplantation should be managed with a reduction in immunosuppression and with heightened surveillance for the development of PTLD.
Assuntos
Transtornos Linfoproliferativos/etiologia , Transplante de Órgãos/efeitos adversos , Cirurgia Torácica , Adolescente , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Causas de Morte , Criança , Pré-Escolar , Feminino , Transplante de Coração/efeitos adversos , Transplante de Coração-Pulmão/efeitos adversos , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/tratamento farmacológico , Herpesvirus Humano 4 , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Transplante de Fígado/efeitos adversos , Pneumopatias/etiologia , Transplante de Pulmão/efeitos adversos , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/tratamento farmacológicoRESUMO
OBJECTIVE: Short-term survival after pediatric heart transplantation is now excellent, but ultimately the efficacy of this procedure will depend on duration and quality of survival. We sought to evaluate the clinical course of long-term survivors of heart transplantation in childhood. METHODS: Patients who had undergone heart transplantation at the university hospitals of Stanford, Columbia, and Pittsburgh between 1975 and 1989 and survived longer than 5 years from transplantation were identified and their clinical courses retrospectively reviewed. RESULTS: Sixty eight children have survived more than 5 years from transplantation, and 60 (88%) are currently alive with a median follow-up of 6.8 years (5 to 17.9 years). Thirteen have survived more than 10 years from transplantation. Renal dysfunction caused by immunosuppressive agents was common, and two patients required late renal transplantation. Lymphoproliferative disease or other neoplasm occurred in 12 patients, but none resulted in death. Coronary artery disease was diagnosed in 13 patients (19%), leading to retransplantation in eight. Death after 5 years was related to acute or chronic rejection in 5 of 8 cases. Two of the deaths were directly related to noncompliance with immunosuppressive medication. All survivors are in New York Heart Association class 1. CONCLUSIONS: Long-term survival with good quality of life can be achieved after heart transplantation in childhood, though complications of immunosuppression remain common. Posttransplantation coronary artery disease is emerging as the main factor limiting long term graft and patient survival.
Assuntos
Transplante de Coração , Sobreviventes , Adolescente , Criança , Pré-Escolar , Doença das Coronárias/diagnóstico , Rejeição de Enxerto/tratamento farmacológico , Hemodinâmica , Humanos , Hipertensão/etiologia , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Lactente , Nefropatias/etiologia , Nefropatias/fisiopatologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Pressão Propulsora Pulmonar , Qualidade de Vida , ReimplanteRESUMO
OBJECTIVES: The primary objective of this study was to compare exercise tolerance, heart rate, and oxyhemoglobin saturation (Sao2) between a traditional progressive maximal exercise test and a self-paced, 6-minute walk test in severely ill children. STUDY DESIGN: Seventeen patients (9 to 19 years of age) performed a progressive maximal exercise test on a cycle ergometer and a self-paced, 6-minute walk test as part of the evaluation for possible heart, lung, or combined heart and lung transplantation. Physical work capacity and peak oxygen uptake were measured during the progressive cycle test. The walk test was performed in a hospital corridor, with patients trying to cover as much distance as possible in 6 minutes at their own pace. Oxyhemoglobin saturation and heart rate were monitored continuously by pulse oximetry and compared between the two tests. RESULTS: The distance walked in 6 minutes correlated with peak oxygen uptake (r = 0.70, p < 0.01) and physical work capacity (r = 0.64, p < 0.005). The minimum (Min) Sao2 on the bike test correlated significantly with Min Sao2 on the walk test (r = 0.82, p < 0.001), with 11 of 17 patients having a lower Min Sao2 on the walk test than the bike test (mean Min Sao2, 84% and 86%, respectively). The peak heart rate did not correlate significantly between the bike and walk tests (r = 0.25), although significantly lower (p < 0.01) values were observed on the walk (148 beats/min) than bike (169 beats/min) test. CONCLUSIONS: The results suggest that the 6-minute self-paced walk test may provide an alternative method for assessing functional capacity in severely ill children, and that Sao2 measured during progressive exercise testing on a cycle ergometer may not reflect the degree of oxyhemoglobin desaturation during self-paced walking in some patients with severe cardiopulmonary disease.
Assuntos
Estado Terminal , Teste de Esforço , Tolerância ao Exercício , Adolescente , Adulto , Criança , Volume Expiratório Forçado , Frequência Cardíaca , Transplante de Coração-Pulmão , Humanos , Transplante de Pulmão , Consumo de Oxigênio , Oxiemoglobinas/análise , Capacidade Vital , CaminhadaRESUMO
BACKGROUND: Mechanical circulatory support for intractable heart failure as a bridge to transplantation has been used infrequently in children. The lack of clinically available ventricular assist devices has resulted in the use of conventional extracorporeal circuits with oxygenator as the main modality for circulatory support. In this study we reviewed our experience with extracorporeal membrane oxygenation (ECMO) support in children with irreversible heart failure who were awaiting heart transplantation. METHODS AND RESULTS: Since 1985, 14 children were placed on ECMO support for circulatory failure and were considered candidates for heart transplantation: 8 children had postcardiotomy contractile failure, 3 had dilated cardiomyopathy, and 3 had viral myocarditis. Five of these children had cardiac arrest and were placed on support during cardiopulmonary resuscitation. Mean duration of ECMO support was 109 +/- 20 hours. Eight patients developed pulmonary edema requiring decompression of the left ventricle, 3 by blade atrial septostomy and 5 by left atrial vent cannula. Nine of 14 received a heart transplant, 1 child recovered spontaneously (myocarditis), and 4 died of sepsis on ECMO. Of the children who received transplants, 6 were early survivors with 1 late death (lymphoproliferative disease), for a total of 7 of 14 (50%) early and 6 of 14 (43%) late survivors. CONCLUSIONS: Our experience suggests that ECMO is an effective means of circulatory support as a bridge to transplantation in children. Decompression of the left ventricle is often required to prevent pulmonary edema. Sepsis and bleeding remain a limitation to prolonged mechanical support with ECMO in children.
Assuntos
Circulação Assistida/métodos , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Transplante de Coração , Adolescente , Cardiomiopatias/cirurgia , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea/efeitos adversos , Parada Cardíaca/terapia , Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/cirurgia , Humanos , Lactente , Recém-Nascido , Seleção de Pacientes , Complicações Pós-Operatórias/cirurgia , Sepse/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
Heart-lung transplantation and lung transplantation have become accepted techniques in adult patients with end-stage cardiopulmonary disease. We report here our experience between July 1985 and March 1993 with 34 children (< 20 years) who underwent heart-lung (n = 18) or lung transplantation (n = 17). Indications for transplantation included cystic fibrosis (n = 9), congenital heart disease with Eisenmenger complex (n = 9), primary pulmonary hypertension (n = 8), pulmonary arteriovenous malformations (n = 2), desquamative interstitial pneumonia (n = 2), Proteus syndrome with multicystic pulmonary disease (n = 1), graft-versus-host disease (n = 1), rheumatoid lung disease (n = 1), and bronchiolitis obliterans and emphysema (n = 1). Twenty-six patients (76%) have survived from 1 to 88 months after transplantation; most patients have returned to an active lifestyle. Of the eight deaths, four were due to infections, two to multiorgan failure, 1 to posttransplant lymphoproliferative disease, and one to donor organ failure. Four of the patients who died had cystic fibrosis. Despite considerable morbidity related to infection, rejection, and function of the heart-lung and lung allograft in some patients, our results with this potentially lifesaving procedure in the pediatric population have been encouraging.
Assuntos
Transplante de Coração-Pulmão/mortalidade , Transplante de Pulmão/mortalidade , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Causas de Morte , Criança , Pré-Escolar , Complexo de Eisenmenger/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto , Humanos , Lactente , Infecções/epidemiologia , Infecções/mortalidade , Pneumopatias/cirurgia , Masculino , Complicações Pós-Operatórias/mortalidade , Análise de SobrevidaRESUMO
The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplant program, which began in 1982. Thirty-two pediatric patients (age range 1 to 18 years) have undergone heart-lung (n = 16), double-lung (n = 14), and single-lung (n = 2) transplantation procedures. The cause of end-stage lung disease was primary pulmonary hypertension (n = 7), congenital heart disease (n = 7), cystic fibrosis (n = 9), pulmonary arteriovenous malformation (n = 2), desquamative interstitial pneumonitis (n = 2), graft-versus-host disease (n = 1), emphysema (n = 1), rheumatoid lung (n = 1), cardiomyopathy (n = 1), and Proteus syndrome (n = 1). Six patients (19%) underwent pretransplantation thoracic surgical procedures. The survival rate was 78% at a mean follow-up of 1.8 years. The survival rate in the 23 recipients without cystic fibrosis was 87% (95% since 1985). The actuarial 1-year survival rate in the nine recipients with cystic fibrosis was 55%. Immunosuppression was cyclosporine (n = 9) or FK 506 (n = 23)-based therapy with azathioprine and steroids. Children were followed up by spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection per patient in the groups treated with cyclosporine and FK 506, respectively, was 1.0 and 1.2 at 30 days, 0.67 and 0.38 at 30 to 90 days, and 2.33 and 0.46 at greater than 90 days (p < 0.001, Fisher exact test).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Transplante de Pulmão/tendências , Adolescente , Criança , Pré-Escolar , Rejeição de Enxerto , Transplante de Coração-Pulmão/estatística & dados numéricos , Transplante de Coração-Pulmão/tendências , Humanos , Terapia de Imunossupressão , Lactente , Infecções/diagnóstico , Infecções/etiologia , Pneumopatias/cirurgia , Transplante de Pulmão/mortalidade , Transplante de Pulmão/estatística & dados numéricos , Preservação de Órgãos , Complicações Pós-Operatórias , Taxa de SobrevidaRESUMO
BACKGROUND: Preoperative hemodynamic support, complex congenital heart disease, and elevated pulmonary vascular resistance present particular challenges for pediatric heart transplantation. This study was performed to identify preoperative factors that influence survival after pediatric heart transplantation over two eras of pediatric heart transplant experience. METHODS AND RESULTS: We retrospectively analyzed demographic, clinical, and hemodynamic data from 67 pediatric patients who underwent heart transplantation between February 1982 and June 1992 and compared survival between two eras (early experience versus late experience). During the early experience (group 1: February 1982 to August 1989), univariate analysis identified congenital heart disease, pretransplant extracorporeal membrane oxygenator (ECMO) support, inotropic and/or ventilatory support (UNOS status I), elevated transpulmonary gradient (at least 15 mm Hg), and elevated pulmonary vascular resistance index (at least 4 Wood units.m2) as preoperative risk factors for early death after pediatric heart transplantation. However, in the late experience (group 2: September 1989 to June 1992), the only risk factor for premature death by univariate analysis was elevated transpulmonary gradient. By multivariate analysis, elevated transpulmonary gradient was the only risk factor for our early, late, and entire experiences. One-year survival after transplantation for congenital heart disease was improved from 46% in group 1 to 73% in group 2 (P < .05). In group 1, only one patient (25%) with pretransplant ECMO support survived 1 year, whereas 66% (four of six) survived more than 1 year in group 2. CONCLUSIONS: Although elevated transpulmonary gradient continues to be a significant risk factor for pediatric heart transplantation, candidates with congenital heart disease, UNOS status I, and pretransplant ECMO support now can be successfully transplanted with reasonable hope for extended survival.
Assuntos
Cardiomiopatias/cirurgia , Cardiopatias Congênitas/cirurgia , Transplante de Coração/mortalidade , Cardiomiopatias/epidemiologia , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/epidemiologia , Transplante de Coração/estatística & dados numéricos , Humanos , Terapia de Imunossupressão , Tábuas de Vida , Masculino , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
The decade from 1982 through 1992 witnessed tremendous growth in pediatric cardiac transplantation. At Children's Hospital of Pittsburgh 66 cardiac transplants were performed during this period (age range 7 hours to 18 years). The cause of cardiomyopathy was congenital (n = 30), cardiomyopathy (n = 29), myocarditis (n = 2), doxorubicin toxicity (n = 2), ischemic (n = 1), valvular (n = 1), and cardiac angiosarcoma (n = 1). Nine children (14%) required mechanical circulatory support before transplantation: extracorporeal membrane oxygenation (n = 8) and Novacor left ventricular assist system (n = 1) (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). The mean follow-up time was 2 years (range 4 months to 8 years). The overall survival in the group was 67%. In children with congenital heart disease (> 6 months of age) the perioperative (30 day) mortality was 66% before mid-1988 (n = 10) and 0% since mid-1988 (n = 11). The late mortality (> 30 days) in children with cardiomyopathy transplanted prior to mid-1988 was 66% (n = 14) and 7% since mid-1988 (n = 15). Since mid-1988 1- and 3-year survival was 82% in children with congenital heart disease and 90% in children with cardiomyopathy. Twenty-six children have had FK 506 as their primary immunosuppressive therapy since November 1989. Survival in this group was 82% at 1 and 3 years. The actuarial freedom from grade 3A rejection in the FK group was 60% at 3 and 6 months after transplantation versus 20% and 12%, respectively, in the 15 children operated on before the advent of FK 506, who were treated with cyclosporine-based triple-drug therapy (p < 0.001, Mantel-Cox and Breslow). Twenty of 24 children (83%) in the FK 506 group are receiving no steroids. The prevalence of posttransplantation hypertension was 4% in the FK 506 group versus 70% in the cyclosporine group (p < 0.001, Fisher). Renal toxicity in children treated with FK 506 has been mild. Additionally, eight children have been switched to FK 506 because of refractory rejection and drug toxicity. FK 506 has not produced hirsutism, gingival hyperplasia, or abnormal facial bone growth. The absence of these debilitating side effects, together with the observed immune advantage and steroid-sparing effects of FK 506, hold tremendous promise for the young patient facing cardiac transplantation and a future wedded to immunosuppression.
Assuntos
Transplante de Coração , Imunossupressores , Tacrolimo/uso terapêutico , Adolescente , Cardiomiopatias/cirurgia , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Oxigenação por Membrana Extracorpórea , Feminino , Rejeição de Enxerto , Cardiopatias Congênitas/cirurgia , Transplante de Coração/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Infecções/etiologia , Rim/fisiopatologia , Transtornos Linfoproliferativos/etiologia , Masculino , Complicações Pós-OperatóriasRESUMO
Lymphoproliferative disease developed in 15 heart and five lung transplant recipients during a decade of heart and lung transplantation from 1980 through 1989. The overall incidence of posttransplant lymphoproliferative disease in patients who survived more than 30 days is 4%. The incidence after heart transplantation is 3.4% and after lung transplantation is 7.9% (p = 0.08). The peak occurrence of posttransplant lymphoproliferative disease is 3 to 4 months after transplantation. However, posttransplant lymphoproliferative disease occurring early versus late (defined as before or after 1 year after transplantation) appears to have different clinical outcomes. The mortality of early onset of posttransplant lymphoproliferative disease as a result of lymphoma is 36%; response to reduction in immunotherapy occurs in 89% and presentation with disseminated disease occurs in 23%. The mortality of late onset of posttransplant lymphoproliferative disease as a result of lymphoma is 70%; no patient responded to reduction in immunotherapy and presentation with disseminated disease occurs in 86% of patients. Epstein-Barr virus primary infection was present in 14 and secondary Epstein-Barr virus infection was present in three of the 20 patients with posttransplant lymphoproliferative disease. The other three patients were positive for Epstein-Barr virus also but had no pretransplant sera for comparison. There is no correlation with immunoprophylaxis or maintenance immunosuppression and the development of posttransplant lymphoproliferative disease in our series.
Assuntos
Ciclosporina/uso terapêutico , Transplante de Coração , Transplante de Coração-Pulmão , Herpesvirus Humano 4/isolamento & purificação , Terapia de Imunossupressão/efeitos adversos , Transplante de Pulmão , Linfoma de Células B/mortalidade , Infecções Tumorais por Vírus/mortalidade , Ciclosporina/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
We have traditionally pushed the limits of conservative candidate criteria for heart transplantation. We have been gratified by our results in the aged, the diabetic, and the mortally ill. Our inclusion of patients with malignant disease underscores our philosophy to include patients as candidates for transplantation for whom the procedure has reasonable expectation of success. We report here our early results of heart transplantation in 11 patients with malignant disease. Our survival rate in this group is 100%, and all patients are leading active lives with no evidence of recurrent or metastatic tumor. Immunosuppression protocols were adjusted on an individual basis determined by the chemotherapy dosage, duration, and relation to transplantation. Whenever possible a 1-year disease-free interval after completion of adequate cancer therapy is desired before transplantation.
Assuntos
Cardiomiopatias/cirurgia , Neoplasias Cardíacas/cirurgia , Transplante de Coração , Neoplasias/complicações , Adulto , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/complicações , Criança , Doxorrubicina/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Taxa de SobrevidaRESUMO
Because coronary atherosclerosis after heart transplantation has been a limiting problem in long-term survival of adults, we reviewed the coronary angiograms, and autopsy data when available, from 21 of 30 children who underwent orthotopic heart transplantation and survived the perioperative period. Six patients had coronary atherosclerosis, and five of these patients died 6 months to 3 years after heart transplantation. The late deaths were sudden and unexpected. Coronary angiography demonstrated several types of lesions, including concentric narrowing, tubular segmental lesions, and abrupt obliteration of major coronary vessels. Risk factors assessed included hypertension, hyperlipidemia, cytomegalovirus infection, type of immunosuppressive regimen, number of rejection episodes, and major histocompatibility antigen mismatches. Only the frequency and duration of rejection episodes seemed to be more prevalent in the patients in whom coronary atherosclerosis developed. Despite the benefits of heart transplantation in treating children with end-stage heart disease, coronary atherosclerosis may limit long-term survival. We suggest that these children should undergo serial coronary angiography to identify those at risk for subsequent events related to coronary artery disease.