Geoffrey Kurland

Posttransplantation lymphoproliferative disorders in pediatric thoracic organ recipients

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.

Immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: A multi-center trial in children with cystic fibrosis

A third generation, purified fusion protein (PFP-3) vaccine was developed to prevent severe respiratory syncytial virus (RSV) disease in high-risk groups. A phase II, multi-center, adjuvant-controlled trial was performed in RSV seropositive children with cystic fibrosis (CF); 151 received the adjuvant-control and 143 received the vaccine. Details of the vaccine-induced immune response are presented. At enrollment, RSV-specific, serum antibodies were comparable between both groups. A highly sensitive and specific serum antibody vaccine profile was established for the PFP-3 vaccine. At post-vaccination and end-of-study, RSV-specific, neutralizing antibody (Nt Ab) and binding antibody (Bd Ab) to the fusion (F) protein were significantly higher in PFP-3 vaccinees. After 28 days post-vaccination, Nt Ab and Bd Ab to F protein titers declined slowly at rates of 0.23 and 0.37 log2 per month, respectively. The PFP-3 vaccine-induced a robust immune response that lasted throughout the RSV season.

Lung Transplantation for Cystic Fibrosis

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 patients 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.

Effects of anaerobic exercise on the immune system in eight- to seventeen-year-old trained and untrained boys

OBJECTIVES To determine the immunologic response to a brief bout of intense exercise in children and to determine the effects of prolonged activity and maturation level of the subjects on this response. STUDY DESIGN We determined counts of leukocytes and their subsets, counts of lymphocytes and their subsets, and natural killer (NK) cell activity and cell number before and 3 and 60 minutes after a Wingate anaerobic test (WAnT) in 16 male swimmers (9 to 17 years of age) and 17 male nonswimmers (9 to 17 years of age). Subjects were also categorized by pubertal status based on Tanner staging and by level of physical activity. The Student t test and analysis of variance were used to determine statistical significance, with values expressed as mean +/- SEM. RESULTS Three minutes after the WAnT, all children had increases in leukocytes (28%), lymphocytes (43%), and NK cells (395%) (p < 0.01). Swimmers had less baseline NK cell activity (54 +/- 6 cytolytic units) than nonswimmers (87 +/- 10 cytolytic units) after the WAnT (p < 0.01), although both groups showed an increase to similar levels of NK activity 3 minutes after exercise. Pubertal effects on these responses were not significant. CONCLUSIONS Our results demonstrate transient leukocytosis, lymphocytosis, and increases in NK cell number and activity in 8- to 17-year-old boys after a brief bout of intense exercise. Formal athletic training appears to be associated with a lower baseline NK cell activity, and yet such activity is still within the normal range for this age group. Further investigations are necessary to determine the impact of such training on overall health and the ability to fight infection.

Experience with pediatric lung transplantation

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.

Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience.

BACKGROUND Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.

Comparative Analysis of Chest Tube Thoracostomy and Video-Assisted Thoracoscopic Surgery in Empyema and Parapneumonic Effusion Associated with Pneumonia in Children

BACKGROUND Controversy exists regarding the optimal management strategy for children having empyema or parapneumonic effusion as a complication of pneumonia. We hypothesized that video-assisted thoracoscopic surgery (VATS)-assisted drainage of pleural fluid and debridement of the pleural space is superior to a chest tube alone in the management of these patients. We further identified predictive factors-namely, presentation, radiographic findings, antibiotic usage, and pleural fluid features-that could predict the need for VATS rather than primary chest tube drainage. METHODS Forty-nine pediatric patients with pneumonia complicated by parapneumonic effusion or empyema treated at the Childrens Hospital of Pittsburgh (1997-2003) were divided into three groups according to the therapy instituted: Primary chest tube, chest tube followed by VATS, or primary VATS. The groups were analyzed in terms of demographics and outcome, as judged by pleural fluid analysis and hospital resource utilization. Demographic and outcome data were compared among groups using one-way analysis of variance and the Student t-test. RESULTS All groups were similar with respect to demographics and initial antibiotic usage. Patients undergoing primary VATS had a higher initial temperature, whereas radiographic findings of mediastinal shift and air bronchograms were more likely to be found in patients who underwent primary chest tube placement. Patients undergoing primary VATS demonstrated a significantly shorter total stay and lower hospital charges than the other groups. Forty percent of children started on chest tube therapy failed even with subsequent VATS, necessitating a significantly longer hospital course (18 +/- 3 vs. 11 +/- 0.8 days; p < 0.05) and higher hospital charges (

Critical issues in pediatric lung transplantation

50,000 +/- 7,000 vs.

Acute myocardial infarction in a young boy with nephrotic syndrome: a case report and review of the literature.

29,000 +/- 1000) than those having primary VATS. CONCLUSIONS Patients treated by primary VATS had a shorter stay and lower hospital charges than patients treated by chest tube and antibiotic therapy alone. There were no demographic, physiologic, laboratory, or chest radiographic data that predicted the selection of VATS as an initial treatment. These data suggest a strategy of primary VATS as first-line treatment in the management of empyema or parapneumonic effusion as a complication of pneumonia in pediatric patients.

Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation

Forty children (aged 1 to 18 years, 27 female and 13 male) have undergone heart-lung (21), double lung (17), and single lung (2) transplant procedures at our center from 1985 through April 1994. The indications for transplantation have been diverse, primary pulmonary hypertension (10), cystic fibrosis (11), congenital heart disease (10), arteriovenous malformation (3), emphysema (1), graft-versus-host disease (1), rheumatoid lung (1), cardiomyopathy (1), desquamative interstitial pneumonitis (1), and Proteus syndrome (1). The actuarial 1-year survival was 73% (mean follow-up 2 years). One-year actuarial survival for disease groups ranged from 60% for cystic fibrosis to 90% for congenital heart disease. We have identified six issues critical to the patient and programatic survival of pediatric lung transplantation. Our experience and management strategies in these areas are reviewed. Cytomegalovirus: Cytomegalovirus disease developed in six of eight patients with cytomegalovirus mismatching (donor +/recipient-) and in seven of 32 patients who survived more than 30 days (23%). All but cytomegalovirus donor -/recipient- patients were treated with ganciclovir for 4 weeks after transplantation. Obliterative bronchiolitis: Obliterative bronchiolitis developed in seven of 32 (25%) patients who survived more than 30 days. Obliterative bronchiolitis was manifest within the first posttransplantation year as a rapid decline in small airway function. Aggressive augmentation of immunosuppression has been used with little success. Posttransplantation lymphoproliferative disease: Posttransplantation lymphoproliferative disease developed in five of 32 (15%) patients who survived more than 30 days developed. One patient died (17% mortality) despite retransplantation. In four patients the disease resolved with reduction in immunosuppression alone, and one required the addition of interferon alfa. Cystic fibrosis: We have changed our management strategies to avoid triple drug immunosuppression, perioperative blood and bronchial cultures, aggressive antimicrobial therapy, and exclusion of patients with panresistant organisms; this has resulted in elimination of infectious mortalities thus far in the pediatric cystic fibrosis group. Airways: In 21 heart-lung recipients with tracheal anastomoses we have had no airway complications. The double and single lung transplant recipients accounted for 34 bronchial and one tracheal anastomoses. Three (9%) bronchial stenoses developed. Two were treated with silicone stents and one with balloon dilation.(ABSTRACT TRUNCATED AT 400 WORDS)