Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic pneumonia syndrome (IPS) refers to diffuse, non-infectious pneumonia that occurs after allogeneic bone marrow transplantation (BMT). We have developed a model of IPS using a well-characterized murine BMT system (B10.BR-->CBA) in which lung injury after BMT can be induced by minor histocompatibility (H) antigenic differences between donor and host. Lung pathology and broncho-alveolar lavage (BAL) fluid were analyzed in transplant recipients before and after both syngeneic and allogeneic BMT. At 2 weeks after BMT, no specific pathologic abnormalities were noted; at 6 weeks, both pneumonitis and mononuclear cell infiltration around vessels and bronchioles were observed only in mice receiving allogeneic BMT. This injury was associated with elevated BAL fluid levels of endotoxin (lipopolysaccharide [LPS]), neutrophils, and tumor necrosis factor alpha. No pathologic organisms were isolated from the respiratory tract of any animal. We also tested the role of endotoxin in the development of this injury. Injection of LPS 6 weeks after transplantation caused profound lung injury only in mice with moderate graft-versus-host disease; dramatic increases in BAL neutrophils and tumor necrosis factor alpha were observed, with alveolar hemorrhage occurring in 4 of 12 of these mice but in no other group. We conclude that (1) this murine BMT system is a potentially useful model of clinical IPS; (2) minor H differences between donor and recipient can be important stimuli in the pathogenesis of IPS; and (3) endotoxin in BAL fluid is associated with lung injury, and excess endotoxin can cause the development of alveolar hemorrhage in this model.
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PMID:An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin. 896 63

Pulmonary complications are a major clinical problem following allogeneic bone marrow transplantation (BMT), contributing to more than 30% of transplant-related mortalities. Idiopathic pneumonia syndrome is responsible for significant mortality among BMT patients. However, the etiology of injury to the lung parenchyma by this disease syndrome is unknown and it has been difficult to evaluate the cellular and molecular mechanisms underlying IPS in the absence of a suitable animal model. To study post-BMT lung disease during graft-versus-host disease (GVHD), we have developed a murine model that utilizes a semi-allogeneic parental --> F1 transplant strategy to induce a mild form of GVHD. Progressive inflammatory lung disease developed in animals with mild GVHD, as indicated by changes in immune cell distribution and cytokine expression in the lungs of transplanted animals. Histologic analysis of lung tissue from GVHD mice at 3 wk post-BMT showed minor immunopathologic changes compared with control mice. In contrast, lungs of GVHD mice at 12 wk displayed histopathologic hallmarks of interstitial pneumonitis, such as prominent perilumenal mononuclear cell infiltration and areas of alveolar congestion. Flow cytometric analysis of lung interstitial cells of GVHD mice revealed an increase in CD8+ T-cells at week 3, which decreased to normal levels by week 12 post-BMT. Simultaneously, the percentage of CD4+ T-cells increased progressively above normal levels and peaked at week 7 post-BMT. Analysis of cytokine mRNA expression in lung tissue indicated that steady state levels of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, interferon-gamma, and IL-12 were significantly elevated in lungs of GVHD mice at 3 wk post-BMT compared with untreated controls. Mice that were transplanted with allogeneic bone marrow alone (BMT controls) also displayed elevated expression of these cytokines, although only IL-6 was significantly higher than in untreated controls. In contrast, at 12 wk after transplantation only TNF-alpha and IL-12 levels remained elevated in GVHD mice, suggesting prolonged macrophage activation. On the basis of these findings, we conclude that allogeneic bone marrow transplantation in this mouse model causes a progressive interstitial pneumonitis, which is characterized by an acute influx of CD8+ T-cells, followed in the chronic phase by a prominent accumulation of CD4+ T-cells, and is associated with persistent production of cytokines known to activate macrophages.
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PMID:Idiopathic pneumonia syndrome in mice after allogeneic bone marrow transplantation. 947 11

Idiopathic pneumonia syndrome (IPS) is a significant clinical problem encountered among patients treated with bone marrow transplantation (BMT). IPS is identified as an inflammatory lung disease characterized by diffuse interstitial pneumonitis and alveolitis leading to interstitial fibrosis in the absence of an identifiable infectious agent. In an earlier study we characterized a murine model of IPS following allogeneic BMT that exhibits several features of human IPS. In this report we show that the lung represents a unique target of post-BMT disease in this model. The kinetics of developing lung disease were found to be markedly different from the kinetics of graft-versus-host disease in other tissues such as liver, colon, ear, skin, and tongue. Mice transplanted by our standard protocol with T-cell-depleted semiallogeneic donor bone marrow plus donor spleen cells in the absence of pretransplant radiation conditioning did not develop lung inflammation or fibrosis characteristic of IPS. Pretransplant radiation conditioning in the absence of BMT also failed to cause IPS, demonstrating an important role for radiation conditioning in the development of BMT-related IPS. The occurrence of lung disease post-BMT was found to be dependent on radiation conditioning in a dose-dependent manner. Finally, thoracic irradiation alone was demonstrated to be sufficient in causing IPS in mice transplanted with bone marrow plus spleen cells, albeit with reduced severity. Based on these findings, we conclude that pretransplant radiation conditioning plays an important role in the development of IPS following allogeneic BMT.
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PMID:Idiopathic pneumonia syndrome after allogeneic bone marrow transplantation in mice. Role of pretransplant radiation conditioning. 1034 Sep 30

Bone marrow transplantation (BMT) is a successful and recognised treatment option for patients with a number of haematological and non-haematological malignant and non-malignant conditions. Pulmonary complications both infectious and non-infectious are common after BMT. Multiple factors are thought to contribute to pulmonary complications, including the type and duration of immunological defects produced by the underlying disease and treatment, the development of graft-versus-host disease (GVHD), and the conditioning regimens employed. These complications are classified as early or late, depending on whether they occur before or after 100 days from transplantation. Early non-infectious pulmonary complications typically include pulmonary oedema, upper airway complications, diffuse alveolar haemorrhage, cytolytic thrombi, and pleural effusion. Bronchiolitis obliterans, veno-occlusive disease, and secondary malignancies occur late after BMT. Idiopathic pneumonia syndrome, GVHD, and radiation induced lung injury can occur in early or late period after BMT.
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PMID:Non-infectious pulmonary complications after bone marrow transplantation. 1215 65

Idiopathic pneumonia syndrome (IPS) is a significant noninfectious complication of hematopoietic stem cell transplantation (HSCT). We compared the incidences and outcomes of IPS among patients who underwent allogeneic HSCT after nonmyeloablative (n = 183) compared with conventional (n = 917) conditioning between December 1997 and December 2001. Patients given nonmyeloablative conditioning were older than those given conventional conditioning (median ages, 53 vs 41 years; P =.001). The cumulative incidence of IPS was significantly lower at 120 days after nonmyeloablative conditioning than conventional conditioning (2.2% vs 8.4%; P =.003). In addition, greater patient age (older than 40 years), diagnosis of acute leukemia or myelodys-plastic syndrome, and severe acute graft-versus-host disease were associated with significantly increased risks for IPS. Among older patients (older than 40 years) given conventional conditioning, high-dose total body irradiation (TBI) was associated with an increased risk for IPS than were non-TBI-based regimens (16% vs 5.8%; P =.001). IPS occurred early after transplantation, progressed rapidly, and was associated with a high mortality rate (75%) despite aggressive support. Initiation of mechanical ventilation and the presence of renal insufficiency at IPS onset were associated with increased risks for death after IPS. These findings support the concept that lung damage from the conditioning regimen plays a crucial role in the development of IPS after HSCT.
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PMID:Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation. 1285 68

Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) annually, 15 to 40% of whom are admitted to the intensive care unit. Pulmonary complications are the most life threatening conditions that develop in HSCT recipients. Both infectious and noninfectious complications occur more frequently in allogeneic HSCT. The management of HSCT recipients requires knowledge of their immune status, appropriate diagnostic evaluation, and early treatment. During the pre-engraftment phase (0 to 30 days after transplant), the most prevalent pathogens causing infection are bacteria and Candida species and, if the neutropenia persists, Aspergillus species. The early post-engraftment phase (30 to 100 days) is characterized by cytomegalovirus (CMV), Pneumocystis jiroveci, and Aspergillus infections. During the late posttransplant phase (> 100 days), allogeneic HSCT recipients are at risk for CMV, community-acquired respiratory virus, and encapsulated bacterial infections. Antigen and polymerase chain reaction assays are important for the diagnosis of CMV and Aspergillus infections. Diffuse alveolar hemorrhage (DAH) and peri-engraftment respiratory distress syndrome occur in both allogeneic and autologous HSCT recipients, usually during the first 30 days. Bronchiolitis obliterans occurs exclusively in allogeneic HSCT recipients with graft versus host disease. Idiopathic pneumonia syndrome occurs at any time following transplant. Bronchoscopy is usually helpful for the diagnosis of the infectious pulmonary complications and DAH.
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PMID:Major complications following hematopoietic stem cell transplantation. 1679 62

Idiopathic pneumonia syndrome (IPS) is a rare complication following stem cell transplant (SCT) and its incidence among pediatric SCT recipients is not known. To assess the incidence of IPS, we retrospectively reviewed the incidence of IPS at our center. IPS is defined as the presence of multilobar infiltrates by chest radiograph or computed tomography scan, need for supplemental oxygenation with declining pulse oximetry and no identifiable pulmonary infection. Between July 1999 and August 2005, 11 of 93 children who received a fully ablative allogeneic SCT (11.8%) developed IPS. All 11 patients had normal pulmonary evaluation before transplant. IPS developed at a median of 17 days (range 8-42 days) after transplant. Recipients of unrelated donor transplant had increased risk of developing IPS. There was a significant association between acute or hyperacute graft-versus-host disease (GVHD) and IPS (P=0.035). All patients had significant hypoxia and five patients required assisted ventilation. IPS was the cause of death in two patients. Although there was complete resolution of respiratory symptoms in the other nine patients, overall transplant-related mortality was significantly higher among patients with IPS (64 vs 17%, P=0.002). IPS is a relatively common complication in pediatric SCT recipients and acute GVHD is an important associated factor.
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PMID:Incidence and outcome of idiopathic pneumonia syndrome in pediatric stem cell transplant recipients. 1681 36

Idiopathic pneumonia syndrome (IPS), defined as widespread alveolar injury, is a severe complication of hematopoietic stem cell transplantation (HSCT) and a clinical syndrome with variable histopathologic correlates and multiple etiologies. Transplantation-associated thrombotic microangiopathy (TMA) is another severe complication of HSCT. TMA occurs when endothelial injury causes thrombosis and fibrin deposition in the organ microcirculation. We present a case of IPS with TMA-related changes in the lungs following HSCT. A 54-year-old woman underwent an allogeneic HSCT for refractory multiple myeloma. During transplantation, cyclosporine was administered for prophylaxis against graft-versus-host disease, but she developed respiratory failure after she was weaned off the drug. A computed tomography scan revealed ground-glass attenuation and reticular opacity in the bilateral whole-lung fields. Bronchoscopy indicated no evidence of infection, and IPS was diagnosed. High-dose steroids and etanercept were ineffective, and she died 1 month after the onset of IPS. Autopsy revealed diffuse alveolar damage, and stenosis or obstruction due to intimal thickening and thrombi resulting from endothelial injury in the arterioles of both lungs. We retrospectively diagnosed TMA based on the histological and clinical findings. To our knowledge, this is the first report suggesting the possible role of TMA in the clinical course of IPS.
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PMID:Idiopathic pneumonia syndrome with thrombotic microangiopathy-related changes after allogeneic hematopoietic stem cell transplantation. 2395 12

Idiopathic pneumonia syndrome (IPS) is a critical complication following allogeneic hematopoietic SCT (HSCT); however, few reports have analyzed the risk factors for IPS in children. A total of 210 consecutive pediatric patients, including 131 boys and 79 girls, with various hematologic malignancies, aplastic anemia or solid tumors who underwent allogeneic HSCT were analyzed to clarify the incidence and risk factors for IPS. Patient and transplantation characteristics after allogeneic HSCT were compared between patients with and without IPS. Cumulative incidence rates of IPS 120 days after allogeneic HSCT were 6.7% (14/210). Of 14 patients with IPS, 11 (78.6%) died after developing IPS. The presence of prior HSCT was more frequent in patients with IPS (IPS group) than in those without IPS (non-IPS group; 35.7 vs 12.8%, respectively, P=0.018). The IPS group contained more patients with acute GVHD (grade II-IV) than the non-IPS group (50.0 vs 18.9%, respectively, P=0.006). The association of these two factors with IPS was further confirmed by multivariate analysis. We should be aware of these risk factors in patients who have undergone allogeneic HSCT.
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PMID:Risk factor analysis of idiopathic pneumonia syndrome after allogeneic hematopoietic SCT in children. 2395 35

Idiopathic pneumonia syndrome (IPS) is a fatal non-infectious respiratory complication that develops after hematopoietic stem cell transplantation (HSCT). Because of the poor prognosis of post-HSCT patients with IPS requiring mechanical ventilatory support, performing extracorporeal membrane oxygenation (ECMO) has been regarded as relatively contraindicated in these patients. A tumor necrosis factor-alpha inhibitor, etanercept, has been reported to be a promising treatment option for post-HSCT patients with IPS; however, the phase III clinical trial of etanercept has recently been terminated without definitive conclusion. If post-HSCT patients with IPS really benefit from etanercept, mechanical ventilation (MV)-dependent IPS patients might be worth receiving ECMO treatment in line with the protective lung strategy. We therefore performed veno-venous ECMO (VV-ECMO), which substantially acted as an extracorporeal carbon dioxide removal, on a 56-year-old post-HSCT male with severe MV-dependent IPS due to graft-versus-host disease. Although a serious bleeding complication due to post-HSCT thrombocytopenia occurred, the VV-ECMO was continued for 11 days. The patient successfully entered remission of the IPS and was finally extubated on the 12th MV day. However, the patient soon complained of dyspnea, probably due to cytomegalovirus infection and/or exacerbation of the IPS, and was reintubated after 3 days of extubation. The patient then rapidly developed irreversible type II respiratory failure despite the administration of etanercept and an anti-cytomegalovirus agent and died on the eighth re-MV day. The autopsy findings of the patient revealed diffuse alveolar damage and alveolar hemorrhage, accompanied with bronchitis obliterans in his lungs, as well as whole body cytomegalovirus infection, which were compatible with the clinical diagnosis of the patient. We think that the legitimacy of this treatment strategy is dependent on the overall prognosis of IPS, which is influenced by the complications induced by immunosuppressants and ECMO, especially infections and bleeding.
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PMID:Concurrent treatment with a tumor necrosis factor-alpha inhibitor and veno-venous extracorporeal membrane oxygenation in a post-hematopoietic stem cell transplant patient with idiopathic pneumonia syndrome: a case report. 2570 9


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