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Objective:To investigate the clinical characteristics and treatment of bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) in children.Methods:Clinical data of 7 patients with BOS after HSCT in the Department of Hematology and Oncology, Children′s Hospital, the First Affiliated Hospital of Zhengzhou University from September 2015 to June 2019, who had a survival of longer than 100 days were retrospectively analyzed.Results:At the last follow-up visit, the incidence of BOS was 4.6%(7/152 cases), including 5 males and 2 females.The median time from HSCT to the diagnosis of BOS was 15 (9-27) months.Among the 7 cases, 5 cases had dry cough and shortness of breath after activity, and 2 cases had no obvious clinical symptoms.Pulmonary function was moderate in 5 cases and severe in 2 cases of obstructive ventilatory disorder.High-resolution CT showed mosaic sign in 5 cases and bronchial wall thickening in 4 cases.Bronchoalveolar lavage (BAL) was performed in 4 cases, and flocculent secretion was found in the bronchus.Membranous substance was formed in the bronchus in 3 cases, and some lumens were completely occluded and dredged by foreign body forceps.After treatment with Fluticasone, Azithromycin and Montelukast sodium (FAM regimen), the pulmonary function of 5 cases(71.4%) was significantly improved, but ineffective in 2 cases.Conclusions:BOS after HSCT in children mainly begins with dry cough and shortness of breath after activity.Regular screening of pulmonary function is beneficial to identify asymptomatic children.BAL can clear inflammatory cytokines, which is conductive to the following drug treatment.If necessary, foreign forceps should be used to dredge the occluded bronchus to relieve symptoms quickly.FAM regimen is an effective treatment method, and timely adjustment of treatment according to the disease situation can improve the prognosis.
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Lung transplantation is an efficacious treatment for end-stage lung diseases in children. Shortage of donor lungs, poor donor-recipient matching, difficult postoperative management, multiple postoperative complications and high fatality jointly restrict the development of pediatric lung transplantation. However, significant progress has been achieved in each transplantation center along with the popularization of organ donation after citizen' s death, advancement of medical science and technology and accumulation of lung transplantation experience. In recent years, clinical application of donor lung from donation after brain death and marginal donor lung repair, maturity of perioperative life support technology and surgical transplantation procedure and reference of management experience after adult lung transplantation have accelerated rapid development of pediatric lung transplantation. In this article, current status and progress on primary diseases, utilization and allocation of donor lungs, selection of surgical techniques, management of postoperative complications and clinical prognosis of pediatric lung transplantation were elucidated, aiming to provide reference for clinical diagnosis and treatment.
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Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.
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La hipertensión arterial pulmonar (HAP) representa el 2,6% de los trasplantes pulmonares (TP), con una mediana de supervivencia condi cional (desde los 30 días del TP) de 9,8 años. Son frecuentes, el rechazo celular agudo (ACR) y la disfunción crónica del injerto (CLAD), mientras que es infrecuente el rechazo mediado por anticuerpos (AMR). El retrasplante pulmonar (RTP) constituye el 4% del TP mundial, debido a complicaciones en la vía aérea, disfunción primaria del injerto, ACR y CLAD. Mujer de 22 años, portadora de HAP idiopática (HAPI) desde el año 2013, trasplantada bipulmonar (TBP) en enero de 2018. A los 16 meses presentó neumonía adquirida en la comuni dad. En una internación posterior, presentó ACR y a pesar de pulsos de metilprednisolona, progresó a requerimientos de cánula de alto flujo y ventilación mecánica no invasiva hospitalaria, caída del VEF1, y tomografía de tórax con vidrio esmerilado difuso y engrosamiento irregular reticular del intersticio subpleural; interpretándose como CLAD a predominio de síndrome de bronquiolitis obliterante (BOS), con presencia de anticuerpos específicos contra el donante (DSA). En enero de 2020 se realizó nuevo TP y ante cross-match positivo, se realizó plasmaféresis y reposición de IgG. Al mes del egreso, no se observaron signos de rechazo en control de biopsias transbronquiales. Entre 2 y 10% de los pacientes con indicación primaria de TP por HAPI son sometidos a retrasplante pulmonar (RTP). La presencia de DSA y el miss-match de HLA, no son contraindicaciones para el RTP.
Pulmonary arterial hypertension (PAH) represents 2.6% of lung transplantations (LT), with a conditional median survival (from 30 days after LT) of 9.8 years. Acute cellular rejection (ACR) and chronic lung allograft dysfunction (CLAD) are common; whereas the antibody-mediated rejection (AMR) is not. Lung retransplantation (LR) accounts for 4% of global LTs for complications in the airways, primary allograft dys function, ACR and CLAD. 22-year-old woman with idiopathic PAH (IPAH) since 2013, who underwent a double-lung transplantation (DLT) in January 2018. 16 months after transplantation she presented community-acquired pneumonia. During a subsequent hospitalization, she presented ACR. Despite the fact that she received pulse methylprednisolone, she required high-flow cannula therapy and hospital non-invasive mechanical ventilation; the FEV1 was reduced and she underwent a chest tomography with diffuse ground glass opacities and irregular reticular thickening of the subpleural interstitium; interpreting the predominance of BOS (bronchiolitis obliterans syndrome) as CLAD, with presence of donor-specific antibodies (DSA). In January 2020, she received a new DLT and due to a positive crossmatch, she was treated with plasmapheresis and IgG replacement. One month after hospital discharge, no signs of rejection were observed at the BTB (bone-patellar tendon-bone) control. Between 2 to 10% of patients with primary indication of LT for IPAH are subjected to lung retransplantation (LR). The presence of DSA and HLA (human leucocyte antigen) mismatch aren't contraindications to LR.
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Posttransplant lymphoproliferative disease (PTLD) is a fatal complication after lung transplantation, which is intimately associated with age, immunosuppression level and Epstein-Barr virus (EBV) infection, etc. Reducing immunosuppression level, rituximab therapy and T cell immunotherapy are common treatments for PTLD. With the rapid development of lung transplantation in China, PTLD after lung transplantation has attracted widespread attention. This article reviews the risk factors, pathological types, clinical manifestations, diagnosis, treatment, prognosis and prevention of PTLD after lung transplantation, aiming to provide reference for early monitoring and management of the incidence and progression of PTLD.
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Chronic lung allograft dysfunction (CLAD) is the largest obstacle to the long-term survival of lung transplant recipients, which represents a series of complicated clinical manifestations of significant and persistent deterioration of lung allograft function after surgery. Due to lack of effective strategies for early diagnosis and prevention, over half of lung transplant recipients will develop CLAD within postoperative 5 years, which is likely to increase to 75% within postoperative 10 years. At present, no drug can be administered to completely prevent or reverse the progression of CLAD. In recent years, since the definition, diagnosis and treatment of CLAD have been updated by International Society of Heart and Lung Transplantation (ISHLT) in 2019, the understanding of CLAD has been significantly deepened within the international community. In this article, comprehensive diagnostic methods and potential treatment strategies of CLAD were explicitly illustrated, aiming to provide theoretical reference and insights for early monitoring and management of the incidence and progression of CLAD.
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Lung transplantation is the ultimate treatment of end-stage lung disease. After transplantation, the 1-year survival rate is 80%, while the 5-year survival rates remaines at around 50% mainly due to bronchiolitis obliterans syndrome (BOS). BOS is regarded as a fibrosing process in the small airways leading to irreversible airway obstruction. A lot of factors are involved in the development of BOS, such as Ischemia/reperfusion injury, infections, oxidative stress, and acute rejection, etc. Studies have shown that early diagnosis of BOS may improve outcome. It is valuable for the long-term survival of lung transplantation to find out several predictors for the BOS. This article reviews the current state of knowledge on predictors for BOS.
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Objective@#To investigate the incidence, risk factors and survival of bronchiolitis obliterans syndrome (BOS) in patients who had undergone haplo-hematopoietic stem cell transplantation (haplo-HSCT) .@*Methods@#This study retrospectively analyzed clinical data of 444 consecutive patients who underwent haplo-HSCT and survived at least 100 days after transplantation in the First Affiliated Hospital of Soochow University between January 2013 and December 2015.@*Results@#By the end of follow-up on January 1, 2018, 25 patients (5.63%) had BOS (BOS group) . The median onset time of BOS was 448 (165-845) d post transplantation, the 1-year, 2-year and 3-year cumulative incidence of BOS was 1.6% (95%CI 1.5%-1.6%) , 4.8% (95%CI 4.7%-4.8%) and 5.8% (95%CI 5.7%-5.8%) , respectively. Among patients with chronic graft-versus-host disease (cGVHD) , the cumulative incidence at the same intervals was 2.8% (95%CI 2.7%-2.8%) , 9.5% (95%CI 9.4%-9.5%) and 11.5% (95%CI 11.4%-11.6%) , respectively. In the multivariate analysis, the risk factors for BOS were high-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD with other organs. The 3-year overall survival (OS) was lower among patients with than those without BOS, but the difference was not significant [71.8% (95%CI 53.9%-89.6%) vs 72.4% (95%CI 68.1%-76.7%) , P=0.400]. Overall 1-year, 3-year survival of patients with BOS from the time of diagnosis was 78.4% (95%CI 61.5%-95.3%) and 37.0% (95%CI 2.5%-71.5%) , respectively, significantly less than those without (93.9% and 89.3%, from day 448 after transplantation, respectively, P<0.001) . Furthermore, we found a significantly higher incidence of transplantation-related mortality (TRM) in patients with compared with patients without BOS (28.2% vs 10.9%, P<0.001) . The main risk factor for OS of BOS patients was the severity of pulmonary impairment at the time of diagnosis. Patients who developed severe BOS had a worse OS than those with moderate and mild BOS (P=0.049) .@*Conclusion@#BOS is a severe pulmonary complication of haplo-HSCT. High-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD were independent risk factors for BOS. Patients who developed BOS had a worse OS than those without BOS. The main risk factor for OS of BOS patients was the severity of pulmonary impairment.
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Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Bronchiolitis Obliterans , General Surgery , Graft Rejection , Hematopoietic Stem Cell Transplantation , Lung , Diagnostic Imaging , Pathology , Lung Transplantation , Mycoses , Tomography, X-Ray ComputedABSTRACT
This article introduced professor WANG Shu-chen's experience in picture treating bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation with tougue picture as the key link. Patients with BOS showed deficiency of essence of tongue crack, which should be treated by warming kidney yang, replenishing essence and marrow; fester tongue for qi disorder, inflammation caused by fire, which should be treated by regulating qi, and clearing heat; exfoliative fur accumulation, which should be treated with blood stasis and toxin, removing blood stasis and toxin; thick and greasy fur, which should be treated by warming spleen and activating spleen.
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Objective@#To investigate the efficacy and prognosis of lung transplantation (LT) for end-stage bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#The clinical data of eight cases with end-stage BOS after allo-HSCT who were treated by LT in our hospital were retrospectively analyzed.@*Results@#Eight patients with hematological malignancy underwent allo-HSCT, and the median age was 23 (12-40) years. The donors are parents or siblings. Severe BOS occurred in 8 patients after allo-HSCT, the median age for LT was 27.5 (13-47) years. The median interval between allo-HSCT and LT was 69 (21-132) months. The median follow-up time for 8 patients after LT was 15 (6-63) months, 7 patients survived, 1 patient died of pulmonary hemorrhage 15 months after LT treatment. Of the survivors, three had BOS again, and one of them received reduplicated lung transplantation.@*Conclusion@#LT is an effective treatment for patients with severe BOS after HSCT.
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PURPOSE: The development of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) deteriorates patients' quality of life. This study aimed to analyze the prevalence, clinical features, risk factors and prognostic factors of BOS. MATERIALS AND METHODS: This retrospective study included patients who underwent allogeneic HSCT from January 2002 to December 2008 and survived for > or =100 days after transplantation. RESULTS: Of 860 patients who survived for > or =100 days, 36 (4.2%) met the diagnostic criteria. The duration of BOS development after transplantation was 466.00 (284.00-642.75) [median (interquartile range)] days. The risk factor for the development of BOS was peripheral blood as the stem cell source with a hazard ratio (HR) of 2.550 [95% confidence interval (CI): 1.274-5.104, p=0.008]. In multivariate analysis, pretransplant FEV1/FVC (HR: 0.956, 95% CI: 0.921-0.993, p=0.020) and time from HSCT to diagnosis of BOS (HR: 0.997, 95% CI: 0.994-0.999, p=0.009) were independent prognostic factors associated with mortality. CONCLUSION: Peripheral blood as a stem cell source is a risk factor for the development of BOS. A decreased pretransplant FEV1/FVC and shorter duration of time from transplantation to diagnosis of BOS are poor prognostic factors for BOS.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Bronchiolitis Obliterans/epidemiology , Disease Progression , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Multivariate Analysis , Prevalence , Proportional Hazards Models , Quality of Life , Respiratory Function Tests , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation, HomologousABSTRACT
Objective: To assess the outcome of patients ≤ 20 years old subjected to lung transplantation. Methods: Retrospective analysis of clinical records of these patients at Las Condes Clinic, Santiago de Chile. Results: Ten patients ≤ 20 years old have been subjected to lung transplantation. The median age at transplant was 15.8 years. The main indication was cystic fibrosis in 8 patients. The average baseline FEV1 was 31.3% of its reference value with progressive improvement in FEV1 being 76,3% after one year and 75,3% after two years, Early complications were infections and rejection. Late complications were mainly viral infections. Six patients achieved to continue their studies. Survival rate at 30 days, 1 and 5 years were 80, 70 and 58% respectively. Conclusion: Lung transplantation is an alternative for children and adolescents with advanced lung disease with acceptable results in long-term survival.
Sólo 45 centros en el mundo desarrollan trasplantes pulmonares en niños. Objetivo: Evaluar resultados de pacientes ≤ 20 años trasplantados de pulmón. Material y Método: Análisis retrospectivo de registros clínicos de estos pacientes en Clínica Las Condes. Resultados: Diez pacientes ≤ 20 años han sido trasplantados de pulmón. La edad promedio al momento del trasplante fue de 15,8 años. La principal indicación fue fibrosis quística en 8 pacientes. El VEF1 promedio basal fue de 31,3% de su valor de referencia, con mejoría progresiva post-trasplante siendo al año de 76,7% y a los 2 años de 75%, Complicaciones precoces fueron infecciones y rechazo. Complicaciones tardías fueron principalmente infecciones de origen viral. Seis pacientes lograron continuar sus estudios. La sobrevida a 30 días, al 1er y 5º año fue de 80%,70% y 58% respectivamente. Conclusión: El trasplante pulmonar es una alternativa válida en niños y adolescentes con enfermedades pulmonares avanzadas con resultados aceptables a largo plazo.
Subject(s)
Humans , Male , Female , Child , Adolescent , Bronchiolitis Obliterans , Lung Transplantation/methods , Lung Transplantation/mortality , Cystic Fibrosis , Forced Expiratory Volume , Medical Records , Survival Rate , Retrospective Studies , Statistical DataABSTRACT
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a life-threatening lung complication after allogenic hematopoietic stem cell transplantation (HSCT). As long-term survival following allogenic HSCT has improved, the number of BOS patients has been steadily increased. However, the survival and treatment of BOS have not improved significantly for decades. Identification of risk factors of BOS would improve the clinical outcome of allogenic HSCT recipients.METHODS: We retrospectively investigated medical records of 147 allogenic HSCT recipients between 2005 and 2014 in Yonsei Cancer Center. Risk factors for BOS were analyzed with Chi-square test, logistic regression analysis, and the Student's t-test.RESULTS: BOS occurred to 23 patients (15.6%). Pulmonary function test (PFT) results before transplantation were similar in all patients, but patients with BOS had a significant decrease in forced expiratory volume in one second (FEV1) after transplantation compared with controls (68.4+/-26.4% vs. 91.6+/-21.0%, P<0.05). Acute graft-versus-host disease (GVHD) (OR 5.98, P=0.009) and peripheral blood as sources of stem cell (OR 4.00, P=0.031) increased risk for BOS, respectively. On the other hand, previously reported risk factors, such as age of donors and recipients, pulmonary infection within 100 days after allogenic HSCT and deference of immunosuppressant were not associated with increased the incidence of BOS in our study.CONCLUSION: We report here the result of a single-center study on the incidence, clinical factors, and outcome of BOS after allogenic HSCT. BOS is an important cause of post-transplantation morbidity and mortality. Risk reduction can be achieved by better prevention and control of BOS.
Subject(s)
Humans , Bronchiolitis Obliterans , Bronchiolitis , Forced Expiratory Volume , Graft vs Host Disease , Hand , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Incidence , Logistic Models , Lung , Medical Records , Mortality , Respiratory Function Tests , Retrospective Studies , Risk Factors , Risk Reduction Behavior , Stem Cells , Tissue DonorsABSTRACT
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a life-threatening lung complication after allogenic hematopoietic stem cell transplantation (HSCT). As long-term survival following allogenic HSCT has improved, the number of BOS patients has been steadily increased. However, the survival and treatment of BOS have not improved significantly for decades. Identification of risk factors of BOS would improve the clinical outcome of allogenic HSCT recipients. METHODS: We retrospectively investigated medical records of 147 allogenic HSCT recipients between 2005 and 2014 in Yonsei Cancer Center. Risk factors for BOS were analyzed with Chi-square test, logistic regression analysis, and the Student's t-test. RESULTS: BOS occurred to 23 patients (15.6%). Pulmonary function test (PFT) results before transplantation were similar in all patients, but patients with BOS had a significant decrease in forced expiratory volume in one second (FEV1) after transplantation compared with controls (68.4+/-26.4% vs. 91.6+/-21.0%, P<0.05). Acute graft-versus-host disease (GVHD) (OR 5.98, P=0.009) and peripheral blood as sources of stem cell (OR 4.00, P=0.031) increased risk for BOS, respectively. On the other hand, previously reported risk factors, such as age of donors and recipients, pulmonary infection within 100 days after allogenic HSCT and deference of immunosuppressant were not associated with increased the incidence of BOS in our study. CONCLUSION: We report here the result of a single-center study on the incidence, clinical factors, and outcome of BOS after allogenic HSCT. BOS is an important cause of post-transplantation morbidity and mortality. Risk reduction can be achieved by better prevention and control of BOS.