T-cell depletion prevents from bronchiolitis obliterans and bronchiolitis obliterans with organizing pneumonia after allogeneic hematopoietic stem cell transplantation with related donors

Bronchiolitis obliterans (BO) and bronchiolitis obliterans organizing pneumonia (BOOP) are late-onset non-infectious pulmonary complications (LONIPCs) following allogeneic hematopoietic stem cell transplantation (HSCT). In the present study 10 of 197 conventionally prepared stem cell recipients developed BOOP after 365 days and 6 patients developed BO 333 days post-transplant. No BOOP or BO was diagnosed following T-cell depletion (p<0.05). Chronic GVHD was ascertained in all BOOP patients and appeared significantly (p<0,001) more frequent in the conventional transplant group. The data confirm a strong association between T-cell activity, chronic GVHD, BO and BOOP and point out the impact of T lymphocytes in the pathomechanism of BOOP.     

Morphologic changes leading to bronchiolitis obliterans in a patient with delayed non-infectious lung disease after allogeneic bone marrow transplantation.

A 37-year-old man developed delayed non-infectious lung disease after undergoing bone marrow transplantation (BMT) for acute myeloid leukaemia. Over a 15-month period, the progression of morphologic changes from cellular interstitial pneumonia to bronchiolitis obliterans organizing pneumonia and cicatricial bronchiolitis obliterans was documented. Pulmonary function tests, high-resolution CT, bronchoalveolar lavage, lung biopsy and extensive microbiological studies were used as diagnostic tools either at onset and during the follow-up. This represents the first reported case in which a model--supported by longitudinal biopsy results--for the evolution of histologic lesions toward bronchiolitis obliterans after BMT is suggested; therapeutic implications are discussed.     

Bronchiolitis obliterans postallogeneic stem cell transplantation: what is new?

Bronchiolitis obliterans (BO) is a severe complication of hematopoietic stem cell transplantation (HSCT). It is considered as a respiratory manifestation of chronic graft-versus-host disease. It is quite similar to the bronchiolitis obliterans after lung transplantation. Classical therapy associates steroids and immunosuppressive drugs, however theses procedure showed a modest efficacy and have an important morbidity. Recent progresses in the physiopathology of BO post-HSCT allow to use new treatments: mTOR inhibitors, immunotherapy, extra-corporeal photochemotherapy, and bronchial anti-inflammatory effects of azithromycin, statins or antileucotriens. This review will focus on the use of these new therapies in BO post-HSCT.     

Bronchiolitis obliterans following haematopoietic stem cell transplantation.

The aim of the present article is to review the available clinical data on bronchiolitis obliterans following haematopoietic stem cell transplantation (HSCT). The data sources used were the Medline database and references from the identified articles related to bronchiolitis obliterans, noninfectious pulmonary complications and HSCT. HSCT is an important treatment for a variety of malignant and nonmalignant conditions. However, the procedure is limited by significant complications that may involve every organ of the body. Pulmonary complications are seen in 40-60% of HSCT recipients. The recent advances in prophylaxis and treatment of infectious complications have increased the significance of late noninfectious pulmonary conditions. Currently, bronchiolitis obliterans is one of the most challenging pulmonary complications facing clinicians who are taking care of haematopoietic stem cell transplantation recipients. This article reviews the clinical and pathological features of this condition, sheds some light on potential mechanisms of pathogenesis, and discusses the available management options.     

A case of bronchiolitis obliterans after allogeneic bone marrow transplantation for acute lymphocytic leukemia]

A case of bronchiolitis obliterans after allogeneic bone marrow transplantation (BMT) for acute lymphocytic leukemia in an 18-year-old woman with both acute and chronic graft-versus-host disease is described. About 160 days after BMT she started complaining of a non-productive cough and exertional dyspnea. Pulmonary function testing revealed obstructive respiratory dysfunction. High-resolution CT (HRCT) scan of the lungs showed areas of parenchymal hypoattenuation with air-trapping, which was more emphasized with expiratory HRCT. She had many of the risk factors for bronchiolitis obliterans, such as total body irradiation, pretreatment with cyclophosphamide, chronic graft-versus-host disease and a low IgG level. Her symptoms were progressive and bronchiectasis developed. She died of respiratory failure 3.5 years after BMT. Bronchiolitis obliterans is an important complication of BMT which the clinician must take into account.     

Nodular pulmonary lesions in children after autologous stem cell transplantation: a source of misinterpretation

In children with malignant disorders, autologous haematopoietic stem cell transplantation (HSCT) represents a therapeutic option, but several possible complications, such as life-threatening pulmonary disease, make appropriate diagnostic procedures essential. We describe two cases with bronchiolitis obliterans with organizing pneumonia after HSCT, with a brief review of important differential diagnoses.     

Bronchiolitis obliterans organizing pneumonia in a patient with chronic myelogenous leukemia developing after initiation of interferon and cytosine arabinoside

A 59-yr-old man developed fevers, shortness of breath, persistent cough and weight loss, shortly after initiation of therapy with interferon-alpha 2a and cytosine arabinoside for treatment of chronic myelogenous leukemia. Radiologic pulmonary infiltrates and lung tissue biopsy were consistent with bronchiolitis obliterans organizing pneumonia (BOOP). After discontinuation of the chemotherapeutic drugs, the pneumonic symptoms and chest roentgenogram infiltrates resolved. This report suggests that treatment with interferon-alpha, in combination with cytosine arabinoside, may produce the rare complication of BOOP.     

Post-transplant bronchiolitis obliterans.

Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischaemia/reperfusion injury and infections have made intermediate-term survival after lung transplantation an achievable goal. However, chronic allograft dysfunction in the form of bronchiolitis obliterans remains a major hurdle that threatens both the quality of life and long-term survival of the recipients. It affects up to 50-60% of patients who survive 5 yrs after surgery, and it accounts for >30% of all deaths occurring after the third postoperative year. This article discusses the alloimmune-dependent and -independent risk factors for bronchiolitis obliterans, the current understanding of the pathogenesis of bronchiolitis obliterans based on results of animal and human studies, the clinical staging of the complication, strategies that may contribute to the prevention and/or early detection of bronchiolitis obliterans, and suggestions for future research.     

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease

Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis.     

Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation

Pulmonary complications develop in 30-60% of hematopoietic stem cell transplants (HSCT). The main, late onset, non-infectious complications include Bronchiolitis obliterans (BO), Bronchiolitis obliterans organizing pneumonia (BOOP), and idiopathic pneumonia syndrome (IPS). BO and BOOP occur almost exclusively in allogeneic HSCT, and have 61% and 21% mortality rates, respectively. BOOP responds favorably to corticosteroids. IPS has less than 15% 1-year survival.     

Graft versus host-associated pulmonary disease and other idiopathic pulmonary complications after hematopoietic stem cell transplant

Noninfectious conditions are now the major pulmonary causes of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The idiopathic pneumonia syndrome (IPS) remains one of the more common and serious pulmonary complications within months after transplantation. Epidemiological data suggest that, although graft versus host disease (GVHD) reactions may play an etiological role, the major contributing factor is conditioning-related toxicity. Among lung conditions that are more closely associated with GVHD are both obliterative bronchiolitis (usually occurring months to years after HSCT) and bronchiolitis obliterans organizing pneumonia (BOOP). The former is an inexorably progressive condition, whereas BOOP behaves similarly to idiopathic BOOP seen in other populations. Also addressed in this article are engraftment syndrome, diffuse alveolar hemorrhage, and pulmonary veno-occlusive disease. Knowledge of these complications is now a part of the contemporary practice of pulmonary medicine, no longer isolated to the transplant pulmonologist.     

Pneumothorax derived from bronchiolitis obliterans after marrow transplantation

Long-term survival has become achievable after bone-marrow transplantation, but various pulmonary diseases due to chronic graft-vs.-host disease have been recognized. Particularly, bronchiolitis obliterans is a life-threatening complication with no effective remedy. Bilateral pneumothorax associated with bronchiolitis obliterans is rare, but it requires careful attention. In a 42-year old man with intractable pneumothorax after bone marrow transplantation and surgical procedures, extensive thoracolysis was effective as an acute treatment for this disease.     

A lung transplant in a woman with bronchiolitis obliterans following an allogenic bone marrow transplant

Graft-versus-host disease is a major complication for bone marrow transplant recipients and is often a cause of late mortality. It can affect any tissue, and involvement of the lungs--target organs of particular importance--can lead to chronic respiratory failure due to bronchiolitis obliterans. We report the case of a lung transplant in a woman who developed bronchiolitis obliterans after receiving a marrow transplant to treat bone marrow aplasia. Three years later, clinical course was satisfactory, with full functional recovery.     

骨髓移植术后非感染性肺部并发症的诊断与治疗进展

骨髓移植是当今治疗血液系统肿瘤、实体肿瘤、代谢和遗传性疾病的重要手段，骨髓移植术后多达一半的病人会出现肺部并发症，其中由于大量免疫抑制剂的应用、移植物抗宿主病（graft versus host disease，GVHD）等因素造成的非感染肺部并发症给l临床诊治工作带来极大困难，往往是骨髓移植病人术后发病和死亡的重要因素。根据发病时间早晚，可分为早期并发症（例如特发性肺炎综合征、骨髓植入综合征、弥漫性肺泡出血等）；晚期并发症（例如闭塞性细支气管炎、淋巴细胞增生性疾病等）。本文即对骨髓移植后相关并发症的诊断和治疗进展作一综述。     

Bronchiolitis obliterans organizing pneumonia: a distinct pulmonary complication in cystic fibrosis

Organizing pneumonia in cystic fibrosis has hitherto been considered a nonspecific reparative process. We report on an adult patient with cystic fibrosis and histologically proven bronchiolitis obliterans organizing pneumonia, who experienced sustained clinical improvement under corticosteroid therapy. This case suggests that bronchiolitis obliterans organizing pneumonia may be a distinct pulmonary complication in cystic fibrosis and improve with specific therapy.     

Bronchiolitis obliterans and the risk of pneumothorax after transbronchial biopsy

The safety of bronchoscopy and specifically transbronchial biopsy has not been studied in patients with bronchiolitis obliterans. We discuss two patients with bronchiolitis obliterans as a complication of graft versus host disease following allogeneic stem cell transplant. Both underwent bronchoscopy and transbronchial biopsy, which was complicated by pneumothoraces. Patients with bronchiolitis obliterans have an increased risk of spontaneous air leak syndromes. Although no data exists regarding the safety of transbronchial biopsies in patients with airflow obstruction in general, they appear to have increased rates of pneumothoraces following transthoracic biopsies. It is important to consider the potentially increased risk of pneumothoraces when deciding to pursue bronchoscopy and transbronchial biopsy in patients with bronchiolitis obliterans.     

Bronchiolitis obliterans organizing pneumonia and rheumatoid arthritis

Bronchiolitis obliterans, with or without organizing pneumonia, can be a serious and life-threatening complication of rheumatoid arthritis. We describe a case of bronchiolitis obliterans organizing pneumonia in a patient who recently developed rheumatoid arthritis, presenting as a severe respiratory insufficiency. Diagnosis was made by means of open lung biopsy. Treatment with corticosteroids induced a quick response and substantial improvement of the respiratory symptoms. A simultaneous strong rise in titres of serological tests suggests a relationship between the bronchiolitis obliterans organizing pneumonia and the rheumatoid arthritis.     

Bronchiolitis obliterans organizing pneumonia as a complication of allogeneic bone marrow transplantation.

We report a patient who underwent two allogeneic bone marrow transplants for chronic myelogenous leukemia, initially in 1984 and again after relapse in 1990, who developed an identical pulmonary syndrome at a similar interval following each transplant. The patient presented with a non-productive cough, bilateral inspiratory crackles, and multiple patchy infiltrates on chest X-ray. Pulmonary function testing revealed a restrictive abnormality but no obstructive defects. The appearance of this pulmonary disorder after each transplant coincided with the development of chronic graft-versus-host disease. In both instances, this pulmonary syndrome completely reversed with corticosteroid therapy. The patient's chest computed tomographic scan and lung biopsy specimens were consistent with the diagnosis of bronchiolitis obliterans with organizing pneumonia (BOOP). While bronchiolitis obliterans has been reported following allogeneic transplant, BOOP has not previously been reported in this setting.     

The spectrum of noninfectious pulmonary complications following hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant and nonmalignant conditions. Pulmonary complications, infectious and noninfectious, are a major cause of morbidity and mortality in these patients. The recent advances in prophylaxis and treatment of infectious complications increased the significance of noninfectious pulmonary conditions. Acute lung injury due to diffuse alveolar hemorrhage or idiopathic pneumonia syndrome are the main acute complications, while bronchiolitis obliterans remains the most challenging pulmonary complications facing clinicians who are taking care of HSCT recipients. There are other noninfectious pulmonary complications following HSCT that are less frequent. This report provides a clinical update of the incidence, risk factors, pathogenesis, clinical characteristics and management of the main noninfectious pulmonary complications following HSCT.     

Living-Donor Lobar Lung Transplantation for Broncho-Bronchiolitis Obliterans after Allogeneic Hematopoietic Stem Cell Transplantation: Does Bronchiolitis Obliterans Recur in Transplanted Lungs?

We report a successful case of living-donor lobar lung transplantation (LDLLT) for therapy-resistant broncho-bronchiolitis obliterans (BBO) after allogeneic hematopoietic stem cell transplantation (HSCT). Bronchiolitis obliterans (BO) is one of the late-onset noninfectious pulmonary complications that occur after allogeneic HSCT and is usually resistant to immunosuppressive therapy. A 17-year-old girl with acute lymphoblastic leukemia (ALL) had undergone allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling in 1997. Five years later, she relapsed with ALL and was treated with chemotherapy following stem cell rescue and donor lymphocyte infusion from the original BMT donor. Eight months later, BBO resistant to immunosuppressive therapies, including rituximab, developed in combination with chronic graft-versus-host disease (GVHD). In February 2004, the patient underwent LDLLT from 2 other family members who were mismatched at 3 HLA loci. The patient has been in good health for more than 30 months following LDLLT and shows no sign of BBO in the transplanted lungs, just as with other patients who have undergone lung transplantation for BO associated with chronic GVHD. LDLLT may therefore be considered a viable therapeutic option for the treatment of BO after allogeneic HSCT.