Hematopoietic stem cell transplant–related airflow obstruction

Dudek, Arkadiusz Z.; Mahaseth, Hemchandra

doi:10.1097/01.cco.0000208782.61452.08

Cited by 11 publications

(9 citation statements)

References 33 publications

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“…Infected patients were tested for airflow obstruction (AFO) and radiological signs of pneumonia. AFO was defined as an FEV1/FVC ratio <0.7 or a decrease of the FEV1 >20%, as suggested by Dudek and Mahaseth . According to an institutional protocol, patients with AFO and/or signs of pneumonia were considered to have LRTID and were treated with IV RBV dosed according to Schleuning et al.…”

Section: Methodsmentioning

confidence: 99%

Successful systemic high‐dose ribavirin treatment of respiratory syncytial virus‐induced infections occurring pre‐engraftment in allogeneic hematopoietic stem cell transplant recipients

Gueller

Duenzinger

Wolf

et al. 2013

Transplant Infectious Dis

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Section: Methodsmentioning

confidence: 99%

Successful systemic high‐dose ribavirin treatment of respiratory syncytial virus‐induced infections occurring pre‐engraftment in allogeneic hematopoietic stem cell transplant recipients

Gueller

Duenzinger

Wolf

et al. 2013

Transplant Infectious Dis

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“…The exact incidence of OB after HSCT in pediatric patients is unknown. Estimates vary greatly depending on the population studied, and whether clinical or histopathological criteria are used 71. Studies have identified many potential risk factors, but GVHD remains the only consistent association 69,72.…”

Section: Graft Versus Host Disease (Gvhd) and Related Disordersmentioning

confidence: 99%

Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients: Non‐infectious and long‐term complications

Gower

Collaco

Mogayzel

2006

Pediatric Blood & Cancer

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Pulmonary complications are among the most frequently encountered sequelae of pediatric hematopoietic stem cell transplantation (HSCT). Non-infectious complications are becoming increasingly more common in this unique population. This review addresses the diagnosis and management of non-infectious manifestations of lung disease in pediatric HSCT patients and briefly discusses the long-term pulmonary function of childhood HSCT survivors.

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“…Corticosteroids are contained in many of the current regimens but are still associated with a high rate of progressive airway obliteration and subsequent mortality. 17 Treatment of steroid-refractory cGVHD patients with rituximab, a B cell-depleting anti-CD20 mAb, has shown a beneficial role in resolution of autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis, 18 as well as cGVHD. [19][20][21][22] Aggregate analysis of 6 trials of steroid-refractory cGVHD showed overall response rates of 29%-36% for oral, hepatic, gastrointestinal, and lung cGVHD and 60% for cutaneous cGVHD.…”

Section: Introductionmentioning

confidence: 99%

Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans

Srinivasan

Flynn

Price

et al. 2012

Blood

219

187

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Chronic GVHD (cGVHD) poses a significant risk for HSCT patients. Preclinical development of new therapeutic modalities has been hindered by models with pathologic findings that may not simulate the development of human cGVHD. Previously, we have demonstrated that cGVHD induced by allogeneic HSCT after a conditioning regimen of cyclophosphamide and total-body radiation results in pulmonary dysfunction and airway obliteration, which leads to bronchiolitis obliterans (BO), which is pathognomonic for cGVHD of the lung. We now report cGVHD manifestations in a wide spectrum of target organs, including those with mucosal surfaces. Fibrosis was demonstrated in the lung and liver and was associated with CD4 ؉ T cells and B220 ؉ B-cell infiltration and alloantibody deposition. Donor bone marrow obtained from mice incapable of secreting IgG alloantibody resulted in less BO and cGVHD. Robust germinal center reactions were present at the time of cGVHD disease initiation. Blockade of germinal center formation with a lymphotoxin-receptor-immunoglobulin fusion protein suppressed cGVHD and BO. We conclude that cGVHD is caused in part by alloantibody secretion, which is associated with fibrosis and cGVHD manifestations including BO, and that treatment with a lymphotoxin-␤ receptorimmunoglobulin fusion protein could be beneficial for cGVHD prevention and therapy. (Blood. 2012;119(6):1570-1580) IntroductionChronic GVHD (cGVHD) is a significant complication of allogeneic HSCT. 1 Progress in developing interventional strategies to counter cGVHD has been hampered by variable onset and pathologic manifestations of cGVHD, now better defined by the National Institutes of Health consensus conference, 2 and a dearth of robust preclinical venues that closely mimic conditions in which cGVHD is generated and manifested. 3 Although the exact causes of cGVHD are unknown, higher antibody levels have been associated with autoimmunity and implicated in cGVHD. 4,5 Studies of newly diagnosed patients with extensive cGVHD showed that they had elevated soluble B-cell activating factor (BAFF) levels and anti-ds-DNA antibodies. 6,7 Increased soluble BAFF in cGVHD was associated with higher circulating levels of pre-germinal center (GC) B cells and post-GC plasmablasts. 8 B cells from cGVHD patients are hyperresponsive to TLR-9 signaling and have up-regulated CD86 levels, 9 which suggests an important participatory role for B cells in establishing cGVHD and emphasizes the need for further investigation into the immunologic role of B cells in cGVHD pathogenesis.Existing murine cGVHD models simulate one or more of the pathologic manifestations, such as increased serum antibodies (typically anti-DNA antibodies), scleroderma, and fibrosis of skin and liver, and the less common immune complex deposition in kidneys and glomerulonephritis. [10][11][12] The type of multiorgan involvement and alloantibodies seen in cGVHD patients often has not been well represented in these preclinical models. Moreover, some models do not involve conditioning regimens, whereas ot...

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Hematopoietic stem cell transplant–related airflow obstruction

Cited by 11 publications

References 33 publications

Successful systemic high‐dose ribavirin treatment of respiratory syncytial virus‐induced infections occurring pre‐engraftment in allogeneic hematopoietic stem cell transplant recipients

Successful systemic high‐dose ribavirin treatment of respiratory syncytial virus‐induced infections occurring pre‐engraftment in allogeneic hematopoietic stem cell transplant recipients

Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients: Non‐infectious and long‐term complications

Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans

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