Lung injury after pediatric allogeneic hematopoietic cell transplantation (HCT) is a common and disastrous complication that threatens long-term survival. In order to develop strategies to prevent lung injury, novel tools are first needed to comprehensively assess lung health in HCT candidates. Therefore, this study analyzed biospecimens from 181 pediatric HCT candidates who underwent routine pre-HCT bronchoalveolar lavage (BAL) at the University Medical Center in Utrecht, the Netherlands between 2005-2016. BAL fluid underwent metatranscriptomic sequencing of microbial and human RNA and unsupervised clustering and generalized linear models were used to associate microbiome-gene expression data with the development of post-HCT lung injury. Microbe-gene correlations were validated using a geographically distinct cohort of 18 pediatric HCT candidates. The cumulative incidence of post-HCT lung injury varied significantly according to four pre-HCT pulmonary metatranscriptome clusters, with the highest incidence observed in children with pre-HCT viral enrichment and innate immune activation and in children with profound microbial depletion and concomitant NK/T-cell activation (p<0.001). In contrast, children with pre-HCT pulmonary metatranscriptomes containing diverse oropharyngeal taxa and lacking inflammation rarely developed post-HCT lung injury. In addition, activation of epithelial-epidermal differentiation, mucous production, and cellular adhesion were associated with fatal post-HCT lung injury. In a separate validation cohort, associations between pulmonary respiratory viral load, oropharyngeal taxa, and pulmonary gene expression were recapitulated; the association with post-HCT lung injury needs to be validated in an independent cohort. This analysis suggests that assessment of the pre-HCT BAL fluid may identify high-risk pediatric HCT candidates who may benefit from pathobiology-targeted interventions.

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Impaired baseline lung function is associated with mortality after pediatric allogeneic hematopoietic cell transplantation (HCT), yet limited knowledge of the molecular pathways that characterize pretransplant lung function has hindered the development of lung-targeted interventions. In this study, we quantified the association between bronchoalveolar lavage (BAL) metatranscriptomes and paired pulmonary function tests performed a median of 1 to 2 weeks before allogeneic HCT in 104 children in The Netherlands. Abnormal pulmonary function was recorded in more than half the cohort, consisted most commonly of restriction and impaired diffusion, and was associated with both all-cause and lung injury–related mortality after HCT. Depletion of commensal supraglottic taxa, such as Haemophilus , and enrichment of nasal and skin taxa, such as Staphylococcus , in the BAL microbiome were associated with worse measures of lung capacity and gas diffusion. In addition, BAL gene expression signatures of alveolar epithelial activation, epithelial-mesenchymal transition, and down-regulated immunity were associated with impaired lung capacity and diffusion, suggesting a postinjury profibrotic response. Detection of microbial depletion and abnormal epithelial gene expression in BAL enhanced the prognostic utility of pre-HCT pulmonary function tests for the outcome of post-HCT mortality. These findings suggest a potentially actionable connection between microbiome depletion, alveolar injury, and pulmonary fibrosis in the pathogenesis of pre-HCT lung dysfunction.

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Purpose: To evaluate efficacy, safety, Disease-Free Survival (DFS) and Overall Survival (OS) in patients with indolent non-Hodgkin’s lymphoma (NHL) treated with chemotherapy vs. immunotherapy vs immunochemotherapy as first-line therapy, an up-date report. Methods: Patients with indolent NHL were randomized to receive: (A) Rituximab x 6/w, (B) CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisone) x 6 or (C) R-CNOP x 6, at standard doses. Results: 195 patients were included, 183 are evaluable for OS and toxicity (A:62, B:55 and C:66), 144 are evaluable for overall response rate (ORR) and DFS (A:53, B:41 and C:50). Clinical characteristics: 89 male (45.6%), mean age 59±14 (±SD), 148 (75.9%) in stage (III/IV), without significant differences between groups. Overall Response Rate (CR+PR) was: A: 84.9%, B:83.4% and C:90% (P=0.545). Neutropenia grade 3/4 was more frequent in the chemotherapy groups: A: 4.8%, B: 23.6% and C:18.2% (P=0.001) as it was the infectious toxicity (grade 2/4): A:4.8%, B:5.5% and C:15.2% (P=0.07). DFS at 24 months was: A 68%, B:65% and C:70%, (P=0.93) and the OS was A:87%, B:84% and C:78%. P=0.89. Conclusions: We did not find any important differences, between groups, regarding the Overall Response Rate, Disease Free Survival and Overall Survival at 24 months. However, single agent rituximab was better tolerated, with less toxicity in comparison with the chemotherapy containing groups. Based on these findings, it maybe reasonable to use immunotherapy only, as first-line therapy for patients with indolent NHL.

La colangiopancreatografía retrógrada endoscópica (CPRE) es uno de los recursos terapéuticos más importantes para el manejo de las complicaciones biliares del trasplante hepático. Sin embargo, se pueden presentar varias complicaciones: pancreatitis aguda, hemorragia, perforaciones, infecciones y eventos adversos cardiopulmonares. La embolia aérea es una complicación muy infrecuente, severa y potencialmente fatal. Se reporta un caso de embolia aérea post-CPRE en una mujer de 55 años con antecedente de trasplante hepático y estenosis de la anastomosis biliar. Se discute la presentación clínica, el diagnóstico, el tratamiento y los posibles mecanismos involucrados en esta complicación.

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