Risk for complications in patients with hemophagocytic lymphohistiocytosis who undergo hematopoietic stem cell transplantation: myeloablative versus reduced-intensity conditioning regimens

Schechter, Tal; Naqvi, Ahmed; Weitzman, Sheila

doi:10.1586/1744666x.2014.920234

Cited by 9 publications

(4 citation statements)

References 38 publications

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“…Debates about best preparative regimens are ongoing without resolution. Recently, the use of reduced‐intensity conditioning (RIC) regimens has shown favorable outcomes and lower rate of acute complications when compared to conventional HSCT 2 . A prospective national RIC HCT trial for HLH/primary immunodeficiency resulted in low early mortality and 1‐year overall survival (OS) of 80% (HLH only disease 82%), but 66.7% 18‐month OS (HLH only disease 68%) 1 .…”

Section: Literature (Patient#) Marsh Et Al 20137(79) Allen Et Al 2018mentioning

confidence: 99%

Challenges in HLH transplant: Tricks to prevent menace of mixed chimerism

Dalal

2020

Pediatric Blood & Cancer

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Section: Literature (Patient#) Marsh Et Al 20137(79) Allen Et Al 2018mentioning

confidence: 99%

Challenges in HLH transplant: Tricks to prevent menace of mixed chimerism

Dalal

2020

Pediatric Blood & Cancer

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“…Although more than 7500 children receive this treatment annually in the United States and Europe, the success of this therapy is limited by a broad range of post-HCT pulmonary injuries that develop in 10 to 40% of pediatric recipients in response to chemotherapeutic toxicity, infection, and impaired or dysregulated immunity (1)(2)(3). Comprehensive assessment of pulmonary health before HCT conditioning is critical to identify high-risk patients who may benefit from modified conditioning chemotherapy regimens, closer surveillance, and risk-stratified treatments aimed at mitigating the development of irreversible pulmonary toxicity (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates

et al. 2022

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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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“…While more than 7,500 children receive this treatment annually in the United States and Europe, the success of this therapy is limited by a broad range of post-HCT pulmonary injuries that develop in 10-40% of pediatric recipients in response to chemotherapeutic toxicity, infection, and impaired or dysregulated immunity (1)(2)(3). Comprehensive assessment of pulmonary health prior to HCT conditioning is critical in order to identify high-risk patients who may benefit from modified conditioning chemotherapy regimens, closer surveillance, and risk-stratified treatments aimed at mitigating the development of irreversible pulmonary toxicity (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Metatranscriptomic Signatures of Lung Function in Pediatric Hematopoietic Cell Transplant Candidates

Zinter

Versluys

Lindemans

et al. 2021

Preprint

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Rationale: Impaired baseline lung function is associated with mortality after allogeneic hematopoietic cell transplantation (HCT). Limited knowledge of the molecular pathways that characterize pre-transplant lung function has hindered the development of lung-targeted interventions. Objectives: To elucidate the biologic and microbiologic correlates of impaired lung function in pediatric allogeneic HCT candidates. Methods: Between 2005-2016, 104 patients with malignant and non-malignant disorders ages 4-19 years underwent paired pulmonary function testing (PFT) and bronchoalveolar lavage (BAL) a median of 1-2 weeks prior to allogeneic transplant in Utrecht, the Netherlands. Cryopreserved BAL underwent RNA sequencing followed by alignment to microbial and human reference genomes for microbiome and gene expression analyses. Measurements and Main Results: 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. BAL microbiome depletion of commensal supraglottic taxa such as Haemophilus and enrichment of nasal and skin taxa such as Staphylococcus were associated with worse measures of lung capacity and gas diffusion. In addition, impaired lung capacity and diffusion were also associated with gene expression signatures of alveolar epithelial proliferation, epithelial-mesenchymal transition, and downregulated immunity, suggesting a post-injury pro-fibrotic response. Detection of microbial depletion and abnormal epithelial gene expression in BAL enhanced the prognostic utility of pre-HCT PFTs for the outcome of post-HCT mortality. Conclusions: These findings suggest a novel and potentially actionable connection between microbiome depletion, alveolar injury, and pulmonary fibrosis in the pathogenesis of pre-HCT lung dysfunction.

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Risk for complications in patients with hemophagocytic lymphohistiocytosis who undergo hematopoietic stem cell transplantation: myeloablative versus reduced-intensity conditioning regimens

Cited by 9 publications

References 38 publications

Challenges in HLH transplant: Tricks to prevent menace of mixed chimerism

Challenges in HLH transplant: Tricks to prevent menace of mixed chimerism

Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates

Metatranscriptomic Signatures of Lung Function in Pediatric Hematopoietic Cell Transplant Candidates

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