Dataset Information

Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients.

ABSTRACT:

Background

Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes.

Methods

A single-center cohort of 441 lung transplant recipients, spanning a 10-year period, was prospectively screened for HLA antibodies after transplant using flow cytometry-based methods. The prevalence of and predictors for HLA antibodies were determined. The impact of HLA antibodies on survival after transplant and the development of BOS were determined using Cox models.

Results

Of the 441 recipients, 139 (32%) had detectable antibodies to HLA. Of these 139, 54 (39%) developed antibodies specific to donor HLA. The detection of posttransplant HLA antibodies was associated with BOS (HR, 1.54; P=.04) and death (HR, 1.53; P=.02) in multivariable models. The detection of donor-specific HLA antibodies was associated with death (HR, 2.42; P<.0001). The detection of posttransplant HLA antibodies was associated with pretransplant HLA-antibody detection, platelet transfusions, and the development of BOS and cytomegalovirus pneumonitis.

Conclusions

Approximately one-third of lung transplant recipients have detectable HLA antibodies, which are associated with a worse prognosis regarding graft function and patient survival.

SUBMITTER: Snyder LD

PROVIDER: S-EPMC3707175 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients.

Snyder Laurie D LD Wang Ziwei Z Chen Dong-Feng DF Reinsmoen Nancy L NL Finlen-Copeland C Ashley CA Davis W Austin WA Zaas David W DW Palmer Scott M SM

Chest 20130701 1

<h4>Background</h4>Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes.<h4>Methods</h4>A single-center cohort of 441 lung transplant r ...[more]

PMID: 23328795

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Project description:Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor ?, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-? all had high areas under the curve of 0.74-0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor ? were associated with grade II-IV and III-IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide.

Project description:PurposeThis study aimed to describe the survival outcomes and factors associated with prognosis in patients undergoing pulmonary metastasectomy with colorectal cancer (CRC) in a cancer center in South America.Material and methodsA retrospective analysis of patients that underwent lung metastasectomy due to CRC at National Cancer Institute (INC), Colombia between 2007 and 2017 was performed and Kaplan-Meier survival analysis along with log-rank test and Cox regression multivariate analysis were completed.ResultsSeventy-five patients with colorectal adenocarcinoma were included in the study. Of them, 57.3% were women with a median age of 62 years [interquartile ranges (IQR): 18.5]. For 45.3% the adenocarcinoma was located in the rectum and 29.3% had stage IV at diagnosis. 56% had a history of controlled extrapulmonary metastasis and 20% of the cases had a history of the metastasis of the liver. The median follow-up was 36.8 months (IQR: 27.4). Three-year and five-year overall survival (OS) was 57.5% [95% confidence interval (CI), 47.0-70.4] and 33.2% (95% CI, 23.4-47.2), respectively. Patients with bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy carcinoembryonic antigen (CEA), history of liver metastasis, and disease-free interval (DFI) ≤12 months had worse OS. Three-year and five-year disease-free survival (DFS) was 30.1% (95% CI, 20.8-43.6) and 21.6% (95% CI, 13.0-35.9), respectively. Bilateral, more than one pulmonary metastasis, and patients with stage IV at diagnosis had the worst DFS. Multivariate analysis in the Cox regression model showed that abnormal postmetastasectomy CEA [Hazard Ratio (HR):1.97, 95% CI, 1.01-3.86, p = 0.045] and DFI ≤ 12 months (HR: 3.08, 95% CI, 1.26-7.53, p = 0.014) were independent factors for worst OS.ConclusionsThe OS found falls within the wide range described in the world literature but interestingly it falls at the bottom end of this range. The factors associated with worst survival were identified as bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy CEA, history of liver metastasis, and DFI ≤12 months.Contribution to the fieldPulmonary metastasectomy is the standard of care in patients with metastatic CRC. However, the literature supporting this conduct is based on retrospective studies and the only randomized controlled trial conducted to date was stopped due to poor recruitment. Limited information is available in South America about survival and factors associated with prognosis in patients with metastatic CRC. While this study is another series that adds to the many studies across the world that describe the use of pulmonary metastasectomy in CRC, it presents critical data as it is one of the few studies carried out in South America. As described in a wide range of world literature, OS found falls in patients that underwent lung metastasectomy due to CRC however; interestingly, in the South American population analyzed here it falls at the bottom end of this range. This may be explained by a large number of patients included with a history of extrapulmonary metastasis as well as may reflect inadequate patient access to reference cancer centers in Colombia. Factors associated with worst survival in our population were bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy CEA, history of liver metastasis, and interval from diagnosis to development of pulmonary metastasis ≤12 months.

Dataset Information

Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients.

Background

Methods

Results

Conclusions

Publications

Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients.

Similar Datasets

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