Extracorporeal life support as a bridge to pulmonary retransplantation: prognostic factors for survival in a multicentre cohort analysis.

OBJECTIVES: Pulmonary retransplant (ReTx) is considered a controversial procedure. Despite literature reporting outcomes following ReTx, limited data exist in recipients bridged to their ReTx on extracorporeal life support (ECLS). The goal of this study was to investigate the outcomes of recipients bridged to a first-time ReTx by ECLS. METHODS: We performed a retrospective multicentre cohort analysis from 10 centres in Europe, Asia and North America. The primary outcome was overall survival. Risk factors were analysed using Cox regression models. RESULTS: ECLS as a bridge to a first-time ReTx was performed in 50 recipients (ECLS-ReTx). During the study period, 210 recipients underwent a first-time ReTx without bridging on ECLS (regular-ReTx) and 4959 recipients had a primary pulmonary transplant (index-Tx). The overall 1-year (55%) and 5-year (29%) survival was significantly worse for the ECLS-ReTx group.Compared to the index-Tx group, the mortality risk was significantly higher after ECLS-ReTx [hazard ratio 2.76 (95% confidence interval 1.94-3.91); P < 0.001] and regular-ReTx [hazard ratio 1.65 (95% confidence interval 1.36-2); P < 0.001].In multivariable analysis, recipient age ≥35 years, time interval <1 year from index-Tx, primary graft dysfunction as transplant indication, venoarterial-extracorporeal membrane oxygenation and Zurich donor score ≥4 points were significant risk factors for mortality in ECLS-ReTx recipients. CONCLUSIONS: Recipients for ECLS-ReTx should be carefully selected. Risk factors, such as recipient age, intertransplant interval, primary graft dysfunction as transplant indication and type of ECLS should be kept in mind before bridging these patients on ECLS to ReTx.

Extended-criteria donors in lung transplantation in Switzerland: an evaluation of two adapted lung donor scores.

AIM: Various scoring systems aim to assess the quality of organs donated for transplantation on the basis of patient characteristics, clinical examination and laboratory results. How well such scoring systems reflect the practice in lung transplantation in Switzerland has never been studied. Therefore, we evaluated two scoring systems for their ability to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. METHODS: We retrospectively analysed patient data of adult deceased organ donors in Switzerland between 1 July 2007 and 30 June 2014. Included were all donors from whom at least one organ was transplanted. We evaluated two lung donor quality scores, the multicentre-developed Eurotransplant donor score (EDS), and the single-centre-developed Zurich donor score (ZDS). Both scores were slightly adapted to be applicable to Swiss deceased organ donor data. We evaluated whether these scores can predict whether lungs were transplanted or refused by Swiss transplant centres, using univariate logistic regression. We further assessed their discriminative power by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 635 donors included in our analysis, 295 (46%) were accepted as lung donors by one of the two lung transplant centres in Switzerland. Our analysis showed that both scores can predict whether or not a donor lung is likely to be accepted for transplantation in Switzerland. As the score value of a donor increases, the odds of the lung being transplanted significantly decreases (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.51-0.65 for the adapted EDS; OR 0.35, 95% CI 0.28-0.43 for the adapted ZDS). This effect is slightly more pronounced in the adapted ZDS than in the adapted EDS. The discriminatory power of the scores from the AUC was 0.719 (95% CI 0.680-0.758) for the adapted EDS, and 0.723 (95% CI 0.681-0.760) for the adapted ZDS, which for both was deemed fair discrimination. CONCLUSIONS: Both scoring systems are able to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. As an alternative to adapting an established scoring system, a national lung quality score could be derived de novo. This could be based on a logistic regression analysis including the most relevant donor characteristics. However, such a new score would need to be validated on an independent sample and ideally tested for its predictive value in terms of post-transplantation outcome.

Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients.

Carcinoembryonic antigen (CEACAM5) is commonly overexpressed in human colon cancer. Several antigenic peptides recognized by cytolytic CD8+ T-cells have been identified and used in colon cancer phase-I vaccination clinical trials. The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line. However, the immunogenicity of this peptide in humans remains unknown. We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors. Immunogenic-altered peptide ligands with increased affinity for HLA-A*0201 were identified. Importantly, the elicited cytolytic T lymphocyte (CTL) lines and clones cross-reacted with the wild-type CEA(694-702) peptide. Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition. Finally, CEA-specific T-cell precursors could be readily expanded by in vitro stimulation of peripheral blood mononuclear cell (PBMC) from colon cancer patients with altered CEA peptide. However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition. Together, using T-cells to demonstrate the processing and presentation of the peptide CEA694-702, we were able to corroborate its presentation by tumor cells. However, the low avidity of the specific CTLs generated from cancer patients as well as the high-antigen expression levels required for CTL recognition pose serious concerns for the use of CEA694-702 in cancer immunotherapy.