Evaluation of current strategies for surveillance and management of donor-specific antibodies: Single-center study

Daniel Sullivan, Chul Ahn, Ang Gao, Chantale Lacelle, Fernando Torres, Srinivas Bollineni, Amit Banga, Jessica Mullins, Manish Mohanka, Steve Ring, Michael Wait, Matthias Peltz, Pavan Duddupudi, Dhiraj Surapaneni, Vaidehi Kaza

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Abstract

Background: Although the presence of donor-specific antibodies (DSA) is known to impact lung allograft, limited data exist regarding DSA management. Methods: We did a retrospective study at our center evaluating DSA management in adult lung transplant recipients undergoing lung transplantation between January 1, 2010 and June 30, 2014. Study follow-up was completed through October 2017. All recipients were stratified into 2 groups based on the presence or absence of DSA. Those with DSA were evaluated for the impact of treatment of DSA. The primary outcomes were postlung transplant survival and freedom from bronchiolitis obliterans syndrome (BOS), subset of chronic lung allograft dysfunction (CLAD). Simon-Makuch method was used to estimate overall survival and BOS-free survival to account for DSA as time-dependent covariate. Survival differences between the groups were analyzed using time-dependent Cox proportional hazards model. Results: Sixty-four percent of 194 total subjects developed post-lung transplant DSA. Overall survival was different with worse survival in the DSA positive group that never cleared DSA (P =.002). BOS-free survival was lower, but did not reach significance in this group. Response to treatment was poor, with only 12 of 47 (25.5%) who received treatment demonstrating clearance of DSA. Conclusions: Donor-specific antibodies prevalence is high after lung transplantation. Clearance of DSA correlated with improved outcomes. Current therapeutic strategies against DSA are relatively ineffective. Multicenter collaborative studies will be required to evaluate current treatment strategies and other innovative modalities.

Original languageEnglish (US)
Article numbere13285
JournalClinical Transplantation
Volume32
Issue number7
DOIs
StatePublished - Jul 1 2018

Fingerprint

Tissue Donors
Antibodies
Bronchiolitis Obliterans
Survival
Lung
Lung Transplantation
Allografts
Therapeutics
Proportional Hazards Models
Multicenter Studies
Retrospective Studies
Transplants

Keywords

  • chronic lung allograft dysfunction
  • donor-specific antibodies
  • lung transplantation
  • rejection
  • treatment of DSA

ASJC Scopus subject areas

  • Transplantation

Cite this

@article{c52f3f2d87fb4632b24e8d7e2c9b4f70,
title = "Evaluation of current strategies for surveillance and management of donor-specific antibodies: Single-center study",
abstract = "Background: Although the presence of donor-specific antibodies (DSA) is known to impact lung allograft, limited data exist regarding DSA management. Methods: We did a retrospective study at our center evaluating DSA management in adult lung transplant recipients undergoing lung transplantation between January 1, 2010 and June 30, 2014. Study follow-up was completed through October 2017. All recipients were stratified into 2 groups based on the presence or absence of DSA. Those with DSA were evaluated for the impact of treatment of DSA. The primary outcomes were postlung transplant survival and freedom from bronchiolitis obliterans syndrome (BOS), subset of chronic lung allograft dysfunction (CLAD). Simon-Makuch method was used to estimate overall survival and BOS-free survival to account for DSA as time-dependent covariate. Survival differences between the groups were analyzed using time-dependent Cox proportional hazards model. Results: Sixty-four percent of 194 total subjects developed post-lung transplant DSA. Overall survival was different with worse survival in the DSA positive group that never cleared DSA (P =.002). BOS-free survival was lower, but did not reach significance in this group. Response to treatment was poor, with only 12 of 47 (25.5{\%}) who received treatment demonstrating clearance of DSA. Conclusions: Donor-specific antibodies prevalence is high after lung transplantation. Clearance of DSA correlated with improved outcomes. Current therapeutic strategies against DSA are relatively ineffective. Multicenter collaborative studies will be required to evaluate current treatment strategies and other innovative modalities.",
keywords = "chronic lung allograft dysfunction, donor-specific antibodies, lung transplantation, rejection, treatment of DSA",
author = "Daniel Sullivan and Chul Ahn and Ang Gao and Chantale Lacelle and Fernando Torres and Srinivas Bollineni and Amit Banga and Jessica Mullins and Manish Mohanka and Steve Ring and Michael Wait and Matthias Peltz and Pavan Duddupudi and Dhiraj Surapaneni and Vaidehi Kaza",
year = "2018",
month = "7",
day = "1",
doi = "10.1111/ctr.13285",
language = "English (US)",
volume = "32",
journal = "Clinical Transplantation",
issn = "0902-0063",
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TY - JOUR

T1 - Evaluation of current strategies for surveillance and management of donor-specific antibodies

T2 - Single-center study

AU - Sullivan, Daniel

AU - Ahn, Chul

AU - Gao, Ang

AU - Lacelle, Chantale

AU - Torres, Fernando

AU - Bollineni, Srinivas

AU - Banga, Amit

AU - Mullins, Jessica

AU - Mohanka, Manish

AU - Ring, Steve

AU - Wait, Michael

AU - Peltz, Matthias

AU - Duddupudi, Pavan

AU - Surapaneni, Dhiraj

AU - Kaza, Vaidehi

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Background: Although the presence of donor-specific antibodies (DSA) is known to impact lung allograft, limited data exist regarding DSA management. Methods: We did a retrospective study at our center evaluating DSA management in adult lung transplant recipients undergoing lung transplantation between January 1, 2010 and June 30, 2014. Study follow-up was completed through October 2017. All recipients were stratified into 2 groups based on the presence or absence of DSA. Those with DSA were evaluated for the impact of treatment of DSA. The primary outcomes were postlung transplant survival and freedom from bronchiolitis obliterans syndrome (BOS), subset of chronic lung allograft dysfunction (CLAD). Simon-Makuch method was used to estimate overall survival and BOS-free survival to account for DSA as time-dependent covariate. Survival differences between the groups were analyzed using time-dependent Cox proportional hazards model. Results: Sixty-four percent of 194 total subjects developed post-lung transplant DSA. Overall survival was different with worse survival in the DSA positive group that never cleared DSA (P =.002). BOS-free survival was lower, but did not reach significance in this group. Response to treatment was poor, with only 12 of 47 (25.5%) who received treatment demonstrating clearance of DSA. Conclusions: Donor-specific antibodies prevalence is high after lung transplantation. Clearance of DSA correlated with improved outcomes. Current therapeutic strategies against DSA are relatively ineffective. Multicenter collaborative studies will be required to evaluate current treatment strategies and other innovative modalities.

AB - Background: Although the presence of donor-specific antibodies (DSA) is known to impact lung allograft, limited data exist regarding DSA management. Methods: We did a retrospective study at our center evaluating DSA management in adult lung transplant recipients undergoing lung transplantation between January 1, 2010 and June 30, 2014. Study follow-up was completed through October 2017. All recipients were stratified into 2 groups based on the presence or absence of DSA. Those with DSA were evaluated for the impact of treatment of DSA. The primary outcomes were postlung transplant survival and freedom from bronchiolitis obliterans syndrome (BOS), subset of chronic lung allograft dysfunction (CLAD). Simon-Makuch method was used to estimate overall survival and BOS-free survival to account for DSA as time-dependent covariate. Survival differences between the groups were analyzed using time-dependent Cox proportional hazards model. Results: Sixty-four percent of 194 total subjects developed post-lung transplant DSA. Overall survival was different with worse survival in the DSA positive group that never cleared DSA (P =.002). BOS-free survival was lower, but did not reach significance in this group. Response to treatment was poor, with only 12 of 47 (25.5%) who received treatment demonstrating clearance of DSA. Conclusions: Donor-specific antibodies prevalence is high after lung transplantation. Clearance of DSA correlated with improved outcomes. Current therapeutic strategies against DSA are relatively ineffective. Multicenter collaborative studies will be required to evaluate current treatment strategies and other innovative modalities.

KW - chronic lung allograft dysfunction

KW - donor-specific antibodies

KW - lung transplantation

KW - rejection

KW - treatment of DSA

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