The impact of pre-transplant allosensitization on outcomes after lung transplantation

doi:10.1016/j.healun.2015.06.003

The Journal of Heart and Lung Transplantation

Volume 34, Issue 11, November 2015, Pages 1415-1422

https://doi.org/10.1016/j.healun.2015.06.003 Get rights and content

Background

Allosensitization can be a significant barrier to transplantation for some patients, and previous studies suggested that pre-transplant allosensitization was associated with worse outcomes after lung transplantation. However, human leukocyte antigen (HLA) antibody testing has evolved significantly over the past 10 years, and current assays are highly sensitive and specific.

Methods

We examined the impact of pre-transplant allosensitization on post-transplant outcomes in the era of solid-phase multiplex HLA antibody detection assays in this retrospective, single-center study of 304 adult transplant recipients between January 1, 2006, and December 31, 2012. We accepted donor organs for allosensitized patients if a virtual crossmatch was compatible with all previously identified antibodies.

Results

In univariate and multivariate Cox proportional hazards models, pre-transplant allosensitization, the calculated panel reactive antibody, and the number of pre-transplant HLA antibodies were not associated with the development of acute cellular rejection, lymphocytic bronchiolitis, donor-specific HLA antibodies, chronic lung allograft dysfunction, or graft failure.

Conclusions

Pre-transplant allosensitization does not adversely affect outcomes after lung transplantation when the potentially reactive HLAs are avoided in the donor by a virtual crossmatch with the recipient.

Section snippets

Study design

We conducted a retrospective cohort study including all patients listed for lung transplantation at our program between January 1, 2006, and December 31, 2011. During this period, 368 patients were listed for transplantation; 3 subsequently underwent transplant at another institution and were excluded. Of the remaining 365 patients, 304 underwent transplant at our center before December 31, 2012, and comprise this cohort. The remaining 61 patients died while on the waitlist, were removed from

Baseline characteristics and histocompatibility

Follow-up was complete through December 31, 2013, and the study included 974 patient-years of follow-up with a mean follow-up of 3.2 ± 1.9 years. Among the 304 recipients, 108 (35.5%) were allosensitized before transplantation, and 196 (64.5%) were not allosensitized (Table 1). Overall, there was no significant difference in baseline characteristics between recipients who were allosensitized and recipients who were not allosensitized (Table 1). Among the 108 allosensitized recipients, 29 (27%)

Discussion

In this study, we examined the impact of pre-transplant allosensitization on post-transplant outcomes in the era of solid-phase multiplex HLA antibody detection assays and virtual crossmatching. Our analysis did not reveal any association between pre-transplant allosensitization and adverse outcomes after lung transplantation. Specifically, we found no association between pre-transplant allosensitization and the development of ACR, LB, DSA, CLAD, or graft failure. Moreover, we found no

Disclosure statement

This work was supported in part the National Institutes of Health (Grant No. HL056643 to T.M. and R.R.H. and Grant No. HL105412 to R.D.Y., T.M., and R.R.H.).

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

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Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.
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Original Clinical ScienceThe impact of pre-transplant allosensitization on outcomes after lung transplantation

Background

Methods

Results

Conclusions

Section snippets

Study design

Baseline characteristics and histocompatibility

Discussion

Disclosure statement

J Heart Lung Transplant

J Heart Lung Transplant

Am J Transplant

J Heart Lung Transplant

J Heart Lung Transplant

Chest

Ann Thorac Surg

J Heart Lung Transplant

Ann Thorac Surg

J Heart Lung Transplant

J Heart Lung Transplant

J Heart Lung Transplant

Original Clinical Science
The impact of pre-transplant allosensitization on outcomes after lung transplantation