High Immunologic Risk Lung Transplantation Using Risk Stratified Induction

Purpose Donor specific antibodies (DSA) are associated with antibody-mediated rejection, chronic lung allograft dysfunction (CLAD) and increased mortality, making lung transplant in the presence of DSA high risk. Our center transplants these patients using risk-stratified induction. We sought was to assess survival and time to CLAD onset in these patients compared to low risk recipients. Methods We reviewed lung transplant recipients transplanted from January 2010 to December 2017. Recipients were assigned to three risk categories: low [no DSA, negative crossmatch (XM)], moderate [positive DSA, negative XM] and high [positive DSA, positive XM]. Patients with DSA were treated with anti-thymocyte globulin and intravenous immune globulin, with five cycles of pheresis for positive XM. Low risk patients received basiliximab. We used Cox regression to test the association between risk category and time to death or retransplant as well as time to CLAD onset, and logistic regression to test the relationship between risk category and severe primary graft dysfunction (PGD). Results 313 patients met inclusion criteria and 76 died during follow up. 256 (81%) were low risk, 27 (9%) moderate and 30 (10%) high. Patients with pre-transplant DSA were younger and more likely to be bridged to transplant. There was no effect of risk status on survival either unadjusted (Figure 1, p=0.83) or adjusted for age, diagnosis, bridging status and transplant type (p=0.65). There was no relationship to time to CLAD onset (p=0.61). Patients with DSA were at increased risk of severe PGD, both unadjusted (p=0.002) and adjusted for age, diagnosis and bridging status (p=0.01), mainly high vs. low risk (adjusted odds ratio 0.29, [95% CI 0.12-0.70]). Conclusion Using a risk stratified induction strategy, DSA at time of transplant was not associated with increased risk of death or CLAD onset in lung transplant recipients, suggesting this is a safe way to improve access for sensitized recipients. The novel PGD association warrants further investigation.