Rabbit antithymocyte globulin for the treatment of chronic lung allograft dysfunction.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. Several treatments have been used to prevent the progression or reverse the effects of CLAD. Cytolytic therapy with rabbit antithymocyte globulin (rATG) has previously shown to be a potential option. However, the effect on patients with restrictive allograft syndrome (RAS) versus bronchiolitis obliterans syndrome (BOS) and the effect of cumulative dosing are unknown. METHODS: The charts of lung transplant patients treated with rATG at Barnes-Jewish Hospital from 2009 to 2016 were retrospectively reviewed. The primary outcome was response to rATG; patients were deemed responders if their FEV1 improved in the 6 months after rATG treatment. Safety endpoints included incidence of serum sickness, cytokine release syndrome, malignancy, and infectious complications. RESULTS: 108 patients were included in this study; 43 (40%) patients were responders who experienced an increase in FEV1 after rATG therapy. No predictors of response to rATG therapy were identified. Serum sickness occurred in 22% of patients, 15% experienced cytokine release syndrome, and 19% developed an infection after therapy. CONCLUSION: 40% of patients with CLAD have an improvement in lung function after treatment with rATG although the improvement was typically minimal.

Association between Allosensitization and Waiting List Outcomes among Adult Lung Transplant Candidates in the United States.

Rationale: Allosensitization may be a barrier to lung transplant. Currently, consideration is not given to allosensitization when assigning priority on the lung transplant waiting list. Objectives: We aimed to examine the association between allosensitization and waiting list outcomes. Methods: We conducted a retrospective single-center cohort study of adults listed for lung transplant at our center between January 1, 2006, and December 31, 2016. We screened candidates for human leukocyte antigen antibodies before listing and examined the association between allosensitization and waiting list outcomes, including likelihood of transplant and death on the waiting list, using a competing risk model. Calculated panel-reactive antibody (CPRA) was used as a continuous measure of allosensitization. Results: Among 746 candidates who were listed for lung transplant during the study period, 263 (35%) were allosensitized, and 483 (65%) were not. In unadjusted analysis, allosensitized candidates had a decreased likelihood of transplant compared with nonallosensitized candidates (subhazard ratio [sHR], 0.71; 95% confidence interval [CI], 0.60-0.83; P < 0.001) and were more likely to die on the waiting list (sHR, 1.66; 95% CI, 1.08-2.58; P < 0.001). In multivariable modeling, increasing CPRA was associated with an increased risk of death and a decreased likelihood of transplant (sHR for death, 1.15 per 10% increase in CPRA; 95% CI, 1.07-1.22; P < 0.001; sHR for transplant, 0.89 per 10% increase in CPRA; 95% CI, 0.86-0.91; P < 0.001). Conclusions: Broad allosensitization was associated with longer waiting times, decreased likelihood of transplant, and increased risk of death among candidates on the waiting list for lung transplant. Consideration of allosensitization in organ allocation strategies might help mitigate this increased risk in highly allosensitized candidates.