Impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death
Levy 2020 trial design and results
Design
Retrospective cohort study of first bilateral lung transplantations performed between 1999 and 2017
Treatment
No treatment of a first episode of stable, subclinical minimal (grade A1) acute cellular rejection found on surveillance biopsy
Control
Time-matched patients with stable, no acute rejection on surveillance biopsy
Population
Recipients of a first bilateral lung transplantation, with first-year surveillance transbronchial biopsies paired with FEV1 measurements
Follow-up
To chronic lung allograft dysfunction or death
Primary endpoint
Chronic lung allograft dysfunction or death
Result
Univariable and multivariable Cox proportional hazards models showed no significant difference in the risk of chronic lung allograft dysfunction or death between patients with a first stable grade A1 rejection and time-matched patients with no acute rejection.
Secondary endpoints
Time to chronic lung allograft dysfunction, mortality, FEV1 trajectory
This largest study to date shows that, in clinically stable patients, an untreated first A1 ACR in the first-year posttransplant is not significantly associated with an increased risk for CLAD or death. Watchful-waiting approach may be an acceptable tactic for stable A1 episodes in lung transplant recipients.
The trial authors, in the published abstract
How it has aged
Addresses a question that surveillance biopsy itself created: what to do about rejection nobody would have found without looking. The answer is reassuring — in clinically stable patients a single grade A1 episode can be watched rather than pulsed with steroids. Retrospective, and confined to a first episode in stable recipients; recurrent or symptomatic rejection is a different question.
Publications
The impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death after lung transplantation
Levy L, Huszti E, Tikkanen J, et al. The impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death after lung transplantation. Am J Transplant 2020 Jan;20(1):241-249.
No significant increase in risk of chronic lung allograft dysfunction or death
Applies to a first, stable, subclinical grade A1 episode
Retrospective cohort spanning transplants from 1999 to 2017