Time since primary transplant and poor functional status predict survival after redo lung transplant

Abstract

Background: In previous studies, lower functional status measured by Karnofsky Performance Status (KPS) correlated with worse survival after redo lung transplant. We hypothesize that combining reduced functional status and time from primary lung transplant will correlate with the etiology of lung allograft failure after primary lung transplant and more accurately predict survival after redo lung transplant.

Methods: This retrospective study was approved by University of Minnesota Institutional Review Board. From the Scientific Registry of Transplant Recipients (SRTR) database, 739 patients underwent redo lung transplant (01/01/2005-8/30/2019). Pre-lung transplant characteristics, KPS, time between primary and redo lung transplant, outcomes, overall survival were evaluated. Paired comparisons were used to compare pre-transplant variables. A Cox regression model was fit to examine re-transplant survival. Due to non-proportional hazards, time between transplants was split into <1-year vs. 1+ years and analyzed with time-dependent coefficients, with follow-up time considered in three segments (0-6, 6-24, 24+ months).

Results: After KPS grouping (10-40%, 50-70%, 80-100%), KPS 10-40% were less likely to be discharged after primary transplant and more likely required mechanical ventilation or extracorporeal membrane oxygenation (ECMO) bridging (P<0.001). Redo lung transplant survival was worse in the KPS 10-40% group who more likely underwent lung transplant <1 year after primary lung transplant. Mortality was significantly higher for patients who underwent redo lung transplant within one year of primary transplant when KPS was 10-40% (P<0.001). These patients were more likely to require redo lung transplant due to primary graft failure or acute cellular rejection.

Conclusions: Functional status and time from primary lung transplant are strong predictors of outcome after redo lung transplant. We categorized redo lung transplant recipients in two distinct groups. One group has early allograft failure and poor functional status with a very poor prognosis after redo lung transplant. The other group has chronic allograft failure and overall better functional status with relatively better survival after redo lung transplant. Salvage redo lung transplant for primary allograft failure or acute rejection is associated with low one year survival.

Keywords: Karnofsky Performance Status (KPS); Redo lung transplant; lung allocation score (LAS).

Figure 1

Flow diagram showing patient selection. LTx, lung transplant; N, number.

Figure 2

Patients undergoing redo LTx (y-axis) stratified by pre-transplant KPS group (bars along upper margin of the graph; lowest: KPS 10–40%, intermediate: KPS 50–70%, highest: KPS 80–100%) and time from first transplant [x-axis (years) where the width of each bar represents a 3-month period]. Patients in the lowest KPS group had the greatest number of re-transplants, frequently occurring within <1 year. LTx, lung transplant; KPS, Karnofsky Performance Status.

Figure 3

Probability of survival of redo LTx recipients with respect to functional status and time after transplant and duration of time since first transplant. (A) Kaplan-Meier curve showing patient overall survival after lung re-transplantation according to functional status at time of re-transplant. Patients with lowest functional status (KPS 10–40%) had the lowest probability of survival (P<0.001). (B). Kaplan-Meier curve depicting re-transplant survival for patients with KPS (10–40%), depending on the duration of time since first transplant (0–1 vs. >1 year, P<0.001). (C) Kaplan-Meier curve depicting re-transplant survival for patients with KPS (50–70%), depending on the duration of time since initial transplant (0–1 vs. >1 year, P=0.72). (D) Kaplan-Meier curve depicting re-transplant survival for patients with KPS (80–100%) depending on the duration of time since initial transplant (0–1 vs. >1 year, P=0.96). LTx, lung transplant; KPS, Karnofsky Performance Status.

Figure 4

Kaplan-Meier curves for all-cause mortality in redo LTx recipients according to time from primary LTx. Redo LTx recipients from 2005–2019 were grouped in quartiles according to the time between primary LTx and redo LTx. The presence of non-proportional hazards for time since first transplant is clear from this figure. LTx, lung transplant.

Figure 5

Etiology of lung allograft failure after primary LTx with respect to time between primary LTx and redo LTx (0–1 vs. >1 year). Primary lung non-function and chronic rejection were the leading causes of redo transplant in patients transplanted <1 and >1 year since primary LTx. LTx, lung transplant.

Figure 6

Kaplan-Meier survival analysis stratified based on cause of first LTx failure (acute rejection, chronic rejection, and primary non-function). LTx, lung transplant.

Figure 7

Overall trend of redo LTx from 01/01/2005 to 9/1/2019 based on the SRTR database. Trends in redo LTx requiring assistance based on Karnofsky scores, no assistance (80–100%), some assistance (50–70%), and total assistance (10–40%), were analyzed yearly. LTx, lung transplant; SRTR, Scientific Registry of Transplant Recipients.

Figure 8

Overall trend of timing of redo LTx since primary LTx from 01/01/2005 to 9/1/2019 based on the SRTR database. LTx, lung transplant; SRTR, Scientific Registry of Transplant Recipients.

Figure 9

Overall trend of the indication for redo LTx from 01/01/2005 to 9/1/2019 based on the SRTR database. Bar graph demonstrates number of redo lung transplants for different indications (for example: acute rejection, chronic rejection, other, primary non-function) performed each year. NA, not applicable; LTx, lung transplant; SRTR, Scientific Registry of Transplant Recipients.