Epidemiology, risk factors, and outcomes of lung retransplantation: An analysis of the International Society for Heart and Lung Transplantation Thoracic Transplant Registry

Abstract

Background: Lung retransplantation is a complex surgical decision that represents the only potential treatment option for recipients suffering from lung allograft failure. We sought to describe the modern landscape of lung retransplantation and to compare the relative importance of selected clinical, donor, and recipient factors on mortality in the year following lung retransplantation.

Methods: We conducted a retrospective cohort study of first-time adult recipients of deceased donor lung retransplants reported to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 2005 through June 2017. In addition to describing the characteristics of lung retransplant recipients, we examined 1 year survival overall, and by initial transplant-retransplant procedure type, recipient age, retransplant indication, and time-to-lung retransplantation (i.e., inter-transplant interval). We used the Somers' D_xy rank correlation statistic for censored data to assess the relative importance of several potential prognostic risk factors for mortality in the year following lung retransplantation.

Results: Our cohort included 1,597 lung retransplant recipients. 2005 was the first year with more than 100 retransplants, and since 2007, 138 to 188 retransplants (approximately 4%-6% of all transplants) were reported annually to the ISHLT Registry. The median inter-transplant interval was 3.4 years (interquartile range: 1.6-6.2 years). Forty-three percent of the cohort had an obliterative bronchiolitis retransplant indication, whereas 17% had primary graft failure. One-third (32%) were retransplanted within 2 years of their primary transplant, and 64% received a double lung transplant both times, whereas 36% received consecutive single lung transplants. Six-month and 1 year survival (82% and 76%) were higher for double-double lung retransplant recipients than for single-single recipients (76% and 69%). The 3 strongest prognostic factors for 1 year mortality were the inter-transplant interval (decreasing hazard with longer intervals), donor age (increasing hazard with older age), and need for mechanical ventilation preceding lung retransplantation.

Conclusions: Retransplants comprise approximately 5% of annual lung transplants worldwide. The factor most strongly associated with 1 year mortality in this population was the duration of time since the primary lung transplant, with a persistent reduction in risk as more time elapses.

Keywords: allograft failure; end-stage lung disease; epidemiology; lung transplant; retransplantation.

Figure 1.

Geographical distribution and frequency of lung retransplantations reported to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry since 1990 through the latest year of data collection in 2017. The right x-axis and red line indicate the % out of all adult, deceased donor lung transplants (primary and retransplants) reported in the Registry.

Figure 2.

Kaplan-Meier survival estimates for 1-year survival following lung retransplantation.

Figure 3.

Kaplan-Meier survival estimates for 1-year survival following lung retransplantation by (A) initial transplant-retransplantation procedure type combination, (B) recipient age category at retransplantation (C) retransplant indication (obliterative bronchiolitis [OB] versus non-OB), and (D) inter-transplant interval. The cohort includes all first-time lung retransplantation recipients in the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 4^th, 2005 to June 30^th, 2017.

Figure 4.

Recipient-age adjusted association between the inter-transplant interval and 1-year mortality using a restricted cubic spline with 3 knots at the following values: 90 days, 730 days, and 3,491 days (i.e., the 90^th decile), (A) overall and (B) stratified by initial transplant-retransplantation procedure type combination. The cohort includes all first-time lung retransplantation recipients in the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 4^th, 2005 to June 30^th, 2017.

Figure 5.

Exploratory multivariable Cox proportional hazards regression analysis of factors associated with 1-year mortality. Panel A displays a forest plot of all associations measured using hazard ratios for 1-year mortality. In panel A, hazard ratios for continuous risk factors are shown for the third quartile compared to the first quartile. Panels B and C display the multivariable hazard ratios for the association of the inter-transplant interval and donor age, respectively, with 1-year mortality in the fully adjusted model using the median as the reference category. The cohort includes all first-time lung retransplantation recipients in the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 4^th, 2005 to June 30^th, 2017.

Figure 6.

Somers’ D_xy rank correlation statistics for the prognostic factors in the multivariable Cox proportional hazards regression model for 1-year mortality reported in Figure 5. Retransplant indication indicates obliterative bronchiolitis versus non-obliterative bronchiolitis. The cohort includes all first-time lung retransplantation recipients in the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 4^th, 2005 to June 30^th, 2017.