Leah E. Bennett

The registry of the international society for heart and lung transplantation: eighteenth official report—2001

In this last report of the Registry’s current administration, it is appropriate to review the changes and growth of the Registry during our 7-year stewardship. The total number of thoracic transplant recipients listed in the Registry has grown from 35,972 to more than 73,000 (see Table I). In addition to the increase in sheer volume of data, the breadth and sophistication of the analyses increased, from descriptive and univariate survival analyses to complex multivariate, risk-stratified data that investigate mortality as well as morbidity end-points. In 1993, the number of slides showing thoracic transplant data offered as a service to the members of the International Society for Heart and Lung Transplantation (ISHLT) was in the mid-30s. This year’s slide set offered free as a PowerPointTM file on the ISHLT website will contain 65 data slides. The health of the Registry will continue with a smooth transition to the new directorship.

Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease

BACKGROUND Although certain forms of end-stage lung disease are debilitating, whether the associated mortality rate exceeds that of transplantation is unclear. We undertook analysis to clarify the survival benefit of lung transplantation for various types of end-stage lung disease. METHODS We analysed data for all patients listed for transplantation in the USA for emphysema, cystic fibrosis, or interstitial pulmonary fibrosis in the years 1992-94. The numbers of patients entered on the waiting list, post-transplantation, died waiting, and currently waiting were: emphysema group 1274, 843, 143, and 165; cystic fibrosis group 664, 318, 193, and 59; interstitial pulmonary fibrosis group 481, 230, 160, and 48. A time-dependent non-proportional hazard analysis was used to assess the risk of mortality after transplantation relative to that for patients on the waiting list. FINDINGS The clearest survival benefit from lung transplantation occurred in the cystic fibrosis group. The relative risks of transplantation compared with waiting were 0.87, 0.61, and 0.61 at 1 month, 6 months, and 1 year (p = 0.008), respectively. For interstitial pulmonary fibrosis, the corresponding relative risks were 2.09, 0.71, and 0.67 (p = 0.09). No survival benefit was apparent in the emphysema group. The risks of transplantation relative to waiting were 2.76, 1.12, and 1.10 at 1 month, 6 months, and 1 year, respectively, and the relative risk did not decrease to below 1.0 during 2 years of follow-up. INTERPRETATION These findings suggest that lung transplantation does not confer a survival benefit in patients with end-stage emphysema by 2 years of follow-up. Other benefits not accounted for in this analysis such as improved quality of life, however, may justify lung transplantation for these patients.

The Registry of the International Society for Heart and Lung Transplantation: Seventeenth Official Report—2000

The Registry of the International Society for Heart and Lung Transplantation has grown substantially during the past 5 years, from a little more than 43,000 registered procedures at the end of 1994 to almost 70,000 registered procedures by the end of 1999 (see Table I). The substantial increase during this 5-year period occurred despite overall annual transplant numbers that were flat or that declined. We attribute this increase to obtaining more complete data from national and multinational registries, from capturing new centers that did not previously report, and finally, from direct Internetbased data reporting by individual centers. During this same 5-year period, excluding the annual reports, the Registry has peer reviewed 23 publications, reviews, and book chapters. J Heart Lung Transplant 2000;19:909.

The Registry of the International Society for Heart and Lung Transplantation : Sixteenth Official Report-1999

Over the past 12 months, The Registry of the International Society for Heart and Lung Transplantation added a total of 3673 additional thoracic organ recipients, the smallest number over the past 5 years. In addition, we added 10 new transplant programs to those reporting data. We continue to be in sharing discussions with 4 newer national/ regional databases, and electronic data submission via the Internet has been instituted with approximately 25% of the non-US centers submitting data using the new system. We continue to use the entire data set to calculate multivariate risks rather than the U.S. data set alone, and we have continued to extend the time frame for both univariate and multivariate analyses.

The Registry of the International Society for Heart and Lung Transplantation: Fifteenth Official Report—1998

Over the past 12 months, The Registry of the International Society for Heart and Lung Transplantation added 20 new transplantation programs and a total of 7073 additional thoracic organ recipients. All of the national and multinational registries are now fully integrated into our registry, and electronic data submission via the Internet will be instituted by mid 1998 for those centers not participating in larger registries. For the first time, the entire data set was used to calculate multivariate risks rather than the U.S. data set alone, and we have continued to extend the time frame for both univariate and multivariate analyses. For this report, risk factors for 5-year outcome and morbidity at 3 years are presented.

Influence of graft ischemic time and donor age on survival after lung transplantation

BACKGROUND Increased graft ischemic time and donor age are risk factors for early death after heart transplantation, but the effect of these variables on survival after lung transplantation has not been determined in a large, multinational study. METHODS All recipients of cadaveric lung transplantations performed between October 1, 1987 and June 30, 1997 which were reported to the United Network for Organ Sharing/International Society for Heart and Lung Transplantation (UNOS/ISHLT) Registry were analyzed. Patient survival rates were estimated using Kaplan-Meier methods. Multivariate logistic regression was used to determine the impact of donor and recipient characteristics on patient survival after transplantation. To examine whether the impact of donor age varied with ischemic time, interactions between the 2 terms were examined in a separate multivariate logistic regression model. RESULTS Kaplan-Meier survival did not differ according to the total lung graft ischemia time, but recipient survival was significantly adversely affected by young (-10 years) or old (-51 years) donor age (p = 0.01). On multivariate analysis, neither donor age nor lung graft ischemic time per se were independent predictors of early survival after transplantation, except if quadratic terms of these variables were included in the model. The interaction between donor age and graft ischemia time, however, predicted 1 year mortality after lung transplantation (p = 0.005), especially if donor age was greater than 55 years and ischemic time was greater than 6 to 7 hours. CONCLUSIONS Graft ischemia time alone is not a risk factor for early death after lung transplantation. Very young or old donor age was associated with decreased early survival, whereas the interaction between donor age and ischemic time was a significant predictor of 1 year mortality after transplantation. Cautious expansion of donor acceptance criteria (especially as regards ischemic time) is advisable, given the critical shortage of donor lung grafts.

Heart-lung or lung transplantation for Eisenmenger syndrome.

BACKGROUND The optimal therapy for end-stage Eisenmenger syndrome (ES) is unknown. We analyzed the United Network for Organ Sharing/International Society for Heart and Lung Transplantation Joint Thoracic Registry to determine predictors of survival. METHODS Univariate analysis was performed using Kaplan-Meier survival curves. Groups were compared using the log-rank test. Multivariate analysis was performed using a proportional hazards model. RESULTS There were 605 transplants performed between 1988 and 1998. The causes of ES included atrial septal defect (ASD) in 171, ventricular septal defect (VSD) in 164, multiple congenital anomalies (MCA) in 68 and patent ductus arteriosus (PDA) in 32. Procedures included 430 heart-lung (HLT), 106 bilateral lung, and 69 single lung transplants (LT). Survival after HLT was better than after LT on univariate analysis (p = 0.002). For HLT, survival at 30 days and 1 year was 80.7% and 70.1% compared with 68% and 55.2% for LT. Diagnosis was also a significant predictor of survival (p = 0.011), being best for VSD and MCA (1-year survival 71.4% and 77.6%). There was a highly significant benefit of HLT over LT for VSD patients (p = 0.0001). Diagnosis, the combination of diagnosis and procedure, recipient age, recipient gender, donor age, ischemic time and recipient status were significant in a multivariate model. Multivariate analysis confirmed the superior prognosis of patients with VSD or MCA (p = 0.007 and p = 0.022, respectively) and suggested that the adverse effect of LT was predominately in patients with VSD (risk ratio 1.817, p = 0.035). CONCLUSIONS This analysis suggests that ES recipients are not a homogeneous group. Patients with VSD and MCA have the best prognosis. HLT appears to offer a survival benefit for patients with ES secondary to VSD and should be re-considered as the operation of choice.

Single vs bilateral, sequential lung transplantation for end-stage emphysema: influence of recipient age on survival and secondary end-points

BACKGROUND The appropriate age to perform bilateral, sequential lung transplants (BSLT) in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Although single lung transplant (SLT) offers an advantage in terms of organ availability, the long-term survival may not warrant this strategy in all age groups. METHODS We analyzed 2,260 lung transplant recipients (1835 SLT, 425 BSLT) with COPD recorded in the International Society for Heart and Lung Transplantation/United Network for Organ Sharing thoracic registry between January 1991 and December 1997. To assess mortality, we performed univariate (Kaplan-Meier method and the chi-square statistic) and multivariate analyses (proportional hazards method). Because of incomplete morbidity data in the international registry, only data from U.S. centers (n = 1778, 1467 SLT, 311 BSLT) were used in the morbidity analysis. RESULTS Survival rates (%) computed using the Kaplan-Meier method at 30 days, 1 year, and 5 years for the patients aged < 50 years were 93.6, 80.2, and 43.6, respectively, for the SLT patients, and 94.9, 84.7, and 68.2, respectively, for the BSLT patients. For patients aged 50 to 60 years, survival rates (%) were 93.5, 79.4, and 39.8 for the SLT patients compared with 93.0, 79.7, and 60.5 for the BSLT patients. For those aged > 60 years, SLT survival (%) was 93.0, 72.9, and 36.4, compared with 77.8 and 66.0 for the BSLT group (a 5-year rate could not be completed in this group). The multivariate model showed a higher risk ratio for mortality in patients aged 40 to 57 years who received SLT vs BSLT. Recipient age and procedure type did not appear to affect the development of rejection, bronchiolitis obliterans, bronchial stricture, or lung infection. CONCLUSIONS Single lung transplant may offer acceptable early survival for patients with end-stage respiratory failure. However, long-term survival data favors BSLT in recipients until approximately age 60 years. These data suggest that a BSLT approach offers a significant survival advantage to recipients younger than 60 years of age.

THE RESULTS OF CARDIAC RETRANSPLANTATION: AN ANALYSIS OF THE JOINT INTERNATIONAL SOCIETY FOR HEART AND LUNG TRANSPLANTATION/UNITED NETWORK FOR ORGAN SHARING THORACIC REGISTRY

Background. It is well established that repeat heart transplantation has a significantly worse outcome when compared with primary (first time) transplantation. Defining the risk factors for mortality within this group has been difficult due to small numbers of patients at individual centers. Methods. All cardiac retransplants performed in the United States and registered in the Joint International Society for Heart and Lung Transplantation (ISHLT)/United Network for Organ Sharing (UNOS) Thoracic Registry were analyzed for demographics, morbidity posttransplantation, immunosuppression, and risk factors for mortality. Results. The study cohort included 514 patients of which 81% were male with a mean age of 47±12 years. Time from primary transplant to retransplantation ranged from 1 day to 15.5 years and more than 50% of the patients underwent retransplantation for chronic rejection. More than 60% of patients were in the intensive care unit at the time of retransplantation and more than 40% of the patients were reported to be on some form of life support (ventricular assist device, ventilator, and/or inotropic therapy). Survival for the entire retransplant cohort was 65, 59, and 55% for 1, 2, and 3 years, respectively, but was substantially lower when the intertransplant interval was short. Conversely, when the interval between primary and retransplantation was more than 2 years, 1 year survival postretransplantation approached that of primary transplantation. Additional independent risk factors for mortality for the retransplant cohort included overall cardiac transplant center volume, the use of a ventricular assist device or ventilator, the patient being in the intensive care unit, and recipient age. The four most common causes of death were infection, primary/nonspecific graft failure, chronic rejection (allograft vasculopathy), and acute rejection. Conclusions. The data confirm that repeat heart transplantation is a higher risk procedure than primary transplantation, especially early after the primary heart transplant.

Does human leukocyte antigen matching influence the outcome of lung transplantation? an analysis of 3,549 lung transplantations

BACKGROUND AND OBJECTIVE Human leukocyte antigen (HLA) compatibility has been shown to improve the outcome of renal and cardiac transplantation. However, its impact on outcome following lung transplantation is not clear, with several single-center studies reporting inconsistent results. We studied the influence of HLA matching on survival and the development of rejection and obliterative bronchiolitis after lung transplantation, using data from the United Network for Organ Sharing/International Society for Heart and Lung Transplantation registry. METHODS The study population included adult patients who received cadaveric lung transplants between October 1987 and June 1997 for whom HLA data were available. Two cohorts were examined, depending on the era of transplantation: (1) October 1987 to June 1997 (n = 3,549): Differences in actuarial survival as stratified by either the total number of HLA mismatches or the number of mismatches at each HLA locus were determined using a log-rank test. Multivariate logistic regression models were developed to determine independent predictors of survival at 1, 3, and 5 years following lung transplantation. (2) April 1994 to June 1997 (n = 1,796): The association of HLA mismatching with acute rejection and obliterative bronchiolitis was determined using a chi-squared analysis. RESULTS Only 164 patients (4.6%) received lung grafts with 2 or fewer HLA mismatches. Univariate analyses demonstrated a significant difference in post-transplant survival by mismatch level, with the total number of HLA mismatches (p = 0.0008) and mismatching at the HLA-A locus (p = 0.002) associated with worse survival. Multivariate logistic regression demonstrated that the number of mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality (incremental odds ratios 1.18, p = 0.01, and 1.15, p = 0. 03, respectively). The total number of HLA mismatches predicted 3- and 5-year mortality (incremental odds ratios 1.13 at 3 years, p = 0. 0004, and 1.14 at 5 years, p = 0.0002). However, other covariates such as repeat transplantation, transplantation for congenital heart disease, advanced recipient age, and an early era of transplantation were stronger predictors of mortality. We found no significant association between HLA mismatching and the development of obliterative bronchiolitis, although there was an association between mismatching at the HLA-A locus and acute rejection episodes requiring hospital admission (p = 0.008). We also found no association between mismatching at the HLA-B locus and rejection episodes requiring either hospitalization or the alteration of anti-rejection medications (p = 0.034). CONCLUSION Although the number of HLA mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality and the total number of mismatches predicted 3- and 5-year mortality following lung transplantation, the effect of each covariate was small in this multicenter study of 3,549 patients. Further close follow-up of registry patients is necessary to determine the effect of HLA matching on long-term survival and freedom from obliterative bronchiolitis and rejection following lung transplantation. A prospective study of HLA matching for lung transplantation should not yet be considered in view of the small number of grafts with 2 or fewer mismatches and the modest effect of HLA matching on outcome.