Incidence Of Post-transplant Malignancies Research Articles

P8.017: Post Renal Transplant Malignancy: Single Center Experience

Introduction: Kidney transplantation in patients with end-stage kidney disease improves quality of life and is associated with an increase in survival rates. Malignancies are one of the three major causes of renal recipient´s death with a functioning graft after cardiovascular diseases and infections. The incidence of post-transplant malignancies (PTM) varies between 2.0 and 30%, depending on the characteristics of the population. Aim of study: The aim of this study is to analyze the incidence of PTM in solid organs and organs with hematological origin, excluding non-melanoma skin tumors, in kidney transplant recipients, as well as to evaluate factors associated with global survival in a single center. Materials and methods: Retrospective observational cohort study. Data of 2,146 medical records that underwent kidney transplantation from deceased or living donors between 2000 and 2015 were analyzed. Results: The cumulative incidence of PTM de novo was 5.5% with a mean follow-up of 9 years. During this period, 118 cases of PTM were reported, 103 in solid organ and 15 with hematological origin. The most frequent malignancy was kidney cancer, followed by malignant lung, prostate cancer and nonHodgkin lymphoma. Patients who developed PTM had a lower overall survival compared to those without malignancy (12.2 vs 18.2 years, p <0.001), and for recipients with PTM of hematological origin, mortality was higher in relation to those with solid organ neoplasms (p = 0.03). PTM is an independent risk factor for death in the post-transplant period (HR = 4.75, 95% CI: 3.52 –6.43; p <0.001), as well as the age of the recipient and donor above 60 years. Conclusion: The incidence of renal PTM was 5.5%, with renal neoplasia being the most frequent. PTM was an independent prognostic factor for the patient’s death, being that of hematological origin associated with higher mortality.

P1769POST TRANSPLANT MALIGNANCY - OUR EXPERIENCE

Abstract Background and Aims Cancer is now increasingly recognized as a major cause of death among patients especially after kidney transplantation. Malignancy represent a major burden in transplantation medicine. The Incidence is about 12 fold higher for PTLD and 3.5 fold higher for non-cutaneous malignancy compare to age-matched population. The increased risk is multifactorial and attributed to oncogenic viruses, immunosuppression and altered T cell immunity. In the era of longer graft survival and with the introduction of more potent immunosuppressive medication, malignancy represents a major burden. The incidence of malignancy after renal transplantation is 3 to 5 times higher. Incidence is higher in transplant patients even when compared to patients on hemodialysis. Aim: We attempted to assess the incidence of post-transplant malignancies in patients who underwent renal transplantation at our centre, along with studying the presentation, type and other factors affecting their development. Method We analysed data retrospectively from 626patients who underwent renal transplantation atour centre from January 2003 to September 2018.Pre transplant history, post transplant course including duration on hemodialysis, immunosuppression details and duration till diagnosis of malignancies were collected. Details regarding type of malignancy, histopathology, staging and treatment given and outcome were collected. Results Number of transplant recipient-626. The total number of patients with malignancy is 12. Incidence of malignancy posttransplant is 1.9%.Male-7 and female-6.One patient was detected with 2 malignanciesduring her post transplant period. The types of malignancies encountered were Conclusion The incidence of malignancy – 1.9%.Probable reason for decreased incidence of malignancy is the decreased immunosuppression needed by South Asian people. The most common malignancy was solid organ tumour; tongue being the most common organ. Most common histological variant is squamous cell carcinoma.Non-Hodgkin is more common than Hodgkin. Incidence of malignancy is low. Decision regarding cancer screening should be made on individual basis.

SAT-358 THE INCIDENCE OF MALIGNANCY AND ITS RELATED FACTORS IN PATIENTS UNDERGOING KIDNEY TRANSPLANTATION

Renal transplantation is considered as the treatment of choice for patients with ESRD. The underlying causes of death among renal transplant recipients have changed from early immunologic and nonimmunological failure to cardiovascular disease and malignancy. In this study we evaluated the incidence of malignancy and its related factors in renal transplant patients in Razi Hospital of Rasht over a period of 10 years. In this retrospective study, 549 patients who underwent renal transplantation surgery in Razi Hospital between 2008 and 2019 were studied. Demographic and clinical characteristics of patients and other required information were recorded in a checklist. Required patient information was obtained from the case of pre and post-transplant and outpatient follow-up. In this study, it was found that only the patient's age at the time of renal transplantation in recipients of intervention has a confounding and additive role in incidence of malignancy after transplantation (P=0.0001). It was also found that there was no statistically significant relationship between sex of patients, current smoking status, smoking history, family history of malignancy, number of transplants, post-transplant survival, sun exposure, transplant rejection history, patient follow-up, occupational status, the use of daclizumab (Zenapax ATG) induction and incidence of malignancy after kidney transplantation. Estimates of standardized incidence ratio showed that the incidence of malignancy in kidney transplant recipients was 26.9 higher than the incidence rate in Guilan province and 21.7 higher than the incidence of malignancy in the country. The incidence rate of cancer in kidney transplant patients is 26.9 times higher than Guilan province rate (95% CI: 19.7-35.9) and 21.7 times higher than national rate (95% CI: 15.9-28.9). In this study, the incidence rate of cancer is 792 per 100000-person year. In this study, it was found that only the patient's age at the time of kidney transplantation has a confounding and increasing role in the incidence of post-transplant malignancy. It has also been shown that the most common malignancy in these patients is non-melanoma skin malignancy and Kaposi's sarcoma comes in second.

573P The incidence of post-transplant malignancies in kidney transplantation recipients in King Chulalongkorn Memorial Hospital: A single institute with 44 year’s experience in Thailand

573P The incidence of post-transplant malignancies in kidney transplantation recipients in King Chulalongkorn Memorial Hospital: A single institute with 44 year’s experience in Thailand

Incidence of Post-transplant Malignancy after Renal Transplantation: Single Center Analysis

Background: Immunosuppression after kidney transplantation is associated with increased risk of malignancy, which has become the second most common cause of death among kidney transplant recipients. In this review, we report the incidence of malignancies after kidney transplantation in a single center and evaluate the incidence, characteristics, relationship to immunosuppressive drugs and discuss what clinicians must consider during a follow-up of patients after kidney transplantation. Methods: Between May 1978 and September 2013, a total of 748 kidney transplant patients who were able to undergo a follow-up process through electronic medical records were enrolled in this retrospective cohort study to determine the potential incidence and types of malignancy that may occur after kidney transplantation and the associated impact on patients and graft survival. Results: Among 748 patients, 63 cases of malignancy appeared in 54 patients (7.2%). Gastrointestinal cancer (12 cases, 19%) and post-transplant lymphoproliferative disorder (12 cases, 19%) were the two most common types of malignancy. The second most common type of malignancy was urinary tract malignancy in 10 patients. Two different types of malignancy were diagnosed in nine patients during our follow-up. The overall graft survival in malignancy patients was better, which may mean that malignancy did not affect the overall graft loss. Conclusions: Clinicians should be aware of the incidence of malignancy in transplant patients and perform routine examinations for early detection of malignancy.

Pattern of Malignancy in Living Donor Kidney Transplant Recipients.

Background: Differences exist in the pattern of malignancy in different population groups. Most reports of malignancy have come from deceased donor transplant recipients from developed countries. Material and methods: In a retrospective analysis of 2000 patients who underwent live renal transplantation last 30 yrs (1983-2013), age, sex, type of immunosuppression, interval between transplantation and diagnosis of cancer was recorded. Results: Thirty-nine (1.95%) patients (27 M:12 F) developed 43 malignancies including 29(67.4%) with PTLD and 15 (34.8%) had other carcinomas. Five patients had dual malignancy. Mean age: 40.2 years (range 21 to 62 yrs), mean interval post-transplant was 57.9 mo (3 to 144). Of these 29 patients (1.45%) with PTLD (22M,7 F) 22 (75.8%) patients developed NHL and 7 patients (24.2%) had myeloma. Diagnosis was made by biopsy of the involved organ in 21 patients (72.4%) and aspiration cytology in 5 patients (17.2%). In 3 patients, the diagnosis was made only at autopsy. Only 5 patients (17.2%) developed PTLD within a year of transplantation. Twelve patients developed PTLD 1-5 years and 12 patients 5-10 years after transplantation. Organ involvement was extra-nodal in 18 patients (82%). Thirteen (59%) patients had disseminated disease and 9 (36.4%) had localized involvement of a single organ (brain-3, liver-1, allograft-1, perigraft node-1, retroperitoneal lymph nodes-3). Infiltration of graft was noted in 2 patients. Patients with plasma cell myeloma presented with backache, pathological fracture, unexplained anaemia or graft dysfunction. PTLD was of B cell origin in 20 cases (70%). CD 20 staining was done in 10 recent cases, of which 8 stained positive. Of the 26 patients diagnosed during life, 20 (69%) died within 1 year of diagnosis. All the other cancers were seen after 1 yr of transplant. All the patients with above cancers were managed by stopping antiproliferatives and continuing steroids and managed surgically. Initial immunosuppressive therapy consisted of cyclosporine (CsA), azathioprine(Aza) and prednisolone in 27 patients, only Aza and prednisolone in 8 patients, tacrolimus (Tac), Aza and prednisolone in 2 and Tac, MMF and prednisolone in 2 patients. Conclusion: Although the incidence of post-transplant malignancies was low, careful monitoring of renal transplant recipients for malignancies is required due to the poor response to treatment.

Epidemiology of post-transplant malignancy in Chinese renal transplant recipients: a single-center experience and literature review.

This study investigated the incidence and types of post-transplant malignancy in Chinese renal transplant recipients and the risk factors associated with malignancy. Data from 3,462 patients who underwent renal transplantation at Beijing Friendship Hospital were combined with data from 26 previous reports describing malignancy rates in 27,170 Chinese renal transplant recipients. Between 1974 and 2014, 179/3,462 (5.17 %) patients who underwent renal transplantation at our center developed malignancy. The most common site of malignancy was the urinary system, and the most common type was urothelial transitional cell carcinoma. Combined data from our center and previous reports showed malignancy in 671 (2.19 %) Chinese renal transplant recipients. The ten most common malignancies were urothelial transitional cell carcinoma (n = 283), hepatocellular carcinoma (n = 68), gastrointestinal cancer (n = 63), renal cell carcinoma (n = 42), lymphoma (n = 42), lung cancer (n = 28), breast cancer (n = 19), skin cancer (n = 18), Kaposi's sarcoma (n = 12), and cervical cancer (n = 10). The incidence of post-transplant malignancy in renal transplant recipients was lower in China than the reported rates in other countries, and the most common sites of malignancy were the urinary and digestive system. The relative frequency of malignancy sites differed between northern and southern China. Renal transplant recipients on long-term immunosuppressive therapy should receive careful follow-up, including annual or biannual screening for malignancy in high-risk individuals.

Overall Incidence of Posttransplant Malignancies and Clinicopathologic Features of Thyroid Cancer in Renal Allograft Recipients; 40-years Single Center's Experience

Overall Incidence of Posttransplant Malignancies and Clinicopathologic Features of Thyroid Cancer in Renal Allograft Recipients; 40-years Single Center's Experience

Breast cancer after kidney transplantation: a single institution review

BackgroundImprovements in immunosuppression have resulted in long life expectancy of kidney transplants. Unfortunately, the incidence of post-transplant malignancy (PTM) is increasing. The aim of this study was to evaluate the nature and stage-specific prognosis of post-transplant breast cancer (PTBC) compared with breast cancer in the general population, and to suggest optimal treatment strategies.MethodsA database of 2,139 consecutive kidney transplant patients was reviewed;11 of the patients developed breast cancer. These 11 PTBC cases underwent operations between 1999 and 2011. Next, 2,554 breast cancer patients treated in the same period were reviewed. Kaplan–Meier curves and the log-rank test were used to assess stage-specific survival of breast cancer in our hospital.ResultsIn total, 142 cases experienced post-transplant malignancy (PTM; 6.6%) and 11 (0.5%) developed PTBC. No one required an adjusted dose of immunosuppressive agent. Two stage III patients died. For all breast cancer patients, 5-year survival by stage was 97.7% for stage I, 92.9% for stage II, 78.6% for stage III, and 49.9% for stage IV. The 5-year survival for expected stage III-specific survival was 66.7% and no significant statistical difference was seen compared to that of the total breast cancer patients (P = 0.213).ConclusionsThe prognosis of PTBC was comparable to that of the general population. These results suggest that the use of immunosuppressants per se does not adversely affect breast cancer.

Malignancy after Heart Transplantation: A Systematic Review of the Incidence and Risk Factors Compared with Other Solid Organ Transplants

The continuing improvements in heart transplant (HT) outcomes have increased the risk of developing complications, such as post-transplant malignancy (PTM). Our aims are to focus on the incidence and risk factors in PTM in heart transplant recipients and compare with other solid organ transplantations (SOT). In 20 publications analyzed, the incidence of PTM in individuals undergoing SOT ranges from 4.1% to 16.3%, representing a 2 to 4-fold overall increased risk of cancer over the general population. It seems that the incidence of cancer risk is probably higher in HT than SOT recipients. Cutaneous carcinomas, post-transplant lymphoproliferative disorders (PTLD), carcinomas of lung and liver represent the four most common malignancies in this specific post-transplant population. It is also evident that the risk factors in developing PTM in HT recipients include immunosuppressive therapy, viral infection, older age, tobacco smoking, and unprotected sun-exposure. Transplant physicians should probably increase the threshold of attention for cancer risk surveillance in addition to anti-rejection therapy for graft survivals.

Posttransplant Malignancies in Solid Organ Adult Recipients

De novo posttransplant malignancy (PTM) is a serious complication of transplantation. Incidences may vary among solid organ transplantations (SOTs) and may take to particular screening recommendations and posttransplantation care. Adult recipients, from the U.S. Organ Procurement Transplant Network/United Network for Organ Sharing database (data as of September 3, 2010), of a primary kidney transplantation (KT), liver transplantation (LT), heart transplantation (HT) or lung transplantation (LuT) performed in the United States between 1999 and 2008 were selected. Multiple-organ recipients and those whose grafts failed within 2 weeks after transplantation were excluded. The incidence of PTM (in 1000 person-years) was estimated using the Kaplan-Meier product-limit method and compared with SOT and the general population. The cohort included 193,905 recipients (123,380 KT; 43,106 LT; 16511 HT; and 10,908 LuT). PTM incidence was 8.03, 11.0, 14.3, and 19.8 in KT, LT, HT, and LuT, respectively. In general, PTM recipients were 3 to 5 years older, mostly whites, and are males in all SOTs. In KT, the type of cancer with the highest incidence was posttransplant lymphoproliferative disorder (PTLD, 1.58%), followed by lung (1.12%), prostate (0.82%), and kidney (0.79%) cancers; in LT, PTLD (2.44%), lung and bronchial (2.18%), primary hepatic (0.91%), and prostate (0.88%) cancers; in HT, lung and bronchial (3.24%) and prostate (3.07%) cancers, and PTLD (2.24%); and in LuT, lung and bronchial cancers (5.94%), PTLD (5.72%), and colorectal cancer (1.38%). PTLD, Kaposi sarcoma, and lung and bronchial cancers were increased in all SOTs, when compared with an older (55- to 59-year-old) population. Cancer incidence is different among solid organ transplantations, and ratios may be higher than those in the 55- to 59-year-old population.

Incidence of Post Transplant Malignancies in Renal Transplant Recipients: Single Center Experience

The incidence of malignancy in transplant recipients is known to be higher than that in the general population. However, the types of malignancies vary geographically, and the relative risks for malignancy in transplant recipients are different, compared with that of the general population. We investigated the incidence and characteristics of malignancies after renal transplantation in a single center analysis. A total of 2740 renal recipients who underwent transplantation between June 1990 and Dec 2010 were enrolled in this retrospective study. During the follow-up period, 153 post-transplant malignancies were developed in 148 of 2740 patients. 24 of 148 patients were died from malignancy. The cumulative incidence of cancer at 1, 5, 10, 15, and 20 years was 0.58%, 3.1%, 7.2%, 13.2 %, and 25% respectively. The post-transplant malignancies were detected from 3 to 226 months after transplantation, with a mean duration of 78.1 ± 55.0 months. Post-transplant lymhoproliferative disorder (PTLD) [18 (11.7%)] was the most common malignancy. Risk of Kaposi sarcoma, PTLD, skin cancer, uterine cancer, urologic malignancy, biliary tract cancer, and breast cancer were more than 10-times higher in KT recipients than general population. In conclusion, the incidence of post transplant malignancy increased rapidly with laps of time following transplantation and related with duration of immunosuppressant exposure. A more vigorous cancer surveillance program should be adapted to detect early cancer in early stage especially in long term follow up patients.

Low incidence of malignancy in heart-transplant recipients in Taiwan: an update and comparison with kidney-transplant recipients

Malignancy is the leading cause of death among heart-transplant recipients. There is a higher incidence of post-transplant malignancy in heart-transplant recipients than in kidney-transplant recipients. This study sought to assess the incidence of malignancy in heart-transplant recipients in Taiwan. This is a retrospective chart review. From 1987 to 2008, 291 patients who underwent heart transplantation and survived for more than 1 month were enrolled. Seventeen patients (5.8%) developed de novo malignancies including skin cancers (three), post-transplant lymphoproliferative diseases (seven) and solid-organ malignancies (seven). Solid-organ malignancies affected prostate, liver, urinary bladder, kidney, lung, larynx, pancreas and brain in seven patients. Malignancy was responsible for 7% and 13% of all death for heart-transplant recipients who lived for more than 1 year and more than 5 years. The cumulative incidence of 1.03% at 1 year, 4.2% at 5 years and 8.1% at 10 years in our patients was much lower than the incidences reported in the multicentre registry of the International Society for the Heart and Lung Transplantation and in the Western series. The incidence was especially low for skin cancers. Compared with previous reports of kidney-transplant recipients in Taiwan, the incidence of post-transplant malignancy was not significantly increased. The incidence of post-transplant malignancy was low in Chinese heart-transplant recipients compared with heart-transplant recipients in Western countries. It resulted from a relative rarity of skin cancers in the Chinese population.

High Incidence of Transitional Cell Carcinoma in Kidney Transplant Recipients in Eastern Taiwan

Objective A higher incidence of urinary tract transitional cell carcinoma (TCC) has been reported in both long-term hemodialysis patients and kidney transplant (KTX) recipients in Taiwan than in other countries. Herein, we report a high incidence of urinary tract malignancy, especially TCC, in KTX recipients in eastern Taiwan. Patients and Methods We retrospectively reviewed the medical records, clinical data, and outcomes of 102 KTX recipients in Tzu Chi General Hospital from 1992 to 2008. Overall graft and patient survival, incidence of posttransplant malignancy, and cumulative incidence of TCC after KTX were investigated. Results During a mean follow-up of 45.5 ± 38.5 months after KTX, 12 malignancies were diagnosed in nine recipients. The incidence of post-transplant malignancy in all recipients was 8.2%. TCC was diagnosed in four patients, and all these patients presented with painless gross hematuria and hydronephrosis. Three patients had tumor involvement in the upper urinary tract. TCC occurred at a mean of 56 ± 70.7 months after KTX, and the cumulative incidence of TCC was 4.7% in the first 3 years after transplant. Only one patient with triple cancer died of disseminated cholangiocarcinoma of the distal common bile duct during a mean follow-up of 15.8 ± 9.5 months after surgical treatment of TCC. Conclusion KTX recipients are at extremely high risk of TCC in eastern Taiwan, with an incidence of 3.9%. The cardinal signs of posttransplant TCC are painless gross hematuria and hydronephrosis of the native kidney. Careful, timely urological screening in KTX recipients warrants early diagnosis and good prognosis after aggressive surgical management.

Induction Immunosuppressive Therapy in Renal Transplantation: Does Basiliximab Make the Difference?

The optimal prophylactic induction immunosuppressive therapy to prevent renal transplant rejection remains controversial. Recently, basiliximab efficiency has been reported in several studies. We sought to evaluate the efficiency of induction immunosuppressive therapy with basiliximab in renal transplantation in our unit based upon the acute rejection rate, patient and graft survivals, first hospital admission length, and incidence of infectious or malignant complications during 4 years of follow-up. We retrospectively evaluated the outcome of two groups of renal transplant recipients treated with triple immunosuppressive therapy (cyclosporine, mycophenolate mofetil, and prednisolone) without (group 1, 149 patients) or with (group 2, 104 patients) induction immunosuppression with basiliximab. The two groups did not differ in demographic characteristics, number of hypersensitized patients, cold ischemia time, or donor age. The group receiving basiliximab displayed a significantly lower acute rejection rate (7.6% vs 24%, P = .001) and shorter first hospital admission (14.4 ± 8 vs 19.5 ± 11 days). There was no difference in graft or patient survival, death due to sepsis, or incidence of posttransplant malignancies. Although there was no difference in graft or patient survival, immunosuppressive induction therapy with basiliximab yielded a significant reduction in the acute rejection rate.

TOR INHIBITOR MAINTENANCE IMMUNOSUPPRESSION IS ASSOCIATED WITH A REDUCED INCIDENCE OF POST-TRANSPLANT MALIGNANCIES

O79* Aims: Post-transplant malignancies are a major cause of morbidity and death associated with maintenance immunosuppression following organ transplantation. Calcineurin inhibitors have been shown to promote neoplastic progression both in vitro and in immunodeficient mice while TOR inhibitors (sirolimus [SRL] and everolimus [RAD]) have been shown to inhibit neoplastic progression through several proposed mechanisms. The aim of this study was to determine if TOR inhibitors influence malignancies in human transplant recipients. Methods: Retrospective univariate and multivariate Cox regression analyses for the development of any malignancy (skin, solid, PTLD) were conducted on 36,224 deceased donor primary solitary kidney transplant recipients during 7/1/96-6/30/02, with at least 8 days of graft survival. Recipients were categorized into one of two maintenance discharge immunosuppression regimens: Group 1 (N=32,902) cyclosporine (CYA) or tacrolimus (TAC) without either sirolimus (SRL) or everolimus (RAD) and Group 2 (N=3,322) received either SRL or RAD in combination with CYA or TAC. The majority of the TOR inhibitors were SRL (N=3,242). Because post-transplant cancer incidence is time dependent, solid malignancies within 100 days after transplantation were excluded, and records > 730 days were censored to allow comparable follow-up time between treatment groups. Results of the Cox analysis are presented as relative risk (RR) of any cancer, the 95% confidence limit, and the p-value. Results: Univariate results showed that 27 malignancies were reported in 27 (0.81%) of the 3,322 recipients in the SRL/RAD group, and 618 tumors were reported in 577 (1.75%) of the 32,902 recipients in the CYA/TAC group (p <0.0001). There were 2 PTLD, 4 skin, and 11 solid tumors in the SRL/RAD group and 133 PTLD, 202 skin, and 283 solid tumors in the CYA/TAC group. The results of the Cox regression model are shown in the table.FigureRisk factors not significantly affecting risk of malignancy included induction therapy, recipient peak PRA level, and HLA mismatch level. Conclusions: Post-transplant maintenance immunosuppression with TOR inhibitors is associated with a significant reduction in the incidence of post-transplant malignancies.

Lung transplantation in children.

To report the authors' experience with pediatric lung transplantation (LTX) to provide an overview of patients selected for this procedure and their outcomes. Pediatric LTX differs from adults in many ways, including recipient size, indications, posttransplant care, and rehabilitation. Two hundred seven isolated lung transplants on 190 children under the age of 18 years were performed from 1990 to the present. This represents the single largest series of lung transplants in children in the world. Thirty-two patients were less than 1 year of age, 22 were 1 to 5 years of age, 32 were 5 to 10 years of age, and 121 were 10 to 18 years old. The groups by major diagnostic category were cystic fibrosis (n = 89), pulmonary vascular disease (n = 44), bronchiolitis obliterans (n = 21), pulmonary alveolar proteinosis (n = 12), pulmonary fibrosis (n = 15), and other (n = 26). The average age at the time of transplant was 9.5 +/- 5.9 years (range 36 days to 18 years). Survival by Kaplan-Meier analysis was 77% at 1 year, 62% at 3 years, and 55% at 5 years. There was no significant difference in survival according to primary diagnosis leading to LTX or age at LTX. There were 25 early (<60 days) and 61 late deaths. The most common cause of early deaths was graft failure (13/25, 52%). The most common causes of late death were bronchiolitis obliterans (35/61, 57%), infection (13/61, 21%), and posttransplant malignancies (11/61, 18%). No patient died of acute rejection. In those surviving greater than 3 months (mean follow-up 3.5 years, range 3 months to 11 years), the overall rate of occurrence of bronchiolitis obliterans was 46% (80/175) and the overall incidence of posttransplant malignancies was 24/175 (14%). Major risk factors for the development of bronchiolitis obliterans were age older than 3 years, more than two episodes of acute rejection, and organ ischemic time longer than 180 minutes. In children, LTX is a high-risk but viable treatment for end-stage pulmonary parenchymal and vascular disease. The major hurdle to overcome in long-term survival is bronchiolitis obliterans.