Clinical transplants (Clin Transpl)

Publications in this journal

• Article: Clinical islet transplantation: recent advances in the field.

  Juan S Danobeitia, Luis A Fernandez
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  ABSTRACT: Islet transplantation has emerged as a novel and promising surgical strategy for the treatment of type 1 diabetes mellitus. Almost a decade after the introduction of steroid-free immunosuppression, we have observed steady improvement in the success rate of islet transplantation for the treatment of patients with hypoglycemic unawareness and glycemic lability. However, cell-based therapies face several barriers for widespread success. These barriers include: limited donor pool, innate immune driven inflammation after infusion, acute and chronic immune rejection, and a lack of reliable markers for metabolic follow-up. Recent analysis of data from large multicenter databases suggests that refinements in technical aspects of islet isolation, culture, and immunosuppressive management of the recipient have caused a major and marked improvement observed in recent years in insulin independence rates and metabolic control of the disease. In this review, we highlight the most recent findings published in the literature and focus on important advances in immunosuppression, in vitro beta cell expansion, islet graft assessment, and islet encapsulation, and discuss potential future directions in the field of clinical islet transplantation.
  Clinical transplants 01/2012;
• Article: Liver transplantation at the Ochsner Clinic: programmatic expansion and outcomes improvement.

  Ian C Carmody, Trevor W Reichman, Humberto Bohorquez, Ari J Cohen, David S Bruce, George Therapondos, Nigel Girgrah, Shobha Joshi, George E Loss
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  ABSTRACT: Liver transplantation has become the best and most durable treatment for both acute and chronic liver disease. Over 1400 liver transplants have been performed at the Ochsner Clinic since the first successful transplant in 1987. Since its inception, the program has gone through several changes and advancements and has become one of the largest liver transplant programs in the United States. We have helped evolve steroid sparing immunosuppression and the use of extended criteria, donor organs. Establishment of criteria for the selection of recipients for re-transplantation has resulted in better than expected short and long-term results. Our center has faced the challenge of Hurricane Katrina and overcome it. We have improved steadily in both outcomes and transplants performed. The Ochnser Clinic Liver Transplant program will continue to improve access and outcomes for all patients with liver disease.
  Clinical transplants 01/2012;
• Article: Deceased donor kidney transplantation in the United States from 1988 to 2011: an analysis of the OPTN/UNOS registry.

  Dong Zhu, Matthew J Everly
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  ABSTRACT: In the United States, over 170,000 first solitary deceased donor kidney transplants were reported to the United Network of Organ Sharing registry from 1988 to 2011. The composition of transplant recipients has changed over time. There were notable increases in older patients (31% to 64.5%), non-Caucasian patients (36% to 58%), obese patients (body mass index over 35: 11% to 37%), type II diabetes patients (1% to 28%), and patients with hypertension (17% to 31%). Death with functioning graft was a very important factor in analyzing kidney graft survival. The death-censored graft survival rate could more accurately reflect the relationships between risk factors and survival of kidney grafts. Younger patients, especially those younger than 35, had worse graft survival. Patients with diabetes as the primary disease showed poor graft survival, but the effect was not obvious compared to the majority of other primary diseases. Diabetes, either type I or type II, was a main contributor to patient death. There was notable progress in short-term graft survival over time. Long-term graft survival is still a problem. However, 5-year death-censored graft survival in patients who have survived longer than 1 year has improved by 7.9% from 1993 to today. Delayed graft function could impact both short- and long-term graft survival. Human leukocyte antigen compatibility was a main factor of graft survival. Zero mismatch patients have an 18% better 20-year death-censored graft survival than those with 6 antigen mismatches. Panel reactive antibody (PRA) is also an important factor to graft survival. PRA class I and class II has been reported to UNOS since 2004. PRA class II was slightly more related to graft survival compared to PRA class I.
  Clinical transplants 01/2012;
• Article: Understanding and addressing the humoral immune response in transplant recipients.

  Matthew J Everly
  Clinical transplants 01/2012;
• Article: Liver transplantation at the University of Tennessee Health Science Center in Memphis, Tennessee: the current era 2006-2012.

  Jason M Vanatta, Olexandra Dryn, Teresa Berkley, Sahteesh Nair, James D Eason
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  ABSTRACT: Transplantation at the University of Tennessee Health Science Center in Memphis, which began at the William F. Bowld Hospital and transferred to Methodist University Hospital in 2004, includes pediatric transplantation at LeBonheur Children's Medical Center. The multidisciplinary institute is dedicated to the treatment of patients with end-stage liver and kidney disease and allows those patients access to the integrated expertise of transplant surgeons, hepatologists, and nephrologists. The current, and most successful, era for the program began in 2006, when a change in leadership and clinical vision led to a dramatic increase in clinical activity. These changes have included wider acceptance of potential recipients for liver transplantation and broader use of marginal donor allografts. Streamlined surgical techniques have decreased operative times and have limited blood product usage. Additionally, the program uses an innovative immunosuppression protocol with the world's largest reported series of steroid-free, rabbit anti-thymocyte globulin induction and delayed introduction of tacrolimus in an effort to limit adverse effects of immunosuppression. Such adverse effects may include: infections, post-transplant diabetes mellitus, bone disease, and accelerated fibrosis from recurrent HCV related to steroids and impaired renal function from tacrolimus. These changes have resulted in aggressive donor usage with low complication rates and excellent outcomes.
  Clinical transplants 01/2012;
• Article: Pancreas transplant outcomes for United States and non United States cases as reported to the United Network for Organ Sharing and the International Pancreas Transplant Registry as of December 2011.

  Angelika C Gruessner, Rainer W G Gruessner
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  ABSTRACT: During the last decade, the number of pancreas transplants in the United States (U.S.) has declined by almost 20%, while the number of pancreas transplants performed outside of the U.S. increased. The decline in U.S. numbers is mostly due to the decline in primary pancreas after kidney transplants (PAK). The number of transplants in this category dropped by 50%. The number of simultaneous pancreas/kidney transplants (SPK) only declined slightly. In most cases, pancreas transplants worldwide were performed with a simultaneous kidney transplant (over 90%), which now shows excellent results. In the time period between 2007 and 2011, compared to an earlier era (2002-2006), for transplants in the United States, patient survival at 3 years increased to 93.2%, pancreas graft function to 80%, and kidney function to 87.8%. A significant change could be found in PAK. Three year patient survival increased to 93.6%, and pancreas graft function to 70.5%. With the decline in the number of transplants, a change in donor factors was observed. Especially in solitary transplants, the donors were often younger trauma victims and the pancreas preservation time decreased. Overall, the number of younger recipients decreased.
  Clinical transplants 01/2012;
• Article: Pre-transplant presence of antibodies to MICA and HLA class I or II are associated with an earlier onset of bronchiolitis obliterans syndrome in lung transplant recipients.

  Dennis M Lyu, Todd J Grazia, Alex B Benson, Linda R Cagle, Brian M Freed, Martin R Zamora
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  ABSTRACT: Previous reports using cell-based methods (CDC-AHG) suggest that the presence of pre-transplant HLA Class I and II antibodies are associated with worse survival following lung transplantation. Similarly, antibodies to major histocompatibility complex Class I chain-related gene A (MICA) have been associated with increased graft failure following kidney transplantation. Using highly sensitive solid phase assays, we sought to determine whether the pre-transplant presence of antibodies to MICA or HLA Class I or II predicted short or long-term lung allograft function. Pre-transplant sera screened for antibodies to MICA by Labscreen Single Antigen format and HLA by Luminex (n = 192) revealed antibody presence in 31 (16.1%) and 70 (36.4%) patients, respectively. HLA antibody presence correlated with increased bronchiolitis Obliterans syndrome (BOS)-1 development at 3 years [32.9% (23/70) vs. 18.9% (23/122), p = 0.03] while MICA antibodies correlated with BOS-2 development [32.3% (10/31) vs. 14.9% (24/161), p = 0.02]. The presence of HLA or MICA antibodies correlated with BOS-1 development [32.5% (26/81) vs.18.0% (20/111), p = 0.02] and BOS-2 [24.7% (20/81) vs. 12.6% (14/111), p = 0.02] at 3 years. We found no correlation between antibody presence and episodes of acute cellular rejection or overall survival. We conclude that the presence of pre-transplant HLA or MICA antibodies is associated with earlier BOS onset following lung transplantation.
  Clinical transplants 01/2012;
• Article: Incidences of preformed and de novo donor-specific HLA antibodies and their clinicohistological correlates in the early course of kidney transplantation.

  Yihung Huang, Daniel Ramon, Fu L Luan, Randall Sung, Millie Samaniego
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  ABSTRACT: Our center started routine monitoring of preformed and de novo human leukocyte antigen donor-specific antibodies (DSA) in September 2010 using single antigen beads on the Luminex platform. Recipients with preformed DSA or other high immunological risk factors had serial DSA monitoring at 3, 6, and 12-months posttransplant, and low-risk recipients were screened only at 12-months. Surveillance biopsies were performed at 3, 6, and 12-months post-transplant for all recipients. In addition, for-cause biopsies and DSA testing were performed when clinically indicated for allograft dysfunction. Among 150 adult kidney and kidney/pancreas transplant recipients included in the analysis, 14% had preformed DSA and 7.8% of recipients without preformed DSA developed de novo DSA by 12-months. De novo DSA developed in 25% of recipients on cyclosporine compared to 5% of those on tacrolimus (p = 0.02). The incidences of acute rejection were 34%, 48%, and 70% in recipients with no DSA, with preformed DSA, and with de novo DSA, respectively (p = 0.05). In all recipients with de novo DSA and rejection, the first rejection episode preceded or was concurrent with the emergence of de novo DSA. Despite the difference in rejection incidences, the estimated glomerular filtration rate at 1-year was not significantly different between recipients with or without DSA.
  Clinical transplants 01/2012;
• Article: Cardiac transplantation and mechanical circulatory support at Cleveland Clinic.

  Katherine J Hoercher, Nader Moazami, Randall C Starling
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  ABSTRACT: The cardiac transplantation program at Cleveland Clinic has performed 1,627 adult orthotopic heart transplants, with a current 1-year survival of 96% and a 3-year survival of 82%. The change in the heart allocation system in 2006 has affected our Center by both reducing the number of transplants we perform annually and increasing the percentage of recipients on MCS at the time of transplant. Despite the increased utilization of left ventricular assist devices (LVADs) as a bridge to transplant, we continue to maintain excellent outcomes. The major clinical advances in LVAD technology have allowed us to expand this therapy to ineligible transplant patients, with outcomes that are continually improving. Nevertheless, the field of MCS as permanent therapy is still in its infancy. The number of patients who can benefit from this technology in the U.S. alone is in the thousands, but refinements in patient selection and management are needed to further advance this lifesaving therapy.
  Clinical transplants 01/2012;
• Article: Long-term pancreas allograft survival in simultaneous pancreas-kidney transplantation by era.

  Kayo Waki, Yasuhiko Sugawara, Norihiro Kokudo, Takashi Kadowaki
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  ABSTRACT: Data collected by UNOS from all approved US transplant programs were analyzed. The analysis was based on data for 22,075 diabetic patients who received a pancreas transplant between January 1995 and December 2011. Simultaneous pancreas-kidney (SPK) transplantation was the major therapeutic option for diabetes patients. SPK had better survival than pancreas transplantation alone (PTA) or pancreas-after-kidney (PAK) transplantation. The 5-year pancreas graft survival rate for SPK, PAK, and PTA was 71.3%, 56.6%, and 53.0%, respectively. When long-term SPK pancreas graft survival was examined by transplant era, there was no survival improvement after 1995. The effect of year of transplant was estimated using Cox proportional hazard models. The 5-year pancreas graft survival rate in the eras 1995-1998, 1999-2002 and 2003-2006 were 69.2%, 69.8%, and 72.4%, respectively. For those whose graft survived over one year, the 5-year graft survival rate in those eras was 83.5%, 83.4%, and 85.2%, respectively. The adjusted hazard ratio for overall graft loss by year of transplant for the grafts that survived more than one year in the eras 1999-2002 and 2003-2006 was 1.08 (95% confidence interval [CI], 0.94-1.24) and 0.95 (95% CI, 0.82-1.11), respectively. The survival rate of long-term pancreas grafts remained almost unchanged over time.
  Clinical transplants 01/2012;
• Article: Cell-free DNA as a measure of transplant injury.

  Tara K Sigdel, Minnie M Sarwal
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  ABSTRACT: Organ transplantation is the treatment of choice for patients with end-stage organ failure. The donor organ in the recipient body experiences several immune and non-immune related insults. Improved immunosuppressive drugs and surgical techniques and procedures have helped in the short-term outcome in terms of graft survival. However, in the absence of effective and specific methods of monitoring the transplanted organ, the long-term outcome is still far from satisfactory. Currently available methods are far from optimal as they are either not specific or are invasive. This reality has inspired several groups to look for more effective and semi- or noninvasive methods of diagnosis of transplant injury. Cell-free deoxyribonucleic acid (cfDNA) has been considered a diagnostic biomarker for different health issues including transplant injury. In this review, we have summarized the current status of the utility of cfDNA measurement in the blood and biofluids of solid organ transplant patients as a non-invasive biomarker of allograft injury.
  Clinical transplants 01/2012;
• Article: Factors affecting graft survival within 1-year post-transplantation in heart and lung transplant: an analysis of the OPTN/UNOS registry.

  Hidenori Ohe
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  ABSTRACT: Today, a main focus of the transplant community is the long-term outcomes of lung and heart allograft recipients. However, even early post-transplant survival (within the first post-transplant year) needs improvement, as early graft failure still accounts for many allograft losses. In this chapter, we review the experience of heart and lung transplantation as reported to the Organ Procurement Transplant Network/United Network of Organ Sharing registry and investigate the factors responsible for causing failure in the first post-transplant year. Trends indicate that sicker patients are increasingly being transplanted, thereby limiting improvements in early post-transplant survival. More lung and heart transplant patients are coming to transplant on dialysis. In heart transplant, there is an increase in the number of heart retransplant patients and an increase in patients on extracorporeal membrane oxygenation. For lung transplant, more patients are on a ventilator prior to transplant than in the past 25 years. Given that sicker/riskier patients are now receiving more heart and lung transplants, future studies need to take place to better understand these patients so that they can have the same survival as patients entering transplant with less severe illnesses.
  Clinical transplants 01/2012;
• Article: An analysis of intestinal transplant in the United States.

  Toshiyuki Sasaki
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  ABSTRACT: We performed a retrospective analysis of intestinal transplant patients from United States transplant centers using The Organ Procurement and Transplantation Network/United Network of Organ Sharing (OPTN/UNOS) registry. A total of 2164 intestinal transplants were performed in the United States between 1990 and the end of 2011 and were reported to UNOS. Gender, ethnicity, age at transplant, and original disease had little impact on intestinal allograft survival. We found that a shift in the type of transplant operation [intestine alone, intestine plus liver (I+L), or intestine plus liver and pancreas (I+L+P)] away from I+L, starting in 2005, led to better outcomes. Transplants including the stomach had significantly worse graft survival, and often were performed with the I+L+P method. Even though the outcomes of co-transplant of stomach methods, especially the I+L+P method were shown not to be favorable, in reality, the number of patients receiving the operation is still increasing. Despite the overall improvement in graft survival for intestinal transplants over the last 2 decades, within the 2 decades there is a different story. Graft survival after 2005 compared to seven years before 2005 has not improved. Going forward, there is still significant room for improvement in intestinal transplantation. Based on the improvements over the past 2 decades, there is hope that in the next 2 decades, intestinal transplant will reach the success of renal, cardiac, and liver transplantation.
  Clinical transplants 01/2012;
• Article: Immunosuppression regimens to address alloantibodies in transplant recipients.

  Matthew J Everly
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  ABSTRACT: The purpose of immunosuppression in patients receiving a solid organ transplant is to prevent both acute and chronic rejection, while avoiding the complications of immunodeficiency such as infections and malignancy. Over the last 50 years, immunosuppressive agents have been developed and put into clinical practice to achieve this purpose. The majority of immunosuppressive agents developed during this time have focused on suppressing the T cells. T cell centric immunosuppressive development was a result of the early belief that the T cell caused an allograft to fail. However, emerging evidence from the use of new laboratory techniques has caused the field to reexamine this T cell centric view and focus on the role of the B cells. Today, humoral immunity is thought to be the major cause of allograft loss. As a result, newer immunosuppressive agents are being introduced to deplete the B cell populations in a patient's immune system. However, not all patients may need these immunosuppressive agents. It is only when patients are at high risk for donor specific anti-HLA antibody (DSA) development or when DSAs are present that these immunosuppressive agents may be necessary. This review will focus on the new agents and immunosuppressive regimens that may serve the high-risk subpopulations of solid organ transplant recipients who have or who develop DSA.
  Clinical transplants 01/2012;
• Article: Annual review of transplant: kidney transplant 2012.

  Ty B Dunn, Arthur J Matas
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  ABSTRACT: This chapter highlights contributions to the body of knowledge in kidney transplant for 2012. Specifically, we focus on new developments in alloantibody and chronic allograft injury research. Also, we discuss new immunosuppressant agent trial results. One important new immunosuppressant we cover is belatacept, the first new FDA approved immunosuppressant in many years. Finally, we discuss some key peripheral studies that made 2012 an exciting year in kidney transplant research.
  Clinical transplants 01/2012;
• Article: Changes in IgG subclasses of donor specific anti-HLA antibodies following bortezomib-based therapy for antibody mediated rejection.

  Dinesh Kannabhiran, Matthew J Everly, Jennifer K Walker-McDermott, Sue Tiongko, Rex Friedlander, Prabhakar Putheti, Vijay Sharma, Darshana Dadhania
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  ABSTRACT: The predominant anti-HLA IgG subclass during antibody mediated rejection episodes is IgG1. Class I DSA IgG subclasses respond to single cycle of bortezomib-based therapy more frequently as compared to Class II DSA IgG subclasses. High titer Class II DSA IgG subclasses are less likely to respond to single cycle bortezomib-based therapy. Future studies are needed to determine if the response to bortezomib-based therapy is dependent on the type of DSA and/or the strength of the DSA at the time of antibody mediated rejection episode.
  Clinical transplants 01/2012;
• Article: Flashback to 2002: a retesting and reanalysis suggests an important role of DSA.

  Natalie Reyes
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  ABSTRACT: In 2002, Lee et al. published the first paper describing the effect of HLA antibodies on graft failure in kidney transplant patients, yet remained skeptical as to why some patient grafts were surviving years longer than others while testing positive for HLA antibodies. Through a retesting and reanalysis of these patient samples, we confirm the effect that HLA antibodies had on graft failure. Furthermore, our data suggests an explanation for the discrepancy in patient graft survival lasting significant periods of time with HLA antibodies. Through use of updated technology by Luminex testing, as opposed to the ELISA-based HLA screening used in 2002, we confirm that although patient grafts are surviving significant periods of time with HLA antibodies, these antibodiesare not DSA. Thus, grafts with non-DSA HLA antibodies are able to survive longer than grafts with DSA. The data also proposes that lower DSA MFI values are less detrimental to graft survival as well. Moreover, the recent data also suggests that Class I DSA leads to an even shorter graft survival than Class II only DSA.
  Clinical transplants 01/2012;
• Article: A decade of experience with a single dose of rabbit antithymocyte globulin or alemtuzumab pretreatment for intestinal and multivisceral transplantation.

  Kareem M Abu-Elmagd, Guilherme Costa, Geoffrey J Bond, Kyle Soltys, Lillian Martin, Darlene A Koritsky, Jose R Cunha-Melo, Hiroshi Sogawa, William Irish, Andreas Tzakis, George Mazariegos
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  ABSTRACT: In 2001, we hypothesized that recipient pretreatment with a single-dose of an anti-lymphoid depleting agent followed by tacrolimus monotherapy could promote alloengraftment with minimal long-term immunosuppression. As of November 2010, the protocol was applied to 175 adults: 46 (26%) received rATG (5 mg/kg) and 129 (74%) received alemtuzumab (30 mg). Targeted 12-hour tacrolimus trough levels were 10-15 ng/mL followed by attempts of spaced-dose reduction in selected patients. Steroids were limited to recipients with serum sickness, adrenal insufficiency, and rejection. With a 13% re-transplantation rate, overall 1-, 5-, and 10-year survival was 93%, 70%, and 50% for patients with respective graft survival of 86%, 57%, and 48%. Rejection and infection continued to be leading causes of graft loss. With better patient (p = 0.04) and graft (p = 0.03) survival among alemtuzumab-pretreated patients, cumulative risk of end-stage acute/chronic rejection was similar (p = 0.4) between both antibody cohorts. Tacrolimus spaced-dose reduction was sustainable in 56% of current survivors with 40% of the total population continuing to be steroid-free. However, few of these recipients experienced life-threatening infections and de-novo malignancy. Despite an increase in long-term survival and achievement of partial 'prope' tolerance reported herein, innovative immunosuppressive strategies along with availability of reliable tolerance assays are still required to further improve long-term visceral allograft acceptance.
  Clinical transplants 01/2012;
• Article: Liver transplantation in the MELD era--analysis of the OPTN/UNOS registry.

  Michiko Taniguchi
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  ABSTRACT: OVERVIEW OF THE MODEL FOR END-STAGE LIVER DISEASE (MELD): MELD has been successful in its initial aim of reducing pre-transplant mortality by better organ allocation; at the same time, it generated a new challenge of achieving better posttransplant outcomes by adjusting the hierarchy of allocation to sicker patients. Our analysis of 49,867 adult patients in the MELD era (2002 through 2011) showed a change in the dynamics of the transplant population: the number of patients with higher priority (MELD-exception patients and high-MELD patients) has been progressively increasing while the number of those without priority has remained constant or has been decreasing depending on their disease. The re-transplantation rate has been increasing for high-MELD patients. An increase in number has also observed of major racial groups other than Whites. Overall graft survival-including that for re-transplant-has improved, regardless of MELD levels, during the decade since MELD implementation in 2002. 2. MELD WITH PRIMARY DISEASES: Over the past two decades, the incidence of hepatitis C virus (HCV) has been increasing, and after the inception of MELD, hepatocellular carcinoma (HCC) and non-alcoholic liver disease (NASH) have been progressively increasing. There appears to be a general tendency toward lower graft survival in high-MELD patients in both deceased- and living-donor transplantation. However, this trend differed among the 12 primary diseases, in which significantly lower graft survival was observed in high-MELD patients with alcoholic liver disease (ALD), NASH, autoimmune disorders (AI), HCV, hepatitis B virus (HBV) or non-HCC cancers. Overall, HCV seropositive patients had lower graft survival than HCV seronegative patients. This was also true in each high- and low-MELD group. However, analysis of the primary diseases showed four patterns for the impact of HCV seropositivity related to MELD levels: lower graft survival with anti-HCV regardless of MELD level (with acute hepatic failure, metabolic disorders and HBV); no correlation between the impact of HCV antibodies and MELD levels (with primary biliary cirrhosis [PBC], primary sclerosing cholangitis [PSC] and HCC); lowest graft survival with high MELD scores in the presence of HCV antibodies (with AI, ALD and NASH); and worse survival without HCV (non-HCC cancers). 3. MELD EXCEPTION: Among the primary diseases, the five with a high rate of HCC exception (> 70%) were HCC, HCV, HBV, ALD and AI; the four with a high rate of non-HCC exception (> 60%) were non-HCC cancers, PSC, PBC, and "Others." HCC patients with HCC-exception appear to have derived a greater benefit from transplantation, with better graft survival, than HCC patients without exception. The same beneficial effect of non-HCC exception has been observed with non-HCC cancers, the majority of them cholangiocarcinoma.
  Clinical transplants 01/2012;
• Article: Updates in lung transplantation.

  Martin R Zamora
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  ABSTRACT: The past two years have seen major advances in the lung transplant (LTX) field. In 2010, for the first time, over 3500 lungs were reported to the International Society for Heart and Lung Transplantation Registry. Widening application of extracorporeal life support as a bridge to transplant, or as intra- or postoperative support, has allowed transplantation of critically ill candidates with end-stage pulmonary parenchymal or vascular disease. Ex-vivo lung perfusion expanded the donor pool, allowing transplant teams time to evaluate non-ideal lungs or those from donation after cardiac death donors. While increased activity involving higher risk recipients and donors has resulted in acceptable survival, chronic rejection, or bronchiolitis obliterans syndrome, still limits long-term survival. Emerging histopathologic, radiographic, and physiologic evidence has led to the recognition that BOS is not the only form of chronic lung failure and to the development of a new classification system: chronic lung allograft dysfunction (CLAD). Both allo- and autoimmune mechanisms, as well as nonimmune mechanisms, have been identified in CLAD development. Immunosuppressive and immune modulating agents, recently evaluated in randomized controlled trials, have shown promise in CLAD therapy. This review will outline some of the key advances in LTX in the past year.
  Clinical transplants 01/2012;