Background

End-stage lung disease may derive from different etiologies. The most common indications for lung transplantation are chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, a₁-antitrypsin deficiency, and idiopathic pulmonary arterial hypertension.

Before consideration for transplant, patients should be receiving maximal medical therapy, including oxygen supplementation, or surgical options, such as lung volume reduction surgery for chronic obstructive pulmonary disease. Lung or lobar lung transplantation is an option for patients with end-stage lung disease despite these measures.

A lung transplant refers to single-lung or double-lung replacement. In a single-lung transplant, only one lung from a deceased donor is provided to the recipient. In a double-lung transplant, both the recipient's lungs are removed and replaced by the donor's lungs. In a lobar transplant, a lobe of the donor's lung is excised, sized appropriately for the recipient's thoracic dimensions, and transplanted. Donors for lobar transplant have primarily been living-related donors, with one lobe obtained from each of two donors (generally friends or family members) in cases for which bilateral transplantation is required. There are also cases of cadaver lobe transplants.

Since 2005, potential recipients have been ranked according to the Lung Allocation Score.^1, Patients 12 years of age and older receive a score between 1 and 100 based on predicted survival after transplantation reduced by predicted survival on the waiting list; the Lung Allocation Score takes into consideration the patient's disease and clinical parameters. In 2010, a simple priority system was implemented for children younger than age 12 years. Under this system, children younger than 12 years with respiratory lung failure and/or pulmonary hypertension who meet criteria are considered "priority 1" and all other candidates in the age group are considered "priority 2". A lung review board has the authority to adjust scores on appeal for adults and children.

Regulatory Status

Lung transplantation is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration.

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation Title 21, parts 1270 and 1271. Lung transplants are included in these regulations.

Related Policies

• Heart/Lung Transplant (Policy #100 in the Surgery Section)
• Outpatient Pulmonary Rehabilitation (Policy #009 in the Treatment Section)

1. Known current malignancy, including metastatic cancer
2. Recent malignancy with high risk of recurrence
3. Untreated systemic infection making immunosuppression unsafe, including chronic infection
4. Other irreversible end-stage disease not attributed to lung disease
5. History of cancer with a moderate risk of recurrence
6. Systemic disease that could be exacerbated by immunosuppression
7. Psychosocial conditions or chemical dependency affecting ability to adhere to therapy

8. Coronary artery disease not amenable to percutaneous intervention or bypass grafting, or associated with significant impairment of left ventricular function*; or
9. Colonization with highly resistant or highly virulent bacteria, fungi, or mycobacteria.

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Lung Transplantation for End-stage Pulmonary Disease

Clinical Context and Therapy Purpose

The purpose of lung transplantation in patients who have end-stage pulmonary disease is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does lung transplantation improve the net health outcome in patients with end-stage pulmonary disease?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals with end-stage pulmonary disease.

Before consideration for transplant, patients should be receiving maximal medical therapy, including oxygen supplementation, or surgical options, such as lung volume reduction surgery for chronic obstructive pulmonary disease (COPD).

Interventions

The therapy being considered is a lung transplant. Lung transplantation is provided in a hospital setting with specialized staff and equipment to perform the surgical procedure and provide postsurgical intensive care.

Comparators

The following practice is currently being used to make decisions about reducing the risk of end-stage pulmonary disease: medical management, such as maximal medical therapy, including oxygen supplementation, or surgical options, such as lung volume reduction surgery for COPD. Comparators are performed and managed by a physician in a hospital setting or by the patient (oxygen supplementation).

Outcomes

The general outcomes of interest are overall survival (OS) and treatment-related adverse events (e.g., immunosuppression, graft failure, surgical complications, infections, cardiovascular complications, malignancies). Short-term follow-up ranges from immediate post-surgery to 30 days post-transplantation; lifelong follow-up (10 years or more given current survival data) is necessary due to immunosuppression drugs and risk of graft failure. See the Potential Contraindications section for detailed discussion.

Registry Studies

Paraskeva et al (2018) analyzed survival rates of adolescent lung transplant recipients using data from the International Society for Heart and Lung Transplantation Registry.^2, Patients between 10 and 24 years old represented 9% of the registry data (n=2319) and they were compared with both old and young cohorts. OS in the adolescent cohort was 65% at 3 years, which was similar to that observed in adults between 50 and 65 years of age, but significantly lower than 3-year survival rate among the pediatric subgroup (73%; p=0.006) or adults 25 to 34 years old (75%; p<0.001) and 35 to 49 years old (71%; p<0.001). Within the adolescent group, patients between 15 and 19 years of age had the poorest survival rates at 3 years (59%) compared with 10- to 14-year old patients (73%) and 20- to 24-year old year patients (66%,) (both p<0.001). The registry study was biased toward the inclusion of North American data and potential data entry errors or missing data. There were no data reported on the cause of mortality, differences in regimens, or rates of graft dysfunction between the groups.

One of the International Society for Heart and Lung Transplantation registries contained data from 49453 adult recipients who received lung transplantation (including lung retransplantation) through June 30, 2015, at 134 transplant centers.^3, A total of 55795 lung transplants were performed, of which 53522 (95.9%) were primary transplants and 2273 (4.1%) were retransplants. The overall median survival of patients who underwent lung transplantation was 5.8 years. Estimated unadjusted survival rates were 89% at 3 months, 80% at 1 year, 65% at 5 years, and 32% at 10 years. Patients who survived a year after primary transplantation had a median survival of eight years. In the first 30 days after transplantation, the major reported causes of mortality were graft failure (24.5%) and non-cytomegalovirus (non-CMV) infections (19.1%) while non-CMV infections became the major cause of death for the remainder of the first year. Beyond the first year, the most commonly reported causes of mortality were obstructive bronchiolitis/bronchiolitis obliterans syndrome, graft failure, and non-CMV infections. Beyond 10 years posttransplant, the major causes of mortality were obstructive bronchiolitis/bronchiolitis obliterans syndrome (21.5%), non-CMV infection (16.5%), and nonlymphoma malignancy (13.7%).

Through 2014, another International Society for Heart and Lung Transplantation registry contained a total of 2229 pediatric lung transplants.^4, Most transplants (73%) were done in children between the ages of 11 and 17 years. Median survival in children who underwent lung transplantation was 5.4 years, similar to survival in adults (mean survival, 5.7 years). However, median survival in children was lower (2.2 years) than in adults (5.6 years) for single-lung transplants.

Thabut et al (2010) reported on a comparison between patients undergoing single- and double-lung transplantation for idiopathic pulmonary fibrosis.^5, A retrospective review was conducted of 3327 patients with data in the United Network for Organ Sharing registry. More patients underwent single-lung transplant (64.5%) compared with double-lung transplant (35.5%). Median survival time was greater for the double-lung group at 5.2 years (95% confidence interval [CI], 4.3 to 6.7 years) than the single-lung group at 3.8 years (95% CI, 3.6 to 4.1 years; p<0.001). After adjusting for baseline differences, however, survival times did not differ statistically. The authors concluded that OS did not differ between the groups: single-lung transplants offered improved short-term survival but a reduced long-term benefit, whereas double-lung transplant increased short-term harm but was associated with a long-term survival benefit. Black et al (2014) reported on Lung Allocation Score (LAS) and single- vs double-lung transplant in 8778 patients (8050 had a LAS <75 vs 728 had a LAS³ 75).^6, A significant decrease in survival was seen in single-lung transplant patients with a high LAS compared with double-lung transplant patients with a high LAS, even though operative morbidity was higher (p<0.001).

Yusen et al (2010) reviewed the effect of the LAS on lung transplantation by comparing statistics for the period before and after its implementation in 2005.^7, Other independent changes in clinical practice, which may affect outcomes over the same period of time, include variation in immunosuppressive regimens, an increased supply of donor lungs, changes in diagnostic mix, and increased consideration of older recipients. Deaths on the waiting list declined following the implementation of the LAS system, from approximately 500 per 5000 patients to 300 per 5000 patients. However, it is expected that the implementation of LAS affected patient characteristics of transplant applicants. One-year survival posttransplantation did not improve after implementation of the LAS system: patient survival data before and after were approximately 83%. Long-term survival data are not yet available. Shafii et al (2014) reported on a retrospective evaluation of the LAS and mortality in 537 adults wait-listed for lung transplantation and 426 who underwent primary lung transplantation between 2005 and 2010.^8, Patients on the waitlist who had a higher LAS had a higher mortality rate (p<0.001). In the highest quartile of LAS (range, 47-95), within 1 year of listing, there was a 75% mortality rate. Higher LAS was also associated with early posttransplant survival (p=0.05) but not late posttransplant survival (p=0.4). When other predictive factors of early mortality were taken into account, pretransplant LAS was not independently related to posttransplant mortality (p=0.12).

Section Summary: Lung Transplant for End-Stage Pulmonary Disease

International registry data on a large number of patients receiving lung transplantation (>50000) found relatively high patient survival rates (89% at 3 months, 80% at 1 year, 65% at 5 years, 32% at 10 years). In patients who survived a year, median survival was eight years. After adjusting for potential confounding factors, survival did not differ significantly after single- or double-lung transplant. A subgroup analysis of an international registry study found decreased survival for adolescent patients, especially between 15 and 19 years of age, who received lung transplantation but the study was limited by inclusion bias and lack of data on mortality, differences in treatment regimens, and rates of graft dysfunction.

Lobar Lung Transplantation for End-Stage Pulmonary Disease

Clinical Context and Therapy Purpose

The purpose of lobar lung transplantation in patients who have end-stage pulmonary disease is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does lobar lung transplantation improve the net health outcome in patients with end-stage pulmonary disease?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals with end-stage pulmonary disease.

Before consideration for transplant, patients should be receiving maximal medical therapy, including oxygen supplementation, or surgical options, such as lung volume reduction surgery for COPD .

Interventions

The therapy being considered is a lobar lung transplant. Lobar lung transplantation is provided in a hospital setting with specialized staff and equipment to perform the surgical procedure and provide postsurgical intensive care.

Date (2011) stated that, as of 2011, approximately 400 living-donor lobar lung transplants had been performed worldwide.^9, Procedures in the U. S. decreased after 2005 due to changes in the lung allocation system. Date (2011) reported that size matching between donor and recipient is important and that, to some extent, size mismatching (oversized or undersized grafts) can be overcome by adjusting surgical technique.

Comparators

The following practice is currently being used to make decisions about end-stage pulmonary disease: medical management, such as maximal medical therapy, including oxygen supplementation, or surgical options, such as lung volume reduction surgery for COPD . Comparators are performed and managed by a physician in a hospital setting or by the patient (oxygen supplementation).

Outcomes

The general outcomes of interest are OS and treatment-related adverse events (e.g., immunosuppression, graft failure, surgical complications, infections, cardiovascular complications, malignancies). See the Potential Contraindications section for detailed discussion. Short-term follow-up ranges from immediate post-surgery to 30 days post-transplantation; lifelong follow-up (10 years or more given current survival data) is necessary due to immunosuppression drugs and risk of graft failure.

Systematic Reviews

Eberlein et al (2017) reported on a systematic review of studies on lobar lung transplantation from deceased donors.^10, Reviewers identified nine studies comparing outcomes after lobar lung or lung transplant, all of which were single-center retrospective cohort studies. Seven studies were conducted in Europe and one in Australia and one in North America. One-year survival reported in individual studies ranged from 50% to 100% after lobar lung transplant and from 72% to 88% after conventional lung transplant. In a pooled analysis of data from 8 studies, lobar lung transplant recipients (n=284) had a significantly higher risk of 1-year mortality than lung transplant recipients (n=2777) (relative risk, 1.85; 95% CI, 1.52 to 2.25; p<0.001; I²=0%).

Case Series

Several studies have reported on lobar lung transplantation from living donors. For example, Barr et al (2005) reported on living-donor lobar lung transplants in the U. S.^11, Ninety patients were adults and 43 were children. The primary indication for transplantation (86%) was cystic fibrosis. At the time of transplantation, 67% of patients were hospitalized, and 20% were ventilator dependent. Overall recipient actutimes survival rates at 1, 3, and 5 years were 70%, 54%, and 45%, respectively. There was no statistically significant difference in actutimes survival between adults and children who underwent transplantation. Moreover, survival rates were similar to the general population of lung transplant recipients. The authors also reported that rates of postoperative pulmonary function in patients surviving more than three months posttransplant were comparable with rates in cadaveric lung transplant recipients.

Date et al (2015) reported on a retrospective study comparing 42 living-donor lobar lung transplants with 37 cadaveric lung transplants.^12, Survival rates at 1 and 3 years did not differ significantly between groups (89.7% and 86.1% vs 88.3% and 83.1%, respectively, p=0.55), despite living-donor lobar lung transplant patients having poorer health status preoperatively. For a program in Japan, Date et al (2012) reported on 14 critically ill patients (10 children, 4 adults) who had undergone single living-donor lobar lung transplants.^13, Patients were followed for a mean 45 months. The 3-year survival rate was 70%, and the 5-year survival was 56%. Severe graft dysfunction occurred in four patients. Mean forced vital capacity was lower in patients experiencing severe graft dysfunction (54.5%) than in the other patients (66.5%). The authors postulated that this suggested size mismatching in patients with severe graft dysfunction.

Slama et al (2014) reported on a comparison of outcomes in 138 cadaveric lobar lung transplants (for size discrepancies) with 778 patients who received cadaveric whole-lung transplants, 239 of whom had downsizing by wedge resection of the right middle lobe and/or the left lingula.^14, Survival rates in the lobar lung transplant group at 1 and 5 years were 65.1% and 54.9% vs 84.8% and 65.1% in the whole-lung and downsized by wedge resection group (p<0.001). The lobar lung transplantation group experienced significantly inferior early postoperative outcomes, but in patients who were successfully discharged, survival rates were similar to standard lung transplantation (p=0.168).

Section Summary: Lung Lobar Transplant for End-Stage Pulmonary Disease

There is less data on lung lobar transplants than on whole-lung transplants. The available data reported in case series have suggested reasonably similar survival outcomes, and lung lobar transplants may be the only option for patients unable to wait for a whole-lung. A 2017 systematic review found 1-year survival rates ranging from 50% to 100%.

Lung or Lobar Retransplantation When Meeting Criteria for a Lung Transplant

Clinical Context and Therapy Purpose

The purpose of lung retransplantation in patients who have had a prior lung or lobar transplant and who meet criteria for a lung transplant is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does lung or lobar retransplantation improve the net health outcome in patients with a failed prior lung or lobar transplant?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals receiving a lung retransplant after failing a prior lung or lobar transplant and who would be eligible for a lung transplant.

Interventions

The therapy being considered is lung or lobar retransplantation. Lobar lung retransplantation is provided in a hospital setting with specialized staff and equipment to perform the surgical procedure and provide postsurgical intensive care.

Comparators

The following practice is currently being used to make decisions about treating those whose lung or lobar transplant has failed and would still be considered as meeting eligibility criteria for an initial transplant: medical management, such as maximal medical therapy, including oxygen supplementation, or surgical options, such as lung volume reduction surgery for COPD . Comparators are performed and managed by a physician in a hospital setting or by the patient (oxygen supplementation).

Outcomes

The general outcomes of interest are OS and treatment-related adverse events (e.g., immunosuppression, graft failure, surgical complications, infections, cardiovascular complications, malignancies). See the Potential Contraindications section for detailed discussion. Short-term follow-up ranges from immediate post-surgery to 30 days post-transplantation; lifelong follow-up.

Case Series

Registry data and case series have demonstrated favorable outcomes with lung retransplantation in certain populations, such as in patients who meet criteria for initial lung transplantation.^15,16,17,

Biswas Roy et al (2018) published a single-center retrospective study comparing survival outcomes in 29 patients who received retransplantation for chronic lung allograft dysfunction with 390 patients receiving a primary lung transplant at the same center.^18, Patients receiving retransplantation had significantly higher use of extracorporeal membrane oxygenation support for severe primary graft dysfunction (p=0.019) and underwent cardiopulmonary bypass and re-exploration for bleeding (p=0.019) more frequently than patients receiving primary transplantation (p=0.029). At 1-year follow-up, 89.7% of primary transplant patients were living, as were 89.2% of retransplantation patients. At 5-year follow-up, a greater percentage of the retransplantation group had survived, compared with the primary transplantation group (64.3% vs 58.2%), although the difference was not statistically significant. While high LAS and extended hospital length of stay were both identified as independent mortality risk factors, retransplantation was not (hazard ratio, 1.58; 95% CI, 0.31 to 8.08; p=0.58). Study limitations included its single-center, retrospective design, the potential selection bias for younger patients, and the small size of the retransplantation group. Further, follow-up data at three and five years were incomplete for some patients and patients who were refused retransplantation were not considered in the analyses. However, for appropriately selected patients, retransplantation after chronic lung allograft dysfunction resulted in 1- and 5-year survival rates comparable to those seen after primary lung transplantation.

Registry Studies

The Organ Procurement and Transplantation Network has reported data on lung transplants performed between 2008 and 2015.^19, Patient survival rates after repeat transplants were lower than primary transplants but a substantial number of patients survived. For example, 1-year patient survival was 87.9% (95% CI, 87.2% to 88.7%) after a primary lung transplant and 76% (95% CI, 70.9% to 80.2%) after a repeat transplant. Five-year patient survival rates were 55.9% (54.7% to 57.2%) after a primary lung transplant and 33.8% (28.5 to 39.1%) after repeat transplant.

The International Society for Heart and Lung Transplantation Registry contained data on 2273 retransplantation patients performed through June 2015 (4.4% of lung transplantations).^3, The major causes of death in the first 30 days after retransplantation were graft failure and non-CMV infection, followed by multiorgan failure, cardiovascular causes, and technical factors related to the transplant procedure. Beyond the first year, the most commonly reported causes of mortality were obstructive bronchiolitis/bronchiolitis obliterans, graft failure, and non-CMV infections.

Section Summary: Lung or Lobar Retransplant When Meeting Criteria for a Lung Transplant

Data from registries and case series have found favorable outcomes with lung retransplantation in patients who meet criteria for initial lung transplantation. Given the exceedingly poor survival without retransplantation of patients who have exhausted other treatments, evidence of a moderate level of posttransplant survival is sufficient to suggest treatment efficacy in this patient population.

Potential Contraindications (Applies to all Indications above)

Malignancy

Malignancies are common after lung transplantation, with 21% and 40% of patients reporting 1 or more malignancies at 5 and 10 years posttransplantation, respectively.^15, Skin cancer occurred most frequently, and lymphoproliferative disorders were the malignancies most associated with morbidity posttransplantation.

Human Immunodeficiency Virus Infection

Current Organ Procurement and Transplantation Network policy permits HIV-positive transplant candidates.^20,

The British HIV Association and the British Transplantation Society (2017) updated their guidelines on kidney transplantation in patients with HIV disease.^21, These criteria may be extrapolated to other organs:

• Adherent with treatment, particularly antiretroviral therapy
• Cluster of Differentiation 4 count greater than 100 cells/mL (ideally >200 cells/mL) for at least 3 months
• Undetectable HIV viremia (<50 HIV-1 RNA copies/mL) for at least 6 months
• No opportunistic infections for at least six months
• No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.

Infection with Burkholderia cenocepaciais associated with increased mortality in some transplant centers. A factor that may be considered when evaluating the overall risk of transplant survival.^22, Two articles have evaluated the impact of infection with various species of Burkholderia on outcomes for lung transplantation for cystic fibrosis. In a study by Murray et al (2008), multivariate Cox survival models assessing hazard ratios were applied to 1026 lung transplant candidates and 528 transplant recipients.^23, Of the transplant recipients, 88 were infected with Burkholderia. Among transplant recipients infected with B. cenocepacia, only those infected with nonepidemic strains (n=11) had significantly greater posttransplant mortality than uninfected patients (hazard ratio, 2.52; 95% CI, 1.04 to 6.12; p=0.04). Transplant recipients infected with Burkholderia gladioli (n=14) also had significantly greater posttransplant mortality than uninfected patients (hazard ratio, 2.23; 95% CI, 1.05 to 4.74; p=0.04). When adjustments for specific species or strains were included, the LAS of Burkholderia multivorans-infected transplant candidates were comparable with uninfected candidate scores, and scores for patients infected with nonepidemic B. cenocepacia or B. gladioli were lower. In a smaller study of 22 patients colonized with Burkholderia cepaciacomplex who underwent lung transplantation in 2 French centers, Boussaud et al (2008) reported that the risk of death by univariate analysis was significantly higher for the 8 patients infected with B. cenocepacia than for the other 14 colonized patients (11 of whom had B. multivorans).^24,

An analysis of international registry data by Yusen et al (2016) found that non-CMV infection is a major cause of mortality within 30 days of a lung transplant in adults.^3, A total of 655 (19%) of 3424 deaths after transplants between 1990 and 2015 were due to non-CMV infection. Only 3 (0.1%) of the deaths were due to CMV infection.

Summary of Evidence

For individuals who have end-stage pulmonary disease who receive a lung transplant, the evidence includes case series and registry studies. The relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. International registry data on a large number of patients receiving lung transplantation (>50000) found relatively high patient survival rates, especially among those who survived the first year posttransplant. After adjusting for potential confounding factors, survival did not differ significantly after single- or double-lung transplant. Lung transplantation may be the only option for some patients with end-stage lung disease. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have end-stage pulmonary disease who receive a lobar lung transplant, the evidence includes case series and systematic reviews. The relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. There is less data on lung lobar transplants than on whole-lung transplants, but several case series have reported reasonably similar survival outcomes between the procedures, and lung lobar transplants may be the only option for patients unable to wait for a whole-lung transplant. A 2017 systematic review found 1-year survival rates in available published studies ranging from 50% to 100%. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have a prior lung or lobar transplant who meet criteria for a lung transplant who receive a lung or lobar lung retransplant, the evidence includes case series and registry studies. The relevant outcomes are OS, change in disease status, treatment-related mortality and morbidity. Data from registries and case series have found favorable outcomes with lung retransplantation in patients who meet criteria for initial lung transplantation. Given the exceedingly poor survival prognosis without retransplantation of patients who have exhausted other treatments, the evidence of a moderate level of posttransplant survival may be considered sufficient in this patient population. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

SUPPLEMENTAL INFORMATION

Practice Guidelines and Position Statements

International Society for Heart and Lung Transplantation

Initial Transplant

The International Society for Heart and Lung Transplantation (2006) published consensus-based guidelines on the selection of lung transplant candidates.^25, The guidelines stated that:

"Lung transplantation is now a generally accepted therapy for the management of a wide range of severe lung disorders, with evidence supporting the quality of life and survival benefit for lung transplant recipients. However, the number of donor organs available remains far fewer than the number of patients with end-stage lung disease who might potentially benefit from the procedure. It is of primary importance, therefore, to optimize the use of this resource, such that the selection of patients who receive a transplant represents those with realistic prospects of favorable long-term outcomes..."

In 2014, these recommendations were updated for pulmonary vascular disease.^26, The Society recommended including a transplant list for patients with New York Heart Association class III or IV disease, despite three months or more of combination therapy. Additional clinical indications included a cardiac index of less than 2 L/min/m², a mean right atrial pressure of greater than 15 mm Hg, and a 6-minute walk distance of fewer than 350 meters. Also, recommended for transplant listing were significant hemoptysis, pericardial effusion, or signs of progressive right heart failure. Other common indications for lung transplant include interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, and chronic obstructive pulmonary disease.

Retransplant

Lung retransplantation was addressed briefly, with the consensus statement noting that "criteria for candidate selection for lung retransplantation generally mirror the criteria used for selection for initial lung transplantation."

American Thoracic Society et al

Evidence-based recommendations from the American Thoracic Society and 3 international cardiac societies were published in 2011.^27, For appropriately selected patients with idiopathic pulmonary fibrosis, the group et al recommended lung transplantation (strong recommendation, low-quality evidence)

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently ongoing and unpublished trials that might influence this policy are listed in Table 1.

Table 1. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT00905463	Analysis of Prognosis and Patients Reported Outcomes in Lung Transplant Candidates	272	Mar 2022
NCT00177918	Prospective Evaluations of Infectious Complication in Lung Transplant Recipients	600	Dec 2025

NCT: national clinical trial.]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Lung and Lobar Lung Transplant
Lung Transplant
Lung Transplantation
Transplant, Lung
Transplantation, Lung
Lobar Lung Transplant
Lobar Lung Transplantation
Transplant, Lobar Lung
Transplantation, Lobar Lung

References:
1. Organ Procurement and Transplantation Network (OPTN). Policy 10: Allocation of Lungs. 2018; https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf. Accessed August 29, 2019.

2. Paraskeva MA, Edwards LB, Levvey B, et al. Outcomes of adolescent recipients after lung transplantation: An analysis of the International Society for Heart and Lung Transplantation Registry. J Heart Lung Transplant. Feb 17 2018;37(3):323-331. PMID 28320631.

3. Yusen RD, Edwards LB, Dipchand AI, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart-Lung Transplant Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. Oct 2016;35(10):1170-1184. PMID 27772669.

4. Goldfarb SB, Levvey BJ, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Nineteenth Pediatric Lung and Heart-Lung Transplantation Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. Oct 2016;35(10):1196-1205. PMID 27772671.

5. Thabut G, Christie JD, Kremers WK, et al. Survival differences following lung transplantation among US transplant centers. JAMA. Jul 07 2010;304(1):53-60. PMID 20606149.

6. Black MC, Trivedi J, Schumer EM, et al. Double lung transplants have significantly improved survival compared with single lung transplants in high lung allocation score patients. Ann Thorac Surg. Nov 2014;98(5):1737-1741. PMID 25110334.

7. Yusen RD, Shearon TH, Qian Y, et al. Lung transplantation in the United States, 1999-2008. Am J Transplant. Apr 2010;10(4 Pt 2):1047-1068. PMID 20420652.

8. Shafii AE, Mason DP, Brown CR, et al. Too high for transplantation? Single-center analysis of the lung allocation score. Ann Thorac Surg. Nov 2014;98(5):1730-1736. PMID 25218678.

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Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

32850
32851
32852
32853
32854
32855
32856

S2060
S2061