PATIENT OUTCOMES
In 1992, the group at St. Louis Children’s Hospital reported successful lung transplantation for advanced pulmonary hypertension in five children with congenital heart disease 21. An early study published in 1996 examined outcomes in 24 children with pulmonary hypertension for lung transplantation and reported that seven patients did not meet criteria for listing with seven eventually transplanted (8 died, 2 still active on waitlist at time of study) 22. Using both univariate and multivariate analysis (Cox regression), these investigators identified poor functional status at the time of referral defined as New York Heart Association (NYHA) Functional Class III or IV was significantly associated with and predicted death before transplant22. An important conclusion at that time when lung transplantation was in early development as a treatment option for children with PH, especially candidates with advanced pulmonary hypertension, was that late referral was a major risk factor for death on the waiting list and for early complications after implantation. In a subsequent study from St. Louis published in 2002 of 100 patients after lung transplantation for PH, 45 patients with PH had higher early mortality post-transplant than other pulmonary indications for transplant 23. A single-center study of 53 pediatric lung and heart-lung transplant recipients in Hannover, Germany found that IPAH as an indication for transplant did not significantly influence post-transplant mortality in both univariate and multivariate analyses 24.
Investigating the effect of lung transplantation on IPAH, another report from St. Louis examined 26 children (1.6-18.9 years of age) referred for lung transplant with 19 transplanted and seven died on the waitlist25. Median survival for IPAH compared favorably to all pediatric lung transplant recipients, 5.8 vs. 4.5 years25. The analysis by these investigators found that survival was independent of pre-transplant variables, which included age, weight, intravenous inotropes, intravenous pulmonary vasodilators, and right-sided cardiac pressure severity 25. For those children who died on the waitlist, the differences compared to the transplanted group included significantly higher incidence of supra-systemic right heart pressures and hemoptysis25.
A multi-center, retrospective study by the International Pediatric Lung Transplant Collaborative evaluated outcomes of lung transplant for IPAH in 23 children IPAH with median survival to children who underwent heart-lung transplantation for pulmonary vascular disorders and lung transplantation for other indications26. These investigators reported an overall mortality of 4% at 3 months post-transplant with a median survival for children of 45 months (2-123)26.
To summarize our review of the literature of studies investigating lung transplant outcomes for PH in children shows cohort size studies vary from five to 23 children, with one-year post-lung transplant survival rates ranging between 87-100%. Schaellibaum et al 26estimated a 3-year survival of 84%, and Goldstein et al25 reported a 5-year survival of 61%. With limited literature on this important topic in the pediatric population, a recent study was performed using the United Network for Organ Sharing (UNOS) Registry to evaluate outcomes for children with IPAH after lung and heart-lung transplantation 27. Between May 2005 and December 2015, 75 children (10±6 years) underwent transplant for IPAH (47 lung transplant, 18 heart-lung transplant) with 5-year survival rates of 61% for lung transplant and 48% for heart-lung transplant, with no differences found in survival comparing lung to heart-lung transplant (p  = 0.680) 27.
Looking at the most recent report of the ISHLT Registry, children with IPAH had the best post-lung transplant survival as determined by the Kaplan-Meier method (Figure 1 ) compared to other pulmonary diagnoses 28. However, the cohort of children with PH not IPAH had inferior outcomes across all indications for lung transplant (Figure 1 ) 28. Limiting the analysis to conditional one-year post-lung transplant survival, children with IPAH had a median survival of 12.4 years with a signficant improvement in the outucomes for children with PH not IPAH (Figure 2 ) 28.
The overall survival in the lung transplant and heart-lung transplant cohorts was not significantly different from survival among children undergoing lung transplant or heart-lung transplant for other indications, respectively 27. Older age at transplant was associated with significantly lower mortality after transplantation (p  = 0.036), while no clinical factors such as lung allocation score for children > 12 years of age), status 1A listing (heart-lung transplant cohort) and mean pulmonary artery pressure significantly influenced survival 27. In the 54 children who were listed during the study period who did not undergo transplant, 22 died, 14 experienced improvement of their condition, three refused transplant, and four deteriorated so that they were too sick to transplant 27.
Investigating critically ill pediatric patients who underwent lung transplant, another St. Louis study examined outcomes of children regardless of underlying diagnosis requiring preoperative and post-operative ECMO 14. The IPAH group was the largest who received preoperative ECMO and had the best survival rate after lung transplant 14. IPAH trailed only cystic fibrosis as the largest group requiring post-operative ECMO in children who were critically ill after lung transplant, while remaining as the indication with the best survival rate14.