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.