Lung Transplantation and Survival in Children with Cystic Fibrosis

Armen Hareyan's picture
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Recent study from University of Utah says that lung transplant may not be helpful to children with cystic fibrosis.

The effects of lung transplantation on the survival and quality of life in children with cystic fibrosis are uncertain.

We used data from the U.S. Cystic Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation Network to identify children with cystic fibrosis who were on the waiting list for lung transplantation during the period from 1992 through 2002. We performed proportional-hazards survival modeling, using multiple clinically relevant covariates that were available before the children were on the waiting list and the interactions of these covariates with lung transplantation as a time-dependent covariate. The data were insufficient in quality and quantity for a retrospective quality-of-life analysis.

A total of 248 of the 514 children on the waiting list underwent lung transplantation in the United States during the period from 1992 through 2002. Proportional-hazards modeling identified four variables besides transplantation that were associated with changes in survival. Burkholderia cepacia infection decreased survival, regardless of whether the patient underwent transplantation. A diagnosis of diabetes before the patient was placed on the waiting list decreased survival while the patient was on the waiting list but did not decrease survival after transplantation, whereas older age did not affect waiting-list survival but decreased post-transplantation survival. Staphylococcus aureus infection increased waiting-list survival but decreased post-transplantation survival. Using age, diabetes status, and S. aureus infection status as covariates, we estimated the effect of transplantation on survival for each patient group, expressed as a hazard factor of less than 1 for a benefit and more than 1 for a risk of harm. Five patients had a significant estimated benefit, 315 patients had a significant risk of harm, 76 patients had an insignificant benefit, and 118 patients had an insignificant risk of harm associated with lung transplantation.

Our analyses estimated clearly improved survival for only 5 of 514 patients on the waiting list for lung transplantation. Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality-of-life benefit from lung transplantation. - NEJM

Pediatric Pulmonary Expert Comments on Study of Lung Transplants for Cystic Fibrosis

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Commenting on a study of lung transplantation for children with cystic fibrosis, a leading pediatric pulmonologist calls the study "startling" in an editorial in this week's New England Journal of Medicine that accompanies the study.

Julian Allen, M.D., who holds the Robert Gerard Morse Endowed Chair in Pediatric Pulmonary Medicine at The Children's Hospital of Philadelphia, analyzed the study by a University of Utah research team, which found that cystic fibrosis (CF) patients younger than age 18 did not survive longer after a lung transplant than CF patients who did not receive a lung transplant.

In contrast to a previous study by the same researchers, led by Theodore Liou, M.D., which found a survival advantage for adult transplant recipients when the predicted five-year survival rate without transplantation was 30 percent or worse, the new study found no lower threshold at which transplantation provided better survival in children -- a finding that Allen called surprising.

"The study's results make it clear that physicians must be more judicious than ever in referring children with cystic fibrosis for lung transplantation, with careful consideration of the severity of the child's illness," said Allen. He said that cystic fibrosis centers must provide appropriate social and psychological support to help families make the best choice for their children.

Allen added that it is possible that a lung transplant may improve a patient's quality of life, as the current study had only limited information on that question. He urged that future studies of lung transplantation in CF patients ought to carefully measure quality of life as well as measuring how closely patients adhere to post-transplant medical treatments.

One fact that may change future results, said Allen, is that the new organ allocation system, initiated in 2005, takes into account the severity of a patient's illness, in addition to other factors such as the length of time a patient remains on the waiting list for a donated organ. The system in place when the study was performed allocated lungs based only on the duration of the patient's wait.

Allen's co-author on the editorial is Gary Visner, M.D., a transplant surgeon formerly at The Children's Hospital of Philadelphia, and now at Children's Hospital, Boston.

The Cystic Fibrosis Center at The Children's Hospital of Philadelphia provides comprehensive multidisciplinary care for children with CF, and has been recognized as a model program by the Cystic Fibrosis Foundation. One of the largest programs for cystic fibrosis in the U.S., it also offers lung transplantation among its treatments. The Center staff works in conjunction with the University of Pennsylvania Health System, which provides a program for adult CF patients.

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