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Pre-transplant lung function is predictive of survival following pediatric bone marrow transplantation
Jill P Ginsberg1, Richard Aplenc, Joseph McDonough
1Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Insights
Pre-transplant lung function, particularly diffusion capacity, is often abnormal in pediatric bone marrow transplant (BMT) recipients. Pre-BMT lung function predicts post-transplant survival and morbidity.
Area of Science:
- Pediatric Hematology/Oncology
- Pulmonary Medicine
- Transplant Medicine
Background:
- Pulmonary toxicity is a significant cause of mortality post-bone marrow transplant (BMT).
- Most data on post-BMT lung function is from adults; pediatric data is limited.
- Pre-transplant lung function predicts outcomes in adult BMT recipients.
Purpose of the Study:
- To investigate the predictive value of pre-transplant pulmonary function tests (PFTs) for post-transplant outcomes in pediatric BMT patients.
- To assess changes in lung function following BMT in children.
Main Methods:
- Retrospective analysis of PFTs from pediatric patients undergoing myeloablative BMT at two major children's hospitals.
- Evaluation of pre- and post-transplant lung function parameters, including diffusing capacity.
- Calculation of a Lung Function Score (LFS) combining FEV1 and DLCO.
Main Results:
- A significant proportion (25%) of pediatric BMT patients had abnormal pre-transplant diffusion capacity.
- All lung function parameters declined post-BMT, with slow recovery over years.
- The LFS was strongly associated with post-transplant survival, with increased mortality risk for lower scores.
Conclusions:
- Pre-transplant lung function, especially diffusing capacity, is frequently abnormal in pediatric BMT candidates.
- Lung function typically decreases after BMT and may remain abnormal long-term.
- Pre-transplant lung function is a critical predictor of survival in pediatric BMT recipients.
Background:
Pulmonary toxicity is well described in recipients of bone marrow transplants (BMT), and accounts for a sizeable proportion of post-transplant mortality. The majority of the data on post-transplant pulmonary function is from adults, although several small pediatric case series have been described. In adults, pre-transplant lung function has been predictive of post-transplant respiratory failure and mortality. This use of pulmonary function testing, that is, for pre-transplant risk counseling, is novel but has never been applied to pediatric patients. We hypothesized that in children, as in adults, pre-transplant pulmonary function would also be predictive of outcome post-transplantation morbidity.
Procedure:
Retrospective database analysis of pulmonary function tests of patients undergoing first myeloablative BMT at two large children's hospitals.
Results:
Two hundred seventy-three subjects had at least one pre-transplant PFT, and 317 subjects had at least one post-transplant PFT available for analysis. While the majority of patients had normal or mildly reduced pre-transplant flows and lung volume, 25% had moderately or severely reduced diffusion. All lung function parameters decreased post-transplant with a slow improvement over ensuing years. The Lung Function Score, a combined measurement of FEV(1) and DLCO, was highly associated with post-transplant survival. Hazard ratios for mortality (compared to the best LFS) ranged from 1.654 to 2.454.
Conclusions:
Lung function prior to bone marrow transplant, especially diffusing capacity, is frequently abnormal. Lung function frequently decreases shortly post-transplant and tends to improve over time, but frequently remains abnormal even years after transplant. Post-transplant survival is related to pre-transplant lung function.
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