St. Jude Children's Research Hospital investigators have identified childhood cancer survivors who are at increased risk for deteriorating lung health, in part due to the lifesaving bone marrow transplants they underwent years earlier.
The findings underscore the need for long-term monitoring and early intervention, particularly in high-risk survivors, as well as additional health education, researchers said. Among the measures investigators recommend survivors take to protect their lungs are avoiding tobacco smoke and air pollution as well as undergo immunization against influenza and pneumonia.
The study is the most comprehensive look yet at the long-term lung function of childhood leukemia survivors whose treatment included replacing their own blood-producing stem cells, known as hematopoietic stem cells, with healthy donor cells. The work appears in the April 15 edition of the journal Cancer.
The results are expected to help physicians identify leukemia patients at increased risk for post-transplant lung problems and to adjust treatment in preparation for their transplants. The goal is to cure the cancer and minimize long-term treatment complications.
"These survivors are still young; most are still under age 30. In some cases, their lung function has continued to deteriorate, but they do not yet have symptoms of chronic respiratory problems. Our goal is to prevent that from happening," explained Hiroto Inaba, M.D., Ph.D., the study's lead author and assistant member in the St. Jude Department of Oncology.
The good news is that less than 8 percent of survivors in this study had asthma, chronic coughs or other chronic breathing problems. But investigators are concerned about the 64 percent of patients who scored in the abnormal range on at least one of the nine tests that measured how well their lungs were working.
The research comes as more patients are surviving bone marrow transplants. The work also comes amid a continuing debate about how and for how long to monitor lung function in long-term cancer survivors.
Lung complications are a widely recognized side effect of bone marrow transplantation and cancer treatment. Difficulties include problems that affect the ability of the lungs to expand and contract, to replenish the blood's oxygen supply or to hold enough air. Decreased lung function and respiratory illness during childhood are tied to a higher risk of developing chronic obstructive pulmonary disease (COPD) later in life. COPD is a leading U.S. killer.
This study involved 89 St. Jude patients, half of whom had undergone transplants nearly nine or more years earlier when they were ages 6 through 21. Their lung function was routinely tested, allowing researchers to track changes and identify risk factors, such as pre-existing lung problems or age, associated with a decline.
Those at elevated risk for long-term problems include older survivors who were nearly teenagers when they underwent transplants. "This group showed no sign of pulmonary recovery with extended follow-up," Inaba said. "The lung growth and/or repair could be associated with hormonal effects, and this process might not occur efficiently when damage occurs during puberty and adolescence."
Survivors who had abnormal lung function test results prior to transplants and who developed pneumonia or similarly serious respiratory problems in the year following transplants consistently scored worse on tests of their ability to inhale and exhale. The tests check for signs of restricted breathing and poor air flow, which are associated with a range of lung problems.
Others at higher risk for deteriorating lung function were survivors who also faced a greater risk of cancer relapse plus those whose transplant involved donor stem cells collected from circulating blood. Researchers expected a link between these two survivor groups and abnormal lung function because such patients often undergo more intensive cancer treatments and are at greater risk of treatment-related complications.
The research is part of a long-term study of transplant patients. Wing Leung, M.D., Ph.D., is the senior author of this study and principal investigator of the ongoing follow-up study. Leung is St. Jude director of Bone Marrow Transplantation and Cellular Therapy.
The other authors of this paper are Jie Yang, Jianmin Pan, Dennis Stokes, Matthew Krasin, Ashok Sirnivasan, Christine Hartford and Ching-Hon Pui, all of St. Jude.
The work was supported in part by the National Institutes of Health and ALSAC.
- Hiroto Inaba, Jie Yang, Jianmin Pan, Dennis C. Stokes, Matthew J. Krasin, Ashok Srinivasan, Christine M. Hartford, Ching-Hon Pui, Wing Leung. Pulmonary dysfunction in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Cancer, 2010; 116 (8): 2020 DOI: 10.1002/cncr.24897
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