Survivors of stem-cell transplantation for blood cancers can expect to be nearly as healthy 10 years later as adults who have never had a transplant, according to a recent Hutchinson Center study.
The study, published in the Sept. 20, 2006 edition of the Journal of Clinical Oncology and funded by the National Cancer Institute, is the first of its kind to follow a large group of patients from before their transplant through the 10-year post-transplant period.
"In many areas of health, our survivors are indistinguishable from case-matched controls who participated in this study and had not had a transplant," said lead investigator Dr. Karen Syrjala, head of the Center's Biobehavorial Sciences group.
For example, the study found that transplant survivors and case-matched controls reported similar rates of hospitalization and outpatient medical visits. They had similar rates of diseases and conditions such as asthma, diabetes, high blood pressure, high cholesterol, osteoporosis and hypothyroidism. Comparable numbers in each group were married, were working full-time or defined their jobs as homemakers. The groups had similar psychological health, marital satisfaction and employment. There were no differences between the two groups in terms of smoking, diet or exercise habits.
Some differences remain
On the other hand, Syrjala and colleagues also found that transplant survivors reported more medical problems than controls did. Survivors had a higher incidence of musculoskeletal complaints, such as stiffness and cramping. Almost twice as many survivors as controls had moderate to severe musculoskeletal problems, even after excluding those with avascular necrosis (AVN) or hip replacement due to high-dose steroid therapy for chronic graft-vs-host disease (GVHD). Survivors also reported more sexual issues and increased urinary frequency and leaking than the control group. Nearly one-third of female survivors reported balding or thinning hair. Nineteen percent of survivors reported moderate to severe residual problems from chronic GVHD. Long-term survivors also had higher use rates of antidepressant and anti-anxiety medications. Reported rates of depression were about the same in both groups, but anxiety was marginally higher in transplant survivors.
The study found evidence that physical and social limitations persisted in long-term survivors; study participants reported post-transplant impacts on their social and emotional function as well as more physical limitations. Survivors also indicated somewhat greater fatigue and increased concern about their cognitive ability. There was no difference in the number of patients vs. controls who currently had health insurance, but 24 percent of transplant survivors reported having been denied insurance coverage at some time after the transplant.
In all, survivors reported an average of 3.5 medical problems vs. 1.7 for controls, even though survivors and controls had similar rates of hospitalization and outpatient medical visits.
Syrjala and colleagues made an important and positive observation among 10 percent of the survivors who had suffered relapse and were in complete remission at the time of the study — they were no different from patients who had never relapsed.
"The fact that some patients can relapse and still have healthy, full lives 10 years later and look like everyone else who has gone through a transplant without relapse is really good news," she said. "In the past, relapse after a transplant was always thought to be a very bad sign for quality of life."
The study also indicated no difference in rates of bone thinning (osteoporosis) and hypothyroidism — two problems one would expect to find in transplant survivors. This could indicate that transplant survivors and their physicians aren't aware of the increased risk and aren't screening for these diseases. The researchers urged primary-care providers to screen routinely for these problems, which might otherwise be considered relevant primarily to older populations. Primary-care providers also should screen for new cancers, which occur at increased frequency in transplant survivors.
All of the patients in the study were transplanted at the Hutchinson Center between March 1987 and March 1990. Patients undergoing both allogeneic and autologous transplants were eligible. More than 400 patients consented to the study. After 10 years, 137 of the remaining 147 transplant survivors and an equal number of controls completed a self-report of medical problems, symptoms and health-related quality of life. Most of those surveyed had been treated for leukemia or lymphoma. More than three-quarters received donor cells from a matched relative. There was an almost equal split between males and females. The median age at transplant of the patients surveyed was 36.4 years. Survivors were asked to nominate a case-matched control participant, ideally a biologic sibling of the same gender and within five years of age.
This type of match control was found for 60 percent of the patients. The study survey asked participants about 85 diseases and symptoms and to indicate whether they had these problems now, whether the diseases or symptoms were ever a problem during the past 10 years or were no longer a problem. Twenty-seven diseases or conditions emerged as the most prevalent and were included in the final analysis. The diseases or conditions ranged from asthma to second cancers.
"Ten years after hematopoietic cell transplantation, the 137 survivors were indistinguishable from case-matched controls in many areas of health and psychosocial functioning, although survivors reported a greater number of medical problems and greater limitations in sexuality, insurance and social, emotional and physical roles," the study authors wrote. "Some of these problems are known to be associated with hematopoietic-cell transplantation, while others have not been recognized previously as late concerns."
This type of research is important, Syrjala said, because the number of long-term survivors of stem-cell transplantation is increasing rapidly. For example, patients with acute leukemia or chronic myeloid leukemia who survive without recurrent malignancy for two years after allogeneic stem-cell transplantation (the infusion of stem cells from a donor) have an 89 percent probability of surviving for five or more years. More than 45,000 people worldwide receive stem-cell transplants each year.
The study is important also because information on 10-year survivorship has been sparse. "Although research on late effects has increased, systematic information has not been available to guide oncologists or primary-care physicians in routine monitoring and management of health-care needs after 10 years in this population," the authors wrote.