The burden of chronic health problems experienced by patients after receiving hematopoietic cell transplants (HCTs) is substantial and warrants long-term follow-up care. That is the conclusion of a study in the October 28th issue of Blood (2010;116:3129-3139) led by Smita Bhatia, MD, MPH, Professor and the Ruth Ziegler Chair in Population Sciences at City of Hope Comprehensive Cancer Center.
“The data indicate that in those who have survived 10 years from transplant, the probability of developing severe or life-threatening chronic health conditions exceeds 30 percent,” she said.
“The past two decades have seen a significant improvement in survival among patients undergoing hematopoietic cell transplants, with an attendant increase in the number of long-term survivors.” While transplant physicians are well aware of the fact that these patients are at risk for long-term complications, “this study is the first to quantify morbidity in these survivors.”
Nelson Chao, MD, Division Chief of Cellular Therapy/Bone Marrow Transplantation at Duke Comprehensive Cancer Center, agreed, saying that although the overall conclusions of the study are already fairly well known by transplanters, it is still useful to have all the information documented and published.
Dr. Bhatia and her colleagues (first author was Can-Lan Sun, PhD) examined the prevalence and severity of chronic health conditions reported by 1,022 patients who had undergone hematopoietic cell transplants (HCT) at City of Hope or the University of Minnesota between 1974 and 1998 for hematologic malignancy or severe aplastic anemia and who had survived at least two years. Researchers used 309 nearest-age siblings as a non-cancer comparison group.
Overall, the survivors were twice as likely as their siblings to develop a chronic condition and three and a half times as likely to develop severe or life-threatening conditions.
About 66% of HCT patients experienced at least one chronic health condition, a little more than 50% reported at least two, and 34.5% reported three or more. In comparison, nearly 39% of siblings reported at least one chronic health condition, while only 15% had at least two and 5.5% had three or more.
Additionally, about 18% of HCT survivors reported Grade 3 (severe) or 4 (life-threatening) health conditions such as cardiovascular, gastrointestinal, and musculoskeletal complications and new malignancies, compared with about 8% of siblings.
The cumulative 10-year incidence of a chronic health condition among HCT survivors was 59%, while for severe or life-threatening conditions or death due to chronic health conditions it was nearly 35%.
About 53% of allogeneic HCT survivors had chronic graft-versus-host disease (GvHD).
However, the researchers found no significant difference in overall health complications for allogeneic HCT recipients with and without chronic GvHD, commented Scott Rowley, MD, Director of the Blood and Marrow Stem Cell Transplantation Program at John Theurer Cancer Center at Hackensack (NJ) University Medical Center. Specifically, the prevalence of any chronic health condition was 73% versus 68% in patients with and without GvHD.
While this was true when chronic health conditions of all levels of severity were taken into consideration, the 10-year cumulative incidence of chronic health conditions that were Grades 3 to 5 (lead to death) was 50% in those with chronic GvHD vs 26% in those without, noted Dr. Bhatia.
Furthermore, the prevalence of two or more chronic health conditions was significantly higher in allogeneic HCT recipients with chronic GvHD than in those without (63% vs 49%, respectively). The prevalence of three or more health conditions was also significant, (48% vs 23%, respectively).
Dr. Chao noted that one limitation of the data is that of the 1,468 HCT survivors successfully contacted by the researchers, only about 70% participated. “Are the [other] 30% the ones who are really sick and don't want to bother with the survey or are they cured and back in society and don't want to participate? Depending on the answer, the data might be skewed somewhat,” he said.
Dr. Rowley said that overall, the study was well done, but that an increase in health consequences appears to have occurred over a span of two decades, while treatment 10 years ago for these patients was completely different than it was 20 years ago. With changes in the primary treatment of cancers, “we must remain vigilant for changes in long-term health consequences,” he said.
Additionally, he said, because there were only two centers included in the study, the specific regimens used there could be more or less likely related to subsequent health consequences and may be different from the treatments at other centers.
How to Address Chronic Health Problems
Based on the health problems of HCT survivors, “there needs to be a key change in practice for managing these patients,” said Dr. Bhatia. “We need to ensure that we provide these patients with close follow-up for long periods of time so we can screen them for complications and decrease the severity of these conditions.”
Consequently, the oncology community needs to establish multidisciplinary long-term follow-up programs that are well versed in the unique needs of the survivors, said Dr. Bhatia. Additionally, the study showed that the rate of these complications does not plateau over time, meaning that the need for ongoing care is that much more critical.
The paper also helps illustrate the depth of the problem of chronic GvHD contributing to long-term health conditions in patients, said Dr. Chao, adding that many cancer centers are developing GvHD clinics with multidisciplinary staff that includes hematologists, rheumatologists, dermatologist, oral surgeons, and psychologists. “Treatment of these patients needs to be different from that of standard oncology patients,” he said.
Dr. Rowley noted that oncology patients may also of course need long-term care for health conditions due to treatments such as chemotherapy and radiation regardless of whether or not they have undergone a transplant. “We see this in pediatric groups. A lot of children have curative therapy for a variety of malignancies, but this has long-term health consequences. It has everything to do with going through extensive chemotherapy plus radiation therapy. There are long-term sequelae and an increasing number of survivors.”
Secondary malignancies and possibly some cardiac complications are commonly related to therapeutic exposures, said Dr. Chao. Transplant patients experience a continuum of chemotherapy throughout their treatment, and so chronic effects are frequently cumulative.
“We all know that total body irradiation and radiation before transplant play a role in these health conditions, as do certain chemotherapies,” added Dr. Bhatia. “These treatments are absolutely essential to managing the primary disease, but they also increase the risk of developing chronic health conditions.”
Multidisciplinary care is also necessary for these patients because physicians from different fields can also more adequately address treatment side effects such as dry mouth, vaginal dryness, and sclerodermatous skin changes and provide nutritional support, said Dr. Chao. The type of care over the long-term is a lot broader in nature than that needed in the acute care setting.
Cancer patients also need to participate in comprehensive health evaluations on a regular basis with a primary physician, noted Dr. Rowley. “They need to monitor their blood pressure and check their cholesterol, and also can't ignore prostate exams, breast exams, dental visits, and other types of medical screening.”
However, determining what type of screening cancer survivors of an intermediate age should receive can be challenging, he said. “For example, a young woman who survived Hodgkin's lymphoma is at an increased risk of breast cancer if she received mantle radiation therapy, but do we do mammograms at age 40 or at age 20 in these patients? Do young cancer survivors get a colonoscopy at age 35 or when they're 50?
“Overall, we need to recognize and communicate the problem of chronic health conditions to patients and to whichever physicians they are working with for long-term health care,” Dr. Rowley said. “This needs to be extended to all cancer survivors.”