This article is more than 5 years old. Information may no longer be current.
Hematopoietic cell transplant survivors face greater late morbidity, mortality
Click Here to Manage Email Alerts
Hematopoietic stem cell transplantation survivors experience significantly greater rates of hospitalization and mortality from all causes years after their transplants than cancer survivors who did not undergo HSCT, according to a comparative study published in Journal of Clinical Oncology.
“Few studies of long-term outcomes in hematopoietic cell transplantation survivors have compared outcomes with matched non-HSCT survivors,” Eric J. Chow, MD, MPH, clinical researcher at Fred Hutchinson Cancer Research Center and professor at University of Washington, told HemOnc Today. “With this more nuanced comparison, we showed that overall, HSCT survivors still had a greater burden of most, although not all, serious complications associated with hospitalization and death. For example, HSCT survivors had significantly greater burden of infections and respiratory complications, but at least in our analysis, not circulatory complications or second cancers.”
The use of HSCT to treat high-risk malignancies has increased markedly during the past 25 years. Further, 70% of 2-year HSCT survivors remain long-term survivors, and by 2020, there will be an estimated 250,000 HSCT cancer survivors in the United States.
Most studies of late serious health outcomes following HSCT have focused on original disease relapse, chronic graft-versus-host disease and second cancers.
Chow and colleagues compared estimates of the absolute and relative risks for serious health outcomes affecting 2-year HSCT survivors (n = 1,792; mean age, 47 years), 2-year non-HSCT cancer survivors (n = 5,455; mean age, 49 years) and the general population (n = 16,340; mean age, 48 years).
Median follow-up was 7.1 years for HSCT survivors, 7.2 years for non-HSCT cancer survivors and 7.7 years for the general population.
In the HSCT group, the median time from original diagnosis to transplantation was 9.3 months. Eight percent of HSCT survivors (n = 143) received a subsequent transplant before the 2-year survival landmark.
Late outcomes for all three cohorts were ascertained from state hospital discharge and death registries; the Washington State cancer registry provided information on subsequent cancers.
Overall, HSCT survivors had significantly higher hospitalization rates than non-HSCT survivors (280 vs. 173 per 1,000 person-years, P < .001), as well as greater risk for all-cause mortality (HR = 1.1; 95% CI, 1.01-1.3).
HSCT survivors also had more hospitalizations or death with infections (10-year cumulative incidence, 31% vs. 22%, HR = 1.4; 95% CI, 1.3-1.6) and respiratory complications (27% vs. 20%, HR = 1.4; 95% CI, 1.2-1.5) than the non-HSCT group.
In total, 21.7% (n = 388) of HSCT survivors died during follow-up, compared with 18.3% (n = 997) of non-HSCT cancer survivors and 3.6% (n = 581) of the general population.
HSCT survivors had greater risks for digestive (HR = 1.1; 95% CI, 0.99-01.3), skin (HR = 1.3; 95% CI, 1-1.6) and musculoskeletal complications (HR = 1.3; 95% CI, 1.1-1.5) than the non-HSCT group. Both groups had similar risks of circulatory complications and second cancers, and both groups had significantly higher 10-year cumulative incidences of all major organ–system outcomes than the general population.
Chow and colleagues also noted that although they did not observe a significantly different overall risk for second cancers between HSCT survivors and non-HSCT survivors, specific cancers affecting the skin (primarily melanoma; HR = 4.9; 95% CI, 1.9-12.7) and the oral cavity (HR = 5.4; 95% CI, 1.6-18.4) were more common among HSCT survivors.
“I think the decision to choose HSCT is based typically on what treatment is most likely to cure the patient’s cancer or underlying disease,” Chow said. “Thus, the best way to reduce risk and stay healthy is probably for patients and their providers to be aware of existing HSCT survivorship guidelines. These provide guidance on what things to screen for and how often to screen.
“We hope our work raises awareness of the health issues HSCT survivors face and, in particular, lead others to examine the risk factors for long-term infectious and respiratory complications in more detail,” Chow added. “We also plan to do that in our dataset and patient population, as a follow-up to this study.”– by Chuck Gormley
For more information:
Eric J. Chow, MD, MPH, can be reached at Fred Hutchinson Cancer Research Center, PO Box 19024, M4-C308, Seattle, WA 98109; email: ericchow@u.washington.edu.
Disclosure: Chow reports no relevant financial disclosures. Please see the study for a full list of other researchers’ relevant financial disclosures.
Perspective
Back to Top
On June 21-22, 2016, the NIH hosted a Blood and Marrow Transplant Late Effects Consensus Conference in Washington, D.C. The impetus for this conference was the recognition that blood and marrow transplant survivors are prone to unique complications and late effects that represent interactions between their underlying diagnoses, prior therapies, comorbid illnesses and the transplant process itself. These unique issues were felt to be a growing public health problem in the context of a growing population of blood and marrow transplant survivors that may reach over 500,000 individuals in the United States alone by 2030. The Consensus Conference represented the culmination of a year’s worth of work by different working groups focused on these areas: secondary cancers, psychosocial and quality of life outcomes, immune dysregulation and pathobiology, cardiovascular and metabolic impairment, health care delivery, and research methodology and study design. The findings from these groups, as presented at the conference, have been published in Biology of Blood and Marrow Transplantation.
In this context, the study by Chow and colleagues adds to the growing body of evidence demonstrating the unique risks that hematopoietic stem cell transplant survivors experience. In their analysis, the researchers compared HSCT survivors at 2 years and 5 years with matched cancer survivors who did not undergo HSCT, as well as with noncancer controls, and found elevated risks in HSCT survivors for outcomes that included overall hospitalizations, infectious complications and respiratory complications, among others.
Although adverse outcomes in HSCT survivors were associated with the presence of chronic graft-versus-host disease (cGVHD) or relapse, the widening differences in outcomes at the 5-year landmark in comparison with the 2-year landmark suggested that the differences were not entirely explained by cGVHD and relapse.
Strengths of the study included its large size and the way in which it leveraged data from different sources to detect outcomes in long-term HSCT survivors. In terms of limitations, the researchers acknowledged the potential for unintentional bias related to differences in the HSCT vs. non-HSCT study populations, although the researchers also presented reasons why these effects — such as measurement bias — were likely to be modest.
As with other studies in this area, the analysis by Chow and colleagues is important because of its implications for future research and clinical care involving blood and marrow transplant survivors. On the one hand, it is important for the research community to better understand why HSCT survivors remain at elevated risks for infection and respiratory complications many years after HSCT has occurred. On the other, it is also important to design systems of care that will effectively diagnose and manage these issues as they occur in this population — oftentimes, long after HSCT survivors have left the environment of frequent post-HSCT care at specialized HSCT centers. Challenges like this prompted the recent NIH Consensus Conference, and will remain key issues for blood and marrow transplant survivors and their health care providers in the years ahead.
Click Here to Manage Email Alerts