For years, transplant clinicians have known the tradeoff in older adults: blood or marrow transplant can be curative, but the physiologic cost does not always show up in the first year or two. A new report from the Blood or Marrow Transplant Survivor Study gives that concern a sharper outline, showing that patients who undergo transplant at age 60 years or older face a heavy burden of chronic illness, functional decline, second cancers, and premature mortality after they have already survived the early transplant period.
The analysis included 1,581 recipients of blood or marrow transplantation who were at least 60 years old at transplant and survived 2 or more years. Median age at transplant was 64 years, and median age at study participation was 70.1 years. Most patients had undergone transplant from 2005 to 2014, and the majority received autologous transplants. Multiple myeloma was the leading indication, followed by non-Hodgkin lymphoma and acute myeloid leukemia or myelodysplastic syndrome.
The results were not reassuring. Severe, life-threatening, or fatal chronic health conditions were reported in 72% of BMT survivors, compared with 51% of sibling controls. After adjustment, transplant survivors had nearly three times the odds of severe or life-threatening chronic health conditions. They also had higher odds of poor general health, functional impairment, activity limitation, and frailty. In practical terms, more than half of survivors reported functional impairment or activity limitation.
Daniel Weisdorf, MD, Professor Emeritus, Division of Hematology, Oncology and Transplantation, University of Minnesota, said the findings reflect the cumulative toll of disease and treatment rather than one single transplant-related injury.
“The cumulative impact of multiple pre-transplant therapies and the transplant conditioning contribute to the added health compromise of older BMT survivors,” Weisdorf said. “Their development of the original need for transplant plus all the treatments received reflect the tissue injuries manifest as these chronic health conditions.”
Mortality remained elevated as well. Compared with the general US population, older BMT survivors had a 5.3-fold higher risk of all-cause mortality. Infection-related death was the standout signal, with a standardized mortality ratio of 35.2. The risk was high after both autologous and allogeneic transplants, though it was particularly elevated among allogeneic recipients. Renal disease mortality was also increased.
That finding raises a clinical question that is hard to ignore: should older transplant survivors undergo more formal, longer-term immune monitoring, rather than follow-up that tapers once the early transplant period has passed? Weisdorf said immune recovery can remain a central problem.
“Transplantation itself requiring a rebuild/reboot of a functioning immune system is often accompanied by immune suppressive drug therapies that may delay establishment of a fully healthy immune system to protect survivors from infection,” he said. “Vaccinations, some preventive antibiotics and education about risky behaviors – inadequately cooked or raw foods, hygiene habits, avoiding smoking and other risky activities may contribute to the safety of transplant survivors.”
Second cancers were another major part of the late-risk picture. The 10-year cumulative incidence of subsequent malignant neoplasms was 28.6%, and survivors had a 3.8-fold higher risk than the general population. Melanoma risk was especially elevated. Autologous transplant recipients had increased risks for myelodysplastic syndrome/acute myeloid leukemia and gastrointestinal cancers, while allogeneic recipients had a higher risk for oropharyngeal cancers.
The study also leaves clinicians with a more day-to-day question: how much survivorship care should be built around frailty, mobility, cardiovascular disease, thrombosis, hearing loss, diabetes, and cancer screening, especially in patients whose original malignancy is controlled? The data suggest that relapse surveillance alone misses much of the clinical burden.
Weisdorf said the success of transplant can also be used as a reason to keep patients engaged in prevention.
“The success of eradicating their original life-threatening malignant disease with transplantation could be, in itself, a motivating factor to promote healthy behavior in BMT survivors,” he said. “But ongoing education about post-transplant risks and informed counseling for patients and their care providers about screening for late effects can help anticipate the continuing hazards that can be avoided or mitigated and yield long term better health in those who have been cured from their original condition by transplantation.”
The study has limits, including self-reported health conditions, possible survival bias, and a median follow-up of 5 years. Even so, the clinical takeaway is plain enough. Older adults are not just surviving transplant. Many are surviving it with complex, persistent health risks that need to be anticipated long before they become irreversible.
