Transplant survivorship: a call to arms

In this issue of Blood, Sun and colleagues from the Bone Marrow Transplant Survivors Study report the chronic health outcomes of more than 1000 survivors of stem cell transplantation. Their results demonstrate a significant burden of chronic conditions among survivors.

There has been a consistent increase in the number of hematopoietic stem cell transplantations performed annually for the past 2 decades. Enabling this expansion of transplantation have been refinements in HLA matching, infectious disease therapy, and general supportive care of the transplant patient. A welcome consequence has been an increased number of long-term survivors. While early health-related outcomes and quality of life have been studied, until recently, the long-term health outcomes of these long-term survivors have not been adequately addressed.

In this issue, Sun et al describe the burden of chronic health conditions among long-term transplantation survivors, and compare the incidence of these chronic health conditions with their siblings.¹  Compared with siblings, transplantation survivors were twice as likely to have any chronic health condition and 3.5-fold more likely to have a serious chronic health condition. Likewise, multiple chronic health conditions were more common among transplantation recipients. The frequency of these health conditions was staggering (cumulative incidence at 10 years: 59%) and was related to the type of transplantation received, with recipients of allogeneic grafts having a higher incidence of chronic health conditions compared with autologous graft recipients. Chronic graft-versus-host disease and the use of an unrelated donor or a total body irradiation–containing conditioning regimen were significant risks for chronic health conditions among allogeneic transplantation recipients.

The cumulative incidence of the chronic health conditions noted in this study increased steadily over time, without an apparent plateau at any time point. Of course, with an aging population this is expected to occur, however, this relationship was noted even for individuals under the age of 40 at the time of transplantation. The implications of this study are obvious, and demonstrate that while transplantation may be curative of the underlying tumor it is not a panacea for the overall health of the patient with a hematologic malignancy. Rather, as many of us have often told our patients, with transplantation we simply trade one set of problems for another. As a consequence, we need to be prepared to care for the transplantation recipient in the long-term.

There are guidelines to address screening studies to prevent the long-term complications of stem cell transplantation,²  however, the degree to which these guidelines are followed at individual centers is likely to be low, as the tests recommended often lie outside the realm of expertise of the transplantation physician, and some require consultation with subspecialists. These tests can be particularly hard to arrange for patients who travel episodically long distances to transplant centers for follow up. Unfortunately, over time, patients who require these services are seen less frequently at the transplant center, and more frequently by primary care physicians, who may not be aware of the long-term complications of transplantation.³  One solution to this problem is the Transplant Survivorship Clinic, a model recently adapted at our Institute. The Survivorship Clinic is staffed by subspecialists in oral medicine, ophthalmology, dermatology, cardiology, and endocrinology, as well as a stem cell transplantation physician. Equally important, however, are the specialists in dietary counseling, exercise physiology, physical therapy, and psychosocial guidance who see patients in this clinic as well. This clinic offers one-stop shopping for patients to obtain screening for the adverse outcomes of transplantation, and to counsel patients on behavior to prevent some of the long-term complications of transplantation. Under the premise that cancer is a “teachable moment,” this multidisciplinary clinic promotes the concept of healthy cancer survivorship. Individualization of care plans is crucial among cancer survivors⁴  because it is known that cancer survivors do not have better patterns of preventative health behavior compared with noncancer patients.⁵ 

While the emergence of chronic health conditions cannot be altered with screening practices alone, hopefully the severity and consequences of the resulting conditions can be altered. This is particularly relevant because more than 10% of the 2-year survivors in the Sun report subsequently died of nonrelapse-related causes. Despite this, it is estimated that 5-year survivors have long-term survival that approaches survival rates in age-matched populations.^6,7  Primary changes to the way transplantation is performed can ultimately lead to fewer long-term heath consequences. The movement away from total body irradiation–based autologous transplantation has reduced the rate of secondary malignancies after autologous transplantation, and it is possible that reduced-intensity allogeneic transplantation may ultimately reduce the rates of some late complications after allogeneic transplantation as well. Only time will tell if this promise of a reduced-toxicity transplantation holds true; preliminary data suggest that long-term cardiovascular and renal health are equivalent regardless of conditioning intensity.^8,9  Changes to the way posttransplantation care is delivered can hopefully have an impact on cancer survivorship as well.

Surviving the underlying transplantable disorder is our first and most important goal, but chronic medical problems are acceptable only to the degree that we identify them and work to ameliorate them. Survivorship after transplantation is a “problem” we strived for years to intentionally create. While we are far from the goal of universal cure for all transplantation recipients, it is high time we become prepared to deal with the consequences of our own therapeutic sucess .