September 30, 2016 | by Elise Lamar
Over the last four decades, bone marrow transplantation (or HCT, for hematopoietic cell transplantation) has emerged as a highly effective treatment for blood cancers. That advance, much of it based on pioneering practices first implemented and then championed at City of Hope, is great news for thousands of long-term survivors of cancers once deemed incurable.
However, as these numbers increase, physicians are increasingly aware that even once that celebrated five-year survival day arrives, health concerns may linger. And statistics back them up: Among five-year survivors of transplant from a donor, mortality rates remain four- to nine-fold higher than those in the general population, lowering life expectancy by 30 percent. Susceptibility to infection and emergence of secondary cancers in part drive these numbers.
But another cause of post--transplant concern is heart disease.
"Recent studies conducted at City of Hope and elsewhere show quite clearly that HCT survivors have significantly higher rates of cardiovascular disease (CVD) such as heart failure, stroke and heart attacks compared to the general population," said pediatric oncologist and hematologist Saro Armenian, D.O., M.P.H., director of the Childhood Cancer Survivorship Program at City of Hope. "Not only is their risk of CVD higher, but many of these conditions develop earlier than you would expect in the general population, significantly impacting survivors' long-term well-being and quality of life."
Recognizing the need for studies to reverse these outcomes, the National Cancer Institute convened a group of international experts in Washington, D.C., to make recommendations relevant to cardiovascular care of transplant patients. Their conclusions appear in the recent issue of Biology of Blood and Bone Marrow Transplantation, where Armenian is the lead author of the report.
The report proposes ways to fill knowledge gaps in three broad areas: arterial disease, cardiac dysfunction and cardiac risk factors. Its recommendations may seem surprising — not because they appear unwarranted, but rather because many sound like "common sense.” That's because long-term follow-up of HCT patients like this is simply not yet routine.
Below is a brief sampler of concerns.
1. Arterial disease
CVD-associated arterial disease occurs in coronary and peripheral arteries, and even in brain, where it is often associated with stroke. Its incidence increases to 22 percent at 20 years after HCT, and that risk is two-fold higher than the general population.
Disease origin may lie in radiation therapy delivered near the heart or to the brain prior to HCT, or from the "conditioning" phase of HCT, when a patient is administered high dose chemotherapy or radiation to kill cancer cells and make way for infusion of donor cells.
In the last decade, physicians have, in some cases, utilized lower dose "reduced intensity conditioning" to eradicate cancer cells. It is not known whether such approaches will result in lower risk of arterial disease, a knowledge gap that needs to be addressed. Additional studies are also needed to examine whether the use of advanced imaging to monitor arterial thickening (a sign of clogging or inflammation) can help with early detection of atherosclerosis in high risk patients.
2. Cardiac dysfunction
These conditions include heart failure, valvular disease and cardiac arrhythmias. "Heart failure is an especially concerning complication after HCT," says Armenian. "Studies show that less than 50 percent of patients survive a diagnosis of heart failure after HCT, a survival rate that is markedly worse than that seen in the general population."
Heart failure describes the heart's inability to pump sufficient blood to peripheral organs. Correcting this condition, which develops over a long — often asymptomatic — period of time, remains a challenge. Thus the report stresses detection of patterns predictive of cardiac dysfunction in HCT patients, over disease treatment.
The report advises that in the absence of overt heart failure, patients could routinely undergo blood pressure screening or assessment by echocardiogram to follow pumping strength of the heart. The report does not advocate their immediate implementation, but rather recommends measures to determine whether such assessments would provide useful information and be cost-effective.
3. Increase in risk factors associated with heart disease
Risk factors specifically addressed include hypertension (high blood pressure), hyperglycemia (high blood sugar), elevated blood lipid levels (cholesterol or triglycerides) and sarcopenic obesity, a form of obesity accompanied by decreased muscle mass.
The report acknowledges that the high incidence of some of these risks in the general population could blur their relevance to transplant. Nonetheless, hypertension is consistently reported as higher in post-HCT patients, and in fact some immunosuppressant drugs administered to block transplant rejection increase blood pressure and raise blood sugar. Evidence also suggests that total body irradiation, administered as part of some conditioning regimens, contributes to type 2 and insulin resistance.
With these risks in mind, the report recommends systematic control of hypertension via either lifestyle changes and/or drug treatment throughout a patient's life — not just immediately following transplant, as well more frequent monitoring of blood sugar, followed up by evaluation to see if interventions actually delayed diabetes or heart disease.
In short, the report makes a compelling case for long-term vigilance when it comes to follow-up of HCT patients and stresses the importance of support for research to encourage low-cost, effective implementation of CVD prevention strategies.
"The growing population of HCT survivors at risk for debilitating chronic health conditions makes it imperative that studies be developed to prevent these conditions," said Armenian. "Collaborative studies among cardiologists, endocrinologists and primary care providers are needed spanning the spectrum from epidemiologic to basic and translational research. These collaborations have the potential to establish new paradigms to improve the care of our most vulnerable HCT survivors."
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