Minimizing and preventing late effects of stem cell transplantation.
At only 5 years old, Heaven Sanchez received radiation, chemotherapy and a transplant of her own stem cells after surgery to remove a brain tumor. Now 9, she has cataracts in both eyes and an underactive thyroid, complications of the powerful treatment regimen that left her cancer-free.
“The doctors told us what the complications might be,” says Heaven’s mother, Stephanie Sanchez of San Antonio. “At the time, the only thing I was thinking was she has to get better. And we have to do whatever we can.”
Cancer survivors, young and old, confront a variety of health problems after stem cell transplantation, according to a growing number of studies. The reason: collateral damage from therapies used to kill cancer. High amounts of radiation and chemotherapy used before stem cell transplantation, and in some cases, in between multiple transplantations, can destroy the cancer with the potential consequence of bodily harm. Chemotherapy and radiation, for example, can cause congestive heart failure and new, or secondary, cancers.
Leukemia and lymphoma survivors at least 10 years out from transplantation are at higher risk for heart disease, blindness, osteoporosis, new cancers and other post-transplantation complications compared with their siblings, according to a study presented at the American Society of Hematology (ASH) annual meeting this past December. The study also included survivors of aplastic anemia and other conditions.
After a 15-year follow-up, researchers found 74 percent of survivors had developed at least one chronic health condition compared with 29 percent of siblings. One in four survivors developed a severe or life-threatening condition compared with 8 percent of siblings.
Long-term health problems can also result from steroids used to treat graft-versus-host disease, a possible side effect of allogeneic transplantation in which the donor stem cells see the patient’s body as foreign and launch an immune system attack. Osteoporosis, for example, is a possible by-product of steroid therapy in both men and women.
Yet patients aren't being regularly told about the risk of health complications later on, says Smita Bhatia, MD, director of the Center for Cancer Survivorship and BMT (Bone Marrow Transplant) Long-Term Follow-up Program at City of Hope in Duarte, Calif. "That's because the data are just emerging on these long-term morbidities, so it will take three to four years before those discussions become incorporated into the standard practice," says Bhatia, senior author of the survivor study presented at the ASH meeting.
Long-term survivors are also at higher risk for a psychological health condition called somatic distress, according to Bhatia's study. Somatic distress occurs when there's no medical underlying cause for a particular symptom, yet a survivor experiences it. It may be in the form of abdominal pain or shortness of breath. "There really isn't much of a clue as to why that is happening," Bhatia says.
In Heaven Sanchez’s case, doctors know what caused her eye cloudiness: radiation she received to the brain and spinal cord. Her vision started to change within two months after she finished treatment. More than three years later, her vision has worsened to the point where she can barely see a few feet in front of her.
“At home, it’s not as bad. But other times, she can’t see who she’s with or where she’s at,” Stephanie says of her daughter. “Especially when we’re in a new place, we have to walk with her and hold her hand to make sure she doesn’t trip over anything.” Heaven’s ophthalmologist wants to delay cataract surgery until it is absolutely necessary. “We may have reached that point,” Stephanie says.
Cataracts are less common today than years ago when patients often received total body irradiation in a single dose, Bhatia says. Once that link was made in the 1980s, transplantation doctors started splitting up the dose. Doctors also started shielding vital organs, such as the lungs, and, when possible, pointing the radiation beam away from the heart.
A more recent shift within the past decade involves some doctors dropping the chemotherapy drug etoposide from the list of stem cell mobilizers, drugs that stimulate the release of stem cells from the bone marrow into the bloodstream for easy collection. “We found a relationship between etoposide and the development of a highly fatal disease called therapy-related leukemia. So the use of etoposide for stem cell mobilization was greatly minimized,” Bhatia says.
But even as improvements are made, survivors need thorough and regular follow-up care. Bhatia recommends survivors get annual physicals, follow a healthy lifestyle and ask their physicians what post-transplantation health complications they’re at risk for and what symptoms to watch for. Most importantly, get screened for those complications, she says. For example, survivors who received anthracycline drugs before transplantation should be screened for heart failure with an echocardiogram or similar test. Survivors at risk for osteoporosis should have bone density scans. And blood tests should check thyroid function and male and female hormone levels. Then, if a problem is found, treat it, Bhatia says.
Insurance, however, doesn’t always cover screening for long-term survivors of stem cell transplantation, despite medical guidelines that have been in place since 2006. If insurance will not pay for recommended screening, Bhatia suggests survivors talk to their doctor about how to find low-cost or free health resources in their community.
Catching health problems early isn’t good enough for researchers like Bhatia. The goal, she says, is to prevent them altogether. “The next step for research is to work at the genetic level to find out why certain patients get these complications and others don’t.” Then, Bhatia says, doctors can use that information to more selectively hand-pick a treatment that will save future patients from a fate of heart disease or another cancer.
For today’s survivors, researchers are testing ways to reverse or at least stop the development of transplantation-related complications. At City of Hope, Bhatia’s colleagues are testing a hormone-modulating therapy to prevent radiation-induced breast cancer and a heart medication to help prevent heart failure.
Back in San Antonio, Heaven regularly sees her pediatric oncologist, endocrinologist and ophthalmologist. They’re monitoring her current post-transplantation complications and watching for any new ones. Otherwise, she’s your average second-grader, right down to loving Justin Bieber and weekend trips to the park.
Learn more about the possible long-term complications of stem cell transplantation, and find guidelines for post-transplantation care from the American Cancer Society and from the National Marrow Donor Program.