Hematopoietic cell transplants: Genetics linked to heart failure
December 8, 2012 | by Roberta Nichols
Hematopoietic cell transplantation (HCT) is a lifesaving treatment for people with cancer and other blood disorders – yet for some patients it can lead to devastating complications, such as congestive heart failure (CHP). The reason may be because of their genetic makeup, City of Hope researchers have found.
“Chemotherapeutic agents called anthracyclines are notorious for causing this problem, but not everyone who gets anthracyclines will develop heart failure,” said lead author Saro Armenian, D.O, M.P.H., medical director, Pediatric Survivorship Clinic, Childhood Cancer Survivorship Program at City of Hope.
In fact, only a small percentage will develop this lethal complication in which the heart becomes too weak to pump blood to other organs.
Most people who develop CHF typically don’t exhibit symptoms until their 70s or 80s. However, cancer patients taking anthracyclines can develop it much earlier and once that happens, “there’s really no going back,” said Armenian.
Some individuals will qualify for a heart transplant, and others will die of heart failure or its complications. There’s a 50 percent chance they’ll die within five years of its onset.”
Doctors have been puzzled why patients react so differently to anthracyclines. Some can tolerate high doses of anthracyclines and never develop heart failure, while others who receive relatively low doses will develop congestive heart failure. “We wanted to explore what accounted for these differences,” said Armenian.
He and his colleagues studied a group of 2,950 patients who were transplanted at City of Hope between 1988 and 2007. Researchers compared patients who developed heart failure to those who did not. They were particularly interested in patients’ DNA makeup.
“There’s that less-than-1-percent variability in human beings that could account for a tremendous amount of difference like hair color and eye color,” said Armenian.
“Why not take that same logic and look at how we respond to the drug, how our body breaks down the drug, and what toxic metabolytes are released as a result of our genetic makeup?”
The researchers found three variations of genes that code for specific proteins that break down the drug.
“Using this information, we were able to create a predictive model that actually accounted for 80 percent of heart failure cases in this population,” Armenian said.
Researchers presented their findings during the American Society of Hematology (ASH) meeting in Atlanta, Dec. 8 to 11.
The finding has important clinical implications, says senior author Smita Bhatia, M.D., M.P.H., director, Center for Cancer Survivorship, and the Ruth Ziegler Chair in Population Sciences at City of Hope. “If you can identify the high-risk group, you can follow them much more aggressively to detect heart failure early and potentially prevent it from progressing.”
“We’ll be able to create a profile of high-risk individuals based on their genetic makeup and use that information to screen them and treat them better,” said Armenian. “We want to keep the excellent cure rates but also minimize the toxicities associated with them,” he added.
This study was supported by National Institutes of Health grants, including P30 CA33572, 2 K12 CA001727 and P01 CA30206.