By analyzing transplant patient demographics such as age and gender, treatment strategy (i.e., pre-HCT chemotherapy and chest radiation), and presence of cardiovascular risk factors such as high blood pressure, diabetes, and high cholesterol, researchers have been able to create a clinical profile to determine which patients are likely to develop heart failure after transplant. However, this current profile is limiting, as it fails to accurately explain the wide variability in the risk of heart failure between individual patients. Importantly, it does not account for how individuals' genetic makeup can exacerbate their risk of developing heart failure.
Seeking additional insight into how genetics can influence the risk for developing heart failure later in life, researchers conducted a case-control study to identify the genetic pathways that may make certain transplant survivors more sensitive to the toxicities of pre-transplant chemotherapy and subsequently increase their risk of heart failure. In this study, the investigators evaluated specific genes responsible for the breakdown of anthracyclines into toxic byproducts (CBR1, CBR3, NQO1, MRP1, and MRP2), defense from oxidative stress, a condition that causes damage to healthy heart cells (NCF4, RAC2, CYBA, SOD), iron overload (HFE), and blood pressure and heart rate regulation (AGT, AGTR1, ACE and ADRB1, ADRB2) in 77 patients with leukemia, lymphoma, and myeloma who underwent a transplant at City of Hope between 1988 and 2007 and later developed congestive heart failure. Investigators matched the survivors with 178 controls (transplant survivors who did not experience heart failure).
After comparing the genetic makeup of the transplant survivors who developed heart failure to their controls, researchers found that patients who had variations in the MRP2,
|Contact: Andrea Slesinski|
American Society of Hematology