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Blood cells verticalThe National Heart, Lung and Blood Institute (NHLBI) has awarded a $3.87 million, five-year grant to help OSUCCC – James researchers lead a multi-center study of thrombotic microangiopathy (TMA), a severe and life-threatening complication in patients undergoing hematopoietic stem cell transplant (HCT) as treatment for blood cancers.

Principal investigator (PI) for this R01 grant study—titled MIDAS: Microangiopathy, Endothelial Damage in Adults Undergoing Stem Cell Transplantation—is Sumithira Vasu, MBBS, an associate professor-clinical in the Division of Hematology at Ohio State and member of the Leukemia Research Program at the OSUCCC – James. Spero Cataland, MD, a professor in the Division of Hematology, is co-PI.

In their grant abstract, the researchers state that approximately 9,000 HCT procedures are performed in the United States annually and that reported frequencies of HCT-TMA are highly variable due to lack of routine screening. They also state that HCT-TMA, which is characterized by thrombosis (blood clots) in capillaries and arterioles, is associated with anemia, renal dysfunction and neurological symptoms.

The researchers note that HCT-TMA appears to result from endothelial injury, or damage to the lining of blood vessels, and that “extensive data indicate decline in endothelial health as people age, suggesting that HCT-TMA might be more frequent or severe in older persons.”

Because there is no other reported prospective study of HCT-TMA in adults, risk factors and outcomes for this condition are unknown, the researchers write, adding that this knowledge gap will be addressed by their study, which hypothesizes that the etiology and risk factors for HCT-TMA are different in adults than children, and that these differences should modify potential diagnostic and therapeutic strategies.

“We propose to identify strategies that will define HCT recipients with increased susceptibility to HCT-TMA occurring early after transplantation, and later after establishment of graft-vs.-host disease (GVHD),” they state. “Identifying endothelial injury occurring post-HCT at the earliest possible time will allow for prompt clinical intervention and interruption of the cycle of endothelial injury and complement activation.”

In summary, they write, this study will provide data to identify patients at highest risk of HCT-TMA and to allow testing of future clinical interventions, such as studies of endothelial-protecting agents or interferon inhibitors for HCT-TMA, as well as the development of evidence-based guidelines for screening and diagnosis of HCT-TMA in adults.

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