Defining the pathophysiology of HLH in Hematologic Malignancies
Dr. Michael Jordan
Cincinnati Children’s Hospital Medical Center
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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening histiocytic disorder that has been recognized for decades as both a condition which runs in families and one which can occur sporadically in individuals with cancer and other medical conditions. In fact, most cases of HLH in adults are associated with various cancers, and the number of these cases has increased dramatically in the last decade. Unfortunately, understanding of cancer-associated HLH has lagged far behind our understanding of familial HLH. In the latter, successful laboratory and clinical studies have enabled us to deeply understand the disease and develop safer therapies to improve these patients’ outcomes. No one understands how cancer can cause HLH, but it is clear that this form of HLH has a very poor prognosis – by most estimates 80-90% of these individuals die within a year of diagnosis.
To better understand how cancer-associated HLH develops and how it could be better treated, we have collected information and samples from an international group of these patients. We have already found and published an improved way to diagnose cancer- HLH. In our most recent studies, we have extensively compared blood protein markers from patients with cancer-HLH and those with familial HLH. Surprisingly, we found many similarities, which suggest that the underlying immunologic processes in these two different forms of HLH are more similar than expected. In the current project, we propose to study how specific immune cells and pathways may be contributing to HLH development in patients with cancer, and to define which aspects of abnormal immune activation in these patients is most associated with early death. By defining what immune cells are critical and which immune actions are most harmful to patients, we will take a major step towards identifying new targets for therapy. These studies will advance our understanding and lead to translational clinical trials which will finally improve the outcomes for these patients.