The OHI index predicts early mortality from organ dysfunction and survival benefit from etoposide in patients with lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that complicates hematologic malignancies. The Optimized HLH Inflammatory (OHI) index, based solely on the combined elevation of soluble CD25 (sCD25; >3900 U/mL) and ferritin (1000 ng/mL) levels, predicts mortality more effectively than the conventional HLH criteria. This study aimed to determine whether mortality in OHI-positive (OHI+) patients is primarily caused by lymphoma or inflammation-related causes. In a multicenter, retrospective study of patients with newly diagnosed lymphoma with sCD25 and ferritin measurements available, patients were classified as OHI+ or OHI negative (OHI-). The 1-year and 3-year overall survival (OS), event-free survival, and causes of death were analyzed, along with predicted vs observed mortality based on other lymphoma-relevant prognostic indexes. Among 135 patients with lymphoma (70 OHI- and 65 OHI+), OHI+ patients had significantly lower OS at 1 year (33% vs 81%; P < .0001) with a median survival of 190 days. OHI+ patients had a 13-fold increased mortality risk (odds ratio, 13.3; 95% confidence interval, 6.0-28.5) despite similar predicted OS based on conventional indexes (72% vs 65%; P = .46). Mortality causes differed significantly. A total of 58% of OHI+ patients died from multiorgan failure, whereas only 6% died from progressive lymphoma. In contrast, 43% of the OHI- patients died from lymphoma progression. The incorporation of etoposide into lymphoma-directed treatment was associated with improved OS in OHI+ T-cell lymphomas (P = .007). These findings underscore the clinical significance of the OHI index as a prognostic tool in lymphoma, to elucidate the mechanisms of mortality, and to identify a high-risk subgroup for which tailored treatments may lead to improved outcomes.