An optimized combination of sCD25 and ferritin with the OHI index improves mortality prediction in patients with HMs. (A) Binary linear regression for the OHI index (combination of sCD25 and ferritin) was performed to calculate the predicted probabilities of diagnosing HLH (per HLH-2004) and prediction of mortality at 500 days. ROC for the predicted probabilities to predict HLH-2004 is presented on the left, and ROC for the predicted mortality probabilities at day 500 is presented on the right. (B) ROC analysis for sCD25 and ferritin identifying mortality by day 500 is shown. The blue arrow indicates the optimal point identified in the prior ROC analysis for identifying patients meeting the HLH-2004 criteria (Figure 2B). The red arrow indicates the pertinent point on the curve identified as the best balance between sensitivity and specificity (with the highest Youden index) for identifying mortality. These values were determined as the OHI index values. The table shows the sensitivity (Sens) and specificity (Spec) of the OHI for identifying ≥5 HLH-2004 parameters. The sensitivity and specificity were calculated by using a contingency table. (C) Kaplan-Meier curves of patients classified at the initial presentation (utilizing initial measurement) by HLH-2004 (blue), OHI (sCD25 ≥3900 U/mL and ferritin ≥1000 ng/mL, red), and “optimized” HLH-2004, O-HLH2004 (the same framework as HLH-2004 but with sCD25 ≥3900 U/mL and ferritin ≥1000 ng/mL, gray). The number at risk is presented for each group. Statistics were calculated with the log-rank (Mantel-Cox) test. *P < .05. All diagnostic indices were highly distinct between patients who were positive and negative (P < .0001).