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The IL-10/IL-6 Ratio and the Risk Score: Two Cytokines-Based Predictors for Malignancy-Associated Hemophagocytic
Coralie Bloch1,2,3, Stephanie Chhun4,5, Nanthara Sritharan1
1Clinical Research Unit, Avicenne University Hospital, AP-HP, Bobigny, France.
The predictive value of cytokines (CK) for malignancy-associated adult hemophagocytic lymphohistiocytosis (M-HLHa) remains uncertain. We evaluated a cytokine-based Risk Score (RS) and the IL-10/IL-6 Ratio to predict M-HLHa. Adult patients (n = 112) from the French HLH cohort (NCT02113917) with complete data for nine key HLH related CK measured by Luminex were first analyzed. Logistic regression was performed, and a RS was subsequently derived and internally validated. In a post hoc analysis, the IL-10/IL-6 ratio obtained using the ELLA cytokine assay was evaluated in 75 patients, 54 of whom also had Luminex testing, plus 25 additional patients from the cohort. The RS and IL-10/IL-6 ratio were then jointly assessed in the 54 patients with results from both platforms. Among the 112 patients, 45 had M-HLHa and 67 non M-HLHa; median age was 48 years and 64 (57%) were male. Eight variables were associated with M-HLHa, of which four were retained in the logistic model: age > 48 years (2.9[1.12-7.33], p = 0.03), TNF-α ≤ 43 pg/mL (3.2[1.16-8.61], p = 0.02), IL-18 > 574 pg/mL (4.9[1.89-12.75], p = 0.001), and IL-10/IL-6 ≥ 1.5 (2.7[1.01-7.31], p = 0.04), with respective weights of 11, 12, 16, and 10. A RS ≥ 20 increased the odds of M-HLHa 17-fold (17.2 [5.4-54.5], p < 0.0001). The IL-10/IL-6 ratio alone (n = 75) showed good performance (AUC 0.83). In the 54 patients with both assays, the RS and IL-10/IL-6 ratio preserved their diagnostic performance (AUC 0.87 and 0.79, respectively). These data support the RS and IL-10/IL-6 Ratio as useful tools to improve the identification of M-HLHa in adults. Trial Registration: clinicaltrials.gov NCT02113917.
The predictive value of cytokines (CK) for malignancy-associated adult hemophagocytic lymphohistiocytosis (M-HLHa) remains uncertain. We evaluated a cytokine-based Risk Score (RS) and the IL-10/IL-6 Ratio to predict M-HLHa. Adult patients (n = 112) from the French HLH cohort (NCT02113917) with complete data for nine key HLH related CK measured by Luminex were first analyzed. Logistic regression was performed, and a RS was subsequently derived and internally validated. In a post hoc analysis, the IL-10/IL-6 ratio obtained using the ELLA cytokine assay was evaluated in 75 patients, 54 of whom also had Luminex testing, plus 25 additional patients from the cohort. The RS and IL-10/IL-6 ratio were then jointly assessed in the 54 patients with results from both platforms. Among the 112 patients, 45 had M-HLHa and 67 non M-HLHa; median age was 48 years and 64 (57%) were male. Eight variables were associated with M-HLHa, of which four were retained in the logistic model: age > 48 years (2.9[1.12-7.33], p = 0.03), TNF-α ≤ 43 pg/mL (3.2[1.16-8.61], p = 0.02), IL-18 > 574 pg/mL (4.9[1.89-12.75], p = 0.001), and IL-10/IL-6 ≥ 1.5 (2.7[1.01-7.31], p = 0.04), with respective weights of 11, 12, 16, and 10. A RS ≥ 20 increased the odds of M-HLHa 17-fold (17.2 [5.4-54.5], p < 0.0001). The IL-10/IL-6 ratio alone (n = 75) showed good performance (AUC 0.83). In the 54 patients with both assays, the RS and IL-10/IL-6 ratio preserved their diagnostic performance (AUC 0.87 and 0.79, respectively). These data support the RS and IL-10/IL-6 Ratio as useful tools to improve the identification of M-HLHa in adults. Trial Registration: clinicaltrials.gov NCT02113917.
