The <scp>IL</scp> ‐10/ <scp>IL</scp> ‐6 Ratio and the Risk Score: Two Cytokines‐Based Predictors for Malignancy‐Associated Hemophagocytic Lymphohistiocytosis in Adults (M‐ <scp>HLHa</scp> )

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.

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Journal
American Journal of Hematology
Published
2026-06-16
DOI
https://doi.org/10.1002/ajh.70410
Primary Topic
Autoimmune and Inflammatory Disorders Research
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article

The IL ‐10/ IL ‐6 Ratio and the Risk Score: Two Cytokines‐Based Predictors for Malignancy‐Associated Hemophagocytic Lymphohistiocytosis in Adults (M‐ HLHa )

David Launay, Stéphanie Chhun, Nanthara Sritharan, Felipe Suarez et al.
American Journal of Hematology
Autoimmune and Inflammatory Disorders Research
article

The IL ‐10/ IL ‐6 Ratio and the Risk Score: Two Cytokines‐Based Predictors for Malignancy‐Associated Hemophagocytic Lymphohistiocytosis in Adults (M‐ HLHa )

David Launay, Stéphanie Chhun, Nanthara Sritharan, Felipe Suarez, Raphaël Lhote, Morgane Cheminant, Yves Lepelletier, Marine Gil, Geneviève de Saint Basile, Marc Michel, Jean‐François Viallard, Olivier Hermine, Coralie Bloch‐Queyrat, Marouane Boubaya, Jean‐Marie Michot, Francois Liffermann, C. Larroche, Louis Terriou, Geoffrey Urbansk, Estibaliz Lazaro, Olivier Lambotte, the French HLH Study Group, Pierre Morel
article en

Abstract

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.

American Journal of Hematology
Hôpital Necker-Enfants Malades (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), Institut Gustave Roussy (FR), Centre Hospitalier Universitaire de Lille (FR), Institut Necker Enfants Malades (FR), Université Sorbonne Paris Nord (FR), Sorbonne Paris Cité (FR), CEA Paris-Saclay - Etablissement de Fontenay-aux-roses (FR), Centre Hospitalier de Lens (FR), Immunology from Concept and Experiments to Translation (FR), Hôpital Cardiologique du Haut-Lévêque (FR), CEA Paris-Saclay (FR), Infectious Disease Models and Innovative Therapies (FR), Hôpital Avicenne (FR), Délégation Paris 6 (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier de Dax –Côte d’Argent (FR), Institute of Normal and Pathological Physiology of the Slovak Academy of Sciences (SK), Bicêtre Hospital (FR), Institut des Maladies Génétiques Imagine (FR), Université d'Angers (FR), Université Lille Nord de France (FR)
Openalex Percentile: Top 9%
Autoimmune and Inflammatory Disorders Research
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