Cytotoxic T-cell activation profile in critically ill children with malignancies and hemophagocytic lymphohistiocytosis.

Background: The early identification of hemophagocytic lymphohistiocytosis (HLH) in critically ill children with malignancies is challenging. The value of an activated cytotoxic T-cell profile in diagnosing HLH in this group of patients is unknown.

Methods: Critically ill children with malignancies who suffered from persistent cytopenia in the pediatric intensive care unit were included. Children were divided into two groups based on how many clinical HLH diagnostic criteria they fulfilled: M-HLH group, ≥5 criteria; hematologic malignancy (HM) group, ≤4 criteria. Flow cytometry tests were performed within 24 h after the patient's admission.

Results: Thirty-seven children who fulfilled the requirements were enrolled. Twenty children were classified into the M-HLH group and 17 into the HM group. The M-HLH group exhibited a higher mortality rate than the HM group. CD38 + HLA-DR + CD8+ T cells% and interferon-gamma (IFN-γ) were elevated in the M-HLH group. The area under the curve values of the two indexes were 0.906 and 0.897 respectively for the identification of M-HLH in the critically ill children, with CD38+/HLA-DR + CD8+ T cells% > 39.66% and IFN-γ > 22.58 exhibiting the best performance.

Conclusion: Cytotoxic T-cell activation profile with CD38 + HLA-DR + CD8+ T cells% and IFN-γ is valuable in the early diagnosis of HLH in critically ill children with malignancies.

Impact: The early diagnosis of hemophagocytic lymphohistiocytosis in critically ill children with malignancies (M-HLH) remains a major challenge for intensivists. Cytotoxic T-cell activation profile with the frequency of CD38 + HLA-DR+ T cells in CD8+ T cells (CD38 + HLA-DR + CD8+ T cells%) and interferon-gamma (IFN-γ) is valuable in the early identification of pediatric M-HLH. These findings will support the future implementation of T-cell activation markers in the clinical management of children with M-HLH.