Liurui Dou

Hemophagocytic lymphohistiocytosis (HLH) has been described as a threshold disease depending on triggering factors and the residual cytotoxic capacity of NK cells. This study aimed to investigate the clinical characteristics of Epstein–Barr virus (EBV)-triggered primary HLH and the prognostic value of EBV-DNA load in EBV-triggered primary HLH cases. We retrospectively analyzed the clinical data of 95 patients with primary HLH treated between January 2013 and January 2024. Based on the peripheral blood EBV status at initial diagnosis, 57 patients were categorized into the EBV-triggered primary HLH group and 38 patients into the non-EBV-triggered primary HLH group. Clinical and functional characteristics, response to treatment, and prognosis were compared between the two groups. Among patients with EBV-triggered primary HLH, the proportion of patients with familial HLH type 2 (FHL2) was significantly lower (P = 0.011), whereas the proportion of patients with X-linked lymphoproliferative disorder (XLP) was higher (P = 0.037). Functional assays showed that in primary HLH patients with gene defects in cytotoxic degranulation, the proportion of EBV-triggered primary HLH patients with reduced NK cell activity and degranulation function was significantly higher (P = 0.026 and P = 0.030). Importantly, multivariate Cox regression analysis identified EBV-DNA > 10,000 copies/mL as an independent risk factor affecting the prognosis of patients with EBV-triggered primary HLH, particularly in non-FHL cases (P = 0.045). EBV-triggered primary HLH is more prevalent in patients with XLP but less frequent in FHL2 patients. High EBV-DNA load is an adverse prognostic factor in EBV-triggered primary HLH patients.

Background: The ratio of C-reactive protein to albumin (CAR) is an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in several solid tumours and chronic lymphocytic leukaemia (CLL). However, no studies have investigated the prognostic value of the CAR in patients with acute myeloid leukaemia (AML). Objectives and Methods: We retrospectively analysed 212 newly diagnosed non-M3 AML patients. Using the receiver operating characteristic curve (ROC) method, the optimal cut-off value for CAR was determined. We investigated the correlations of the pretreatment CAR levels with clinical characteristics, treatment response of induction chemotherapy, overall survival (OS) and event-free survival (EFS). We also assessed the prognostic value of the CAR compared with other inflammation-based prognostic parameters by the area under the curve (AUC). Results: According to the ROC curve, the optimal cut-off value of CAR was 1.015. CAR was associated with age, C-reactive protein (CRP) levels, albumin levels, ferritin levels, bone marrow blast percentage, French-American-British (FAB) classification, immunophenotype and 2017 European Leukemia Net (2017 ELN) risk stratification. Importantly, we found that high CAR was a powerful indicator of a lower complete remission (CR) rate (p< 0.001), worse OS (p< 0.001) and worse EFS (p< 0.001). Subgroup analysis showed that a high CAR was associated with shorter OS and EFS in patients with intermediate risk stratification or those aged ≤ 65 years or those without haematopoietic stem cell transplantation (HSCT). In the multivariate analysis, the CAR was an independent prognostic factor for OS and EFS. Furthermore, the predictive value of CAR for OS is superior to that of CRP, albumin and GPS in de novo AML patients aged ≤ 65 years old. Conclusion: CAR is a simple and effective prognostic marker in patients with AML. It could be an additional prognostic factor that help further precise the current risk stratification of non-M3 AML, particularly for patients in intermediate risk stratification and those aged ≤ 65 years and those who did not undergo HSCT.