Background Hemophagocytic lymphohistiocytosis (HLH) is a category of immunological illnesses that cause out‐of‐control T cells and macrophages to release life‐threatening cytokines. The HLH‐2004 diagnostic criteria are the gold standard for HLH diagnosis, but there is a need to investigate the usefulness of various cytokines for HLH diagnosis. Methods Patients admitted to Beijing Friendship Hospital of Capital Medical University from January 2016 to December 2020 were included in this retrospective study, with 166 patients with confirmed HLH and 142 febrile patients requiring differential diagnosis completing the sum. Multiplex cytokine assays using multifactor liquid phase microarray technology‐based multifactor liquid phase microarray technology were used to detect 33 cytokines. Twenty‐eight cytokines detected using the Luminex analytical platform technology were ultimately included in the analysis. Results Interleukin‐1 receptor antagonist (IL‐1 RA), IL‐18, interferon‐γ (IFN‐γ), and interferon‐induced protein 10 (IP‐10) regulated upon activation normal T cell expressed and secreted (RANTES), eotaxin, growth‐related oncogene α (GRO‐α), and macrophage inflammatory protein‐1 α (MIP‐1α) were higher in the HLH group than in the non‐HLH group, and the differences were statistically significant. Among them, the area under the curve (AUC) for IL‐18 for HLH diagnosis was reported for the first time as 82.69%, with a sensitivity of 76.32% and a specificity of 79.61%; the AUC of IL‐1 RA was 72.34%, with a sensitivity of 62.71% and a specificity of 75.97%; and the AUC of IP‐10 was 71.73%, with a sensitivity of 60.14% and a specificity of 75.15%. Moreover, the AUC of the combined diagnostic tests for IL‐1 RA, IL‐18, IFN‐γ, IP‐10, and RANTES was 99.6%, with a sensitivity of 95.8% and a specificity of 98.6%. Conclusion Our study concluded that multiple cytokines are valid biological markers for the diagnosis of HLH. The findings of this study remain to be validated in an external dataset.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative approach for primary hemophagocytic lymphohistiocytosis (pHLH), but data on adult patients are scarce. Here we present an 8-year experience on HSCT for adult pHLH to reveal the benefits and risks in this population. A total of 29 adult pHLH patients entered this study, at a median follow-up of 29 months (3-112 months), the 5-year probability of survival was 60%. Six patients rejected HSCT, of whom 1 alive in complete response (CR). In 23 patients who underwent HSCT, 5-year survival post-HSCT overall was 73%, and in haploidentical HSCT (haplo-HSCT) cases, 71%. Patients who achieved CR at HSCT had a better outcome than those of partial response (92% vs. 47%, p = 0.013). Neither the use of HLA mismatched donor (75% vs. 72%, p = 0.996) nor the use of donor with monoallelic mutation (74% vs. 71%, p = 0.901) affected the prognosis. Hemophagocytic lymphohistiocytosis status of CR at HSCT was a positive prognostic factor. We concluded that HSCT is a promising method to cure adult-onset pHLH. Achieving CR before HSCT contributes to better outcome. Haplo-HSCT is safe and effective for adult pHLH patients, donors with monoallelic mutations in pHLH related genes but normal cytotoxic functions are reliable.

Background Although most adults are infected by Epstein‐Barr virus (EBV), some patients develop highly lethal diseases associated with EBV infection, including EBV‐hemophagocytic lymphohistiocytosis (EBV‐HLH), chronic active EBV infections (CAEBV), and lymphoma, the pathogeneses of which remain to be investigated. The human leukocyte antigen (HLA) complex may be associated with the viral infection pathway, and, therefore, HLA alleles may be associated with EBV‐related diseases and subpopulations of infected cells, studies related to EBV‐associated diseases, and subpopulations of infected cells that were conducted in China are scarce. Methods In this study, we analyzed the high‐resolution HLA genotypes of 269 patients with EBV‐associated diseases and 213 EBV‐seronegative hematopoietic stem cell donors using PCR‐SBT assay and elucidated the associations of HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 alleles with EBV‐associated diseases in the Chinese population, Benjamini–Hochberg correction to adjust for multiple testing. HLA genotypes were also analyzed in patients with EBV‐associated diseases showing EBV‐infected lymphocyte subpopulations. Results We found that individuals carrying the following alleles showed the following levels of risks: HLA‐DRB1*11 allele, reduced risk of EBV‐related disease (OR [odds ratio]: 0.56; 95% confidence interval [95% CI]: 0.32–0.99; p < .05; Adjust p = .71); HLA‐DQB1*06:02 allele, reduced risk (OR: 0.5699; 95% CI: 0.3486–0.9317; p < .05; Adjust p = .57); and HLA‐B*15:01 allele, increased risk (OR: 1.763; 95% CI: 0.3486–0.9317; p < .05; Adjust p = .57). Patients with EBV‐associated diseases showing the B*15:01 genotype had a higher risk of T‐cell, NK‐cell, and multicell infections than those with other genotype subgroups. Conclusions These findings highlight the importance of HLA genotype for assessing EBV infectivity.