Summary: Haemophagocytic lymphohistiocytosis (HLH) is a severe, even fatal, inflammatory condition. Epstein–Barr virus (EBV) infection‐associated HLH (EBV‐HLH) is one of the most common types of secondary HLH. Etoposide is a key drug in HLH‐94/04 regimen. We sought to identify the importance of etoposide in the initial treatment of EBV‐HLH. Ninety‐three patients with EBV‐HLH of all ages admitted to our centre in 2017 were divided into two groups according to whether the initial treatment contained etoposide or not. The survival of the group whose initial therapy included etoposide (Group 1, 52 patients; 6‐month survival rate 0·769) was significantly better than that of the group whose initial therapy did not include etoposide (Group 2, 41 patients; 6‐month survival rate 0·269) (P < 0·001). In patients aged <18 years old, the survival of Group 1 patients was not significantly better than that of Group 2 patients (P = 0·447), in contrast to patients aged ≥18 years, where the survival of Group1 patients was significantly better than that of Group 2 patients (P < 0·001). We concluded that including etoposide in the initial treatment of EBV‐HLH patients can improve their prognosis, especially adult patients. This may be because that adult patients are recognized as “higher risk” patients.

Hemophagocytic lymphohistiocytosis (HLH) is a rare severe clinical syndrome. HLH manifesting during pregnancy has been paid much attention in recent years. Despite the specificity of pregnancy-related HLH, there has not been any consensus regarding its treatment. According to a previous study, corticosteroid/IVIG is the mainstream therapy; however, the efficacy is controversial. Etoposide is an important agent in the HLH-94 regimen; nevertheless, its use is limited because of possible toxicity to the fetus. Methods: In this study, we summarized 13 cases from 4 medical institutions from April 2011 to April 2018. Treatment regimens and outcomes were observed. The median age was 26 (20–36) years old. The median gestational age was 28 (10–35) weeks. In these 13 patients, 10 were treated with methylprednisolone/IVIG and was effective in only two patients. In 6 patients who used etoposide during their treatment, all achieved remission. The median time from onset of disease to use of etoposide was 36 (17–131) days. Five of these 6 patients were treated with corticosteroids with/without IVIG before etoposide. One patient with pulmonary tuberculosis and one with lymphoma were treated according to etiology and achieved long survival. For treatment of pregnancy-related HLH, particularly for patients who do not respond to corticosteroids/IVIG therapy, etoposide should be used bravely. Nevertheless, suitable dosages and toxic and side-effects require further clinical observation.

Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory status. Lymphoma associated hemophagocytic lymphohistiocytosis (LAHS) is a kind of secondary HLH (sHLH). It suffers the worst outcome among sHLH. Allo-HSCT is often considered necessary. Autologous stem cell transplantation (auto-SCT) is widely used in the treatment of lymphoma, especially for high-risk NHL. There have been no clinical reports on the use of auto-SCT in LAHS in the past 20 years. We retrospectively evaluated 12 LAHS patients who received auto-SCT at our center from January 2013 to January 2020. Follow-up started at the date of LAHS diagnosis and ended at the date of death or last examination. Overall survival (OS) was calculated from the diagnosis of HLH to death of any cause. The median period between diagnosis and auto-SCT is 6.7 months. All 12 patients achieved remission after transplantation. Follow-up to 1 January 2021, 8 patients remained disease-free, 4 patients relapsed and 2 of them died eventually. The median follow-up time is 20.9 months, and the median overall survival time has not been reached yet. The 3-year OS rates was 71%. Compared with LAHS patients who did not undergo transplantation during the same period (median OS time is 3.4 months), patients who underwent auto-SCT had a significantly better prognosis (P=0.001). Even if the lymphoma reaches CR after treatment, auto-SCT still provides a better prognosis compared to CR patients without transplantation (P=0.037). Compared with lymphoma patients without HLH who underwent auto-SCT during the same period, they had a similar prognosis (P=0.350). LAHS, as a common type in secondary HLH, may have a better prognosis after removing the trigger of HLH. In this study, the autologous transplantation in LAHS can significantly improve the prognosis, and provide LAHS a similar prognosis as high-risk lymphoma without HLH.

Novel nude mice model of human NK/T cell lymphoma were established by subcutaneously injecting two NK/T cell lymphoma cell lines into the right axillary region of mice and successful passages were completed by injecting cell suspension which was obtained through a 70‐μm cell strainer. These mice models and corresponding cell clones have been successfully developed for more than 8 generations. The survival rates of both resuscitation and transplantation in NKYS and YT models were 90% and 70% correspondingly. Pathologically, the tumour cells in all passages of the lymphoma‐bearing mice and cell lines obtained from tumours were parallel to initial cell lines. Immunologically, the tumour cells expressed the characteristics of the primary and essential NK/T lymphomas. The novel mice models maintained the essential features of human NK/T cell lymphoma, and they would be ideal tools in vivo for further research of human NK/T cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is one of the most common causes of cancer death worldwide, and responds poorly to the existing treatments. Thus, identifying novel therapeutic targets of DLBCL is urgently needed. In this study, we found that T-lymphokine-activated killer cell-originated protein kinase (TOPK) was highly expressed in DLBCL cells and tissues. Data from the GEPIA database also indicated that TOPK was highly expressed in DLBCL tissues. The high expression levels of proteins were identified via Western blots and immunohistochemistry (IHC). TOPK knockdown inhibited cell growth and induced apoptosis of DLBCL cells with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium (MTS) and flow cytometry. Further experiments demonstrated that acetylshikonin, a compound that targeted TOPK, could attenuate cell growth and aggravate cell apoptosis through TOPK/extracellular signal-regulated kinase (ERK)-1/2 signaling, as shown by MTS, flow cytometry and Western blots. In addition, we demonstrated that TOPK modulated the effect of acetylshikonin on cell proliferation and apoptosis in U2932 and OCI-LY8 cells using MTS, flow cytometry and Western blots. Taken together, the present study suggests that acetylshikonin suppresses the growth of DLBCL cells by attenuating TOPK signaling, and the targeted inhibition of TOPK by acetylshikonin may be a promising approach for the treatment of DLBCL. GRAPHICAL ABSTRACT