Epstein Barr virus (EBV) can affect 90% of the human population. It can invade B lymphocytes, T lymphocytes and natural killer cells of the host and remain in the host for life. The long latency and reactivation of EBV can cause malignant transformation, leading to various lymphoproliferative diseases (LPDs), including EBV-related B-cell lymphoproliferative diseases (EBV-B-LPDs) (for example, Burkitt lymphoma (BL), classic Hodgkin’s lymphoma (cHL), and posttransplantation and HIV-related lymphoproliferative diseases) and EBV-related T-cell lymphoproliferative diseases (EBV-T/NK-LPDs) (for example, extranodal nasal type natural killer/T-cell lymphoma (ENKTCL), aggressive NK cell leukaemia (ANKL), and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). EBV-LPDs are heterogeneous with different clinical features and prognoses. The treatment of EBV-LPDs is usually similar to that of EBV-negative lymphoma with the same histology and can include chemotherapy, radiotherapy, and hematopoietic stem cell transplant (HSCT). However, problems such as serious toxicity and drug resistance worsen the survival prognosis of patients. EBV expresses a variety of viral and lytic proteins that regulate cell cycle and death processes and promote the survival of tumour cells. Based on these characteristics, a series of treatment strategies for EBV in related malignant tumours have been developed, such as monoclonal antibodies, immune checkpoint inhibitors, cytotoxic T lymphocytes (CTLs) and epigenetic therapy. These new individualized therapies can produce highly specific killing effects on tumour cells, and nontumour cells can be protected from toxicity. This paper will focus on the latest progress in the treatment of EBV-LPDs based on pathological mechanisms.

Background: Hemophagocytic lymphohistiocytosis (HLH) patients who need intensive care usually have multiple organ failure and poor prognosis. However, the clinical characteristics, therapeutic efficacy and outcome in these critically ill HLH patients have remained unclear. Methods: We performed a retrospective study of 50 critically ill HLH patients from September 2013 to October 2022. Patients’ information was collected, and the overall survival rate was estimated. Results: Fifty HLH patients need intensive care, and the median sequential organ failure assessment (SOFA) score was 8. 66.00% patients had septic shock, 60.00% had disseminated intravascular coagulation (DIC) and 56.00% had acute respiratory distress syndrome (ARDS). 64.00% patients needed vasoactive drugs, 60.00% needed invasive or non-invasive positive pressure mechanical ventilation, and 12.00% needed continuous renal replacement therapy (CRRT). Among 18 patients received the etoposide-based regimens, the median time for 17 patients to remove ECG monitoring was 13 days (4– 30 days); the median time to remove respiratory support in 10 patients was 8.5 days (4– 21 days); the median time for 5 patient to convert from dominant DIC to non-dominant DIC was 4 days (1– 14 days) and the median time for 6 patients to stop using vasoactive drugs was 10 days (2– 14 days). After 4 weeks of treatment, 7 patients were evaluated as NR, 6 achieved PR, and 5 could not be evaluated. The ORR was 55.56%. Up to the last follow-up, the OS rate of patients receiving etoposide-based regimens was 66.67%. In contrast, all 32 HLH patients in other groups died. Univariate analysis showed that PCT > 0.5 ug/L, PT prolonged > 6 s, TBil > 25umol/L, respiratory failure, renal failure, liver failure and did not receive etoposide- based regimens were the negative factors affecting survival (P = 0.001, 0.017, 0.043, 0.001, 0.000, 0.029, 0.000). Conclusion: HLH patients who need intensive care timely used etoposide-based HLH regimens might rescue critically ill patients successfully.

Acute Myeloid Leukemia (AML) is a highly heterogeneous malignant hematologic cancer with poor clinical outcome. The presence of leukemia stem cells (LSC) is a significant factor contributing to the failure of AML treatments and frequent relapses. The quiescent and plastic nature of LSC decreases cell death under conventional chemotherapy. Programmed cell death (PCD) plays a critical role in the development and progression of various cancers including AML. We hypothesized that the expression of PCD gene in LSCs may predict the therapeutic outcome of AML patients in the clinic. In this study, we comprehensively analyzed the expression of PCD gene and identified the unique expression patterns of cell death genes of LSC. By integrating PCD- and LSC-related genes, we identified eight LSC death genes with prognostic values: OAZ1, S100A4, MPG, IL2RA, MMRN1, CDK6, HOXA9, and XIRP2. Based on these genes, we developed a leukemia stem cell prognostic death score (LSCD) and a prognostic nomogram. Our findings revealed that LSC, particularly Quiescent LSPC, exhibits a high LSCD score. AML patients with high LSCD score group showed characteristics of significant immune dysfunction and worse prognosis. Additionally, predictions regarding FDA-approved drugs indicated that the high LSCD score group is less sensitive to Venetoclax but more sensitive to Crenolanib, Tandutinib, or Midostaurin. In summary, we developed an LSCD model that shows the predictive potential of clinical prognosis and drug sensitivity. This model provides meaningful insights for personalized treatment of AML patients.

Although CD30-directed chimeric antigen receptor (CAR)-T cell therapy has demonstrated antitumor activity in CD30+ lymphomas, its therapeutic efficacy rema

Background: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease group. Ibrutinib's monotherapy or combination therapy is effective in relapsed/refractory (R/R) DLBCL. However, the treatment response in R/R DLBCL varies from 15% to 90% with different regimens, and the tolerance remains controversial. Areas of Uncertainty: The efficacy and safety of ibrutinib monotherapy or combination therapy in patients with R/R DLBCL remain uncertain. Data Sources: The PubMed, CBM, MEDLINE, Cochrane Library, and Embase databases were searched from their inception to July 2021. Therapeutic Advances: The total complete remission rate (CRR) and overall response rate in R/R DLBCL patients treated with ibrutinib were 26% and 49%, respectively. The CRR of ibrutinib combination therapy was significantly higher than the ibrutinib monotherapy (45% vs. 19%). Moreover, the CRR of patients was 40% in double expressing lymphoma, 35% in central nervous system lymphoma, and 33% in nongerminal center B-cell–like (non-GCB) DLBCL, which was higher than the 8% in those with the GCB subtype. The pooled median PFS and overall survival were 5.57 and 10.17 months, respectively. GCB-DLBCL had the worst overall survival (5.1 months). Nevertheless, we found that combination regimens had no survival advantage compared with monotherapy (P > 0.05), indicating that combination therapy was only a transitional treatment and bridge for chimeric antigen receptor T cells or other treatments. Moreover, 12% of patients on ibrutinib combination therapy had ≥grade 3 adverse events compared with 9% on ibrutinib monotherapy. Conclusions: Ibrutinib monotherapy or combination therapy was safe and effective in treating R/R DLBCL with tolerable adverse reactions.