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Abstract Background The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). Methods 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. Results Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P

Background Chimeric antigen receptor natural killer (CAR-NK) therapy holds great promise for treating hematologic tumors, but its efficacy in solid tumors is limited owing to the lack of suitable targets and poor infiltration of engineered NK cells. Here, we explore whether immunogenic cell death (ICD) marker ERp57 translocated from endoplasmic reticulum to cell surface after drug treatment could be used as a target for CAR-NK therapy.Methods To target ERp57, a VHH phage display library was used for screening ERp57-targeted nanobodies (Nbs). A candidate Nb with high binding affinity to both human and mouse ERp57 was used for constructing CAR-NK cells. Various in vitro and in vivo studies were performed to assess the antitumor efficacy of the constructed CAR-NK cells.Results We demonstrate that the translocation of ERp57 can not only be induced by low-dose oxaliplatin (OXP) treatment but also is spontaneously expressed on the surface of various types of tumor cell lines. Our results show that G6-CAR-NK92 cells can effectively kill various tumor cell lines in vitro on which ERp57 is induced or intrinsically expressed, and also exhibit potent antitumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the antitumor activity of G6-CAR-NK92 cells is synergistically enhanced by the low-dose ICD-inducible drug OXP.Conclusion Collectively, our findings suggest that ERp57 can be leveraged as a new tumor antigen for CAR-NK targeting, and the resultant CAR-NK cells have the potential to be applied as a broad-spectrum immune cell therapy for various cancers by combining with ICD inducer drugs.

Objectives The aim of this retrospective study was to evaluate the safety and efficacy of SEAM regimen followed by auto-SCT in lymphoma.Patients and methods We retrospectively reviewed the records of patients with lymphoma who underwent auto-SCT with SEAM conditioning regimen from January 2010 to June 2018 at our centre. In total, 97 patients were analysed.Results The median time to neutrophil engraftment and platelet engraftment was 9.5 days (range, 7–15 days) and 12 days (range, 7–25 days), respectively. Grade 3–4 nausea/vomiting, mucositis and diarrhoea were observed in 21.6%, 36.1%, and 11.3% of patients, respectively. Treatment-related mortality at 100 days occurred in 2 patients (2.1%). After a median follow-up time of 53.9 months, the 3-year incidence of disease relapse or progression was 34%. The estimated progression-free survival and overall survival at 3 years were 62% and 75%, respectively. Compared with previous studies using BEAM as the conditioning regimen, this study shows that the SEAM regimen has a comparable efficacy and safety profile.Conclusions The SEAM regimen is feasible and might be an ideal alternative to BEAM regimen for lymphoma auto-SCT.

Primary diffuse large B cell lymphoma of the central nervous system (CNS DLBCL) is a rare malignancy with a distinct genetic profile. The clinicopathological significance of the mutation patterns remains unknown. Forty cases of primary CNS DLBCL were subjected to targeted exome sequencing covering 413 genes, including MYD88, CD79B and PIM1. Mutational analysis recognized two groups. The CDP (including CD79B and/or PIM1mutations) group was identified in 27 cases (67.5%), and the non-CDP (without CD79B and PIM1 mutations) group was identified in 13 cases 32.5%). The CDP group tended to occur in older patients (median age 57.0 vs. 48.4 years, p=0.015). Patients in the CDP group had a significantly longer 2-year overall survival (OS) (76% and 40%, p=0.0372) than those in the non-CDP group. Multivariate analysis revealed that age less than 60 years, no MYC and BCL2 double expression, and CDP group were three independent risk factors indicating favorable OS. PyClone analysis revealed the subcloning heterogeneity between the groups. In addition, transcriptional sequencing was successfully performed in 8 cases. A total of 131 genes were significantly differentially expressed between these two groups. The major categories of biological processes that were significantly altered between these two groups related to intracellular metabolism mechanisms. We developed a new molecular classification to divide CNS DLBCL into CDP and non-CDP groups based on CD79B and PIM1 mutational status. Patients with PIM1 and/or CD79B mutations had favorable long-term survival after high-dose methotrexate-based polychemotherapy.