Outcomes in patients with multiple myeloma receiving salvage treatment after BCMA-specific CAR-T therapy: A retrospective analysis of LEGEND-2.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has shown profound efficacy and manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). However, determining the best course of treatment for post-CAR-T therapy relapse remains a significant challenge. We conducted a retrospective analysis of patients from the phase I LEGEND-2 study (NCT03090659) enrolled at the Xi'an site, analysing the first salvage line of therapy and outcomes in patients with RRMM who progressed after receiving LCAR-B38M CAR-T therapy. Of 45 eligible patients, 34 (76%) had progressive disease (PD). Overall response rate (ORR) to salvage treatment was 50.0%. Median progression-free survival (PFS) after starting salvage treatment was 16.3 months. Median PFS of patients receiving proteasome inhibitor (PI)-based combination therapy was longer (28.2 months) than that of patients receiving a second BCMA CAR-T (including LCAR-B38M; 3.9 months, p = 0.0022) or chemotherapy (1.67 months, p = 0.0001). All patients with extramedullary disease at baseline (n = 11) progressed after CAR-T therapy; ORR to salvage therapy was 25.0% and median PFS was 9.7 months. In conclusion, salvage therapy in patients with PD after receiving LCAR-B38M CAR-T cells produced moderate efficacy, with better outcomes for PI-based salvage regimens.

The fabrication of ZIF-L derived ZnS/MoS2@NC anode materials for remarkable lithium-ion storage.

The enhancement of electrochemical performance in lithium-ion batteries can be achieved through the incorporation of MoS2 with carbon materials and various metal sulfides. In this investigation, a MoS2/ZnS heterostructure was devised incorporating a two-dimensional nitrogen-doped carbon nanosheet (NC) backbone. The synthesis of ZnMo-ZIF-L precursors was achieved by introducing a Mo source in a 1:1 molar ratio during ZIF-L synthesis. Subsequent to high-temperature carbonization and vulcanization treatment, ZnS/MoS2@NC composite materials were successfully synthesized. Compared to the unvulcanized ZnO/MoO3@NC and MoS2 samples, the ZnS/MoS2@NC composite exhibits remarkable lithium storage performance. At a current density of 500 mA g-1, the initial discharge specific capacity is 2547 mAh g-1, with an initial charge specific capacity of 1674 mAh g-1, resulting in a first Coulombic efficiency of 65.76%. Furthermore, this composite material demonstrates optimal rate capabilities and a significant pseudocapacitance contribution. The nitrogen-doped carbon framework effectively mitigates volume effects, while the heterostructural design provides more active sites for lithium ions, thereby enhancing lithium storage performance.

Synthesis of Hierarchical CdS/NiS Photocatalysts Using Ni-MOF-74 as Template for Efficient Ethanol Conversion and Hydrogen Production under Visible Light.

The conversion of ethanol into high-valuable chemicals and H2 by photocatalytic process provides a sustainable approach to produce carbon-chain-prolonged chemicals and hydrogen energy. In this article, Ni-MOF-74 was added to fabricate the hierarchical CdS/NiS-N composites with an elevated specific surface area during the hydrothermal synthesis of CdS microsphere, and the Ni-MOF-74 facilitate the self-assemble growth of CdS and provide a source of Ni for the formation of NiS. The as-prepared photocatalyst was subjected to photocatalytic ethanol conversion, and the hierarchical composite material CdS/NiS-N (100) formed by adding 100 mg of Ni-MOF-74 exhibits the highest photocatalytic activity and stability in an ethanol aqueous solution with a water content of 10 %. Under visible light irradiation, the conversion rate of ethanol reached 15.2 % at the photocatalytic reaction of 5 h. The selectivity of 2,3-butanediol(2,3-BDO) was 25 %, and the selectivity of acetaldehyde(AA) was 63 %. Through various characterizations, it has been proven that a large specific surface area and the coupling interface between CdS and NiS are key factors in improving photocatalytic performance. This work provides an effective strategy for constructing photocatalysts with coupled cocatalysts/semiconductors and large specific surface areas.

A comprehensive analysis of coagulopathy during anti-B cell maturation antigen chimeric antigen receptor-T therapy in multiple myeloma, a retrospective study based on LEGEND-2.

Chimeric antigen receptor (CAR)-reprogrammed T cell therapy is a novel and powerful treatment against hematological malignancies. Cytokine release syndrome (CRS) and other potentially life-threatening toxicities are known side effects which need appropriate management and supportive care. Coagulopathy is a common and severe CAR-T-related adverse event, while a comprehensive profile of coagulopathy in patients with multiple myeloma (MM) undergoing CAR-T cell therapy has not been reported. Therefore, we performed a comprehensive analysis of coagulopathy in 51 patients with r/r MM given anti-B cell maturation antigen CAR-T cell therapy. We found that 49% of patients had coagulation disorders, and 29% of patients experienced disseminated intravascular coagulation (DIC). Severe CRS, abnormal liver function and higher tumor burden were risk factors for the CAR-T-related coagulopathy. We found that the serum IL-6 level and alanine aminotransferase level were potential indicators for CAR-T-related DIC. Furthermore, we found that coagulation disorders occurred within 1 month after CAR-T cell infusion, mainly between days 10 and 13, which was 2-5 days later than the beginning of CRS and simultaneous with the beginning of abnormal liver function and the peak of CRS. In addition, although patients with coagulation dysfunction had a trend for better outcomes and prognosis, no statistical significance was found. In conclusion, our research provided a comprehensive understanding of CAR-T-related coagulopathy in MM. Upon timely and standardized treatment, coagulopathy was manageable in most cases.

Correction to: Serum peptidome based biomarkers searching for monitoring minimal residual disease in adult acute lymphocytic leukemia.

[This corrects the article DOI: 10.1186/s12953-014-0049-y.].

LncRNA SNHG5 regulates SOX4 expression through competitive binding to miR-489-3p in acute myeloid leukemia.

OBJECTIVES: Currently, lncRNA plays an important role in the occurrence and development of acute myeloid leukemia (AML), including SNHG5. However, the role and mechanism of SNHG5 in AML remains unclear. In this study, we explored the regulatory mechanism of SNHG5 in the development of AML. METHODS AND RESULTS: QRT-PCR was used to investigate the expression of SNHG5, miR-489-3p, and SOX. The proliferation and apoptosis of AML cells were analyzed by cell transfection, cell counting kit-8 (CCK8), and flow cytometric analysis. Moreover, the expression analysis of marker proteins was detected by western blot. Through luciferase activity assay, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP), we proved that SNHG5 could bind miR-489-3p and SOX4 which might be the target gene of miR-489-3p. RESULTS: We first found that SNHG5 was up-regulated in both AML patient bone marrow samples and various AML cell lines. Second, we found that knockdown of SNHG5 inhibited proliferation of AML cells and promoted apoptosis. It was found that SNHG5 could bind miR-489-3p, and the relative expression of SNHG5 was negatively correlated with miR-489-3p. Further results suggested that SOX4 might be the target gene of miR-489-3p. Finally, our experimental data indicated that knockdown of SNHG5 could reduce the tumor volume and down-regulated SOX4 levels in vivo. CONCLUSIONS: Our results demonstrated that SNHG5 affected the expression of SOX4 through binding miR-489-3p to regulate proliferation and apoptosis of AML, which might act as a prospective prognostic biological marker and a promising therapeutic target for AML.

Silencing of Gal-7 inhibits TGF-ß1-induced apoptosis of human airway epithelial cells through JNK signaling pathway.

Apoptosis of epithelial cells is regarded as the initial pathological process of many lung diseases, including asthma. Previous studies have identified that galectin-7 (Gal-7), a regulator of apoptosis, was overexpressed in bronchial epithelial cells in asthma. However, the effect and mechanism of Gal-7 in the progression of asthma is still unclear. In this study, we investigated the expression and role of Gal-7 in the apoptosis of bronchial epithelial cells BEAS-2B upon TGF-ß1 stimulation. TGF-ß1 significantly induced apoptosis of BEAS-2B cells, as determined by flow cytometry. Western blot results revealed that the mRNA and protein expression of Gal-7 were obviously increased after TGF-ß1 stimulation. Small interfering RNA (siRNA)-mediated knockdown of Gal-7 abrogated TGF-ß1-evoked cell apoptosis. Simultaneously, increased Bcl-2 expression, decreased Bax expression and the cleavage of poly ADP-ribose polymerase (PARP) and caspase-3 activity were also monitored in TGF-ß1-treated cells after Gal-7 siRNA transfection. Gal-7 silence also inhibited TGF-ß1-induced c-Jun N-terminal kinase (JNK) phosphorylation in BEAS-2B cells. Furthermore, anisomycin, a specific activator for JNK, reversed the effect of Gal-7 siRNA on cell apoptosis induced by TGF-ß1. These results demonstrate that Gal-7 silence attenuates TGF-ß1-induced apoptosis in bronchial epithelial cells through the inactivation of JNK pathway. Therefore, Gal-7 may act as a potential target for asthma treatment.

NPAS2 regulates proliferation of acute myeloid leukemia cells via CDC25A-mediated cell cycle progression and apoptosis.

Promoted proliferation and associated suppression of apoptosis at various stages of myeloid differentiation are well-known features of acute myeloid leukemia (AML), but understanding of the molecular processes involved remains limited. As a crucial circadian agent, neuronal PAS domain protein 2 (NPAS2) is widely recognized as a promising predictor of clinical outcome in various malignancies. Nevertheless, the understanding of its influence on AML is insufficient. Using KD cells and expression assays, we carried out detailed investigation of the role of NPAS2 in AML in vivo and in vitro. Firstly, we found that NPAS2 expression was elevated in AML cells both in vivo and in vitro. NPAS2 knockdown via lentiviral infection clearly suppressed proliferation of MV4-11 and MOLM-14 cells. Additionally, NPAS2 knockdown caused G1/S cell cycle arrest (CCA), which inhibited CDC25A expression. Moreover, NPAS2 knockdown promoted cell death, as evidenced by increased caspase-3 cleavage, and change in Bcl2/Bax production. Excessive CDC25A expression eliminated G1/S CCA triggered by NPAS2 knockdown and death of NPAS2 knocked down MOLM and MV4-11 cells. The expression of CDC25A was stabilized by NPAS2, which induced cell cycle progression and participated in suppression of cell death by modulating caspase-3 cleavage, and expression of Bcl2/Bax. We therefore indicated NPAS2 to be a crucial modulator of survival as well as proliferation. Our research sheds light on the etiology of the proliferation of promyelocytes modulated via NPAS2 with regard to AML.

miR-345-5p regulates proliferation, cell cycle, and apoptosis of acute myeloid leukemia cells by targeting AKT2.

Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease, which is caused by hematopoietic stem cell abnormalities. Epigenetic regulation, especially of microRNAs (miRNAs), mostly results from external or environmental effects and is critical to AML. In this study, for the first time, we report that decreased expression of miR-345-5p facilitates the proliferation of leukemia cells in AML. Further study demonstrated that AKT1/2 was the target of miR-345-5p and was responsible for the dysregulation of leukemia cell proliferation and apoptosis. Inhibition of AKT1/2 ameliorated this malignant effect, which provides new insight into AML diagnosis, treatment, prognosis, and next-step translational investigations.

A Robust Solid Electrolyte Interphase Layer Augments the Ion Storage Capacity of Bimetallic-Sulfide-Containing Potassium-Ion Batteries.

Metal-organic framework-derived NiCo2.5 S4 microrods wrapped in reduced graphene oxide (NCS@RGO) were synthesized for potassium-ion storage. Upon coordination with organic potassium salts, NCS@RGO exhibits an ultrahigh initial reversible specific capacity (602 mAh g-1 at 50 mA g-1 ) and ultralong cycle life (a reversible specific capacity of 495 mAh g-1 at 200 mA g-1 after 1 900 cycles over 314 days). Furthermore, the battery demonstrates a high initial Coulombic efficiency of 78 %, outperforming most sulfides reported previously. Advanced ex situ characterization techniques, including atomic force microscopy, were used for evaluation and the results indicate that the organic potassium salt-containing electrolyte helps to form thin and robust solid electrolyte interphase layers, which reduce the formation of byproducts during the potassiation-depotassiation process and enhance the mechanical stability of electrodes. The excellent conductivity of the RGO in the composites, and the robust interface between the electrodes and electrolytes, imbue the electrode with useful properties; including, ultrafast potassium-ion storage with a reversible specific capacity of 402 mAh g-1 even at 2 A g-1 .

MicroRNA-103 confers the resistance to long-treatment of adriamycin to human leukemia cells by regulation of COP1.

Adriamycin (ADR) is an anti-cancer drug which offers improvement in survival for acute myeloid leukemia (AML) patients. However, the drug resistance is almost inevitable. Increasing evidences suggested that microRNAs (miRNAs) were associated with cancer chemo-resistance. Here, we aimed to explore the possible mechanism of miR-103 affected resistance to ADR in AML cells. Different concentrations of ADR were used to induce K562 and KASUMI-1 cells, and miR-103 mimic, inhibitor were transfected into K562 and KASUMI-1 cells. Cell viability and proliferation were determined by trypan blue staining and MTT assays for evaluating K562 and KASUMI-1 cells drug resistance. The relationship of miR-103 and COP1, Trib1, and C/EBPα were analyzed by qRT-PCR and Western blot. Cell proliferation, viability were detected again. Besides, the expressions of main factors of cell cycle and PI3K/AKT signal pathway were analyzed by Western blot. Results showed that ADR inhibited cell viability and proliferation in K562 and KASUMI-1 cells. However, K562 and KASUMI-1 cells appeared drug resistance for 50 passages at 0.8 µM of ADR. In addition, miR-103 expression was up-regulated in ADR-resistant K562 cells (K562/ADR) and overexpression of miR-103 increased K562 cells drug resistance via promoting cell viability and cell cycle-related factors expressions. COP1 was positively regulated by miR-103, suppression of miR-103 recovered K562/ADR cells drug resistance by regulation of COP1, Trib1, and C/EBPα. Besides, miR-103 blocked PI3K/AKT signal pathway by regulation of COP1. These data indicated that miR-103 was up-regulated in drug resistant cells and it may regulate ADR-resistance by regulation of COP1 in AML cells.

Infusion of leukocytes from HLA haplo-identical familial donors as an adjuvant in the HLH-2004 protocol to treat the virus-associated adult hemophagocytic lymphohistiocytosis: a retrospective study of 26 patients.

Adult hemophagocytic lymphohistiocytosis (HLH) is a fatal disease with poor survival and a limited role of drug therapies. To help to recognize virus and enhance survival, we infused leukocytes derived from human leukocyte antigen (HLA) haplo-identical familial donors to patients. We retrospectively investigated 26 adult virus-associated hemophagocytic syndrome (VAHS) patients' medical records from 2006-2017. Eleven of the 26 patients accepted relatives' derived leukocytes infusions in addition to drug therapies recommended in the HLH-2004 protocol. The leukocyte doses ranged from 0.75 to 3.30×108 per kilogram of body weight. The other 15 patients accepted immunosuppressive and supportive therapies referred to in the HLH-2004 protocol. We compared the treatment outcomes of the two groups of patients. Patients in the cell infusion group had a lower viral load (P = 0.023) and better laboratory results and prolonged overall survival (60.44 vs. 20.18 weeks, P = 0.047). A factor that might relate to overall survival is platelet count (P = 0.032), except for the leukocyte infusions (P = 0.012). For patients without acceptable donors, infusions of leukocytes from HLA haplo-identical familial donors could be a feasible treatment to prolong overall survival as an adjuvant to drug therapies.

Well-Aligned Au/TiO2 Nanorods by Magnetron Sputtering with Enhanced Photocatalytic Properties.

In this work, we demonstrate the feasibility of preparing Au/TiO2 nanorods via a dc magnetron sputtering at room temperature and heat-treatment at 500 °C in air for 2 h. The heat treatment leads to the migration of Au atoms into TiO2 nanofilm to form Au/TiO2 nanorods with Au nanoparticles embedded in the TiO2 nanorods of anatase phase. The Au nanoparticles in the TiO2 nanorods suppress the charge recombination. These Au/TiO2 nanorods showed high absorption and intensive response to the visible light and had improved photocatalytic properties in comparison with pure TiO2 nanoparticles formed by using similar method.

A novel multi-epitope vaccine from MMSA-1 and DKK1 for multiple myeloma immunotherapy.

The identification of novel tumour-associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro. To improve the immunotherapy, we constructed a multi-epitope peptide vaccine by combining epitopes derived from MMSA-1 and Dickkopf-1 (DKK1). The effector T cells induced by multi-epitope peptide vaccine-loaded dendritic cells lysed U266 cells more effectively than MMSA-1/DKK1 single-epitope vaccine. In myeloma-bearing severe combined immunodeficient mice, the multi-epitope vaccine improved the survival rate significantly compared with single-epitope vaccine. Consistently, multi-epitope vaccine decreased the tumour volume greatly and alleviated bone destruction. The frequencies of CD4+ and CD8+ T cells was significantly increased in mouse blood induced by the multi-epitope vaccine, indicating that it inhibits myeloma growth by changing T cell subsets and alleviating immune paralysis. This study identified a novel peptide from MMSA-1 and the multi-epitope vaccine will be used to establish appropriate individualized therapy for MM.

Horse versus rabbit antithymocyte globulin in immunosuppressive therapy of treatment-naïve aplastic anemia: a systematic review and meta-analysis.

The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.

Association of Interleukin-10 Polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA Nephropathy in a Chinese Han Population: A Case-Control Study.

BACKGROUND/AIMS: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis worldwide. Previous studies indicated that IL-10 single nucleotide polymorphisms (SNP) play an important role in IgAN pathogenesis, but the results were controversy. This study aimed to investigate the association between IL-10 SNPs (rs1800872, rs1800871, and rs1800896) with IgAN in a Chinese Han population. METHODS: We conducted a case-control study that included 351 patients with IgAN and 310 age-, gender- and ethnicity-matched healthy controls. Three promoter SNPs (rs1800872, rs1800871, and rs1800896) of IL-10 were genotyped by Sequenom MassARRAY. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. RESULTS: We found that the rs1800896 did not correlate with IgAN risk, whereas rs1800872 and rs1800871 were significantly associated with increased IgAN risk in all genetic models. The haplotype analysis indicated that the CCA haplotype was associated with increased IgAN risk (OR = 1.36; 95% CI = 1.05-1.75). Moreover, there were no associations between these SNPs and blood pressure or gender, whereas the rs1800896 variant was correlated with higher 24-hour urine protein in patients with IgAN. CONCLUSION: Taken together, these results suggest that IL-10 is a susceptibility gene in patients with IgAN.

Lack of association between cytotoxic T-lymphocyte antigen-4 gene polymorphisms and lymphoid malignancy risk: evidence from a meta-analysis.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms have been associated with susceptibility to lymphoid malignancies. However, results from the published single studies are inconsistent. Therefore, the present meta-analysis was conducted to get a more accurate estimation of the relationship between CTLA-4 gene polymorphisms and the lymphoid malignancy risk. We identified nine independent studies accounting for 3090 subjects up to January 30, 2016. Summary odds ratios (OR) and 95 % confidence intervals (CI) were used to evaluate the risk of lymphoid malignancies. Overall, no significant association was found between +49A/G (rs231775), -318C/T (rs5742909), and +6230A/G (rs3087243) CTLA-4 gene polymorphisms and lymphoid malignancies. Furthermore, ethnicity (Asian and Caucasian) and histopathology subgroup analyses (non-Hodgkin's lymphoma) also failed to detect an association between the studied polymorphisms and lymphoid malignancy risk. Our study shows that common CTLA-4 gene polymorphisms may not contribute to lymphoid malignancy susceptibility based on the current evidence.

Comparison of porcine anti-human lymphocyte globulin and rabbit anti-human thymocyte globulin in the treatment of severe aplastic anemia: a retrospective single-center study.

OBJECTIVES: To compare the safety and efficacy of porcine antilymphocyte globulin (pALG) and rabbit antithymocyte globulin (rATG) in treating severe aplastic anemia (SAA). METHODS: Seventy-seven patients with SAA that received immunosuppressive therapy between July 2004 and December 2013 at the Department of Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University, were retrospectively analyzed. Forty-five patients received treatment including pALG (pALG group), and 32 patients received treatment including rATG (rATG group). Effective treatment rates between the two groups 1 yr after the treatment were compared; Kaplan-Meier 5-yr survival curve and log-rank test compared survival rates between the groups. All adverse responses were recorded. RESULTS: The 1-yr overall response rate in the pALG group (83.78%) was significantly higher than that in the rATG group (66.67%, P = 0.036), and the 5-yr overall survival rate in the pALG group (82.22%) was also higher than that in the rATG group (68.75%), but the difference was not statistically significant (P = 0.32). The incidence of adverse events was similar in the two groups, and no treatment-related deaths occurred. CONCLUSIONS: The efficacies, survival, and safety profiles of pALG-based treatments are similar to or even better than those of rATG-based treatments. These results may help guide the clinical use of pALG in immunosuppressive therapy for SAA.

High-Intensity Chemotherapy is Associated with Better Prognosis in Young Patients with High-Risk Diffuse Large B-Cell Lymphoma: A 10-Year Single-Center Retrospective Cohort Study.

BACKGROUND Patients <60 years old with high-risk diffuse large B-cell lymphoma (DLBCL) receiving standard RCHOP(E) treatment display high relapse rates. Here, we compared this standard regimen to a high-intensity regimen in terms of recurrence and long-term survival. MATERIAL AND METHODS Newly diagnosed DLBCL patients <60 years old who were treated at the Second Hospital Affiliated with Xi'an Jiaotong University between January 2004 and December 2013 (n=198, 18-60 years) were included in the study. The high-intensity group included 107 patients (54.0%) who received >8 courses of chemotherapy (high-dose CHOP, CHOP-E, EPOCH, MAED, MMED, and HyperCVAD). The control group included 91 patients (46.0%) who received 6-8 courses of CHOP-based treatment. Response rate (RR), survival, relapse, and adverse effects were compared. RESULTS Baseline characteristics of the patients were similar between the 2 groups. Median follow-up was 64.5 months. RR in the high-intensity and control groups was 88.8% and 84.6% (P=0.387), respectively; 5-year overall survival was 66.4% and 36.3% (P<0.001), respectively; 5-year progression-free survival was 56.1% and 28.6% (P<0.001), respectively; 5-year disease-free survival was 54.2% and 24.2% (P<0.001), respectively; and relapse rate during follow-up was 29.5% and 67.5% (P<0.001), respectively. There were no significant differences in adverse effects between the 2 groups. CONCLUSIONS High-intensity chemotherapy is associated with better prognosis of patients <60 years old with newly diagnosed high-risk DLBCL.

Extended Course and Increased Dose of Initial Chemotherapy for Extranodal Nasal Type Natural Killer/T (NK/T)-Cell Lymphoma in Patients <60 Years Old: A Single-Center Retrospective Cohort Study.

BACKGROUND Extranodal NK/T-cell lymphoma (ENKTL) of the nasal type is highly invasive and relatively resistant to chemotherapy. This study aimed to assess the efficacy and safety of an extended chemotherapy regimen with increased dose intensity. MATERIAL AND METHODS This was a retrospective cohort study of 69 patients <60 years old with an ECOG score 0-2 treated for ENKTL at the Second Affiliated Hospital of Xi'an Jiaotong University between January 2004 and December 2013. The outcomes were compared between patients who received >8 courses of high-intensity chemotherapy (n=37) vs. 6-8 courses (n=18) and <6 courses (n=14) of conventional chemotherapy. Regimens included improved CHOP, CHOP-E, EPOCH, MAED, MMED, SMILE, and Hyper-CVAD with an increased dose intensity in the >8 courses group. RESULTS The mean follow-up was 52 months (8 to 82 months). Remission rate did not differ significantly when compared among the 3 groups after 3 courses of chemotherapy (83.8%, 77.8%, and 78.6%, respectively, overall P=0.834), but the 5-year overall survival (OS) differed significantly (63.5%, 45.1%, and 22.9%, respectively, overall P=0.030), as did progression-free survival (PFS) (59.1%, 36.0%, and 15.1%, respectively, overall P=0.020), disease-free survival (DFS) (54.1%, 35.5%, and 12.9%, respectively, overall P=0.022), and total relapse rate throughout follow-up (37.04%, 50.0%, and 88.89%, respectively, overall P=0.027). There were no differences in adverse effects among the 3 groups. CONCLUSIONS These results suggest improved OS, PFS, DFS, and relapse rate in young patients with ENKTL receiving >8 courses of high-intensity chemotherapy.