Quality of life and related demographic factors in long-term survivors of childhood non-Hodgkin's lymphoma. / å„¿ç«¥éžéœå¥‡é‡‘æ·‹å·´ç˜¤é•¿æœŸç”Ÿå­˜è€ ç”Ÿæ´»è´¨é‡åŠç›¸å ³äººå£å­¦å› ç´ ç ”ç©¶.

OBJECTIVES: To evaluate the quality of life and related demographic factors in long-term survivors of childhood non-Hodgkin's lymphoma (NHL). METHODS: A retrospective analysis was performed on the medical and demographic data of the NHL patients who received treatment in the Sun Yat-sen University Cancer Center and achieved long-term survival at follow-up, with an age of <18 years at initial diagnosis and a present age of ≥18 years. A questionnaire survey was performed using 36-Item Short-Form Health Survey (SF-36) and the symptom subscale of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30). The health status of long-term survivors of NHL was evaluated by comparing the scores of various dimensions of the SF-36 scale of general adult population in the United States (American norm) and those of the SF-36 scale of general adult population in Hong Kong, China (Hong Kong norm). The correlation between the score of each dimension of the scale and demographic characteristics was evaluated. The symptoms of long-term NHL survivors were evaluated according to the score of QLQ-C30 scale. RESULTS: A total of 23 patients with NHL with complete follow-up data were enrolled. The pathological types included diffuse large B-cell lymphoma in 10 patients, Burkitt lymphoma in 4 patients, T-cell lymphoblastoma in 5 patients, B-cell lymphoblastoma in 3 patients, and natural killer/T cell lymphoma in 1 patient. All patients received the chemotherapy regimen containing anthracyclines and alkylating agents. The median present age was 26.2 years (range: 16.9-55.8 years), and the median age at initial diagnosis was 10.4 years (range: 2.4-17.6 years). Among the 23 patients, 6 were married and had children and 2 had chronic diseases. There was no significant difference between the long-term survivors and the US norm in role physical, general health, role-emotional, and mental health (P>0.05), while the long-term survivors had significantly better scores of the other dimensions than the US norm (P<0.05). Similar results were obtained for the comparison between the long-term survivors and the China Hong Kong norm. Age at initial diagnosis was negatively correlated with the scores of social functioning, role physical, and general health in the SF-36 scale (P<0.05), and the present age of patients was positively correlated with the score of physical functioning and was negatively correlated with the score of general health (P<0.05). The urban and rural distribution of patients was related to the general health status (P<0.05). In addition, the long-term survivors of childhood NHL had relatively low scores of the symptom domain of QLQ-C30, and few moderate or severe symptoms were found. CONCLUSIONS: Long-term survivors of childhood NHL tend to have a good overall health status, with no significant differences compared with the general population. Age at initial diagnosis is the main demographic factor that affects patients' quality of life. Citation.

[Role of c-Myc in mesenchymal stromal cell-mediated drug resistance in acute leukemia cells].

OBJECTIVE: To explore the role of c-Myc in mesenchymal stromal cell-mediated drug resistance and elucidate the molecular mechanism of acute myeloid leukemia (AML) from the version of tumor microenvironment. METHODS: AML cell lines U937 and KG1a were co-cultured with mesenchymal stromal cells (MSC) from bone marrow of healthy donors between January to March 2012. The AML cell lines plated alone was cultured as controls. Apoptosis induced by mitoxantrone was measured by flow cytometry and Annexin V/PI double and 4'-6-diamidino-2-phenylindole (DAPI) staining. And c-Myc protein was detected by Western blot under both culturing conditions. After a pre-treatment of c-Myc inhibitor 10058-F4, the apoptosis of AML cell was also evaluated. RESULTS: Apoptosis of AML cells (U937 and KG1a) significantly decreased during co-culturing with MSC (9.88% ± 1.53% vs 42.83% ± 2.03%, P = 0.004;20.60% ± 2.87% vs 42.53% ± 5.29%, P = 0.030). Drug resistance was implicated. The co-culturing of AML cells with MSC significantly induced an up-regulation of c-Myc. The inhibition of c-Myc with 10058-F4 could induce apoptosis of AML cells. After an addition of 10058-F4 into the co-culture system, the apoptotic rate of KG1a cells significantly increased from 23.87% ± 1.55% to 57.23% ± 3.88% (P = 0.009). Similarly the apoptotic rates spiked from 16.07% ± 2.11% to 53.47% ± 4.08% in U937 cells (P = 0.004) to overcome the stromal cell-mediated drug resistance. CONCLUSIONS: The co-culturing of AML cells and MSC induces an up-regulation of c-Myc protein so as to cause the emergence of chemoresistance. Therefore targeting c-Myc protein may provide a novel therapeutic strategy of AML.

Influence of diabetes mellitus on the biochemical parameters and outcomes of multiple myeloma.

OBJECTIVE: The incidence of MM in most registries remains stable or showing only a slightly increase. However, prevalence of MM is increasing due to the increase in overall survival in the last two decades. The aim of this study was to observe changes in biochemical parameters during the diagnosis and treatment of MM. METHODS: A retrospective analysis was made of the biochemical indicators, survival time, and related adverse events of 196 patients with MM. RESULTS: Of the 196 patients with MM, 26 were diagnosed with DM (DM-MM group) at the first diagnosis, 31 with steroid-induced diabetes mellitus (SID-MM group) during treatment, and 139 without DM (MM group). There was no significant difference between the three groups in the mean age of onset, sex ratio, incidence of hypercalcemia, renal dysfunction, anemia, abnormal lactate dehydrogenase, and median value of D-dimer and fibrinogen during diagnosis and treatment. There was no significant difference in survival time between the SID-MM and MM groups, but there was a significant difference between the DM-MM and MM groups. CONCLUSION: There was no significant difference between the three groups in the incidence of hypercalcemia, anemia, and renal function impairment. The survival time of patients with DM was shorter than that of patients without DM.

[Clinical features and outcome analyses of newly-diagnosed multiple myeloma with extramedullary involvements].

OBJECTIVE: To explore the clinical features and prognostic factors of newly-diagnosed multiple myeloma (MM) with extramedullary (EM) involvements. METHODS: The clinical features, efficacies, survival rates and prognostic factors were retrospectively analyzed in 46 MM patients with EM (group A) from January 2000 to October 2011. And another 53 MM patients without EM (group B) were selected as the controls. RESULTS: The median age of Group A was 58 years. Compared with group B, the incidence of EM was associated with a higher level of ß2-microglobulin (ß2-MG) and extensive bone disease. The most common location of EM was soft tissues. And the total effective rates of groups A and B were 58.5% (24/41) and 78.8% (41/52) respectively. The difference was statistically significant (P = 0.042). The median follow-up time was 28(2-88) months. The estimated overall survival (OS) of the patients with EM was significantly shorter than those without EM (42.6 vs 53.9 months, P = 0.009). Log-rank univariate analysis showed that the number of osteolytic lesions ≥ 3, ß2-MG ≥ 5.5 mg/L, hemoglobin ≤ 110 g/L and albumin ≤ 30 g/L were poor prognostic factors in MM patients with EM. Multivariate analysis with Cox model showed only the number of osteolytic lesions ≥ 3 (OR = 2.327, 95%CI: 1.282 - 4.224) and ß2-MG ≥ 5.5 mg/L (OR = 2.677, 95%CI: 1.092 - 6.566) were statistically significant. CONCLUSIONS: Multiple EM lesions may be involved in MM patients. For the patients with EM, the response to conventional chemotherapy is poor and the prognosis is unfavorable, especially for those with a high level of ß2-MG or the number of osteolytic lesions ≥ 3.

Immune-Related LncRNAs as Prognostic Factors for Pediatric Rhabdoid Tumor of the Kidney.

Background: Immune-related long noncoding RNAs (IrlncRNAs) are recognized as important prognostic factors in a variety of cancers, but thus far, their prognostic value in pediatric rhabdoid tumor of the kidney (pRTK) has not been reported. Here, we clarified the associations between IrlncRNAs and overall survival (OS) of pRTK patients and constructed a model to predict their prognosis. Methods: We accessed RNA sequencing data and corresponding clinical data of pRTK from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. An expression profile of immune-related genes (Irgenes) and lncRNAs of pRTK was extracted from the RNA sequencing data. IrlncRNAs were defined by co-expression analysis of lncRNAs and Irgenes. The limma R package was used to identify differential expression IrlncRNAs. Univariate and multivariate Cox regression analyses were conducted to build a prognostic IrlncRNAs model. The performance of this prognostic model was validated by multimethods, like ROC curve analysis. Results: A total of 1097 IrlncRNAs were defined. Univariate Cox regression analysis identified 7 IrlncRNAs (AC004791.2, AP003068.23, RP11-54O7.14, RP11-680F8.1, TBC1D3P1-DHX40P1, TUNAR, and XXbac-BPG308K3.5) and were significantly associated with OS. Multivariate regression analysis constructed the best prognostic model based on the expression of AC004791.2, AP003068.23, RP11-54O7.14, TBC1D3P1-DHX40P1, and TUNAR. According to the prognostic model, a risk score of each patient was calculated, and patients were divided into high-risk and low-risk groups accordingly. The survival time of low-risk patients was significantly better than high-risk patients (p < 0.001). Univariate (hazard ratio 1.098, 95% confidence interval 1.048-1.149, p value <0.001) and multivariate (hazard ratio 1.095, 95% confidence interval 1.043-1.150, p value <0.001) analyses confirmed that the prognostic model was reliable and independent in prediction of OS. Time-dependent ROC analysis showed that 1-year survival AUC of prognostic model, stage, age, and sex was 0.824, 0.673, 0.531, and 0.495, respectively, which suggested that the prognostic model was the best predictor of survival in pRTK patients. Conclusions: The prognostic model based on 5 IrlncRNAs was robust and could better predict the survival of pRTK than other clinical factors. Additionally, the mechanism of regulation and action of prognosis-associated lncRNAs could provide new avenues for basic research to explore the mechanism of tumor initiation and development in order to prevent and treat pRTK.

[Immunomodulatory effects of mesenchymal stem cells derived from the bone marrow in acute leukemia patients].

OBJECTIVE: To study the immunomodulatory effects and mechanisms of mesenchymal stem cells (MSC) derived from the bone marrow in acute leukemia patients in vitro. METHODS: Bone marrow mononuclear cells from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) were obtained and cultured in low serum medium. The immunophenotypes were assessed by FACS and immunol histochemistry. The levels of cytokines were evaluated by enzyme linked immunosorbant assay (ELISA). T-cell suppression ability was evaluated by Transwell chamber assay. Moreover, the immunoregulatory ability of AML- and ALL-derived MSC was detected by mixed lymphocyte culture assay. RESULTS: ALL-derived MSC showed a typical fibroblast-like morphology. They were positive for CD29, CD44 and CD105, the positive rate were 98.81%, 99.25% and 90.52%, respectively, while negative for CD31, CD45 and CD34. Moreover, ALL- and AML-derived MSC didn't express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). ALL and AML derived MSC could secret several cytokines, such as TGF-ß1 (567.58 ± 52.64 and 357.15 ± 33.52), HGF (647.27 ± 102.54 and 219.67 ± 62.37), IL-6 (59.67 ± 15.69 and 54.35 ± 12.31) and IL-11 (102.58 ± 23.54 and 78.21 ± 9.67), the level of secretion of TGF-ß1 and HGF were higher in ALL bone marrow derived MSC than that of in AML bone marrow derived MSC. ALL and AML derived MSC significantly suppressed T lymphocyte proliferation in a dose-dependent manner, the counts per minute (CPM) were (3.58 ± 0.54) × 10(4), (2.87 ± 0.33) × 10(4), (1.78 ± 0.51) × 10(4) and (1.15 ± 0.15) × 10(4) for AML derived MSC, and CPM were (1.96 ± 0.31) × 10(4), (1.57 ± 0.28) × 10(4), (0.91 ± 0.41) × 10(4) and (0.22 ± 0.11) × 10(4) for ALL derived MSC when MSC were 0.5 × 10(4), 1 × 10(4), 2 × 10(4) and 5 × 10(4). In addition, the CPM was (4.01 ± 0.72) × 10(4) in control group. The immunosuppressive ability was different between MSCs derived from AML and ALL. The immunosuppressive effect of ALL derived MSC could be reversed by anti-TGF-ß1 and anti-HGF antibody. CONCLUSION: ALL-derived MSC show immunoregulatory effect in vitro and this effect is achieved through cytokines. But MSCs derived from AML display abnormal changes in T-cell suppression ability.

[Expression of stromal cell derived factor-1/CXCR4 biology axis in myelodysplastic syndromes].

OBJECTIVE: To explore the expression of stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 in myelodysplastic syndromes (MDS). METHODS: A total of 59 patients with a diagnosis of MDS were divided into low-grade (n = 33) and high-grade (n = 26) groups according to international prognostic scoring system (IPSS). Bone marrow (BM) samples were collected. The SDF-1 and VEGF levels in BM plasma, CXCR4 expression on BM CD34(+) cell and the apoptosis of CD34(+) cells were measured. RESULTS: The SDF-1 levels in MDS patients were significantly higher than those of normal controls [(689 ± 190) ng/L, P < 0.05]. And the low-grade group was significantly higher than that of high-grade group [(2301 ± 413) vs (1173 ± 501) ng/L]. CXCR4 expression on CD34(+) cells were significantly higher in high-grade group (68.1% ± 18.8%) than that of both low-grade (21.0% ± 9.7%) and control groups (19.4% ± 5.3%) (P < 0.05). Apoptotic rate of CD34(+) cells were 54.8% ± 10.2% in low-grade group, 24.3% ± 7.9% in high-grade group and 18.5% ± 8.7% in control group. It significantly increased in low-grade group versus other groups (P < 0.05). VEGF levels were significantly higher in MDS patients in low-grade group [(286 ± 97) ng/L] and high-grade group [(407 ± 168) ng/L] versus control group [(157 ± 46) ng/L, P < 0.05]. A positive correlation was found between apoptosis of CD34(+) cells and SDF-1 levels in low-grade group (r = 0.805, P < 0.05), VEGF levels and CXCR4 expression rate in high-grade group (r = 0.683, P < 0.05). CONCLUSION: The expression of SDF-1/CXCR4 is significantly abnormal in MDS patients. And it is correlated with apoptosis and angiogenesis. Intervention of SDF-1/CXCR4 axis may provide a new therapeutic target.

[Clinical Analysis of B-Cell Non-Hodgkin Lymphoma Treated with Modified Conditioning Regimen].

OBJECTIVE: To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma. METHODS: 36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis. RESULTS: The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis. CONCLUSION: The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.

Frequent amplification of HDAC genes and efficacy of HDAC inhibitor chidamide and PD-1 blockade combination in soft tissue sarcoma.

BACKGROUND: The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival. METHODS: Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study. RESULTS: The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1. CONCLUSIONS: The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.

[Research Advance of Exosomes in the Immune Microenvironment of Hematological Malignancies--Review].

Exosomes are microvesicles that can be secreting in many kinds of cells, under the condition of normal and pathology. Exosomes contain abundant proteins, miRNAs and RNA fragments, which play an important role in communicating between cells, especially non-contact cells. The interaction between blood tumor cells and immune microenvironment is inseparable from the involvement of exosomes. Exosomes are involved in the interaction among tumor cells, NK cells, T cells, stromal cells and endothelial cells, such as promoting the proliferation of blood tumor cells, helping blood tumor cells to achieve immune evasion, promoting angiogenesis and migration of tumor cells. Therefore, exosomes are closely related to the diagnosis, treatment and prognosis of hematological tumors. In this review, the basic characteristics of exosomes, the important role of exosomes in the immune microenvironment of hematological tumors, and the research progress of exosomes in clinical applications was sammrized briefly.

[Clinical Characteristics of 219 Patients with Primary Gastrointestinal Non-Hodgkin's Lymphoma].

OBJECTIVE: To analyze the clinical and pathological characteristics of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL) patients, and to explore the factors affecting the patients' survival and prognosis. METHODS: The clinical data of 219 patients with PGI-NHL diagnosed in our hospital from March 2009 to April 2016 was collected and retrospectively analyzed. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison among the groups, and Cox regression was used for multivariate analysis. RESULTS: Among the 219 patients with PGI-NHL, 126 patients were males and 93 patients were females. 182 patients were IPI 0 to 2 and 37 patients were IPI 3 to 5. There were 205 cases (93.6%) of B cell phenotype and 14 cases (6.4%) of T cell phenotype. 140 patients (63.9%) were patients with primary gastric NHL, including 85 DLBCL and 19 MALT. 79 cases (36.1%) were patients with primary intestinal NHL, including 46 DLBCL, 4 MALT, 7 FL, 3 MCL and 4 Burkitt lymphoma. 23 cases were HP positive and received anti-HP therapy. 57 cases and 32 cases received surgery and chemotherapy respectively. 84 cases received combination treatment of surgery and chemotherapy and 11 cases received combination treatment of radiotherapy and chemotherapy. Overall survival (OS) of indolent B-cell non-Hodgkin's lymphoma was longer than that of invasive B-cell non-Hodgkin's lymphoma, which shows better prognose. Kaplan-Meier analysis showed that there was no difference between progression-free survival (PFS) and OS in the patients with different origin sites, age and sex. There was no significant difference in PFS between B-cell and T-cell-derived patients, whereas OS of B-cell-derived PGI-NHL patients was longer than that of T-cell-derived PGI-NHL patients. The OS and PFS of patients with IPI 0-2 were longer than those of patients with IPI 3-5. According to Lugano and Ann Arbor staging systems, there was no difference in prognosis of patients between phase I/II and III/IV. The prognosis of patients treated with surgery alone was worse than that of patients treated with combination therapy, and the prognosis of patients with surgery combined with chemotherapy was not significantly different from that of patients with chemotherapy alone. CONCLUSION: B-cell phenotype, indolent and low IPI score lymphoma indicate better prognosis, while that of different origin site, sex and age shows no different in prognosis. Surgery is used only for emergency case or pathological materials, and these patients should be treated with chemotherapy-based combined treatment.

Comparison of Long-Term Outcomes and Sequelae Between Children and Adult Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy.

PURPOSE: Our purpose was to compare long-term survival outcomes and sequelae between child and adult nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy. METHODS AND MATERIALS: Data on 285 patients with NPC aged ≤18 years at diagnosis and treated with intensity modulated radiation therapy between January 2004 and November 2016 were retrospectively reviewed. A propensity score matching method was adopted to screen matched adult patients with NPC at a ratio of 1:3. Survival outcomes and treatment-related toxicities between child and adult groups were compared. RESULTS: In total, 159 children and 477 adult patients with NPC were included in this study. The 5-year overall survival, distant metastasis-free survival, locoregional relapse-free survival, and disease-free survival between children and adults were 89.2% versus 83.6% (P = .144), 88.7% versus 83.5% (P = .124), 96.4% versus 89.1% (P = .013), and 86.5% versus 77.3% (P = .021), respectively. Subgroup analyses revealed that the young age was an independent prognostic factor of overall survival, distant metastasis-free survival, and locoregional relapse-free survival in the advanced N stage (N2-3) group and disease-free survival in the advanced T stage (T3-4) group and N2-3 and stage III-IVA groups. The most common sequela was ototoxicity (68.9%) in child patients and xerostomia (70.8%) in adult patients. Adult survivors had a significantly higher incidence of grade 3 to 4 late toxicities in xerostomia (17.6% vs 8.9%; P = .004), skin dystrophy (9.3% vs 3.7%; P = .022), neck fibrosis (8.3% vs 4.4%; P < .001), and radiation encephalopathy (0.8% vs 0; P = .006). Child survivors were more likely to develop grade 3 to 4 growth retardation and endocrine insufficiency (3.0% vs 0.3%; P = .014). CONCLUSIONS: Child patients with NPC achieved significantly better survival outcomes but fewer late toxicities than adult patients. However, we should pay great attention to growth problems of child survivors.

Ultrasound elastography of ethanol-induced hepatic lesions: in vitro study.

OBJECTIVE: To study the value of ultrasound elastography in evaluation of ethanol-induced lesions of liver. METHODS: Alcohol with a dose of 2 ml was injected into a fresh porcine liver under ultrasound guidance to create stiff necrosis. Then freehand elastography of the lesion from the identical scan plane was obtained with SONOLINE Antares system using VF10-5 probe at about every 30 seconds till 6 minutes later. The original high quality radiofrequency data were acquired through an ultrasound research interface which was provided by the ultrasound system. Then, corresponding elastograms were produced offline using cross-correlation technique and compared with gross pathology findings. RESULTS: Gray-scale sonogram showed a hyperechoic area with acoustic shadow below appeared immediately after alcohol injection. The hyperechoic area tended to be diffuse and its boundary to be illegible with time. On the contrary, the ethanol-induced lesion in elastogram appeared as a low strain hard region surrounded by high strain soft hepatic tissues, with clear but irregular boundaries. Sequential elastograms with the sketched lesion boundaries showed that the lesion area increased in the first 3 minutes after ethanol injection, and then reached a plateau which corresponding to gross specimen. CONCLUSION: Ultrasound elastography is capable of detecting and evaluating the diffusion of ethanol-induced hepatic lesion, and more sensitive and accurate than routine sonography.

[Comparison of Different Staging Systems and Prognostic Analysis in 68 Cases of Primary Intestinal Diffuse Large B Cell Lymphoma].

OBJECTIVE: To compare the prognostic value of different staging systems in primary intestinal diffuse large B cell lymphoma（PI-DLPCL）, and their correlation with clinicopathological characteristics，treatment and prognosis of PI-DLBCL. METHODS: A total of 68 patients with PI-DLBCL were recruited from January 2009 to July 2017. All the patients underwent staging by using TNM, Lugano, Blackledge and Musshoff system, survival curves for the PI-DLBCL patients were plotted using the Kaplan-Meier method and were judged by the log-rank test. The accuracy of each staging system for predicting survival of PI-DLBCL patients was evaluated by calculating the area under curve(AUC) of the receiver operating characteristic(ROC). The correlation of the 4 staging systems, clinical features patients and treatment regimes with PFS and OS were analysed. RESULTS: The median follow-up time was 52 (1-105) months, the median PFS time was 41(1-86) months, patients did not reached the median OS time. The most frequently involved site was ileocecal (30.9%), followed by small intestine (29.4%) and colon (29.4%), multiple sites involvement (7.4%) and rectum (2.94%)．The PFS and OS rates at 5-year were 44.9% and 51.1%, respectively. Kaplan-Meier survival curves and log-rank test results showed that using different staging systems to describe the cumulative retention rates of PFS and OS in PI-DLBCL patients, none of the 4 staging systems can distinguish the survival curves of each stage significantly. The results of ROC curve showed that the prediction ability of the Lugano staging system was better than other staging system for 1 year PFS （AUC=0.826；P=0.015）and 1 year OS（AUC=0-792；P=0.001） in PI-DLBCL patients. The 3 year PFS rate in the operation+chemo or radio-therapy group (62 cases) and the single operation group (6 cases) were 53.9% and 16. 7%,respectively（P=0.116），The 3 year OS rate were 66.7% and 16.7%（P=0.015）,respectively. Patients who received chemotherapy combined with rituximab had a higher 3-year PFS(66.0％ vs 44.0％，P=0.139) and 3.year OS(70.2% vs.39.2%，P=0.148).The patients with ileocecal lesion had higher PFS rate and OS rate than other sites(P<0.05). Multivariate Cox regression analysis indicated that only bone marrow invasion was an independent prognostic factor in patients with PFS. CONCLUSION: Bone marrow invasion is an independent risk factor for PFS in patients with PI-DLBCL , according to this limited preliminary data，Lugano staging system for stratifying and predicting the prognosis of PI-DLBCL patients is better than other staging system.

[Life Quality and Its Related Factors of Patients with Multiple Myeloma during Maintenance Therapy].

OBJECTIVE: To evaluate the quality of life (QOL) on patients with multiple myeloma(MM) during maintenance therapy and to explore the related factors important for QOL. METHODS: The demography, clinical and laboratorial data of 66 MM patients during maintenance therapy were collected and explored by using a cross-sectional question naire(EORTC QLQ C30 V 3.0). The statistical analysis was performed using Nowegram normal mode(NM) and reference values(RV) of MM patients which were used as control. RESULTS: In comparison with Nowegran normal mode, the scores of general health status, physical function, role function and social function of patients during maintenance therapy were lower than those of normal mode (61.3, 73.9, 65.4 and 65.2 vs 75.3, 89.9, 83.3 and 85.8 respectively), while the scores of constipation and financial difficulty were higher than those of normal mode(16.7 and 44.4 vs 10.7 and 9.7 respectively) (P<0.05). In comparison with reference values, the scores of general health status, emotional and coguitive functions of patients during maintenance therapy were significantly higher than those of reference values(61.3, 81.7 and 84.3 vs 55.7, 71.3 and 78.1 respectively) (P<0.05). In addition, the maintenance therapy yet decreasd the scores of fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss and constipation of patients, but increased the score of financial difficulty of patients (P<0.05). The age of initial diagnosis, serum LDH level, peripheral neuropathy, high ratio of own expense and underlying diseases were main factors affecting the general health status of patients (P<0.05), while the decrease of Hb level, increase of blood Ca++ level and accompanied genetic changes negatively influence the QOL (P<0.05), while the high culture level showed positive effect on QOL (P<0.05). The choise of drugs for maintenace (therapy thalidomide and bortezomib) not had significant effect on QOL of patients. CONCLUSION: The maintenance therapy can improve the QOL of MM patients, the age at initial diagnses, serum LDH level, peripheral neuropathy and high ratio of own expence are the main factors affecting the QOL of MM patients.

[Ultrasound elastography of ethanol-induced hepatic lesions].

OBJECTIVE: To study the value of ultrasound elastography in the evaluation of ethanol-induced lesions of liver. METHODS: Alcohol with a dose of 2 ml was injected into a fresh porcine liver under ultrasound guidance to create stiff necrosis. Then freehand elastography of the lesion from the identical scan plane was obtained with Siemens SONOLINE Antares system using VF10-5 probe at about every 30 seconds till 6 minutes later. The original high-quality radio-frequency data were acquired through an ultrasound research interface provided by the ultrasound system. Corresponding elastograms were then produced offline using cross-corre-lation technique and compared with gross specimen. RESULTS: A hyperechoic area with acoustic shadow below appeared immediately after alcohol injection. The hyperechoic area diffused and its boundary was illegible following injection. On the contrary, the ethanol-induced lesion in elastography appeared as a low strain hard region surrounded by high-strain soft hepatic tissues with clear but irregular boundaries. Sequential elastograms with the lesion boundaries sketched showed that the lesion area grew in the first 3 minutes after ethanol injection and then reached a plateau, which corresponded to the gross specimen. CONCLUSION: Ultrasound elastography can be used to detect and evaluate the diffusion of ethanol-induced hepatic lesion.

[Progress of Auto-HSCT for Treatment of DLBCL--Review].

Diffuse large B cell lymphoma（DLBCL）is the most common non-Hodgkin's lymphoma in adults，accounting for 30%-40% of non-Hodgkin's lymphoma in adults. The treatments of this lymphoma mainly include chemotherapy，radiotherapy and autologous hematopoietic stem cell transplantation. A large amount of studies show that autologous hematopoietic stem cell transplantation considered as the main treatmant approach can be used for primary high-risk young and relapsed or refractory DLBCL patients. Many scholars have evaluated the effectiveness of autologous hematopoietic stem cell transplantation for primarily high-risk young and relapsed or refractory DLBCL patients，and tried to improve the effectiveness of transplantation that showed some advantagcs for DLBCL patients.

[Advances in the Molecular Diagnosis and Therapy of Relapsed/Refractory Diffuse Large B-cell Lymphoma -Review].

Diffuse large B-cell lymphoma (DLBCL) is biologically aggressive and most common pathological type of non-Hodgkin's lymphoma (NHL), and about one-third of these patients are refractory or relapsed ultimately. Based on the molecular heterogeneity, DLBCL can be divided into 3 main molecular subtypes: germinal center B-cell like (GCB), activated B-cell like (ABC) and primary mediastinal B-cell lymphoma (PMBL). Arising from B cells at distinct stages of differentiation, these subtypes are also diverse in mechanisms of oncogenic activation. So targeting specific oncogene addictions within the DLBCL subtypes offers a more-precise approach to therapy in comparison with the traditional chemotherapies, undoubtedly bringing a bright hope for the treatment of relapsed/refractory DLBCL. In this article, the advances in diagnosis and therapy of GCB-DLBCL, ABC-DLBCL and PMBL relapsed/refractory diffuse large B-cell lymphoma are summarized.

[Clinical Analysis of Maintenance Therapy with Thalidomine and Bortezomib for Multiple Myeloma].

OBJECTIVE: To evaluate the therapeutic effect and adverse reactions of the maintenance therapies with Thalidomine or Bortezomib in the patients with newly diagnosed multiple myeloma (MM), so as to provide a reference for clinical treatment. METHODS: A retrospective analysis was conducted to compare the progression-free survival (PFS), overall survival (OS) and adverse reaction rate of 23 MM patients received the maintenance therapies of Bortezomib and of 68 MM patients received maintenance therapy of Thalidomine. RESULTS: The maintenance therapy with Bortezomib could extend the PFS of MM patients as compared with Thalidomine (PFS rate of patients on the maintenance therapy of Bortezomib in 12th, and 24th month was 100%, 88.89%, and that of Thalidomine-treated group was 72.31%, 47.54%). What's more, some specific patients could get better 2-year PFS rate in Bortezomib group than that in Thalidomine group, such as older than 65 years old, after autologous hematopoietic stem cell transplantation(ASCT), having genetic changes, extramedullary lesions, poor renal function, low serum free light chain ratio, high ß2-MG, anemia, high LDH, VGPR of induction and consolidation therapy. The OS rate of Bortezomib on 18th, 24th and 30th month was 100%, 88.89%, 80% verus 91.52%,83.63%,72.90% of the group with thalidemide at the same time. As for 2-year OS rate, the Bortezomib group was higher than Thalidomine without statistical differences. However, the patients such as older than 65 years old, poor renal function and with extramedullary lesions, would also get higher 2-year OS rate from Bortezomi. Bortezomib and thalidomide could cause bone marrow suppression, peripheral neuritis and other adverse reactions. CONCLUSION: The efficacy of maintenance therapy with Bortezomib is superior to thalidomide. As a conclusion, bortezomib is a better option for maintenance therapy of MM patient.

[Clinical Analysis on the Therapeutic Efficacy of Autologous Hematopoietic Stem Cell Transplantation in 56 Multiple Myeloma Patients].

OBJECTIVE: To evaluate the therapeutic efficacy and prognosis of autologous stem Hematopoietic cell transplantation (auto-HSCT) in multiple myeloma (MM) patients. METHODS: A retrospective study was conducted for 56 patients diagnosed with MM and then received auto-HSCT in our hospital from December 2008 to September 2016. RESULTS: All the patients successfully underwent hematopoietic reconstruction without transplantation-related mortality (TRM). The complete response (CR) rate of all the patients after induction chemotherapy was 23.2% (13/56), while the CR rate of these patients with auto-HSCT increased to 78.6% (44/56) (P<0.01). The CR plus VGPR (very good partial response) rates of these 56 patients after induction chemotherapy and auto-HSCT were 53.6%（30/56）and 94.6%（53/56） respectively (P<0.01). The median progression-free survival (PFS) time and median overall survival (OS) time were 37 and 71 months, respectively. The median PFS time in the patients with induction therapy containing bortezomib was 37 months, however, the median OS time did not reach to 71 months; the median PFS (P<0.01) and the median OS (P<0.01) in the patients with the induction chemotherapy without bortezomib was 27 and 51 months, respectively. Univariate analysis demonstrated that the patients maintained CR or VGPR after auto-HSCT or with less than 6 cycles of induction chemotherapy significantly correlated with PFS (P<0.01). CONCLUSION: auto-HSCT can further increase the CR rate, prolong PFS and OS time. Sequential auto-HSCT after bortezomib-based therapy is the first line therapy for the transplant-eligible MM patients. Maintenance treatment is beneficial to the sustained CR+VGPR patients after auto-HSCT.