[A Real-World Single-Center Study of Adult Hodgkin's Lymphoma].

OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

[Analysis of the Prognostic Value and Risk Factors of Early Relapse for Newly Diagnosed Multiple Myeloma Patients in the Era of Novel Agents].

OBJECTIVE: To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma（NDMM） and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment. METHODS: The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival（PFS） was more than 12 months, they were divided into early relapse group（≤12 months） and late relapse group（＞12 months）. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase（LDH） level, Extramedullary disease (EMD), International Staging System（ISS） stage, Revised International Staging System （R-ISS） stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization（FISH）, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse. RESULTS: 170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups（P<0.001）. Fifteen patients（56.0％）in early relapse group obtained ≥VGPR, and 113（77.9%） patients in late relapse group, the difference was statistically significant（P=0.011）. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse. CONCLUSION: The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.

[Clinical Characteristics and Prognosis Affecting-Factors of the Patients with Burkitt Lymphoma].

OBJECTIVE: To investigate the clinical characteristics and treatment outcome of patients with Burkitt lymphoma. METHODS: The clinical data of 27 patients with Burkitt Lymphoma were collected and retrospectively analyzed, the clinical characteristics, laboratory data, survival and the factors affecting the prognosis were also analyzed. RESULTS: Among the 27 patients (mainly for adults), the median age was 30 (15-83) years old, the ratio of male and female was 3.5∶1. There was no EB virus infection in all the patients, 92.6% of the patients showed extranodal organs involvement, 40.7% of them were leukemic stage, 85.2% patients belonged to Ⅲ and Ⅳ stage, 74.1% patients belonged to high/high-middle risk according to IPI index. In the terms of molecular biology, five patients were treated with next-generation sequencing test, and the MYC gene mutations were detected out in alt the patients, and the most common mutations were CCND3, ID3 and TP53. The overall response rate (ORR) for all the patients was 85.2%, the complete response (CR) rate was 63.0%, and the partial response rate was 22.2%, the 5-year progression-free survival rate and overall survival rate of the patients was 76.6% and 76.6%, respectively, which showed that the efficacy of the patients in high-dose methotrexate treatment group was higher than that in the non-high high-dose methotrexate treatment group. For the patients treated with LMB89 chemotherapy, the CR was 78.6%, ORR was 100%, the 5-year survival rate was 92.9%, which was superior to the patients treated with other regimens. Auto-hematopoietic stem cell transplantation as consolidation treatment could improve the prognosis for those patients who could not tolerate high-dose chemotherapy. Univariate analysis showed that ECOG score, the level of LDH>500 U/L, WBC level, CNS involvement, short-term effect and LMB89 regimen were the risk factors affecting the prognosis of the patients. CONCLUSION: The adult Burkitt lymphoma are highly aggressive. For the patients in high-dose methotrexate treatment group, especially LMB89 regimen can improve the survival of the patients, and to choose HSCT as a consolidation treatment can be a choice for those patients who could not tolerate high-dose chemotherapy.

[Analysis on Clinical Characteristics and Prognosis of 47 Patients with Extranodal NK/T Cell Lymphoma].

OBJECTIVE: To investigate the clinical features and prognostic factors of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of patients with ENKTL from November 2009 to November 2019 was collected and retrospectively analyzed to clarify the clinical features of ENKTL, and evaluate the factors that affected survival and prognosis. RESULTS: Forty-seven patients with ENKTL were collected, median age was 40 (12-82) years old, and more common in males than females, at the ratio of 1.47∶ 1. The median follow-up was 28 (1-112) months, and 5-year overall survival (OS) rate was 49.3%. The 5-year OS rates of the subjects with ECOG performance stage 0-1 and ≥2 were 51.6% and 0 (P=0.001), respectively. The 5-year OS rates of International Prognostic Index (IPI) score 0-1 and ≥2 were 60.0% and 40.6% (P=0.027), respectively. The 5-year OS rates of Ann Arbor staging Ⅰ/Ⅱ and stage Ⅲ/Ⅳ were 61.3% and 31.7% (P=0.005), respectively. The 5-year OS rates of the patients with presentation of B symptoms and without presentation of B symptoms were 79.0% and 30.1% (P=0.013), respectively. The 5-year OS rates of plasma EBV-DNA level < 5×102/ml and ≥ 5×102/ml were 60.4% and 33.3% (P=0.003), respectively. The 5-year OS rates of the patients receiving chemotherapy alone, combined chemotherapy and radiotherapy, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) were 12.9%, 86.5%, and 62.5% (P=0.001), respectively. Univariate analysis showed that ECOG score, IPI score, Ann Arbor staging, B symptoms, the copy number of EBV-DNA, and treatment regimens were statistically significant for OS. Multivariate analysis showed that ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens were independent factors of ENKTL OS. CONCLUSION: ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens are independent prognostic factors for OS of patients with ENKTL.

[Clinical Characteristics and Prognosis of 84 Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To explore the prognostic factors of elderly AML patients, as well as the application and prognostic value of comprehensive geriatric assessment（CGA） in elderly AML patients in China, so as to determine a suitable comprehensive assessment method that can predict survival and guide treatment of patients in Chinese people. METHODS: Retrospective analysis was performed on the medical records of 84 AML patients aged over 60 years old, and diagnosed in our department from October 2007 to December 2017, and the clinical, pathological and comprehensive evaluation of related prognostic factors was analyzed. RESULTS: The median age of all patients was 70 (60-91) years old, ratio of male to female was 1.9∶1 (55∶29) , the median OS time was 9 (1-125) months, 1 year OS rate was 35.3%, and 5 year OS rate was 12.6%. The age grouping, remission of induction chemotherapy, whether refractory/relapse, WBC count grouping at initial diagnosis, levels of lactate dehydrogenase and creatinine were risk factors for OS. Remission of induction chemotherapy, whether refractory/relapse, WBC count grouping and co-infections at initial diagnosis, levels of lactate dehydrogenase, and ECOG score were the risk factors for DFS. In the assessment of comorbidities, the two score classifications of charlson comorbidity index(CCI) were the risk factor of OS, however,whose effects for DFS were not statistically different. The effects of 3 score classifications of hemaotopoietic cell transplantation comorbidity index (HCT-CI), 4 score classifications of comulative illness kating scale for geriatrics (CIRS-G) and 3 score classifications of CIRS-G on OS and DFS were not statistically different. The impact of the ACA index on OS and DFS was statistically significant in elderly patients. All indexes related with patients self factors and disease-related factors were no independent prognostic factors for OS and DFS, so the judgment of prognosis needs to be comprehensively evaluated. CONCLUSION: The prognosis and treatment selection of elderly AML patients should be combined with traditional clinical and pathological prognostic factors as well as comprehensive assessment of the elderly patients.

Autologous hematopoietic stem cell transplantation as first-line consolidation therapy can improve the prognosis of diffuse large B-cell lymphoma with high expression of MYC protein.

Myc-positive diffuse large B-cell lymphoma has lower curative efficacy and long-term survival than its negative counterpart, even when treated with R-CHOP regimen. The present study aims to determine whether the use of autologous hematopoietic stem cell transplantation as a consolidation therapy can improve the curative efficacy in this type of patients after achieving the best effect of chemotherapy for the first time. The data of 50 patients with Myc-positive diffuse large B-cell lymphoma were retrospectively analyzed. Autologous transplantation was performed for 23 patients, while transplantation was not performed for 27 patients. The clinicopathological features and survival conditions were compared. The 1-year and 3-year progression-free survival (PFS) rates were 66.7% ± 0.9% and 57.7% ± 1.0%, respectively, in the non transplantation group, and 100% and 82.1% ± 0.1%, respectively, in the transplantation group (P = .021). The 1-year overall survival (OS) rate for these two groups was 88.7% ± 0.6% vs 100%, respectively, while the 3-year OS rates for these two groups was 78.6% ± 0.1% vs 91.3% ± 0.1%, respectively (P = .176). Hematopoietic stem cell transplantation performed after chemotherapy is a risk factor for OS. Autologous hematopoietic stem cell transplantation as a consolidation therapy in the early stage can improve the prognosis of patients with Myc-positive diffuse large B-cell lymphoma.

Adenosine A2A Receptors Mediate Anti-Inflammatory Effects of Electroacupuncture on Synovitis in Mice with Collagen-Induced Arthritis.

To study the role of adenosine A2A receptor (A2AR) in mediating the anti-inflammatory effect of electroacupuncture (EA) on synovitis in collagen-induced arthritis (CIA), C57BL/6 mice were divided into five treatment groups: Sham-control, CIA-control, CIA-EA, CIA-SCH58261 (A2AR antagonist), and CIA-EA-SCH58261. All mice except those in the Sham-control group were immunized with collagen II for arthritis induction. EA treatment was administered using the stomach 36 and spleen 6 points, and stimulated with a continuous rectangular wave for 30 min daily. EA treatment and SCH58261 were administered daily from days 35 to 49 (n = 10). After treatment, X-ray radiography of joint bone morphology was established at day 60 and mouse blood was collected for ELISA determination of tumor necrosis factor alpha (TNF-α) levels. Mice were sacrificed and processed for histological examination of pathological changes of joint tissue, including hematoxylin-eosin staining and immunohistochemistry of A2AR expression. EA treatment resulted in significantly reduced pathological scores, TNF-α concentrations, and bone damage X-ray scores. Importantly, the anti-inflammatory and tissue-protective effect of EA treatment was reversed by coadministration of SCH58261. Thus, EA treatment exerts an anti-inflammatory effect resulting in significant protection of cartilage by activation of A2AR in the synovial tissue of CIA.

[Acute myeloid leukemia with t(11;12)(p15;q13) translocation: two cases report and literature review].

OBJECTIVE: To investigate the clinical and laboratory features of acute myeloid leukemia (AML) with t(11;12)(p15;q13) translocation. METHODS: Two cases of AML with t(11;12)(p15;q13) translocation were reported and the related literatures were reviewed. RESULTS: The diagnosis of AML-M3 was supported by morphological, cytochemical staining and electron microscope tests. A rare t(11;12)(p15;q13) translocation, but not classical t(15;17)(q22;q12) translocation and PML- RARα fusion gene, was detected in both cases. Both of the patients were refractory to differentiation induction therapy such as retinoic acid and arsenic trioxide. CONCLUSION: AML is a group of heterogeneous disease derived from hematopoietic stem cell. Cytogenetic characteristic is important for diagnosis, prognosis stratification and therapy selection. Because of the heterogeneity of clinical and molecular features, it is unsuitable to classify AML with t(11;12)(p15;q13) as AML with recurrent cytogenetic aberration. This group of disease may benefit from allogeneic hematopoietic stem cell transplantation.

[Effect of metformin on acute promyelocytic leukemia cell line NB4 and its mechanism].

The purpose of this study was to investigate the effect and molecular mechanism of metformin (Met) on biological characteristics of acute promyelocytic leukemia (APL) cell line NB4. NB4 cells were treated with various concentrations of Met for different time, MTT method was used to detect cell proliferation, the alteration of cell apoptosis was analyzed by flow cytometry, and the change of cell adhesion ability was examined by cell adhesion assay. NB4 cells were pretreated with U0126, a specific inhibitor for extracellular signal-regulated kinase (ERK) phosphorylation, ERK phosphorylation was assessed by Western blot analysis, apoptosis and cell adhesion ability were evaluated by flow cytometry and cell adhesion test respectively. The results showed that Met could inhibit the cell proliferation, induce the cell apoptosis and increase the ability of cell adhesion. The pretreatment of NB4 cells with 5 µmol/L U0126 could effectively inhibit the phosphorylation of ERK, and reduce cell apoptosis and adhesion induced by 5 mmol/L Met. It is concluded that Met can inhibit the proliferation and promote the apoptosis and adhesion of NB4 cells. MEK/ERK signaling pathway may be one of the molecular mechanisms of metformin on NB4 cells.

[Study on expression of PTEN gene and its pseudogene PTENP1 in acute leukemia and correlation between them].

OBJECTIVE: To investigate the expression of PTEN (phosphatase and tension homology deletion on chromosome 10, PTEN) and its pseudogene PTENP1 in acute leukemia (AL) and correlation between them, and to explore the role of PTENP1 on the PTEN expression in AL cells. METHODS: PTEN and PTENP1 mRNA expression were evaluated in bone marrow (BM) samples from 138 newly diagnosed AL patients and 15 healthy controls by quantitative real-time RT-PCR (qRT-PCR). pCDH1-PTENP1 3'UTR-GFP lentivirus vectors were constructed. 293T cells were transfected by calcium phosphate precipitation to produce retrovirus. HL-60 cell line was infected with the retroviral vectors expressing pCDH1-GFP and pCDH1-PTENP1 3'UTR-GFP respectively. The flow cell sorter was used to sort the HL-60 with GFP positively expressed. The mRNA expression of PTEN and PTENP1 was detected by qRT-PCR, the expression of PTEN protein by western blot, and the impact of PTENP13'UTR on the proliferation of HL-60 cells by MTT assay. RESULTS: AML patients showed significantly lower PTEN and PTENP1 mRNA expression in BM compared to healthy controls. Correlation analysis showed that the expression of PTEN and PTENP1 mRNA were positively correlated (P < 0.05). The 108 cases of PTENP1(+) AML were classified according to the prognostic classification of 2011 NCCN Clinical Practice Guidelines in AML, there was no difference among different subgroups. HL-60 cell line was infected with the retroviral vectors expressing pCDH1-GFP (control group) and pCDH1-PTENP1 3'UTR-GFP respectively. Compared with the control group, PTENP1 mRNA level of HL-60 infected with the retroviral vectors expressing pCDH1-PTENP1 3'UTR-GFP increased significantly, and PTEN mRNA level also increased. While the PTEN protein level and the cell growth rate of the PTENP1 3'UTR group didn't change significantly. CONCLUSION: PTEN and PTENP1 mRNA expression level of BM cells from AL patients is significantly lower. There is a positive correlation between expression of PTEN and PTENP1 mRNA. PTENP1 may regulate the expression of PTEN in mRNA level.

Design and analysis of structure-activity relationship of novel antimicrobial peptides derived from the conserved sequence of cecropin.

We have de novo designed four antimicrobial peptides AMP-A/B/C/D, the 51-residues peptides, which are based on the conserved sequence of cecropin. In the present study, the four peptides were chemically synthesized and their activities assayed. Their secondary structure, amphipathic property, electric field distribution and transmembrane domain were subsequently predicted by bioinformatics tools. Finally, the structure-activity relationship was analyzed from the results of activity experiments and prediction. The results of activity experiments indicated that AMP-B/C/D clearly possessed excellent broad-spectrum activity against bacteria, whereas AMP-A was almost inactive against most of the bacterial strains tested. AMP-B/C/D showed more potent activity against Gram-positive bacteria than against Gram-negative bacteria. By utilizing bioinformatics analysis tools, we found that the secondary structure of the four cation peptides was mainly alpha-helix, and the result of CD spectrum also displayed that all the peptides had considerable alpha-helix in the presence of either 50% TFE or SDS micelles. AMP-C showed much better activity than other peptides against most of the bacteria tested, owing to its remarkable cation property and the amphipathic character of its N-terminal. The study of structure-activity relationship of the designed peptides confirmed that amphipathic structure and high net positive charge were prerequisites for maintaining their activities.

[Significance of quantitative detection of bcr-abl mRNA in chronic myeloid leukemia patients after allogeneic hematopoietic stem cell transplant].

The objective of this study was to analyze the level of bcr-abl mRNA in peripheral blood (PB) after allogeneic stem cell transplantation (allo-SCT) in chronic myeloid leukemia patients, providing a experimental basis for diagnosing early relapse. bcr-abl mRNA levels in 78 PB and bone marrow (BM) samples from 15 CML patients after allo-SCT were detected by using real-time quantitative PCR. The results indicated that levels of bcr-abl mRNA before transplantation were high (median 29.303%) and decreased greatly (median 0) at the first month after allo-SCT. During the first year after allo-SCT, the patterns of serial bcr-abl transcripts varied in number, but the overall bcr-abl transcript levels significantly decreased at 6 months after allo-SCT. Majority of patients with undetectable or very low levels of bcr-abl mRNA were monitored after 1 year following transplantation. The hematological features of BM and PB in all detected patients remained normal. PB and BM bcr-abl values were not different significantly and had the similar trend of changes. It is concluded that the bcr-abl mRNA levels in CML patients change greatly early after allograft. Serial monitoring measurements for bcr-abl mRNA contribute to understanding the trend of change and effect of transplantation, also can be a guidance for starting therapy. But detectable levels of bcr-abl mRNA during the first 6 months do not indicate relapse. Measurements of bcr-abl mRNA of PB may be more suitable for routine monitoring long-term disease status in CML after allo-HSCT.

[JAK3 mRNA level in graft versus host disease patients: a preliminary study].

OBJECTIVE: To quantify peripheral blood mononuclear cell JAK3 mRNA levels after allogeneic haematopoietic stem cell (allo-HSCT) transplantation, and to explore its relationship with graft vs host disease (GVHD). METHODS: Serial monitoring of JAK3 mRNA levels by fluorescent quantitative reverse transcriptase polymerase chain reaction (FQ-RT-PCR) technique was performed on 26 cases (83 samples) after allo-HSCT. RESULTS: The mean JAK3/ABL expression levels was 8.71 in 14 patients without GVHD; the JAK3/ABL expression level was 31.94 in one patient with acute GVHD (aGVHD); the mean JAK3/ABL expression levels was 19.23 in 11 patients with chronic GVHD (cGVHD), and the cGVHD was diagnosed at the mean time of six months (3 - 12 months). The JAK3/ABL expression levels did not change in 4 patients one month after allo-HSCT, however, the levels increased again when GVHD were diagnosed in these 4 patients, and the JAK3/ABL expression levels decreased again when GVHD was remitted. CONCLUSION: The JAK3 expression level related to the remission and relapse in patients with GVHD.