Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Chimeric antigen receptor T cell(CAR-T)therapy has produced remarkable results in the treatment of hematological tumors.The BCMA antigen is widely expressed on the surface of multiple myeloma cells and is a suitable,efficient target for CAR-T therapy.BCMA CAR-T cell therapy has a high response rate for relapsed or refractory patients in particular,and CAR-T cells are still detectable in most patients 1 year after infusion.However,drug resistance and disease recurrence remain key problems in clinical management.In this paper,we discuss the response factors and resistance induction mechanism of BCMA CAR-T cell therapy from several perspectives,such as the immune es-cape of multiple myeloma cells,CAR-T product factors,previous treatment regimens,and tumor immune microenvironment inhibition.We also propose possible optimization strategies in order to provide reference for future exploration.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Objectives:To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) .Results:The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 ( P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 ( P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 ( P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (| r| = 0.193-0.457, all P<0.001) , PV (| r| = 0.192-0.529, all P<0.01) , and MF (| r| = 0.180-0.488, all P<0.001) , respectively. Conclusions:HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

Objective:In this study, we aimed to determine the change and clinical significance of serum level Apo A1 in MM patients.Methods:In total, 412 multiple myeloma patients were examined. SPSS 22.0 was used for data analysis. Correlation analysis was performed using linear correlation or Spearman rank correlation coefficients. Measurement data were analyzed with the t-test, Mann-Whitney U-test, or oneway analysis of variance (ANOVA) . Used the ROC curve to calculate the cutoff value and compared the OS and PFS between high Apo A1 subgroup and low Apo A1 subgroup with Kaplan-Meier survival analysis.Results:Our study showed that value of Apo A1 in the patient group was lower than that in the control group (0.89 g/L vs 1.24 g/L, P<0.05) . We found that Apo A1 dynamically changed with different MM stages. As it was increased when the disease was in remission, and decreased after disease in progression. According the result of multivariate analysis Apo A1 reduction become the independent risk factors of MM. On the basis of Kaplan-Meier survival analysis between high Apo A1 subgroup and low Apo A1 subgroup, we found higher Apo A1 patienta had longer OS rate and PFS. Conclusions:Apo A1 is a useful biomarker of tumor burden and a prognostic factor of multiple myeloma.

Exosome,being a kind of extracellular vesicles transporting the bioactive substances,is featured by the physiological function of anti-tumor immunity and promoting angiogenesis.Different types of cells can release different kinds of exosomes that can play a key role in the occurrence and development of a variety of diseases.In recent years,domestic and foreign research has showed that the amount and type of exosome are associated with the disease state and prognosis of multiple myeloma patients,which provides a new way for diagnosis,prognosis assessment and target therapy for multiple myeloma.This paper reviews the recent progress of exosomes in multiple myeloma.

Objective To explore the influencing factors of therapeutic effect and prognosis in patients with angioimmunoblastic T cell lymphoma (AITL). Methods The clinical data of 48 patients with AITL were collected in order to evaluate its therapeutic effect and the influencing factors of prognosis. Results In the 48 patients with AITL, complete remission (CR) was in 15 cases, partial remission (PR) was in 16 cases, and the total effective rate was 64.58%(31/48). The recent total effective rate in patients of international prognostic index (IPI) score ≤2 scores was significantly higher than that in patients of IPI score >2 scores: 84.00% (21/25) vs. 43.48% (10/23), and there was statistical difference (P<0.05). The 1-year, 2-year and 3-year overall survival rates were 75.00%(36/48), 52.08%(25/48) and 35.42%(17/48), and the median survival time was 24.5 months. The patients of Ann Arbor stage Ⅰ-Ⅱ, IPI score ≤ 2 scores, Ki-67<50% and using CHOP combined with asparaginase (ASP) regimen had a higher 3-year overall survival rate compared with the patients of Ann Arbor stage Ann Arbor stage Ⅲ -Ⅳ, IPI score >2 scores, Ki-67 ≥ 50% and using CHOP regimen: 8/13 vs. 25.71%(9/35), 52.00% (13/25) vs. 17.39% (4/23), 55.00% (11/20) vs. 21.43% (6/28) and 48.28% (14/29) vs. 3/19, and there were statistical differences (P<0.05). Conclusions AITL is a kind of disease with poor prognosis. IPI score is the important influencing factor of recent therapeutic effect. The Ann Arbor stage, IPI score, Ki-67 levels and using contained ASP chemotherapy are the important factors of prognosis in patients with AITL.

OBJECTIVETo evaluate the effects of Embelin on HL-60 cells by the impact of oxidative stress on DNA double-strain breaks (DSBs).

METHODSHL-60 cells were treated with Embelin in different concentration (3, 10, 30, 100, and 300 μg/ml) for 24 h, and inhibitory effects was examined by CCK-8 assay. Reactive oxygen species (ROS) levels were evaluated by flow cytometry using DCFH-DA. Comet assay was used to detect the extent of DSBs.

RESULTSEmbelin inhibited proliferation of HL-60 cells in a dose-dependent manner. At the concentration of 10, 30, 100, and 300 μg/ml, the inhibition rate was (12.74 ± 2.27)%, (23.49 ± 1.96)%, (30.30±1.89)%, and (57.55 ± 3.59)% (P<0.05). Embelin also lead to high level of intracellular ROS and deterioration of DNA damage (P<0.05). When HL-60 cells were pretreated with ROS scavenger N-acetyl-l-cysteine (NAC) for 2 h and then treated with 300 μg/ml Embelin for 24 h, the intracellular ROS level declined and DSBs relieved (P<0.05). Meanwhile, embelin-induced cell viability significantly declined to (32.75 ± 2.70)% (P<0.05).

CONCLUSIONEmbelin induced the death of HL-60 cells by increasing the generation of intracellular oxidation and the oxidative stress, which drived the damage of DNA double-strand.

Acetylcysteine ; Apoptosis ; Benzoquinones ; Cell Survival ; Comet Assay ; DNA Damage ; Fluoresceins ; HL-60 Cells ; Humans ; Oxidative Stress ; Reactive Oxygen Species

Adult ; Asparaginase ; Humans ; Hypertriglyceridemia