Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis.

OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. METHODS: Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. RESULTS: Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. CONCLUSION: Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma that affects B lymphocytes. It can develop in the lymph nodes and can be localized or generalized. Despite DLBCL being considered potentially curable, little research has been conducted on the relationship between the body's immune response and DLBCL. AIM: To study the expression and significance of T-regulatory cells (Tregs) interleukin (IL)-35, IL-10, and transforming growth factor-beta (TGF-ß) in DLBCL. METHODS: Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University (Zhejiang Province, China) between January 2017 and June 2022 and treated with standard first-line regimens were reviewed. Three patients were lost to follow-up; thus, 79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy: Incipient (new-onset and treatment-naïve), effectively treated, and relapsed-refractory. Thirty healthy individuals were included in the control group. The expression of peripheral blood T lymphocytes and their associated factors IL-35, IL-10, and TGF-ß in the four groups were observed. RESULTS: In contrast to the successfully treated and normal control groups, both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive (+) Tregs (P < 0.05), whereas the proportion of CD8+ Tregs did not differ substantially between the groups. Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups (P < 0.05). There was no statistically significant distinction in the expression level of TGF-ß between the groups (P > 0.05). The correlation between IL-35 and IL-10 concentrations was significantly positive, with a correlation coefficient of 0.531 (P < 0.05). The correlation between IL-35 and TGF-ß concentration was significantly positive, with a correlation coefficient of 0.375 (P < 0.05). The correlation between IL-10 and TGF-ß concentration was significantly positive, with a correlation coefficient of 0.185 (P < 0.05). The expression concentrations of IL-35, IL-10 and TGF-ß were apparently and positively correlated (P < 0.05). CONCLUSION: Tregs IL-35, and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center: A retrospective analysis.

BACKGROUND: Follicular lymphoma (FL) is a type of B-cell lymphoma that originates at the germinal center and has a low malignancy rate. FL has become the most common inert lymphoma in Europe and America but has a relatively low incidence in Asia. AIM: To explore the clinical features, curative effects, and prognostic factors of FL. METHODS: Completed medical records of 49 patients with FL who were admitted to the Ningbo First Hospital from June 2010 to June 2021 were examined. These patients were definitively diagnosed by pathological biopsy or immunohistochemical staining. The diagnostic criteria were based on the 2008 World Health Organization classification of lymphomas. Ann Arbor staging was performed according to the imaging and bone marrow examination results. Risk stratification of all patients was performed based on the International Prognostic Index (IPI), age-adjusted IPI, Follicular Lymphoma International Prognosis Index (FLIPI), and FLIPI2 to compare the efficacy of different treatment regimens and analyze the related prognostic factors. RESULTS: The age of onset in patients ranged from 24 to 76 years, with a median age of 51 years. Most patients developed the disease at 40-59 years of age, and the male:female ratio was 1.6:1. No significant difference was noted in the curative effect between the non-chemotherapy, combined chemotherapy, and other chemotherapy regimens (P > 0.05). Hemoglobin (Hb) level < 120 g/L, Ki-67 value > 50%, bone marrow involvement, and clinical stages III-IV were associated with a poor prognosis of FL (P < 0.05). However, the influence of other indicators was not statistically significant. Risk grouping was performed using the FLIPI, and the results showed that 24.5%, 40.8%, and 34.7% of patients were in the low-, moderate-, and high-risk groups, respectively. According to the survival analysis results, the survival rate of patients was lower in the high-risk group than in the other low-risk and moderate-risk groups (P < 0.05). CONCLUSION: FL mainly occurs in middle-aged and elderly men, primarily affecting lymph nodes and bone marrow. Hb level, Ki-67 value, bone marrow involvement, and clinical staging were used to evaluate prognosis.

The novel HLA-C*12:368 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*12:368 differs from HLA-C*12:03:01:01 by one nucleotide in exon 4.

T-cell immunoglobulin mucin molecule-3, transformation growth factor ß, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma.

BACKGROUND: The effects of T-cell immunoglobulin mucin molecule-3 (Tim-3), transforming growth factor ß (TGF-ß), and chemokine-12 (CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) have not been elucidated. AIM: To examine the correlation between Tim-3, TGF-ß and CXCL12 expression and DLBCL prognosis. METHODS: Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups, respectively. The expression of Tim-3, TGF-ß, and CXCL12 was detected immunohistochemically. Patients were followed up for 3 years, and progression-free survival was recorded. Cox multifactorial analysis was performed to analyze the risk factors for poor prognosis. RESULTS: The positive expression rates of Tim-3, TGF-ß, and CXCL12 were higher in DLBCL tissues than in non-cancerous (control) tissues (P < 0.05). One-year post-surgery, the positive expression rates of Tim-3, TGF-ß, and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment (P < 0.05). The 3-year progression-free survival of 97 patients with DLBCL was 67.01% (65/97). Univariate analysis revealed that clinical stage, bone marrow infiltration, International Prognostic Index (IPI) score, Tim-3 positivity, TGF-ß positivity, and CXCL12 positivity were associated with poor prognosis (P < 0.05). Multivariate Cox regression analysis demonstrated that clinical stage III-IV, bone marrow infiltration, mediate-to-high-risk IPI scores, Tim-3 positivity, TGF-ß positivity, and CXCL12 positivity were independent risk factors affecting prognosis (P < 0.05). CONCLUSION: DLBCL tissues exhibit high positive expression of Tim-3, TGF-ß, and CXCL12, and a high expression of all three indicates a poor prognosis.

[The Genetic and Prognostic Characteristics of AML-MRC Patients].

OBJECTIVE: To investigate the genetic and prognostic characteristics of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) patients. METHODS: There were 230 non-M3 AML patients treated in Ningbo First Hospital enrolled, among which 58 patients were newly diagnosed AML-MRC, the patients were followed up and SPSS 25.0 was used to statistically analyze. RESULTS: There were 49 patients performed genetic testing, 29 patients (59.2%) showed chromosomal abnormalities, including 7q- 8 cases (16.3%), 5q- 6 cases (12.2%), 5 cases (10.2%) of 17p abnormalities, 13 cases (26.5%) of highly abnormal complex karyotypes (CK) (≥5 unrelated chromosomal abnormalities), CK contained chromosomal abnormalities such as +8, 5q-, and 12 cases (24.5%) of monosomal karyotypes (MK). Genetic testing was performed in 37 patients, and 24 (64.9%) patients showed genetic mutations, among which ASXL1 mutation was the most common (8 cases, 21.6%), followed by TET2 mutation in 6 cases (16.2%). Kaplan-Meier analysis showed that AML-MRC patients with high CK (P=0.012), 5q- abnormalities (P=0.038), and TP53 mutations (P=0.008) had poor overall survival. CONCLUSION: AML-MRC has unique genetic characteristics, and high CK, 5q- and TP53 mutations are poor prognostic factors.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

[Effects of Dasatinib on the Expansion, Subsets, Receptor Expression and Cytotoxic Function of NK Cells in Vitro].

OBJECTIVE: To investigate the effect of dasatinib on the expansion of NK cells in vitro, as well as the subsets, receptor expression and cytotoxic function of NK cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult volunteers and cultured with SCGM added IL-2 and IL-15 for expansion of NK cells. In this culture system, dasatinib of different concentrations were added. Cell counting and phenotyping by flow cytometry were used to evaluate the amplification efficiency of NK cells. FCM was used to detect the expression of receptors on the surface of NK cells and the distribution of subsets. Subsequently, degranulation assay and CFSE/7AAD based cytotoxicity assay were used to detect the effects of dasatinib on NK cytotoxicity against leukemia cell line K562 cells. RESULTS: The expansion efficiency of NK cells in vitro could be increased by dasatinib at the concentration range of 5-50 nmol/L, and the expansion efficiency of NK cells reached the peak at 20 nmol/L of dasatinib. The NK cytotoxicity against K562 cells in dasatinib cultured group at the concentration of 20 nmol/L was significantly higher than that in control group. For the cells cultured by disatinib in vitro, the MFI of CD226, NKP46 and NKG2D was up-regulated; the ratio of NKG2A+CD57- subset was down-regulated, while the ratio of NKG2A-CD57+ subset was up-regulated.The degranulation response of NKG2A-CD57+ NK cells to K562 cells was stronger than that of NKG2A+CD57- NK cells. CONCLUSION: The results shows that appropriate dose of dasatinib(20 nmol/L) can increases the amplification efficiency of NK cells, simultaneously up-regulates the expression of NK activating receptors and increases the NKG2A-CD57+ subset, which lead to the enhancement of NK cytotoxicty against leukemia cell lines.

[Clinical Features of Pregnant Women with Thalassemia in Non Endemic Area].

OBJECTIVE: To investigate the clinical features of pregnant women with thalassemia in non endemic area, and to prevent the births of babies with intermedia or major thalassemia. METHODS: Two hundred and thirty-five pregnants women with thalassemia diagnosed from March 2015 to April 2016 in our hospital were enrolled and retrospectively analysed. The blood routine and hemoglobin electrophoresis were performed respectively by XN-9000 automatic blood cell analyzer and HYDRASYS hemoglobin electrophoresis apparatus. The three commonest deletion of α-thalassemia, the three non-deletion α-thalassemia and 21 known ß-thalassemia mutation were all detected by fluorescence melting curve analysis. RESULTS: Among 235 pregnant women of thalassemia, the majority were ß-thalassemia, which were followed by α-thalassemia and composite thalassemia. Most pregnant women showed a mild anemia, and suffered from microcytic anemia, but less suffered from iron deficiency anemia. The ratio of second-child pregnant women was increased, and the ratio was close to one third both in α-thalassemia and ß-thalassemia patients, and 75% patients were composite thalassemia. HbF was found to be more in native pregnant women with ß-thalassemia. Hemoglobin isomer was easy to found in the pregnant with α-thalassemia, and they were all non native. The genotype of --sea were found majority in both native and non native pregnant women with thalassemia. The genotype of IVS-II-654 made up a large majority(55.38%) in native pregnant with ß-thalassemia, as well as one of whose parents was native pregnant women. The genotypes of CD41-42,IVS-II-654 and CD17 were found to be a large majority in non native pregnant women, each of them accounted for 30%. CONCLUSION: More pregnant women with thalassemia are founded to be in non endemic area, and shows their own unique clinical features. It is certainly to detect thalassemia mutation in their spouse and their babies, to prevent the births of babies with intermedia or major thalassemia.

Tip of the iceberg: roles of circRNAs in hematological malignancies.

Circular RNAs (circRNAs) are a new class of covalently closed RNA molecules whose 3'- and 5'-ends are linked by a back-splicing event. Emerging evidence has shown that circRNAs play a vital role in the occurrence and development of many diseases and are promising biomarkers and therapeutic targets. However, knowledge of circRNAs in hematological malignancies is limited. In this review, the biogenesis, categories, characteristics, and functions of circRNAs are summarized, especially the roles of circRNAs in hematopoiesis and hematological malignancies.

[Effect of Chromosomal Karyotype on the Prognosis of Patients with Acute Promyelocytic Leukemia in Condition of the Maintenance Treatment Based on Arsenic Trioxide].

OBJECTIVE: To investigate the effect of chromosomal karyotype on the prognosis of patients with acute promyelocytic leukemia (APL) in condition of the maintenance treatment based on arsenic trioxide. METHODS: The patients with acute promyelocytic leukemia for last 12 years in our hospital were retrospectively collected. The patients mainly treated with arsenic trioxide in maintenance protocol were selected and followed up. All the patients were divided into 3 groups according to cytogenetic data: single t (15; 17) group, t (15; 17) with additional chromosomal abnormality (ACA) group, and normal karyotype group. Then, the prognostic significance of ACAs and complex karyotype were investigated in APL patients. RESULTS: There were 57 cases in the single t (15; 17) group, in which 8 cases died in the first month after induction treatment with early mortality rate of 14%. There were 21 patients in t (15; 17) with ACA group, in which 4 cases died in the first month with early mortality rate of 19%. There were 15 cases in normal chromosome group, in which 5 cases died in the first month with the early mortality rate of 33.3%. There was no statistical difference in the early mortality among 3 groups. All the remaining 76 patients achieved complete hematological remission. These patients were followed up. The median follow-up time was 43.9 months. Among them, only 2 patients in single t (15; 17) group and 1 patient in t (15; 17) with ACA group relapsed. No patient relapsed in normal karyotype group. The relapse rate was 3.5% in single t (15; 17) group and 4.2% in t (15; 17) with ACA group, respectively. There was no statistical difference in the overall survival and disease-free survival rates among 3 groups. Further analysis showed that the patients with complex chromosome karyotypes had lower relapse-free survival rates, but overall survival rates were not significantly different in 3 group. CONCLUSION: In general, ACA can not affect the prognosis of patients with acute promyelocytic leukemia in condition of the maintenance treatment based on arsenic trioxide, but the complex chromosomal karyotype may reduce the relapse-free survival rates.

[Clinical Significance of Monosomal Karyotype in MDS].

OBJECTIVE: To investigate the frequency, karyotype characteristics and prognosis significance of monosomal karyotype (MK) in newly diagnosed MDS patients. METHODS: The clinical, laboratorial and follow-up data of 202 MDS patients received the chromosome karyotype test in Department of Hematology, Ningbo Hospital of Zhejiang University from 2009 to 2018 were analyzed retrospectively, the monosomal karyotype features, clinical characteristics and their effects on the prognosis of MDS patients also were analyzed. RESULTS: Among 202 cases of MDS, 25 (12.38%) confirmed to be the MK. The abnormality of chromosome 5 (60.00%), 7 (56.00%), 17 (56.00%), 15 (56.00%), 13 (40.00%) and 20（40.00%）were common in monosomal karyotype. MK+-MDS (MDS with monosomal karyotype) patients had higher bone marrow blast percentage than MK--MDS (MDS without monosomal karyotype) patients, the median are 6.25% and 3.00% (P＜0.01) respectively, but there were no difference in age, sex, hemoglobin level, white blood cell count, neutrophile granulocyte percentage, platelet count, blood blast percentage, serum ferritin, folic acid and vitaminB12 between MK+-MDS and MK--MDS. The overall survival time of MK+-MDS and MK--MDS patiens with chromosome 3, 5, 7, 13, 15, 17 abnormalities was significantly shorter than MK--MDS and AK+MK--MDS patients (MDS with abnormal karyotype but without monosomal karyotype) , the MK+-MDS patients had a median survival time of 7.33 months, but the median survival time had not been reached in MK--MDS and AK+MK--MDS patients had not been reached by the end of the follow-up, and could not be assessed (P＜0.01). CONCLUSION: The monosomal karyotype is a poor prognosis factor for newly-diagnosed MDS patients. The poor prognosis suggested by monosomal karyotype may be related with the abnormality of 3, 5, 7, 13, 15 and 17 chromosome.

[Clinical Characteristics and Karyotype Analysis of Myelodysplastic Syndrome Patients with TP53 mutation].

OBJECTIVE: To investigate the clinical characteristics of myelodysplastic syndrome (MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients. METHODS: The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed. RESULTS: Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5 (23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower (P=0.001, P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group (P=0.002, P＜0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and ß2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group (P＜0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk. CONCLUSION: MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.

Comparison of therapeutic efficacy and complications between autologous stem cell transplantation and chemotherapy for large B-cell lymphoma: a meta-analysis.

OBJECTIVE: To contrast the clinical effects and complications for the treatment of large B-cell lymphoma between autologous stem cell transplantation and chemotherapy. METHODS: Multiple databases were searched to identify relevant studies. Articles that met the inclusion criteria were included. RESULTS: A total of 11 studies including 795 patients were involved, which eventually met the eligibility criteria. 385 and 410 samples were included in ASCT group and chemotherapy group respectively. The heterogeneity test suggested that clinical efficacy (RR = 1.29, 95% CI [1.17, 1.42], P < 0.00001; P for heterogeneity = 0.0002, I2 = 72%), side effects (RR = 1.72, 95% CI [1.15, 2.58], P = 0.009; P for Heterogeneity < 0.0001, I² = 85%) and overall 5-year survival rate (RR = 1.16, 95% CI [1.05, 1.29], P = 0.004; P for Heterogeneity = 0.008, I² = 58%) were significantly different between ASCT group and chemotherapy group, while non-disease 5-year survival rate (RR = 1.24, 95% CI [1.04, 1.48], P = 0.02; P for Heterogeneity = 0.22, I² = 24%) appears insignificantly. CONCLUSIONS: This study presents a comprehensive summary and critical assessment of the current evidence for the treatment of large B-cell lymphoma. The evidence shows that the clinical efficacy of ASCT was better than that of chemotherapy to some extent, but ASCT might lead to more possibility of complications.

[Effects of Bone Marrow Mesenchymal Stem Cells on the Biological Characteristics of Migrating and Homing in Multiple Myeloma Cells].

OBJECTIVE: To construct a co-culture system for bone marrow mesenchymal stem cells (BMMSC) and multiple myeloma (MM) cells, and to investigate the effects of co-cultured BMMSC on the migrating and homing of multiple myeloma cells. METHODS: The BMMSC from the transgenic mice with green fluorescent protein (GFP) fetal bone were cultured by adherent screening. A co-culture system of BMMSC and MM cell line XG-7 cells was constracted, the proliferation and apoptosis of cells were determined by trypan blue exclusion and Annexin V/PI, respectively, MDC staining was employed to detect the autophagy. The moving direction distribution of molecule in BMMSC and XG-7 cells labeled with PE-CD138 in co-culture process were observed dinamically by confocal microscopy. RESULTS: After co-culture with GFP-BMMSC, the resistance of XG-7 cells to apoptosis and autophagy were enhanced; at the same time, their proliferation increased. Apoptosis rates of XG-7 cells directly and indirectly co-cultured with BMMSC were (6.23 ± 0.12)% and (6.97 ± 0.03)% respectively, which were lower than that of XG-7 cells cultured alone (17.90 ± 1.46)% (P < 0. 01). There was low level of autophagy in XG-7 cells co-cultured with BMMSC. XG-7 cells are highly polarized and contained a specialized membrane domain with specific protein and lipid components to contact with BMMSC under confocal microscope. After methyl-ß-cyclodextrin treatment, the molecules were normally enriched in the specialized domain. CONCLUSION: BMMSC can protect XG-7 cells from apoptosis and autophagy, and obviously promote the proliferation of XG-7 cells, and can influence the migrating and homing of multiple myeloma cells.

[Effect of umbilical cord blood mesenchymal stem cells on peripheral blood lymphocyte subsets].

OBJECTIVE: This study was aimed to investigate the effect of mesenchymal stem cells (MSCs) on subsets and cytokine secretion of T lymphocytes. METHODS: Umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) were isolated by density gradient and were cultared by amplifying culture. The subsets and cytokine secretion of T lymphocytes were detected by flow cytomety after being co-cultured with UCBMSC. RESULTS: The proliferation of lymphocytes was inhibited. CD4(+)T cell subsets were increased, CD8(+)T cell subsets decreased when co-cultured with UCBMSC; Th1 and Tc1 level significantly reduced, while Th2 and Tc2 level slightly increased. CONCLUSION: The UCBMSC can inhibit the proliferation of lymphocytes, especially CD8(+)T cell subsets. In addition, UCBMSCs can reduce Th1 and Tc1 cells, and increase Th2 and Tc2 cells. UCBMSC may have the clinical application potential for preventing and remedying GVHD.