ct curative effect and prognosis of multiple myeloma.

Objective:To explore the curative efficacy of tandem autologous stem cell transplantation (ASCT) for high-risk multiple myeloma (HRMM).Methods:From January 2017 to December 2021, retrospective analysis was conducted for 240 initially diagnosed HRMM patients. According to different treatment protocols after induction chemotherapy, they were further assigned into three groups of tandem ASCT (n= 20) ,single ASCT (n=80) and non-transplantation (n= 140). Rates of deep response (very good partial response and above) before and after transplantation and differences in 2-year progression-free survival (PFS) and overall survival (OS) were compared among three groups. The prognostic factors of HRMM were examined by univariate and multivariate analyses.Results:In single ASCT group, the rates of deep responses were 67.50% (54/80) after induction chemotherapy and 80.00 % (64/80) post-ASCT ( P=0.072). There were no significant statistical differences. In tandem ASCT group, the rates of deep response were 65.00% (13/20) after induction chemotherapy and 95.00 % (19/20) post-ASCT ( P=0.018). There were significant statistical differences. The 2-year PFS of tandem ASCT, single ASCT and non-transplantation groups were (75.00±2.90) %, (71.25±3.00) % and (61.43±3.10) % respectively. No statistically significant difference existed in 2-year PFS rates between single ASCT and non-transplantation groups, as well as between tandem ASCT and single ASCT groups ( P=0.365 and P=0.052). Significant difference existed in 2-year PFS between tandem ASCT and non-transplantation groups ( P<0.032). Two-year OS rates of tandem ASCT, single ASCT and non-transplantation groups were (90.00±3.50) %, (78.75±2.70) % and (62.86±2.50) % respectively. No statistically significant difference existed in 2-year OS rate between single ASCT and non-transplantation groups, as well as between tandem ASCT and single ASCT groups ( P=0.071 and P=0.057). Significant difference existed in 2-year OS between tandem ASCT and non-transplantation groups ( P=0.003). Univariate and multivariate analyses indicated that the independent prognostic factors affecting PFS were multi-hit, stages RISS-Ⅲ and failure to achieve very good partial response (VGPR) after four cycles of induction therapy and non-tandem ASCT. The independent prognostic factors affecting OS were multi-hit, stages RISS-Ⅲ and non-tandem ASCT. Conclusion:Tandem ASCT not only significantly improves the depth of remission but also further enhances 2-year PFS/OS of HRMM patients. It is a recommended treatment for HRMM.

Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M₃ and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M₀, 24 cases of M₁, 56 cases of M₂, 39 cases of M₄, 63 cases of M₅, 6 cases of M₆ and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD⁺ DNMT3A R882⁺ group (group A), FLT3-ITD⁺ DNMT3A R882^- group (group B), FLT3-ITD^- DNMT3A R882⁺ group (group C) and FLT3-ITD^- DNMT3A R882^- groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.

AIM:To determine the biological feature of circulating endothelial cells (CECs) in acute promye-locytic leukemia ( APL) patients before and after treatment , and to analyze the relationship between CECs and the clinical characteristics .METHODS: The CECs were sorted from peripheral blood by magnetic-activated cell sorting and then counted by 3-color flow cytometry.The cells were identified by immunofluorescence staining for the expression of CD 146, CD31, CD144, VEGFR-2, CD45 and CD133.The CECs were cultured in vitro, and the tube formation and colony-forming rate were determined .RESULTS:Increased quantity of CECs was observed in CD 34 positive group and group with WBC >10 ×109/L (P<0.05).The quantity of CECs had a significant difference among low risk , medium risk and high risk groups (P<0.05).The positive rate of CD133 and quantity of CECs significantly reduced in 32 APL patients when they gain complete remission after treatment (P<0.05).The amount of tube formation and colony-forming rate were significant-ly reduced after treatment (P<0.05).The ratio of CECs quantity from APL patients after treatment to that before treatment had a negative correlation with arsenic concentration in urine on day 7 during As2O3 treatment (P<0.05).CONCLU-SION:Accurately counting CECs may be helpful for evaluating prognosis and designing treatment strategy .

Objective To analyze the prognostic impact of Ikaros family zinc finger 1(IKZF1)mutation on adult Philadelphia chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) patients.Methods IKZF1 mutation was detected in 63 adult Phi positive ALL patients at diagnosis using capillary electrophoresis.Recruited patients were treated in our center and other three hospitals in Ningbo from January 2014 to January 2017.Clinical data were collected and retrospectively analyzed.Results Thirty-nine (61.9％) patients were positive IKZF1 mutation in this cohort.The white blood cell (WBC) count in IKZF1 mutation group was significantly higher than that of mutation negative group [(64.6±11.3)× 109/L vs.(33.7±5.6)×109/L,P＜0.05].Patients with WBC count over 30×109/L accounted for 56.4％ in IKZF1 mutation group.Complete remission (CR) rate in the IKZF1 mutation group was also lower than that of negative group after induction chemotherapy (64.1％ vs.75.0％,P＞0.05).IKZF1 was a negative prognostic factor but not independent factor for survival by univariate and multivariate analyses.Patients were divided into chemotherapy and allogeneic transplantation groups.The 3-year overall survival (OS) rate and 3-year leukemia-free survival (LFS) rate in IKZF1 mutation group were significantly lower than those of negative group in both transplantation group (42.3％ vs.59.3％;31.2％ vs.50.0％;respectively,both P＜0.05) and chemotherapy group (24.8％ vs.40.0％;19.0％ vs.34.3％;respectively,both P＜0.05).Conclusion IKZF1 mutation is a poor prognostic factor for adult Ph1 positive ALL patients.

Objective: To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML). Methods: A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared. Results: During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group (P<0.05). The difference of posaconazole group and voriconazole group was not significant (P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05]. Conclusions Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.

OBJECTIVETo investigate the expression level and regulation mechanism of miR-720 as well as the association of miR-720 expression with leukemia biological characteristics.

METHODSExpression and promoter methylation of miR-720 were determined by quantitive PCR and pyrosequencing in 38 patients with AML and 20 normal controls. Lentivirous-mediated miR-702 overexpression was constructed in AML cell line kasumi-1. The cell proliferation, apoptosis, cycle, colony formation, migration and P53-mediated apoptosis pathway were determined.

RESULTSAML patients showed significantly lower miR-720 expression compared with normal controls (0.69±0.09 vs 3.00±0.46, P<0.01); The methylation level of miR-720 promoter region in AML patients were significantly higher than normal controls [(75.56±2.35)% vs (47.65±2.78)%, P<0.01]. miR-720 overexpression in kasumi-1 cells induced significantly increased cell apoptosis (P=0.017), elevated apoptosis sensitivity to etoposide (P=0.004), and reduced cell proliferation (P<0.01). miR-720 overexpression also induced reduced colony formation (P=0.005), cell cycle arrest in G(1)/G(0) phase and decreased migration ability in kasumi-1 cells. In addition, overexpression of miR-720 significantly induced increased cell apoptosis-related proteins including P53 and Bax, and activation of NF-κB signal transduction pathway. After kasumi-1 cells were treated with 1uM decitabine for 48 hours, miR-720 promoter methylation reduced significantly, and miR-720 expression significantly increased.

CONCLUSIONThe expression of miR-720 in AML patients reduced significantly, and DNA methylation-mediated epigenetic silencing of miR-720 contributed to maintain the malignant characteristics of AML.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; MicroRNAs ; genetics ; Promoter Regions, Genetic