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Objective:To investigate the efficacy and related influencing factors of autologous hematopoietic stem cell transplantation(auto-HSCT)as first-line consolidation therapy for newly diagnosed elderly patients with diffuse large B cell lymphoma(DLBCL).Methods:Retrospective study of clinical characteristics, therapeutic effect, and prognostic factors of newly diagnosed DLBCL elderly patients with an International Prognostic Index(IPI)score≥3 who underwent auto-HSCT in the Affiliated People's Hospital of Ningbo University from January 2015 to August 2020.Results:Among the 31 patients, 18 were males and 13 were females, with a median age of 65(60-75)years.The 13 cases(41.9%)were involved in 2 sites outside lymph nodes, and 13 cases(41.9%)were involved in bone marrow.IPI medium and high risk(IPI=3 points)was found in 21 cases(67.7%), high risk(≥4 points)in 10 cases(32.2%). Before transplantation, 21(67.7%)patients achieved complete remission(CR), and the other 10(32.3%)patients were in the partial remission(PR). All patients after transplantation achieved hematopoietic reconstitution.The median time for neutrophil and platelet engraftment were 10(9-16)days and 12(8-58)days respectively.During a median follow-up of 20.9(3.1 to 73.0)months after transplantation, transplant-related mortality within 100 days was 3.2%(1/31). The 2-year overall survival(OS)and progression-free survival(PFS)were(77.2±8.4)% and(72.7±8.3)%, respectively.Multivariate Cox analysis showed that the achieved partial remission status before auto-hematopoietic stem cell transplantation[OS( HR=30.064, 95% CI: 2.231-405.209, P=0.010), PFS( HR=9.165, 95% CI: 1.926-43.606, P=0.005)], and CD34 + cell count in graft <3×10 6/kg[OS( HR=12.004, 95% CI: 1.234-116.807, P=0.032), PFS( HR=6.115, 95% CI: 1.325-28.221, P=0.020)]were the independent poor prognostic factor affecting both OS and PFS in elderly lymphoma patients. Conclusions:Auto-HSCT may improve the survival rate of carefully selected elderly patients with DLBCL.Pretransplant disease status and the number of CD34 + cells in the graft are important factors to predict the efficiency of auto-HSCT of the patients.
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To explore prognostic factors in intermediate-risk acute myeloid leukemia (AML) patients with minimal residual disease (MRD) negativity (MRD<0.1%,MRD-)receiving autologous hematopoietic stem cell transplantation (auto-HSCT).A total of 59 intermediate-risk AML patients with MRD-were treated with auto-HSCT from January 2015 to September 2021 at Affiliated People′s Hospital of Ningbo University. The clinical data and laboratory results were collected retrospectively. Efficacy, clinical outcome and prognostic factors were analyzed. Univariate analysis was conducted by using log-rank test, the multivariate analysis by Cox proportional risk model.Among 59 patients, there were 27 males and 32 females with median age of 55 (31-69) years old.The median follow-up was 761(317-1 861)days. The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 76.1%±11.4% and 73.4%±11.6% respectively.The univariate analysis showed that age older than 50 years, TET2 gene mutation (TET2 +), achieving MRD negativity over 30 days (MRD 30+) were unfavorable factors of OS ( χ2=6.20, 33.20, 7.18; P=0.013,<0.001, 0.007). TET 2+, WT1 gene mutation (WT1 +), CD34 +cells<2×10 6/kg, MRD 30+were negative factors of EFS ( χ2=17.29, 4.47, 3.94, 9.393; P<0.001, 0.035, 0.047, 0.002).Multivariate analysis showed that MRD 30+, TET2 + were independent prognostic factors of OS and EFS (OS: HR=9.251, 25.839, P=0.036, 0.001;EFS: HR=5.851, 9.199, P=0.043, 0.002). Intermediate-risk AML patients with MRD 30+or TET2 + have very poor prognosis after auto-HSCT. Alternative regimens should be investigated.
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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.
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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.
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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.
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Objective To explore the clinical efficacy of decitabine combined with HAG or HAG-like regimen for newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) patients.Methods Thirty-one newly diagnosed (18 cases) and relapsed/refractory (13 cases) AML patients receiving decitabine combined with HAG or HAG-like regimen in Yinzhou Hospital Affiliated to Medical School of Ningbo University from January 2014 to December 2017 were analyzed retrospectively.Results The outcome of 18 newly diagnosed AML patients showed that the overall response rate (ORR) was 77.8 ％ (14/18),including 13 patients achieved complete response (CR) / CR with incomplete blood count recovery (CRi),and the 1-year overall survival (OS) rate was 39.2 ％,the l-year disease free survival (DFS) rate was 32.5 ％.The outcome of 13 relapsed/refractory AML patients showed that the ORR was 53.8 ％ (7/13),including 6 patients achieved CR/CRi,and the 1-year OS rate was 22.4 ％,the 1-year DFS rate was 7.7 ％.Eleven patients were transformed from myelodysplastic syndromes (MDS),the ORR was 90.9 ％ (10/11),including 9 patients achieved CR/CRi,and the 1-year OS and DFS rates were 63.8 ％ and 37.5 ％ respectively.The main adverse events of infection and bleeding were caused by myelosuppression,and non-hematological toxicity included gastrointestinal and liver dysfunction.After the anti-infection and supportive treatment,all 31 patients were safely through bone marrow suppression,with no treatment-related deaths.Conclusions Decitabine combined with HAG or HAG-like regimen is an effective and safe treatment strategy for hypoplastic newly diagnosed and relapsed/refractory AML patients.It is produced relatively higher curative effect for AML patients with MDS transformation.
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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.
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Objective To observe the clinical effect of sequential therapy with micafungin and reduced -dose voriconazole in prevention of invasive fungal infections in patients received allogeneic hematopoietic stem cell transplantion (Allo -HSCT).Methods 28 patients received the treatments for prevention of fungal infection with micafungin 50 mg per day from pretreatment to 30 days,then oral voriconazole at a dose of 1 00 mg two times per day until 90 days after Allo -HSCT.The occurrence of invasive fungal infection and the side effects of both medicine were observed during 1 80 days after Allo -HSCT.Results 8 patients(28.6%)developed above grade 2 acute graft verse host disease(GVHD),2 patients developed grade 3 GVHD among the 8 patients.Two case with GVHD were cured by voriconazole with the therapeutic dose who occurred probably pulmonary invasive fungal infection at two months after Allo -HSCT.There were no other patients diagnosed fungal infection.No toxic efect were observed during the clinical observation during treatment with micafungin.5 patients appeared mild liver function abnormalities during treatment with voriconazole,and liver dysfunction were improved by symptomatic treatment.2 cases developed transient auditory hallucination and visual impairment induced by voriconazole.Conclusion Micafungin and reduced -dose voricon-azole are effective and safe prophylaxis in prevention early invasive fungal infection after HSCT.
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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 .
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Objective Carbon/carbon ( C/C) composites are a potential material for bone repair .To improve the hydrophilicity and biological activity of C/C composites , polydopamine coating was prepared on the surface of C /C composites.Methods By changing the coating time and coating environment ( oxygen or air atmosphere ), a series of polydopamine coating samples were prepared . The water contact angle test , scanning electron microscope , energy dispersive spectrometer , atomic force microscope and protein adsorption test were used to characterize the properties of different samples.Then, the data were analyzed to optimize preparation conditions .Results When the concentration of dopamine was 2.0 g/L,and the coating time was 30 min (oxygen atmosphere) +11.5 h (air atmosphere), the water contact angle was decreased from 64.0°(blank sample) to 25.9°, suggesting that the hydrophilicity was improved greatly . The results of the scanning electron microscope , energy dispersive spectrometer and atomic force microscope showed that the coating was uniform and dense .The amount of protein adsorption per sample was 0.2817 mg.Conclusion The polydopamine coating on the C/C composites improves its hydrophilicity and biological activity , which indicates that the polydopamine coated C/C composites will be a new potential material for bone tissue repair .
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Objective To investigate the therapeutic effect of insulin combined with oral hypoglycemic agents on cognitive function of patients with Alzheimer′s disease(AD) and diabetes mellitus(DM).Methods We retrospectively reviewed 135 cases of AD patients with type2 DM(T2DM) admitted to our hospital between March 2011 and March 2013. According to drug use , they were randomly divided into two groups , oral hypoglycemic drug group ( group A, 65 cases ) and insulin combined with oral hypoglycemic drug group (group B,70 cases).After 12 months of follow-up, the Mini Mental State Examination (MMSE) score by Folstein et al and Clinical Global Impression Scale (CGI) were used to assess their cognitive function .Results After 12 months of treatment , the MMSE score decreased significantly in group A ( P=0.000), but not in group B(P=0.281).Also, CGI-C scores showed significant deterioration for all domains after 12 months in group A vs group B(P=0.001).Conclusion Insulin therapy can effectively slow down the decline of cognitive function in patients with AD .
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<p><b>OBJECTIVE</b>To investigate the expression level and regulation mechanism of miR-720 as well as the association of miR-720 expression with leukemia biological characteristics.</p><p><b>METHODS</b>Expression 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.</p><p><b>RESULTS</b>AML 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.</p><p><b>CONCLUSION</b>The 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.</p>
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , DNA Methylation , Epigenesis, Genetic , Leukemia, Myeloid, Acute , Genetics , Pathology , MicroRNAs , Genetics , Promoter Regions, GeneticABSTRACT
ct curative effect and prognosis of multiple myeloma.
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Objective To determine the results of treatment combining all-trans-retinoic acid(ATRA)in childhood acute promyelocytic leukemia(APL).Methods 22 children with newly diagnosed APL received induction therapy with ATRA followed by 3 courses of consolidation chemotherapy:daunorubicin,idarubicin,homoharringtonine or aclacinomycin plus cytosine arabinoside.A maintenance therapy was then administered with ATRA and these reigems for 36 months.Results Early deaths from diffuse intravazcular clotting and intracranial hemorrhage occurred in two patients.The other children achieved a complete remission(CR).By June 2007,the estimated disease-free survival rates at 1,3 and 5 years were 100%,93.3% and 84.7%;respectively.The side effects of ATRA were xerosis eutis and xerocheilia,headaches,nausea and vomiting,hepatic function lesion and ATRA syndrome.Conclusion Remission induction therapy with ATRA is effective and safe for newly diagnosed childhood APL.The maintenance therapy combined chemotherapy with ATRA can improve the long-term effects of APL patients.The main causes of death in APL children is diffuse intravascular clotting and intracranial hemorrhage.The side effects of ATRA can be tolerated.