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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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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 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 investigate the in vitro cytotoxic effects of targeted silencing of long non-coding RNA colorectal cancer associated transcripts 2(CCAT2)by siRNA on multiple myeloma cell RPMI 8226 and U266.Methods Two strands of siRNA targeting at CCAT2,including siCCAT2-1 and siCCAT2-2,were transfected into RPMI 8226 and U266 cells at logarith-mic growth phase by liposome.The siRNA with the best silencing efficiency was screened for the subsequent experiments as ex-periment group by real-time fluorescence quantitative PCR(qPCR).The cells transfected with scramble sequence served as nega-tive control group and cells without transfection as blank control group.The cell proliferation rates were measured by cell count-ing kit-8.The apoptotic rates were measured by Annexin Ⅴ-FITC/PI double staining via flow cytometry.The mRNA levels of apoptosis related genes were detected by qPCR method.The numbers of invasive and metastatic cells were detected by Tran-swell method.Results The CCAT2 levels of multiple myeloma cell lines were reduced after transfection with siCCAT 2-1 and siCCAT2-2 in comparison with cells of negative control group and blank control group(P<0.05).The inhibition rates of RPMI 8226 and U266 cells were higher by transfection with siCCAT 2-2 than transfection with siCCAT2-1(P<0.05),and siCCAT2-2 was chosen to verify the cytology function.The inhibitory rates of RPMI 8226 and U266 cells in the experimental group was higher than those in the control group and the negative control group in a time dependent manner(P<0.05).Compared with RPMI 8226 cells of other two groups,the apoptotic rates and mRNA levels of Bax and Bad were increased but number of trans-membrane cells and mRNA level of Bcl-2 were decreased in experimental group(P<0.05).There was no significant difference between the control group and the negative control group on the above indices(P>0.05).Conclusion In multiple myeloma cell lines,siRNA targeting CCAT2 expression can inhibit the proliferation,invasion and metastasis and induce apoptosis of CCAT2, which may be valuable in the prevention and treatment of multiple myeloma.
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AIM: To evaluate the expression of fibroblast growth factor receptor 3 (FGFR3) in acute lymphocytic leukemia (ALL) patients and its contribution to the proliferation of circulating endothelial cells (CECs).METHODS: The mRNA expression levels of FGFR3 in 44 patients with ALL were assayed by RT-PCR.Overall survival (OS) rates of the patients in FGFR3+ group and FGFR3-group were estimated by Kaplan-Meier analysis.The CECs were sorted from peripheral blood by magnetic-activated cell sorting and then counted by 3-color flow cytometry.The cell counts, antigen expression, growth curve and colony forming rate of the CECs in the 2 groups were determined.The FGFR3 expression of CECs was identified by immunofluorescence staining.RESULTS: The positive rate of FGFR3 mRNA expression was 43.2% in 44 ALL patients with normal karyotype.T-ALL expressed higher level of FGFR3 than B-ALL (P<0.05).FGFR3 was over-expressed in ALL patients with bone marrow blast proportion ≥5% (P<0.05).The probability of OS was significantly lower in FGFR3+ group than that in FGFR3-group (P<0.05).The sorted CECs highly expressed CD31, CD144, VEGFR-2 and CD146, and rarely expressed CD45.The counts of CECs and expression level of CD133 significantly increased in FGFR3+ group compared with FGFR3-group.The same result of the amount of colony formation was observed (P<0.05).There was significant difference at 3 time points of cultured CECs count in vitro between FGFR3+ group and FGFR3-group (P<0.05).The positive rate of FGFR3 expression of CECs from 19 ALL-FGFR3+ patients was (29.00±15.71)%.CONCLUSION: The over-expression of FGFR3 gene in ALL may be helpful to evaluate the prolife-ration of CECs, and become a double target with anti-tumor and anti-angiogenesis effects to offer more choice for molecular therapy in the future.
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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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ct curative effect and prognosis of multiple myeloma.