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Objective:To observe the efficacy and safety of decitabine combined with chemotherapy in treatment of relapsed/refractory T lymphoblastic lymphoma/leukemia (T-LBL/ALL) with TP53 mutation.Methods:The clinical data of a T-LBL/ALL patient with TP53 mutation who had recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treated with decitabine combined with chemotherapy in the First Affiliated Hospital of Soochow University in June 2018 were retrospectively analyzed and the relevant literature was reviewed.Results:The patient, a 42-year-old male, diagnosed as T-LBL/ALL with TP53 mutation by comprehensive examination underwent sibling-matched donor allo-HSCT after a second complete remission. The patient relapsed 8 months later and was treated with decitabine combined with CLAG regimen to achieve complete remission again. And then, he had leukemia-free survival until now through maintenance treatment with decitabine.Conclusion:Decitabine combined with chemotherapy may be a safe and effective treatment option for relapsed T-LBL/ALL patients with TP53 mutation after allo-HSCT.
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OBJECTIVE@#To explore the feasibility of detecting maternal hereditary mitochondrial tRNA@*METHODS@#We performed sequence analysis of mitochondrial DNA in blood samples from 2070 cases of maternal hereditary mitochondrial disease in the First Affiliated Hospital of Wenzhou Medical University, and identified 3 patients with m.15927G>A mutation.Buccal swabs and blood samples were obtained from the 3 patients (mutation group) and 3 normal volunteers (control group).After extracting whole genomic DNA from all the samples, the DNA concentration and purity were analyzed.The PCR products were subjected to dot blot hybridization, Southern blot hybridization, and DNA sequencing analysis to verify the feasibility of detecting m.15927G>A mutation using buccal swabs.@*RESULTS@#There was no significant difference in DNA concentration extracted from buccal swabs and blood samples in either the mutation group or the control group (@*CONCLUSIONS@#Buccal swabs collection accurate is an accurate and sensitive method for the detection of m.15927G>A mutation.
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Humans , DNA, Mitochondrial/genetics , Mitochondria , Mutation , RNA, Transfer , Sequence Analysis, DNAABSTRACT
Objective:To explore the effect of dialectical diet on traditional Chinese medicine (TCM) syndrome score of cirrhotic ascites patients based on "Gu Ben Kai Qu" theory.Methods:From March 2019 to January 2020, 84 patients with liver cirrhosis and ascites admitted to Shuguang Hospital Affiliated to Shanghai University of TCM were randomly divided into two groups according to the different dialectical types of the subjects, 14 cases in each group. Three non-syndrome differentiation diet groups were given routine nursing care of liver cirrhosis ascites. On the basis of routine nursing, the corresponding medicinal diet was selected according to syndrome differentiation based on "Gu Ben Kai Qu" theory. Patients with spleen and kidney yang deficiency syndrome selected Shenqi lean meat decoction. Patients with Yin deficiency of liver and kidney selected Wolfberry and ophiopogon spareribs decoction. Patients with qi stagnation and blood stasis syndrome selected Danggui Sanqi spareribs decoction. The TCM syndrome score scale for liver disease and the curative effect evaluation of cirrhosis ascites were used to evaluate the effect.Results:Eighty effective cases were included. On the first day of admission, the 14th day and the second week after discharge, the TCM syndrome scores of liver disease were as follows: the group (a1b1) with the spleen and kidney yang deficiency syndrome was 46.38±8.56, 34.20±8.42, 31.40±4.22, respectively. The group (a1b2) with the liver kidney yin deficiency syndrome was 41.50±8.71, 31.35±8.63, 31.12±4.94. The group(a1b3) with the qi stagnation and blood stasis syndrome was 45.92±7.86, 35.17±7.57, 30.83±7.32, respectively. The non-syndrome differentiation diet group (a2b1) with the spleen and kidney yang deficiency syndrome was 46.29±8.38, 39.79±7.65, 36.64±6.83, respectively. The non-syndrome differentiation diet group (a2b2) with the liver and kidney yin deficiency syndrome was 40.50±8.12, 38.10±8.93, 35.38±8.24, respectively. The non-syndrome differentiation diet group (a2b3) with the qi stagnation and blood stasis syndrome was 45.62±7.99, 41.83±7.31, 38.83±7.96, respectively. The comparison of TCM syndrome scores of liver disease at three time points was statistically significant ( χ2 value was 63.998, P<0.05), and the comparison between groups was statistically significant ( χ2 value was 20.993, P<0.05). On the 14th day and the second week after discharge, there were significant differences between the groups with the syndrome differentiation diet and another three groups with non-syndrome differentiation diet ( F values were 3.244, 3.489, all P<0.05). Conclusions:Based on the theory of "strengthening the foundation and opening channels", the syndrome differentiation group can effectively reduce the TCM syndrome score of patients with cirrhosis ascites, improve the symptoms and enhance the curative effect. With the development of time, the score of TCM syndrome in patients with liver disease become lower. On the 14th day of admission, patients with Yin deficiency of liver and kidney given medicated diets had significant effect; patients with spleen kidney yang deficiency syndrome or qi stagnation and blood stasis had significant effect in 2 weeks after discharge; which can effectively improve the clinical symptoms of patients with cirrhosis ascites to worthy of clinical application.
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To explore the value of magnetic resonance diffusion-weighted imaging (MR-DWI) for evaluating inflammatory activity of perianal Crohn's fistula. Methods: A total of 55 patients, who were diagnosed as perianal Crohn's fistula by surgery and/or endoscopy, were assessed retrospectively. All patients, underwent pelvic magnetic resonance imaging (MRI) before and 32 weeks after the treatment, were divided into 2 groups according to their response to treatment: an effective group (34 cases) and an ineffective group (21 cases). The MRI images of patients in the 2 groups were analyzed. The changes of apparent diffusion coefficient (ADC) values before and after treatment in the 2 groups were measured and compared by a paired t-test. An MRI-based score of perianal Crohn's disease severity was calculated as a reference standard, and the correlation between the ADC value and the MRI-based score was analyzed by using a Pearson correlation coefficient method. Results: In the effective group, the ADC values after therapy were significantly greater than those before therapy (P0.05). There was a strong negative correlation between the ADC values (after and before therapy) and the MRI-based scores in all the patients [in the effective group alone (r=-0.672, P<0.01) or in the effective group + the ineffective group (r=-0.638, P<0.01)]. Conclusion: Changes in the ADC values of perianal fistula are related to the fistula activity. MR-DWI and ADC value can accurately evaluate the inflammatory activity of perianal Crohn's fistula.
Subject(s)
Humans , Crohn Disease , Diffusion Magnetic Resonance Imaging , Fistula , Retrospective StudiesABSTRACT
Objective@#To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) .@*Methods@#The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups.@*Results@#There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34+ cells infused were 10.74 (4.80-22.86) ×108/kg and 12.19 (5.14-17.25) ×108/kg (P=0.866) , 3.57 (0.68-7.80) ×106/kg and 4.00 (3.02-8.42) ×106/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups.@*Conclusion@#The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.
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Objective@#Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL.@*Methods@#The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without.@*Results@#The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) .@*Conclusions@#Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.
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Objective@#To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome.@*Methods@#The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen.@*Results@#There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×108/kg in the PNH group and 10.81 (3.96-33.40) ×108/kg in the PNH-AA group (P=0.668) . The median doses of CD34+ cells infused were 5.00 (3.14-8.42) ×106/kg and 3.57 (1.97-6.17) ×106/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) .@*Conclusions@#allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.
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Objective To explore the efficacy of hematopoietic stem cell transplantation (HSCT) for 5 patients with Ph-like acute lymphoblastic leukemia (ALL).Methods Fluorescent in situ hybridization (FISH) was performed for detecting the rearrangement of susceptibility genes.Combined therapy of chemotherapy and ruxolitinib were applied,followed by HSCT.Those failing to achieve complete remission (CR) received an infusion of chimeric antigen T-cells (CAR-T),followed by HSCT once CR was achieved.Four patients accept allogenic HSCT while another auto HSCT.Results Three of them achieved CR after chemotherapy and ruxolitinib.The remaining 2 patients got CR after CAR-T.Four patients remained in CR after HSCT.Early relapse occurred in 1 patient after HSCT.Conclusions Combined therapy of chemotherapy,ruxolitinib and CAR-T are necessary for Phlike ALL patients.HSCT after an initial CR improve patient prognosis.
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Objective@#To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD).@*Methods@#From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (Ctrough) was detected by ultra performance liquid chromatography tandem mass spectrometry.@*Results@#Based on the genotype analysis, 65 subjects were identified as extensive metabolizers’ group (30 cases) and poor metabolizers’ group (35 cases). The Ctrough of the 65 patients were detected for 169 times totally, and there was a significant difference of Ctrough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of Ctrough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ2=11.689, P=0.020).@*Conclusion@#Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their Ctrough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.
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Objective@#To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) treated by hematopoietic stem cell transplantation (HSCT).@*Methods@#Clinical features and prognoses of 63 newly diagnosed Ph+ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed.@*Results@#Of 63 Ph+ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ2=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ2=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ2=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ2=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS.@*Conclusions@#First-line administration of generic dasatinib could improve EFS for Ph+ALL patients treated by HSCT when compered with imatinib.
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Objective@#To evaluate the outcome of combination of haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) with an unrelated cord blood unit for severe aplastic anemia (SAA).@*Methods@#The clinical data of 127 SAA patients [including 74 male and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age as 23.5(3-54) years] received HID-HSCT from September 2011 to April 2017 were analyzed retrospectively. The median interval from SAA diagnosis to transplantation was 2 (0.5-180) months. The conditioning was modified Bu/Cy+ATG/ALG-based (Busulfan + cyclophosphamide + antithymocyte immunoglobulin/antilymphocyte immunoglobulin) regimen. Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. Prophylaxis for graft-versus host disease (GVHD) was by cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX).@*Results@#The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×108/kg in the haploidentical grafts and 2.22 (1.10-7.30)×107/kg in the cord blood units, respectively. The median doses of CD34+ cells infused were 3.49(1.02-8.89) ×106/kg in the haploidentical grafts and 0.56 (0.16-2.27) ×105/kg in the cord blood units, respectively. Of the 127 patients, 5 patients occurred early death, one patient occurred primary graft failure. All 121 surviving patients attained complete haploidentical engraftment. The median durations of myeloid engraftment were 11 (9-28) days and 15 (9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. The incidence of infection was 58.27% (74/127). During a median follow-up of 20.5 (4-60) months, the incidence of grade Ⅱ-Ⅳ acute GVHD was 24.79% (30/121), moderate-severe chronic GVHD was 14.15% (15/106), 4-year estimated overall survival was (78.5±4.3) %, 4-year estimated failure-free survival was (77.4±4.3) %, respectively.@*Conclusion@#Combination of HID-HSCT and an unrelated umbilical cord blood unit was a feasible choice with favorable outcome for SAA patients without matched donors.
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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 probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML).@*Methods@#Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period.@*Results@#There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ2=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively).@*Conclusion@#DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.
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Objective@#To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell.@*Methods@#The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay.@*Results@#①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8+ T cell acquired dim expression of CD4 membrane protein after activation. CD4+T cell and CD8+CD4dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01).@*Conclusions@#CD4 targeted CAR-T has an immunophenotype of CD8+CD4-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4+T cell and CD4+T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4dim target cell.
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Objective@#To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph +ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared.@*Results@#Of 76 Ph+ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ2=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ2=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ2=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ2=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS.@*Conclusions@#There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph+ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph+ ALL patients.
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Objective To explore the clinical features of cytomegalovirus (CMV) and EpsteinBarr virus (EBV) infection after second hematopoietic stem cell transplantation (HSCT).Methods Twenty-five patients after second HSCT from Sep.2009 to Oct.2016 were collected,and CMV and EBV DNA in peripheral blood was detected regularly by polymerase chain reaction (PCR).Factors associated were compared by univariate analysis.Results The total incidence of CMV infection was 52.0％ (13/25) after second HSCT.The incidence of CMV infection was 100％ (2/2),33.3％ (5/15) and 75％ (6/8) in bone marrow group,peripheral blood stem cell group,and mixed group,respectively.Stem cell sources were significantly correlated with CMV infection (P =0.038),however,there was no significant difference in CMV infection rate among three groups (P＞0.05).None of preconditioning regimen,GVHD prophylaxis programs or severity of aGVHD were correlated with CMV infection after second HSCT (P＞0.05).The total incidence of EBV infection was 24.0％ (6/25) after second HSCT.The incidence of EBV infection was 100％ (2/2),6.7％ (1/15) and 37.5％ (3/8) in bone marrow group,peripheral blood stem cell group,and mixed group,respectively.Stem cell sources were significantly correlated with EBV infection (P =0.008).The EBV infection rate in bone marrow group was significantly higher than that in peripheral blood group (P =0.022),however,no significant differences were found between bone marrow group and mixed group,as well as between peripheral blood group and mixed group (P＞0.05).Transplant methods were significantly correlated with EBV infection (P =0.007).The EBV infection rate in haploidentical HSCT group (71.4％) was significantly higher than that in HLA-matched sibling HSCT group (0％) and autologous HSCT group (0％) (P =0.021 and 0.028),however,no significant differences were found between any other two groups (P＞0.05).None of preconditioning regimen,GVHD prophylaxis programs or severity of aGVHD were correlated with EBV infection after second HSCT (P＞0.05).Conclusion The incidence of CMV and EBV infection in patients undergoing second HSCT is high.Stem cell sources and transplant methods are associated with CMV and EBV infection after second HSCT.
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Objective To investigate the efficacy of anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.Methods A total of 80 patients with SR-aGVHD from January 1st 2012 to December 31st 2016 were enrolled in this study.Acute GVHD were classified as classic aGVHD (n=72) and late-onset aGVHD (n=8).Anti-CD25 monoclonal antibodys (mAb) were administrated on days 1,4,8,15,and 22.The efficacy of anti-CD25 mAb was evaluated at day 28 after the initial treatment.The associated factors of clinical outcome were analyzed.Results The overall response (OR) rate of anti-CD25 mAb was 75％ (60/80),with complete response (CR) rate,partial response (PR) rate and no response(NR) rate 52.5％ (42/80),22.5％ (18/80),and 25％ (20/80),respectively.GVHD-relapse was not observed with a median follow-up time of 394.5 days (range,12-1 761 days).The 6-month overall survival (OS) rate was 68.4％ (95％CI 63.2％-73.6％).The 1-year OS rate was 63.1％ (95％CI 57.6％-68.6％),and 2-years OS rate was 50.7％ (95％CI 44.3％-57.1％).Non-relapse mortality (NRM) rate of 1 and 3 years was 32.6％ (95％CI 27.2％-38％) and 41.7％ (95％CI 35.3％-48.1％),respectively.The 1 and 2 years cumulative incidence of chronic graft versus host disease (cGVHD) was 32.9％ (95％CI 26.4％-39.4％) and 38.9％ (95％CI 31.8％-46.0％).By univariate and multivariate analysis,liver involvcment was an independent poor risk factor of SR-aGVHD (OR=4.66,95％ CI 1.145-18.962,P=0.032).Conclusion Anti-CD25 mAb serves as an alternative and effective salvage therapy for SR-aGVHD at present.Liver involvement is a predictive factor of poor response in patients with SR-aGVHD.
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Objective To improve the understanding of the diagnosis and treatment of Philadelphia (Ph) chromosome-like acute lymphoblastic leukemia (ALL) with EBF1-PDGFRB-positive. Methods One case of Ph-like ALL with EBF1-PDGFRB-positive from the First Affiliated Hospital of Soochow University was reported. Whole exome sequencing was applied to detect the EBF1-PDGFRB fusion gene. Fluorescence in situ hybridization (FISH) was used to detect minimal residual disease. Comprehensive treatments including chemotherapy, imatinib and chimeric antigen T-cell (CAR-T) therapy were utilized. Results EBF1-PDGFRB fusion gene in the bone marrow samples was detected by using whole exome sequencing at early diagnosis. The rearrangement of PDGFRB showed continuous negative after comprehensive therapy. The patient achieved continuous molecular remission for 22 months. Conclusions The comprehensive treatments include combined chemotherapy, CAR-T therapy and tyrosine kinase inhibitor can promote the continuous of major molecular remission for EBF1-PDGFRB-positive Ph-like ALL patients.
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Mitochondrial tRNAgene mutation is closely related to acoustic nerve deafness. Some mutations can affect the structure and transcriptional processing of tRNA, for instance m.7444G>A mutation in tRNAprecursor 3' side, m.7472 insC as well as m.7511T>C mutations in the stem and ring of tRNA, may influence tRNAstability, thus affect the synthesis of mitochondrial peptides, reduce the production of ATP and cause deafness. This article focuses on mitochondrial tRNAgene mutations as well as the mechanism underlying hearing loss.
Subject(s)
Humans , Amino Acid Sequence , Base Sequence , Genetic Predisposition to Disease , Genetics , Hearing Loss , Genetics , Mitochondrial Proteins , Genetics , Mutation , Nucleic Acid Conformation , RNA , Chemistry , Genetics , RNA, Transfer, Ser , Chemistry , GeneticsABSTRACT
Objective@#To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR1).@*Methods@#A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases).@*Results@#Of 107 patients (59 males and 48 females) , with a median age of 33 (16-59) years old and a median follow-up of 36.5 (5.3-79.1) months, the overall relapse rate was 20.6% (22/107) , and overall mortality rate was 18.7% (20/107). The 5 years cumulative relapse rate (CIR) of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 39.7%, 6.2%, 14.3% and 5.6%, respectively (P<0.001). The CIR of the observed group was lower than the HD-Ara-C group. The 5 years progression-free survival (PFS) rate of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 44.7%, 93.8%, 85.7% and 78.1%, respectively (P=0.011). The PFS of observed groups were similar, but superior to that in HD-Ara-C group. The 5-year overall survival (OS) in four groups was 54.9%, 100%, 92.9% and 77.4%, respectively (P>0.05). Multiple factors analysis showed that compared to HD-Ara-C regimen, allo-HSCT could improve PFS (HR=0.376, P=0.031) , but not OS (P>0.05) ; micro-transplantation and auto-PBSCT could not improve the PFS or OS (P>0.05).@*Conclusion@#As compared with HD-Ara-C regimen, allo-HSCT could obviously decrease CIR, improve PFS, but treatment-related mortality is high. These results show that auto-PBSCT and micro-transplantation have similar outcomes, compared to HD-Ara-C regimen, so both can be used as a option of consolidation treatment for favorable-risk AML.