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Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.
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Objective We aimed to investigate the expression of IRF4 and apoptosis of the histone deacetylase inhibitor LBH589 against MM cells in vitro,and study the mechanism of apoptosis when LBH589 alone or/and combined with lenalidomide in RPMI8226 cell so as to provide a new strategy for the treatment of multiple myeloma.Methods The cell viability on the growth of RPMI8226 cell were assessed by CCK8 assay.Apoptosis were measured by flow cytometry,The Grandpad software analyzes the statistical significance and evaluates the synergistic effect of the drug.The expression level of the related transcription factor and apoptotic gene protein were determined by western blot.The cell viability on the growth of RPMI8226-R cell were assessed by CCK8.Results LBH589 combined with lenalidomide have significant effect on inhibit cell proliferation and induce apoptosis in a dose-dependent manner.Apoptosis induced by LBH589/lenalidomide alone or combination was shown to involved PARP activation,decreased Bcl-2 and Bcl-xl expression.significantly down regulated transcriptional related factors of IRF4 and c-MYC expression compared with either agent alone.Conclusion LBH589 and lenalidomide alone or combination decrease the expression of transcription factor IRF4 and c-MYC,and have a significant synergistic effect,and highly expression of IRF in RPMI8226-R reduce proliferation inhibition.
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Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is an effective therapy for acute leukemia. But some patients with relapse after transplantation lead to treatment failure. A few patients who have extramedullary relapse after transplantation. The treatment outcome is limited and the overall prognosis is poor. Purely in patients with mammary gland relapse is rare. One case of mammary gland relapse with acute myeloid leukemia after bone marrow transplantation is reported to to increase the understanding of such patients.
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Objective To analyze the genetic characteristics of chromosomes and related fusion genes in acute myeloid leukemia (AML) (non-M3), and to evaluate the prognosis of patients with chemotherapy of DA regimen with different doses of daunorubicin. Methods Fifty-six patients with newly diagnosed non-M3 AML from January 2013 to January 2015 were collected. Adopted short-term culture method was used to treat bone marrow, R-binding chromosome karyotyping was used to detect cytogenetic. Thirty-one types of fusion gene were identified by PCR and 10 % agarose gel electrophoresis. All patients treated by DA regimen were divided into group A, group B and group C according to different dosage of daunorubicin. Then, complete remission (CR) rate and survival time in the 3 groups were observed. The effect of cytogenetic and molecular biology abnormality on the chemotherapy, CR rate and overall survival (OS) of the 3 groups were analyzed by the chi-square test. Results Among the 56 patients, 18 cases (32.1%) had abnormal chromosome karyotype, 6 cases (10.7 %) had abnormal number of chromosome, 16 cases (28.6 %) had abnormal structure of chromosome, and 4 cases (7.1 %) had both abnormal number and structure of chromosome. Meanwhile, the most common abnormal structure was t(8;21), and the most common abnormal quantity were+8, -Y. Detective rate of genetic abnormality was raised to 62.00 % through fusion gene and chromosome karyotype analysis. The total CR rate of DA-induced chemotherapeutic regimen was 73.2 %, and the two-year OS rate was 42.9%. The remission rate of chemotherapy in the middle-risk group was significantly lower than that in the low-risk group (χ 2 = 8.976, P = 0.002), but there was no significant difference between the low-dose chemotherapy group and the standard dose chemotherapy group (P>0.05). The standard dose group showed a significant advantage in the OS rate (χ2= 8.045, P= 0.005). Conclusions Adult acute leukemia has its unique cytogenetic characteristics, which can assist in guiding clinical diagnosis, classification and prognosis. The prognosis of middle-risk patients is significantly lower than the low-risk group. Low-risk patients could benefit from a reduced dose of DA regimen, but the standard dose DA regimen has a significant advantage in long-term survival.
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Objective To evaluate the efficacy and safety and to analyze related complications and potential prognostic factors of allogeneic hematopoietic stem cell transplantation(allo-HSCT ) on hematological malignancies .Methods Patients with hemato-logical malignancies who underwent allo-HSCT from June 2010 to June 2015 were investigated in this retrospective study .Accord-ing to the donor types ,it was divided into compatriots sibling-matched transplantation group (n = 52) and haploid transplantation group (n= 98) .The preconditioning regimens were busulfan/cyclophosphamide ,and anti-thymocyte globulin were needed in haploid transplantation group .Short-term methotrexate + cyclosporine A + mycophenolate mofetil were used for prevention of graft-ver-sus-host disease .The efficacy and safety and related complications of allo-HSCT were analyzed .Results All patients achieved full donor type engraftment ,which was identified by blood type ,chromosome test and DNA polymorphism .The mean times of neutro-phil and platelet engraftment were 12 d and 16 d in compatriots sibling-matched transplantation group and 13 d and 16 d in haploid transplantation group ,respectively .59 cases (39 .3% ) patients were oral mucosa ulcer ,47 patients (31 .3% ) were bacteria and/or fungal infection ,41 cases (27 .3% ) patients were CMV infection ,48 cases (32 .0% ) were acute GVHD ,43 patients (28 .7% ) were chronic GVHD .The median follow-up time of 23 months (1 - 60 months) ,115 patients (76 .7% ,115/150) were disease-free sur-vival ,including 38 cases (73 .1% ,38/52) in compatriots sibling-matched transplantation group ,77 cases (78 .6% ,77/98) in haploid transplantation group ;35 cases (23 .3% ,35/150) patients were died ,including 14 cases (26 .9% ,14/52) in compatriots sibling-matched transplantation group ,21 cases (21 .4% ,21/98) in haploid transplantation group .Death cause analysis showed that 12 ca-ses (8 .0% ) complications from transplantation related death ,of which 5 cases (3 .3% ) were severe infection ,7 cases (4 .7% ) caused by acute GVHD ,23 cases (8 .7% ) patients died because of the primary disease recurrence .The survival rate and mortality was similar between the two groups (P> 0 .05) .Conclusion Allo-HSCT is safe and effective treatment in hematological malignan-cies .The curative effect and security with haploid transplantation were similar to compatriots sibling-matched transplantation .It is necessary to prevent prognostic impact factors such as acute GVHD and infection early .
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OBJECTIVE:To study protective effects of glutamine (Gln) on cardiac muscle cell in septic model rats. METH-ODS:Rats were randomly divided into sham operation group (normal saline),model group (normal saline) and Gln low-dose, medium-dose and high-dose groups(0.5,0.75,1.0 g/kg)with 10 rats in each group. In these groups,septic rat model was induced by cecal ligation and puncture except sham operation group received sham operation. They were given relevant medicine intrave-nously 10 min after operation,and the characteristics and apoptosis of cardiac muscle cell were observed 12 h after operation. The serum contents of CK,LDH and TnⅠ,and the expression of Bcl-2 and p53 mRNA were all detected. RESULTS:Compared with sham operation group,myocardial necrosis of model group was found,and the serum content of CK,LDH and TnⅠ and apoptotic index increased,and mRNA expression of Bcl-2 in cardiac muscle cell decreased while that of p53 increased,with statistical signifi-cance(P<0.05). Compared with model group,myocardial injury relieved significantly in Gln high-dose and medium-dose groups, and serum contents of CK,LDH and TnⅠ and apoptotic index decreased;mRNA expression of Bcl-2 increased in cardiac muscle cell while that of p53 decreased,with statistical significance (P<0.05). CONCLUSIONS:Gln can improve myocardial injury of septic model rats significantly,by a possible mechanism of down-regulating the expression of p53 gene and up-regulating the ex-pression of Bcl-2 gene.
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Objective To analysis the different causes of death among patients who underwent allogeneic hematopoietic stem cell transplantation in order to explore the disadvantageous factors which affecting the long‐term survival after transplantation . Methods The planned conditioning regimen we used was BU/Cy and associated with mobilized peripheral blood and/or bone mar‐row stem cell .Meanwhile ,we used infection prevention and GVHD control methods .Throughout the treatment we observed the death patients during the allogeneic hematopoietic stem cell transplan‐tation and posttransplant ,however ,the causes of death were retrospectively analyzed .Results Among the 35 death cases ,the reason for 11 patients were relapse ,15 with serious infection (9 cases combine GVHD ,Ⅰ - Ⅱ GVHD 3 cases ,Ⅲ - Ⅳ GVHD 6 cases) ,2 patients underwent hematopoietic failure ,2 patients died of intracranial hemorrhage ,1 patient had pulmonary edema ,1 patient sudden death ,1 patient suffered from intestinal tract because of serious GVHD ,1 patient had a progression of disease ,and 1 hemolytic crisis .With a 100 days transplantation related mortality (TRM ) was 5 .7% ,and transplantation within 100 days to 1 year of TRM was 8 .1% .We received a 3‐year and 5‐year mortality rates of 16 .2% and 16 .7% ,respectively .Conclusion Infection ,GV HD and disease relapse are the most common causes of death a‐mong patients who underwent hematopoietic stem cell transplantation .Deadly infection is commonly observed within one year after transplantation and with which accompanied by the GVHD usually .Patients associated with cGVHD have a lower rate of disease re‐lapse .
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Objective To investigate the clinical manifestations,treatment and prognosis of reversible posterior leukoencephalopathy syndrome (RPLS) after acute lymphoblastic leukemia chemotherapy.Methods The clinical and imaging data of one case with acute lymphoblastic leukemia were analyzed and literatures were reviewed.Results The main clinical presentation of the patient included abdominal distension,repeated fever with fatigue.Depend on the results of the blood routine test and bone marrow relative examinations,the patient was diagnosed as acute lymphoblastic leukemia pro-B cell high risk group.After the induction therapy and consolidation chemotherapy,hypertension and neurological symptoms were appeared.Combined with the imaging examination,it was diagnosed as RPLS.Recieved active treatment,the patient recovered completely,and the imaging test was improved rapidly.Conclusion The causes of RPLS are variety,and its clinical manifestations and imaging test are non-specific.RPLS has a favorable prognosis.The correct diagnosis and treatment are the key points.
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<p><b>BACKGROUND</b>Bone marrow hematopoietic function suppression is one of the most common side effects of chemotherapy. After chemotherapy, the bone marrow structure gets destroyed and the cells died, which might cause the hematopoietic function suppression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that associates with cell proliferation and resistance to apoptosis. The aim of this study was to restore or resist the bone marrow from the damage of chemotherapy by the HO-1 expression of mouse mesenchymal stem cells (mMSCs) homing to the mice which had the chemotherapy-induced bone marrow suppression.</p><p><b>METHODS</b>One hundred and sixty female Balb/c mice (6-8-weeks old) were randomly divided into four groups. Each group was performed in 40 mice. The control group was intraperitoneally injected for 5 days and tail intravenously injected on the 6th day with normal saline. The chemotherapy-induced bone marrow suppression was established by intraperitoneally injecting cyclophosphamide (CTX) into the mice which performed as the chemotherapy group. The mMSCs were tail intravenously injected into 40 chemotherapically damaged mice which served as the mMSCs group. The difference between the HO-1 group and the mMSCs group was the injected cells. The HO-1 group was tail intravenously injected into the mMSCs that highly expressed HO-1 which was stimulated by hemin. The expression of HO-1 was analyzed by Western blotting and RT-PCR. Cell proliferation was measured using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Histopathologic examinations were performed 1 week after injection.</p><p><b>RESULTS</b>Compared with the control group, the expression levels of HO-1 mRNA and protein were significantly higher in the HO-1 group (all P < 0.05), even obviously than the mMSCs group. CTX treatment induced apoptosis and inhibited proliferation. After injected, the white blood cell (WBC), red blood cell (RBC) and platelet (PLT) declined fast and down to the bottom at the 7th day. The bone marrow structure was destroyed incomplete. In vitro, the survival rate of cells in chemotherapy group was less than 50% after 24 hours. In contrast, mMSCs could do a favor to the cellular cleavage and proliferation. They slowed down the cell mortality and more than 50% cells survived after 24 hours. The effects of blocking apoptosis and bone marrow recovery could be more effective in the HO-1 group. In the HO-1 group, it had observed that the bone marrow structure became complete and the hemogram closed to normal at 7th day.</p><p><b>CONCLUSIONS</b>HO-1 played an important role in promoting the recovery of CTX-induced hematopoietic damage. We suggest that HO-1 is able to restore the functions of chemotherapy-induced hematopoietic damage.</p>
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Animals , Female , Mice , Apoptosis , Blood Platelets , Blotting, Western , Bone Marrow , Cell Proliferation , Cells, Cultured , Cyclophosphamide , Toxicity , Erythrocytes , Heme Oxygenase-1 , Genetics , Metabolism , Leukocytes , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Physiology , Mice, Inbred BALB C , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
<p><b>OBJECTIVE</b>A prospective, multicenter and non-interventional prospective study was conducted to evaluate the clinical features of rituximab combined with chemotherapy (R-Chemo) as first-line treatment on newly diagnosed Chinese patients with diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>This was a single arm, prospective, observational multicenter and phase IV clinical trial for 279 patients, who were newly diagnosed as CD20-positive DLBCL from 24 medical centers in China 2011 and 2012, no special exclusion criteria were used. All patients received rituximab based R-Chemo regimes, such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone) and other regimes as the first-line treatment. The treatment strategies were determined by physicians and patients without detailed description for treatment course, dose, interval time and examination. Clinical response and safety of all patients were investigated in 120 days after completion of last dose of rituximab.</p><p><b>RESULTS</b>Of 279 patients, 258 with stage I-IV who received at least 1 cycle of rituximab treatment and completed at least one time of tumor assessment were enrolled into intention-to-treat analysis, including 148 male and 110 female. The median age of all patients was 57.2(12.8-88.4) years. ECOG performance statuses of 0 or 1 were observed in 91.1% of patients, international prognostic index levels in the low-risk and low-middle-risk groups in 76.4% of patients, the tumor diameters smaller than 7.5 cm in 69.0% of patients. All patients received 6 median cycles of R-Chemo treatment every 24.4 days. R-CHOP treatment was shown to improve the clinical response with overall response rates of 94.2%. Common adverse events included anemia, marrow failure, leukopenia, thrombocytopenia, digestive diseases, infection and liver toxicity. All adverse events are manageable.</p><p><b>CONCLUSION</b>Non-interventional clinical trial of R-Chemo remains the standard first-line treatment for newly diagnosed patients with DLBCL in real clinical practice, which is consistent with international treatment recommendations for DLBCL patients. R-Chemo can provide the clinical evidence and benefit as the first-line standard treatment for Chinese patients with DLBCL.</p>
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Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal, Murine-Derived , Therapeutic Uses , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Prospective Studies , Rituximab , Treatment OutcomeABSTRACT
BACKGROUND:Bone marrow mesenchymal stem cels can differentiate into renal tubular epithelial cels. It is speculated that mesenchymal stem cels may have a therapeutic role in chronic renal dysfunction. OBJECTIVE: To study the effect of bone marrow mesenchymal stem cels on the aging kidney of rats and its possible mechanism. METHODS: Aging models were established in rats. Rat bone marrow mesechymal stem cels cultured in vitro were labeled by 5,6-carboxyfluorescein diacetate, succinimidyl ester, and then injected into the ratsvia the tail vein. Under a fluorescence microscope, the cellhoming was observed. The contents of urea nitrogen and creatinine in serum of rats were tested by automatic biochemical analyzer. The overlaying of blue fluorescent 2-(4-amidinophenyl)-6-indolecarbamidine dihydrochloride and the specific protein of red fluorescent tubular epithelial cels (keratin protein) was detected by indirect immunofluorescence and computer image stacking technique. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cels could arrive the kidney of rats. Compared with the model group, the contents of urea nitrogen and creatinine in serum were decreased in the treated group (P < 0.05). The treated group showed a smal amount of double positive cels. These findings indicate that rat bone marrow mesenchymal stem cels may differentiate into renal tubular epithelial cels, which may be one of mechanisms that improve the aging kidney of rats.
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Objective To observe the curative effects of bezafibrate combined medroxyprogesterone acetate in the treatment of AML .Methods 40 cases of AML patients were collected and devided into experimental group (bezafibrate combined medroxypro-gesterone acetate ,6 cases) ,control group (chemotherapy ,28 cases) and non-treatment group (6 cases) ,then through a prospective analysis we studied the curative effects and related results of bezafibrate combined medroxyprogesterone acetate in the treatment of AML .Results The median survival time of the experiment group (accepted bezafibrate combined medroxyprogesterone acetate ) was 15 weeks ;the median survival time of the control group (accepted chemotherapy ) was 24 weeks ;the median survival time of the giving up group(accepted any therapy ) was 8 weeks .Conclusion Bezafibrate combined medroxyprogesterone acetate could prolong the survival time of AML patients and there were no obvious adverse reactions .
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<p><b>BACKGROUND</b>There are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia (CML). Heme oxygenase-1 (HO-1), as one of the most important oxidation-regulating enzymes in vivo, suggests the onset and progression of cancer when highly expressed. Furthermore, HO-1 level is related with the occurrence and development of hematological diseases. But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto. This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.</p><p><b>METHODS</b>A total of 60 peripheral blood and bone marrow (BM) samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR. Routine blood test was performed to detect the changes of leukocyte and platelet counts. The proportion of primitive cells in BM was detected by flow cytometry. The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis. The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.</p><p><b>RESULTS</b>Relative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors (P < 0.0001), which were 0.57±3.78 and (1.417±1.125)×10(-6), respectively. HO-1 expression level in CML patients was 0.061 5±0.062 4, which decreased to 0.009 4±0.006 7 upon CMoR, and remained remarkably higher 0.016 3±0.017 5 than that of normal donors (1.417±1.125)×10(-6), P < 0.001. When relapse occurred, HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse. According to progression of CML, HO-1 expression level in CML patients increased from CP (0.009 5±0.017 6) to AP (0.028 0±0.055 7) and then to BP (0.276 7 ± 0.447 0). And there was a linear correlation between HO-1 expression and proportion of primitive CML cells. The diagnostic accuracies and cutoff values of HO-1 expression for CML-CP, CML-AP, and CML-BP were 1.0, 0.748, and 0.965, respectively, as well as 0.000 070, 0.001 917, and 0.020 696, respectively.</p><p><b>CONCLUSION</b>HO-1 may be a potential molecular indicator for the progression and relapse of CML.</p>
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Female , Humans , Male , Bone Marrow , Metabolism , Flow Cytometry , Gene Expression , Heme Oxygenase-1 , Blood , Genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Diagnosis , Pathology , Predictive Value of Tests , Real-Time Polymerase Chain ReactionABSTRACT
Objective To investigate the effect of CCAAT/enhancer-binding protein homologeus protein (CHOP) in Tan Ⅱ A treated acute promyelocytic leukemia (APL) cells.Methods APL cell differentiation was monitored by morphology and membrane differentiation antigens; expression of CHOP was inhibited by siCHOP; mRNA and protein expression of CHOP in Tan Ⅱ A-intervened APL cells were examined by RT-PCR and Western blot.Results Expression of CHOP was increased in Tan Ⅱ A induced differentiated APL cells (proteins levels 1.933±0.987 vs 0.537±0.110,F =114.852,P ＜ 0.01,mNRA levels 1.587±0.815 vs 0.713±0.090,F =52.256,P ＜ 0.01),combination of CHOP gene silencing with Tan Ⅱ A treatment induced strong APL cell differentiation [(50.767±1.241) ％ vs (16.167±2.122) ％,F =989.431,P ＜ 0.05] and apoptosis [(89.233±5.581) ％ vs (27.433±2.957) ％,F =308.961,P ＜ 0.05].Conclusion CHOP acts as a negative regulator in Tan Ⅱ A induced differentiation.Inhibition of CHOP may be a promising therapeutic strategy.
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ObjectiveTo observe the efficiency of hematopoietic stem cell transplantation to the treatment of hematological malignancies and explore prevention and treatment of the complications correlated with HSCT. Methods110 patients with hematological malignancies which were treated by HSCT were recruited. 61 patients were treated with autologous peripheral blood hematopoietic stem cell transplantation (auto-PBSCT), 49 patients were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Among them,there were 28 patients were used by all HLA-identical sibling allo-PBSCT,20 patients were used by haploid allogeneic bone marrow and peripheral blood stem cell transplantation, one case of acute lymphoblastic leukemia in children were treated with cord blood stem cell transplantation.Results109(99.1％) patients acquired hemopoietic reconstruction. The median time of neutrophils≥0.5×109/L, and platelets≥20×109/L were 10 days and 12 days in auto-PBSCT,and were 12 days and 15 days in allo-PBSCT.The incidence of Ⅰ-Ⅲ degree of acute GVHD (aGVHD) in allogeneic transplantation was 28.6 ％(14/49),however,the incidence of chronic GVHD (cGVHD) was 32.6 ％(16/49).The median follow-up time was 36 (1～60) months.84 patients (76.4 ％) were disease-free.Among them,73.8 ％(45/61) were in auto-PBSCT group,(79.6 ％)39/49 were in allo-HSCT group.26 patients (23.6 ％) were died.There were 26.2 ％(16/61) who were in auto-PBSCT group died of disease relapse,3.3 ％(2/61) had disease relapse.There was no transplant-related deaths.18.4 ％(9/49) who were in allo-HSCT group died of disease relapse, 6.1％(3/49)had disease relapse, 2.0 ％(1/49)died of transplant-related deaths. ConclusionHematopoietic stem cell transplantation is a safe and effective way for the treatment of malignant hematopathy patients,also an important mean for treatment of blood diseases.
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ObjectiveTo evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) in treatment of hematologic malignancies and observe hematopoietic reconstitution, graft versus host disease (GVHD) occurrence,transplant-related complications and the outcome of disease.Methods20 patients with hematologic malignancies cured by allo-HSCT were analyzed retrospectively. 15 males and 5 females patients were enrolled, and the median age was 39(8-59)years. Mobilization of donor’ s stem cells using rhG-CSF program 3 days before transplantation.Conditioning regimen:the patients with HLA-matched used modified Bu/Cy programs,the patients with HLA-mismatched (with 1 to 3 loci mismatched) used the modified Bu/Cy+ ATG program;the patient with T-ALL and the patient with MM used Flu+Bu/Cy program. GVHD prevention programs: mycophenolate mofetil + cyclosporine + short course methotrexate. Results20 patients were successfully engrafted,the median time of absolute neutrophil count (ANC) ＞ 0.5×109/L was 13 (12-17) days,the median time of Plt ＞ 20×109/L was 16(12-23)days, and the hematopoietic reconstitution was rapid in those patients who were transplanted by the donors with the collected amount of CDh cells ＞ 2.5× 106/kg (recipient body weigh) or the collected amount of mononuclear cell ＞ 5.0×10s/kg (recipient body weigh).No severe hemolytic reaction occurred in 11 cases of blood group incompatibility between donor and recipient after transplantation,11 cases (55 ％) developed acute GVHD (aGVHD):4 cases Ⅰ degree aGVHD,4 cases Ⅱ degree aGVHD,2 cases Ⅲ degree aGVHD,1 case Ⅳ degree aGVHD,all patients were improved after treatment.All patients attained complete remission (CR) after transplantation.Follow-up 6 (2-14) months,1 patient died in 5 months after transplantation because of leukemia relapse, 1 case died in 4 months after transplantation because of self-disabling autoimmune hemolytic cyclosporine, chronic GVHD(cGVHD)and multiple organ failure,the remaining patients still were in CR state.ConclusionAllo-HSCT is the effective way to treat hematologic malignancies. Engraftment is closely related with the quantity of hematopoietic stem cells from donor.Blood group incompatibility was not an obstacle for transplantion.Relapse,GVHD,infection are the major cause of death after transplantation.
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Objective To investigate expression of 7 kinds of immune related human cytokines (IL-2, IL-4, IL-12, IL-13, IFN-γ TNF-α, MIP-1α) in CML patients. Methods Pure monoclonal antibody on the prepared NC membrane glass slides under certain environmental condition to make human eytokines protein microarray were spotted and serum samples (25 patients, 25 the normais) were collected. Cytokines concentration in the serum with the protein microarray were tested by ELISA. Results IL-4 and IL-12 serum concentration in CML patients are lower than that of the normal (P <0.05). However. No statistic difference of MIP-1α was found between CML patients the normal. Conclusion Cell mediated immunity and humoral immunity of CML patients are both inhibited in some extent and the expression of MIP-1α may be inhibited by p210 in CML patients.
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BACKGROUND: Rituximab single or in combination with CHOP regimen for treatment of CD20-positive non-Hodgkin lymphoma has achieved good curative effects. Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve the curative effects and increase survival rate of patients with non-Hodgkin lymphoma. However, the curative effects of these two methods remain disputed. OBJECTIVE: To investigate the efficiency of rituximab in combination with AHSCT on CD 20-positive non-Hodgkin lymphoma. METHODS: Six patients with CD 20-positive non-Hodgkin lymphoma (stage IV) underwent AHSCT and rituximab administration. 375 mg/m~2 rituximab was intravenously administered 2-4 times prior to AHSCT, twice prior to and after peripheral blood stem cells mobilization and preprocessing, respectively, as well as once every 3 months after AHSCT. RESULTS AND CONCLUSION: The mean number of mononuclear cells and CD 34-positive cells was 5.13×10~(-8)/kg and 4.75×10~(-6)/kg, respectively. Following AHSCT, all 6 patients presented normal hematopoietic functions, neutrophils exceeded 0.5×10~(-9)/L at 9-15 days and blood platelet counts exceeded 20×10~(-9)/L at 12-19 days. Hemorrhagic cystitis, interstitial pneumonia, cytomegalovirus infection, or hepatic venous obstruction was not observed during the whole process of AHSCT in each patient. At 6-32 months, patients completely recovered. These results indicate that rituximab in combination with AHSCT is a good method for treatment of CD20-positive non-Hodgkin lymphoma and rituximab maintenance therapy could prevent disease recurrence.
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BACKGROUND:Autologous peripheral blood hemopoietic stem cell transplantation(HSCT)in combination with high-dose chemotherapy significantly improves complete remission and survival rate of multiple myeloma patients.However,the relapse rate is high.Bortezomib is 26S proteasomes inhibitor,and effective on the primary treatment of multiple myeloma.OBJECTIVE:To evaluate the curative effect of HSCT in combination with bortezomib and high dose-melphalan for multiple myeloma.METHODS:A retrospective analysis of 3 patients with a stage-ITT multiple myeloma admitted to Department of Hematology,Affiliated Hospital of Guiyang Medical College from October 2006 to May 2007,was conducted.Chemotherapy and granulocyte colony-stimulating factor were used to mobilize autologous peripheral blood hemopoietic stem cells.All patients were pretreated with 200 mg/m2 melphalan via intravenous drip 3 days before transplantation,followed by HSCT 48 hours after drug termination.RESULTS AND CONCLUSION:All patients obtained prompt and sustained hematopoietic reconstitution,and bone marrow depression restored 30 days following HSCT.Case 1 and 2 obtained complete remission,and case 3 obtained partial remission.Results show that HSCT in combination with bortezomib and high-dose melphalan is a safe and feasible treatment on multiple myeloma.The patients have good tolerance to pretreatment.
ABSTRACT
It is difficult for the patients of refractory leukemia to complete remission (CR) and long-term disease-free survival (DFS), and it was always been the hot spots of research in the field of hematologic malignancies. The diagnostic criteria of refractory leukemia were adjusted constantly at domestic and foreign, the high-risk factors about refractory leukemia were found constantly too. New molecular markers that represent mutations or gene overexpression have been identified such as FMS-like tyrosine kinase-3 and nucleophosmin,which will enhance the ability to more accurately prognosticate for patients with acute myeloid leukemia. The treatment of patients with refractory or relapsed acute myeloid leukemia remains challenging. Multiple new agents with tremendous potential were in development and clinical trials. Such as applying resistance reversal agents,enhancing molecular targeted therapy, improving the technology of hematopoietic stem cell transplantation,empoldering the new drugs, and forming a new chemotherapy program etc. Monoclonal antibodies and peptide vaccination with leukemia-associated antigens also brought the hopes of increasing the remission and cure rates for patients with acute myeloid leukemia.