Diagnostic efficacy of hypersensitivity quantitative fecal immunochemical test in colorectal cancer and advanced adenoma / 中华消化杂志

Objective:To evaluate the diagnostic efficiency of hypersensitivity quantitative fecal immunochemical test (hs-qFIT) in colorectal cancer (CRC) and advanced adenoma.Methods:From July to December 2020, consecutive patients aged 50 to 75 years who underwent colonoscopy in Qilu Hospital of Shandong University, and had the Asia-Pacific colorectal screening score of medium or high risk were enrolled. All patients were requested to complete two hs-qFIT before colonoscopy. The diagnostic efficacy of hs-qFIT for CRC and advanced adenoma were assessed. Receiver operating characteristic curve of hs-qFIT in CRC diagnosis was drawn and the area under the curve (AUC) was calculated.Results:A total of 811 patients including 20 (2.5%) cases of CRC, 47 (5.8%) cases of advanced adenoma, 206 (25.4%) cases of non-advanced adenoma, 219 (27.0%) cases of non-adenomatous polyp, 76 (9.4%) cases of other colorectal lesions and 243 (30.0%) cases of non-colorectal lesions were involved. When the fecal hemoglobin cut-off values were 10, 30, 50, 75 and 100 ng/mL, the positive rates of hs-qFIT detection were 17.9% (145/811), 10.9% (88/811), 8.3% (67/811), 7.4% (60/811) and 5.8% (47/811), respectively. When the cut-off value of fecal hemoglobin decreased from 100 ng/mL to 10 ng/mL, the sensitivity of hs-qFIT for CRC diagnosis increased from 90.0% to 100.0%, and the specificity decreased from 96.3% to 84.2%; and the sensitivity of hs-qFIT for the diagnosis of advanced adenoma increased from 19.1% to 66.0%, and the specificity decreased from 95.0% to 85.1%. The AUC of hs-qFIT for the diagnosis of CRC and advanced adenoma were 0.981 (95% confidence interval ( CI) 0.970 to 0.992) and 0.846 (95% CI 0.807 to 0.886), respectively. When the optimal cut-off values were taken, the sensitivity and specificity were 100.0% and 91.2% for the diagnosis of CRC, and 66.0% and 85.3% for the diagnosis of advanced adenoma, respectively. Conclusion:Hs-qFIT can help the early screening of CRC and advanced adenoma.

Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety / 医学前沿

Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). In 2007, a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients. This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment. The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total = 140 mg/ day), respectively. The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1% (versus 50.8% at 18 months), and the median time to MCyR was 12.7 weeks. All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response. The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64% (16/25), with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up; the median time to CHR was 16.4 weeks. The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months. The most frequently reported AEs (any grade) included pleural effusion, headache, and myelosuppression. These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.

Chemotherapy after chidamide pretreatment in high-risk and refractory lymphoid malignancy: report of 16 cases / 白血病·淋巴瘤

Objective To analyze the therapeutic effects of chemotherapy after chidamide pretreatment in 16 cases of high-risk and refractory lymphoid malignancy. Methods The efficacy and adverse reactions of 16 patients with high-risk and refractory lymphoid malignancy who received chidamide combined with chemotherapy after 3 days pretreatment of chidamide were analyzed. Results Sixteen patients included 6 males and 10 females, and the median age was 49.5 years old (23-88 years old). The median course of previous systemic chemotherapy was 4 (range 0-22). Among 14 patients who received induction chemotherapy, 7 patients achieved complete remission (CR), 7 patients achieved partial remission (PR). Fourteen patients had achieved clinical efficacy, and the overall response rate (ORR) was 100 %. After 2 cases had remission , the patients who entered this regimen for consolidation chemotherapy also had durable CR. The median follow-up time was 13 months (range 2-24 months) until December 2017. Nine cases had overall survival (OS), 7 cases died and 9 cases had progression-free survival. Common adverse effects of the chemotherapy included mild and controllable gastrointestinal reactions after chidamide. Conclusion Chemotherapy after chidamide pretreatment may improve the effect and prognosis of high-risk or refractory lymphoid malignancy.

A prospective multi-center trial of non-interventional and observational study of lenalidomide in Chinese patients with multiple myeloma / 中华内科杂志

Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309

A prospective, multi-centre clinical trial to evaluate the early clinical efficacy and safety of a generic imatinib in treating patients with chronic phase of chronic myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the early hematologic, cytogenetic and molecular responses in newly diagnosed patients with chronic myelogenous leukemia in chronic phase（CML-CP）and initially treated with a generic imatinib（Xinwei）, manufactured by Jiansu Hansoh Pharmaceutical Group Co., Ltd.</p><p><b>METHODS</b>107 newly diagnosed patients of CML-CP, whose ages were above 18- year- old and who had never received any tyrosine kinase inhibitor（TKI）were treated with Xinwei 400 mg QD. The hematologic, cytogenetic and molecular responses were assessed at 3- and 6-month, and adverse effects were evaluated throughout the study.</p><p><b>RESULTS</b>107 patients were treated with Xinwei for at least 3 months, 54 of them were treated for 6 months or more. At 3- month, the complete hematologic responses（CHR）rate were 98.1%（105/107）; 47/57（82.5%） patients achieved major cytogenetic response（MCyR）, and 20/57 （35.1%） patients complete cytogenetic response（CCyR）; BCR- ABLIS was ≤10% in 77/106 patients （72.6%）, 11 of them（10.4%）achieved major molecular response（MMR, BCR-ABLIS was ≤0.1%）. At 6-month, the CHR rate was 100%（54/54）; 28/39 patients（71.8%）achieved CCyR; BCR-ABLIS was ≤1% in 37/54 patients （68.5% ）, 18 of them （33.3% ） achieved MMR. The grade Ⅲ leukopenia, thrombocytopenia and anemia rates were 19.5%, 23.0% and 13.8%, respectively. No grade Ⅳ hematologic toxicity occurred. The common non- hematologic toxicities were edema（74.7%）, nausea（48.3%）, bone pain（42.5%）, rash（36.8%）, diarrhea（34.5%）, fever（23.0%）, cramp（11.5%）and impaired liver function （3.4%）. No patient experienced grade Ⅳ non- hematologic toxicity. No adverse effects related death occurred.</p><p><b>CONCLUSION</b>Our results revealed the excellent early haematology, cytogenetic and molecular responses and safety of Xinwei in treating patients with CML-CP.</p>

Generation and identification of P210(T315I-BCR/ABL) transgenic mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To construct the P210(T315I-BCR/ABL) transgenic mice model.</p><p><b>METHODS</b>The transgenic vector in which the P210(T315I-BCR/ABL) gene and eGFP gene was derived by APN/CD13 promoter was constructed and microinjected into the single-cell fertilized eggs of C57 mice. Transgene integration was conformed by PCR genotyping and P210(T315I-BCR/ABL) expression levels was evaluated by RT-PCR. The CML phenotype was confirmed by blood routine examination, Wright's staining for peripheral blood and bone marrow smears, HE staining for organs of transgenic mice.</p><p><b>RESULTS</b>Three transgenic mice lines with high expression of P210(T315I-BCR/ABL) gene and eGFP gene was selected. Compared with the wild type mice, the levels of WBC, platelet and neutrophil granulocyte of transgenic mice began to increase gradually at 2 months, and increase to 23.9×10⁹/L, 4 136×10⁹/L, and 74.6% respectively at 6 months. The remarkable hyperplasia of granulocytes was seen in the peripheral blood and bone marrow smears with splenomegaly infiltrated by leukemic cells.</p><p><b>CONCLUSION</b>The P210(T315I-BCR/ABL) transgenic mice was constructed and provided a model to explore the mechanism of T315I CML and screen out the drug for T315 CML patient.</p>

Correlation between point mutation in ABL kinase and clinical outcome of chronic myeloid leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the association of different types of ABL tyrosine point mutations and imatinib resistance to probe the relation between ABL tyrosine point mutations and the prognosis of patients with chronic myeloid leukemia (CML).</p><p><b>METHODS</b>Nested reverse transcriptasepolym erase chain reaction was performed on samples from 70 patients to amplify the ABL kinase domain. Then, the amplified product was purified and sequenced in both direction. The homologous analysis was performed in combination of clinical data.</p><p><b>RESULTS</b>The ABL domain point mutations were detected in 32 patients (45.7%) including 16 patients in chronic phase (CP), 6 patients in accelerated phase(AP)and 10 patients in blast phase (BP), which were detected as T315I, E255K, C475Y, Y253H, G321W, G250E, F317L, E258K, F359V, E459K and F311I, respectively. Sokal score with intermediate and high risk and Ph+ chromosome with complex karyotype were important risk factors for ABL domain point mutations. The 5-year overall survival (OS) was not significantly different between the patients with or without ABL domain point mutations (78.1% vs 84.2%, P=0.985), while the 5-year cumulative event-free survival (EFS) of two groups were 34.4% and 68.4% (P=0.034), respectively. The rate of complete cytogenetic response was higher in patients treated with allogenic hematopetic stem cell transplantation (allo-HSCT) compared with patients merely treated with second-generation tyrosine kinase inhibitors or chemotherapeutics (P=0.001).</p><p><b>CONCLUSION</b>Patients with ABL domain point mutations had poor efficacy and prognosis compared to those without ABL domain point mutations. Detection of ABL domain point mutations in CML-CP was helpful for the adjustment of therapeutic options and improvement of prognosis. And allo-HSCT was a more effective therapy for patients with advanced phase.</p>

Comparison of clinical efficacy between HLA-mismatched related and HLA-matched unrelated donor hematopoietic stem cell transplantation for hematopoietic malignancies / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the clinical efficacy of HLA- mismatched related donor (MRD) and HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies.</p><p><b>METHODS</b>174 patients with hematopoietic malignancies undergoing allogeneic HSCT (allo-HSCT) (82 from MRD and 92 from MUD) between June 2002 and December 2012 were enrolled in this retrospective study. Hematopoietic engraftment, graft versus host disease (GVHD), relapse, overall survival (OS) and disease-free survival (DFS) were compared between MRD and MUD group.</p><p><b>RESULTS</b>There was no significant difference between MRD and MUD group in terms of age, gender, disease type and disease status before transplantation (all P>0.05). The incidence of Ⅰ-IV acute GVHD (aGVHD) was 62.2% and 54.3% in MRD and MUD group (P=0.295); the incidence of III-IV aGVHD between the two groups was 15.9% and 9.8% (P=0.229). The incidence of chronic GVHD (cGVHD) was 28.4% and 45.1% in MRD and MUD group (P=0.036), but there was no significant difference in the incidence of extensive cGVHD between the two groups (9.0% vs 12.2%, P=0.525). The mortality of GVHD was 8.5% and 10.9% in MRD and MUD group (P=0.605). The 10-year OS and DFS were (50.1±6.1)% and (48.8±6.1)% in MRD group, compared with (50.5±6.7)% and (46.3±6.2)% in MUD group (P=0.501, P=0.873, respectively). The 10-year cumulative relapse rate was (21.5±5.7)% and (37.6±7.3)% in MRD and MUD group (P=0.194).</p><p><b>CONCLUSION</b>MRD is equivalent to MUD in efficacy and safety. Without HLA- matched related donors, MRD is superior to MUD because donor source is unlimited and transplantation could be made promptly according to disease status.</p>

Effect of histone deacetylase inhibitor LBH589 on proliferation, apoptosis and drug resistance of acute myeloid leukemia cell line HL60/ADM / 白血病·淋巴瘤

Objective To investigate the effect of histone deacetylase inhibitor LBH589 on proliferation,apoptosis and drug resistance of chemoresistant acute myeloid leukemia cells HL60/ADM.Methods HL60/ADM cells were treated with LBH589.Proliferation,apoptosis and adriamycin IC50 were evaluated by MTT assay and AnnexinV-FITC/PI stain.The change in MRP1 expression and intercellular adriamycin accumulatiom were analyzed by flow cytometry.Results Effective proliferative inhibition and apoptotic induction in HL60/ADM cells were observed after treatment with 10-80 nmol/L LBH589 with maximal effect detected after treatment with 70 nmol/L LBH589 for 60 hours.However,inhibition ratio remain unchanged with the further increase of drug dose and incubation time (P ＞ 0.05).Downregulation of MRP1 [(93.90±4.20) ％ vs (76.19±6.53) ％],upregulation of adriamycin accumulation [(8.53±0.68) ％ vs (25.67±1.34) ％] and decrease in adriamycin IC50 [(6.833±0.319) μg/ml vs (1.382±0.104) μg/ml] were induced by the treatment with 20 nmol/L LBH589 (P ＜ 0.01),whose reversal fold was 4.9.The expression of acetylated histone 3 after treatment with LBH589 was higher than that before treatment (P ＜ 0.01).However,relative p-Akt levels after treatment for 24 h and 48 h were 1.07±0.09 and 0.59±0.01,respectively,which were lower than that before treatment (2.03±0.12) (P ＜ 0.01).Meanwhile,expression levels of p53 were 0.57±0.04 and 1.31±0.09,respectively,which were higher than that before treatment (0.21 ±0.02) (P ＜ 0.01).Conclusion Treatment with LBH589 has the capability of inhibiting proliferation and inducing apoptosis,as well as increasing intercellular adriamycin accumulation and sensitivity through downregulation of MRP1 expression and inhibition of PI3K-Akt signaling pathway in HL60/ADM cells.

Impact of rhG-CSF mobilization on TH17/Treg cells in donors' peripheral blood / 中华器官移植杂志

Objective To explore the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) mobilization on TH17/Treg cells and its impact on suppressor of cytokine signaling-3 (SOCS3) gene expression in CD4+ T cells in donors' peripheral blood.Method Sixteen donors were injected subcutaneously with rhG-CSF 5 μg/kg every day for 5 consecutive days for peripheral blood stem cells mobilization.At the first 0,3,5 day,the mononuclear cclls (MNCs) in peripheral blood or graft and serum specimens were taken.The CD4 + T cells in MNCs were sorted using immuno-magnetic beads.The ratio of TH 17 and Treg cells in MNCs,cytokines concentrations of IL-17A,IL-21,ID23 and TGFβ1 in serum,and SODC3 gene expression in CD4+ T cells were detected by using flow cytometry,ELISA,and reverse transcription real-time quantitative PCR (RT-qPCR),respectively.Results (1)The ratio of Th17 cells (CD3+ CD8 CD17+) and Treg cells (CD4+ CD25+ Foxp3+) in MNCs in peripheral blood and graft at the first 0,3 and 5 days after mobilization was (2.69 ± 0.81) ％,(0.91 ± 0.33) ％,(0.35 ± 0.12) ％,(0.21 ± 0.05) ％,and (0.56 ± 0.24) ％,(0.72 ± 0.22％),(1.59 ± 0.54) ％,(3.38 ± 0.52) ％,respectively,showing a significant declining and increasing trend respectively (P＜0.05); (2)The cytokine concentrations in serum at the first 0,3 and 5 days after mobilization were 7.33 ± 0.89,5.78 ± 1.03 and 3.32 ± 0.84 μg/L for IL-17A; 124.56 ± 15.18,117.12 ± 14.45 and 64.94 ± 11.25 μg/L for IL-21 ; 183.52 ± 59.35,280.49 ± 69.75 and 393.62 ± 57.25μg/L for TGF-β1 (P＜0.01) ; and 45.89 ± 6.95,46.25 ± 7.44 and 47.45 ± 10.75 μg/L for IL-23,respectively.The IL-17A and IL-21 concentrations showed significant declining trend,contrarily TGF-β1 with an increasing trend,while IL-23 concentration had no change.After rhG-CSF mobilization,the SOCS3 gene expression in CD4 + T cells of peripheral blood and graft at the first 0,3,5 days was gradually increased.Conclusion rhG-CSF suppresses Th17 cells and promotes regulatory T cells generation,meanwhile decreases IL-17A and IL-21 and elevates serum TGF-β1 concentrations,and contributes to CD4 + T cells differentiation to Tregs,probably by elevating SOSC3 gene expression in CD4+ T cells.

Bortezomib combined with homoharringtonine or arsenious acid induced apoptosis in HL-60 cells and its mechanism / 白血病·淋巴瘤

Objective To explore the apoptosis effect induced by bortezomib combined with homoharringtonine or arsenious acid in HL-60 cell line and the mechanism.Methods Cell' s apoptosis was demonstrated by MTT assay and Hoechst33342 staining.Expression of bcl-2,Caspase-9,Caspase-3 and PARP protein was detected by Western blot.Results HL-60 cells' apoptosis could be induced by bortezomib,homoharringtonine and arsenious acid respectively.Proliferation inhibition of HL-60 cells could be enhanced significantly when treated by bortezomib combined with homoharringtonine or arsenious acid compared with treated by any of the three drugs alone (P ＜ 0.05).At the same time morphology shows the apoptosis induced by drugs combined is more obviously than by one drug.Western blot showed bcl-2 protein was down-regulated and Caspase-9,Caspase-3 and PARP proteins were all cleaved activation when cells were treated by 15 μmol/ L arsenious acid alone,but only cleaved activation of PARP and down-regulation of bcl-2 protein be detected when cells were treated with 30 nmol/L homoharringtonine alone,expression of Caspase-9 and Caspase-3 had no change compared with the control.The changes of associated proteins were paralleled with the cell' s apoptosis when treated with combined drugs.Conclusion HL-60 cells' apoptosis effect is inhanced significantly when bortezomib combined with homoharringtonine or arsenious acid.Arsenious acid and bortezomib can inhibit caspase signaling pathway and down-regulate the expression of bcl-2 protein together,but homoharringtonine and bortezomib can only down-regulate the expression of bcl-2 protein and induce cleaved activation of PARP together.

Long-term outcomes of nilotinib treatment for chronic myelogenous leukemia patients with imatinib resistance or intolerance / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the long-term clinical efficacy and safety of nilotinib in the treatment of chronic myelogenous leukemia (CML) patients with imatinib resistance or intolerance.</p><p><b>METHODS</b>Twenty-six CML patients with imatinib resistance or intolerance received nilotinib treatment at the dose of 400 mg once or twice daily. The patients were followed up for nearly 5 years with regular monitoring of the hematologic, cytogenetic and molecular biological markers and recording of the clinical manifestations and biochemical indicators to evaluate the therapeutic effect and adverse events.</p><p><b>RESULTS</b>The median duration of nilotinib therapy was 17 (1-56) months, and the patients were follow up for a median of 51 months. At the last follow-up, 16 (61.5%) patients achieved a complete hematologic response, 13 (50.0%) achieved a major cytogenetic response, 9 (34.6%) achieved a complete cytogenetic response, and 7 (26.9%) achieved a major molecular response accumulatively. Nonhematologic adverse events were mostly of grade l or 2. The most common adverse effects possibly related to nilotinib were increased bilirubin (69.2%) and rash (57.7%). Grade 3 or 4 hematologic adverse events included thrombocytopenia (53.8%), neutropenia (26.9%) and anemia (19.2%). The patients in chronic and remission phase had better efficacy and fewer hematological side effects than those in advanced phase.</p><p><b>CONCLUSION</b>Nilotinib is an effective and safe treatment option for imatinib-resistant or -intolerant CML patients, especially for those in chronic and remission phase.</p>

Autologous peripheral blood hematopoietic stem cell transplantation in the treatment of three cases of severe pemphigus / 中华皮肤科杂志

ObjectiveTo explore the clinical efficacy and safety of autologous peripheral blood stem cell transplantation(APBSCT) in the treatment of pemphigus.MethodsTotally,3 patients with pemphigus vulgaris who responsed poorly to 6-month treatment with glucocorticoids or immunosuppressants or experienced aggrevation of disease and developed treatment-related complications,received APBSCT and were followed up for more than 5 years.There were 1 male and 2 females with an average age of 27.3(21-39) years.The mobilization program included cyclophosphamide (CTX) 4 g/m2,recombinant human granulocyte colonystimulating factors(G-CSF) and Rituximab 375 mg/m2,and the preconditioning regimen included intravenous CTX (50 mg/kg per day on days -6,-5,-4,-3),antithymocyte globulin at 2.5 mg/kg per day(on days -3,-2,-1 and 0) and Rituximab (600 mg/d on days 0 and 7).ResultsAll the 3.patients were successfully engrafted.The mean time for peripheral reconstruction:white blood cells 13.3 days (from day 11 to 16),platelet 16.3 days (from day 16 to 17).Monitoring of immunity indices and related antibodies showed no abnormality and the immune system was well reconstructed.No serious complications occurred during the follow up,and the patients' quality of life was obviously improved.ConclusionAPBSCT may be an effective and safe option for the treatment of pemphigus.

Determination of imatinib in human plasma and its significance / 白血病·淋巴瘤

As the first line of therapy for chronic myeloid leukemia, the outcome of imatinib is encouraging. The plasma concentration of imatinib is correlated with remission rate and survival, and affected by α1 acid glycoprotein(AGP) and those drugs which will change the activities of cytochrome P450(CYP3A4). It is conductive for the treatment of CML by monitoring the plasma concentration of imatinib.

Clinical study of 64 patients with invasive fungal infection in hemopathic neoplasms treated with caspofungin / 白血病·淋巴瘤

Objective To study the efficacy and safety of caspofungin for the invasive furlgal infection in hematopathic neoplasms patients.Methods The retrospective study of effeacy,influencing factors and adverse reaction in 64 patients with hematopathic neoplasms have been treated with capofungin from January 2007 to February 2009.The SPSS13.0 software Was used for statistic analysis.Results The overall efficacy in 64 patients was 54.7%.The median of effective time for patients with fever and non-fever were 1(1-10) day and 12.5(2-30) days,respectively.There were no significant difference in age,detection of fungus,duration time of neutropenia,hematopoietic stem cell transplant,sraft versus host disease,immunoppressive agents,CT scans,loading dose of caspofungin and salvage therapy between two groups.Drug-related toxicities was low and reversible. Conclusion This study strongly supported caspefungin as an option for empiric and salvage antifungal therapy,and therapeutic effect of caspefungin was not influenced by immune state,neutrophils and CT scans,drug-related toxicities was low.

Combined transplantation of bone marrow and umbilical cord blood of same sibling in eight children with beta-thalassemia major / 中国组织工程研究

OBJECTIVE: To investigate the curative effect of combined transplantation of bone marrow and umbilical cord blood of same sibling in children with β-thalassemia major.METHODS: Eight thalassemia major patients undergoing combined transplantation of bone marrow and umbilical cord blood of same sibling aged from 4.0 to 7.5 years, 5 boys and 3 girls, were recruited at the Department of Pediatrics, Nanfang Hospital,Southem Medical University from January 2005 to March 2009. The patients were classified into three classes according to Pesarothalassamia classification, class Ⅰ to class Ⅱ 7 cases and class Ⅲ 1 case. Donors ranged 1-4 years received 10 μg/kg per day of subcutaneous granulocyte colony-stimulating factor (G-CSF) for 5 consecutive days. Bone marrow was harvested on the fifth day. Bone marrow and umbilical cord blood of the same sibling then were transfused into the patient.RESULTS: Recovery of hematopoiesis was gained in all patients 4 weeks following transplantation. Seven patients suffered from infection of different degree. Four patients developed mild venous occlusive disease. Two patients developed grade Ⅰ acute graft-versus-host disease (GVHD), and one developed grade Ⅰ chronic GVHD. Seven patients were alive and one died of pulmonary infection and heart failure 32 days following transplantation.CONCLUSION: Combined transplantation of granulocyte colony-stimulating factor primed bone marrow and umbilical cord blood of same sibling in children with β-thalassemia major is safe and effective with promising results. However, complications should be paid high attention following transplantation.

Expression of Ang-2 gene in acute lymphatic leukemia and its clinical significance / 白血病·淋巴瘤

Objective To study the expression levels and its clinical significance of angiopoietin 2 (Ang-2) gene in acute lymphatic leukemia(ALL). Methods The qualitative detection method was established with SYBR Green Ⅰ by real-time fluorescent quantitative PCR, and Ang-2 mRNA was measured in 51 cases of pre-therapeutic ALL. In addition, the expression of Ang-2 gene was also analyzed in 20 cases of non-malignant hematological diseases. Results The expression of Ang-2 gene was found in all the patients, and Ang-2 expression level in ALL patients was significantly higher than that of the controls (P<0.05). No significant relationship was found between Ang-2 expression level and clinical characteristics (age, haematogloblin, WBC count, platelet count, LDH, blast cells in peripheral blood, blast cells in bone marrow). The expression level of Ang-2 have no effect on one year replase rate and survival rate in ALL. Conclusion Ang-2 expression level in ALL patients was higher than that in non-malignant hematological diseases, and there may be no relationship with clinical manifestation, treatment and prognosis.

A multi-centers clinical study of difierent treatment outcomes of 332 patients with multiple myeloma / 中华内科杂志

Objective To describe the demographic and clinical characteristics of patients with the diagnosis of multiple myeloma(MM)and to analyse the outcome of difierent regimens for the treatment of MM.Methods The study reviewed 332 MM cases diagnosed within the period from January 1,2002 to December 31,2002.These patients were tracked via their records to a total period of three years.Results First-line treatment:Totally 332 patients were included,among them 325(97.9%)patients received chemotherapy and 7(2.1%)patients received stem cell transplantation(SCT);Second-line treatment:197 patients were included,among them 190(96.5%)patients received chemotherapy and 7(3.6%)patients received SCT;Third-line treatment:92 patients were included,among them 88(95.7%)patients received chemotherapy and 4(4.4%)patients received SCT.Major adverse effects were follows:severe infection 19.3%,severe anaemia 19.3%,phlebothrombosis 1.2%,thrombocytopenia 16.9%,fever associated with neutropenia 18.1%.Conclusions Some curative effects can be achieved by using traditional treatment plans to treat patients suffering from MM,but new methods are expected to improve the prognosis.

A clinical study of chronic disseminated candidiasis in patients with acute leukemia / 中华内科杂志

Objective To deepen the understanding of chronic disseminated candidiasis(CDC)in patients with acute leukemia(AL).Methods CDC was investigated in 119 AL patients who received induction chemotherapy from August 2004 to May 2005.Clinical manifestations,laboratory tests,imaging modalities,diagnosis and treatment were investigated retrospectively.Results Three patients(2.5%) were identified to be suffering from CDC.All the three patients had an absolute neutrophil count (ANC)＜0.5 × 109/L for more than 15 days.Two patients had normal ANC when they were diagnosed to have CDC.The common manifestations in these three patients were persistent fever,splenohepatomegalia and percussion pain in hepatic region.Meanwhile,2 of them were accompanied with cough,expectoration and dyspnoea.The abnormal laboratory test observed during the course of infection in two of them was increase of alkaline phosphatase.Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the three patients:two of them showed multiple nodular patchy shadOW$in lungs.Nuclear magnetic resonance imaging showed multiple abnormal signal in liver,spleen and kidneys in one of the patients.Two patients had positive bleed fungal cultures and histologic examination in one of the patients were positive for Candida tropicalis.Two patients received amphotericin B therapy empirically,but it was replaced by amphotericin B colloid dispersion (ABCD) later in one and combined with voficonazole in another because of unresponsiveness to the drug.One patient took a favorable turn after receiving ABCD therapy for 45 d,which was replaced by voriconazole because of the emergence of fever after disconfinuation of ABCD.All the three patients received further chemotherapy smoothly after the diagnosis of CDC.Conclusion The diagnosis of CDC remains difficult.Fungal blood cultares and histologic examination have been considered in many studies as the golden standard for the diagnosis of CDC.Amphotericin B is the cornerstone of treatment in patients with CDC and lipid formulations of amphotericin B can be used in CDC patients who are intolerant of or refractory to conventional amphotericin B.Voriconazole has a favorable response for refrectory/relapse patients and could be used for second line trectment.The development of CDC in patients with acute leukemia does not preclude further chemotherapy.

Immunal reconstitution after autologous purified CD+34 cells transplantation in patients with systemic lupus erythematosus / 中华内科杂志

Objective To investigate the variation of immune index in patients with systemic lupus erythematosus (SLE) treated with autologous purified CD+34 cells transplantation and to clarify the relationship with pathogenesis and prognosis. Methods Flow cytometry (FCM) and enzyme linked immunosorbent assay(ELISA) were used to test lymphocyte subsets, C3, C4, CH50, autoantibodies and immunoglobulin for 18 cases of SLE before and after transplantation. Results The results showed that the ratio of all the T cell subsets reduced obviously in early postgraft and recovered gradually in 1 to 3 months after transplantation except CD45 RO+CD+4 cells. The levels of serum C3, C4, CH50 increased significantly after transplantation. No case relapsed within one year after transplantation, but 2 patients relapsed one year after transplantation. The levels of the indexes in the patients with relapse were significantly lower than those in the patients with persistent remission, including C4 in the entire course, CH50 in the 3rd and 12th month after transplantation and CD45 RA+ CD+8 cells in the 6th month after transplantation. However, the ratio of CD45 RO+ CD+4 cells in the first month after transplantation in the patients with relapse was higher than that in the patients with persistent remission. Conclusion Autologous purified CD+34 cells transplantation is effective for treating SLE. Survey of immune indexes before and after transplantation is important to investigate the pathogenesis of SLE. Moreover, these immune indexes can be used to predict therapeutic efficacy of SLE.