Detection of promoter and 3′ UTR mutation in A20 gene of a case with T cell lymphoma cell leukemia / 中华血液学杂志

Objective@#To clarify the characteristics of the A20 regulatory changes by analyzing mutations in the non-coding region of the A20 gene in patients with T-cell lymphoma leukemia (T-LCL) .@*Methods@#PCR and nucleotide sequence analysis were used to detect mutations in the non-coding region of the A20 gene, and DNA samples from PBMCs of 52 cases of T-LCL and 99 healthy controls.@*Results@#A missense mutation (c.-672T>G) was detected in the A20 gene promoter from one T-LCL patient, which has been registered as a SNP (rs139054966) in gene bank. Meanwhile, a new mutation was detected in the 3′ UTR mRNA (3916 (C>G) ) . These two mutations were absent in other T-LCL samples and controls.@*Conclusion@#The rs139054966 (c.-672T>G) and 3916 (C>G) mutations in the A20 gene were detected in T-LCL patients for the first time. There was also rs139054966 located on the binding region of the transcription factor P53, and its significance remained to be further clarified.

The prognostic value of the international prognostic index, the national comprehensive cancer network IPI and the age-adjusted IPI in diffuse large B cell lymphoma / 中华血液学杂志

Objective@#To explore the prognostic value of the international prognostic index (IPI), the national comprehensive cancer network IPI(NCCN-IPI)and the age-adjusted IPI (aa-IPI) in diffuse large B cell lymphoma.@*Methods@#A total of 311 patients with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2003 to 2012 in Nanfang hospital were included. All patients were divided into CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) and R-CHOP (rituximab, CHOP) groups. Survival analysis was compared among IPI, NCCN-IPI and aa-IPI models. Discrimination of three different prognostic models was assessed using the Harrell’s C statistic.@*Results@#A total of 311 patients were analyzed. Among them, 128 patients were treated with CHOP regimen and other 183 patients were treated with R-CHOP regimen. In CHOP groups, both NCCN-IPI (5-year OS: 59.7% vs 26.8%, P<0.001) and aa-IPI (5-year OS: 71.0% vs 25.0%, P<0.001) showed better risk stratification for low-intermediate and high-intermediate group than the IPI (5-year OS: 47.6% vs 36.6%, P=0.003). However, in the patients treated with R-CHOP, NCCN-IPI showed better risk stratification in low, low-intermediate, high-intermediate groups (5-year OS: 96.0% vs 83.0% vs 66.5%, P=0.009). According to the Harrell’s C statistic, C-index of IPI, NCCN-IPI and aa-IPI for overall survival (OS) were 0.546, 0.667, 0.698 in CHOP group and 0.611,0.654, 0.695 in R-CHOP group respectively. In patients younger than 60 years old, C-index of IPI, NCCN-IPI and aa-IPI for OS were 0.534, 0.675, 0.698 in CHOP group and 0.584, 0.648, 0.695 in R-CHOP respectively.@*Conclusion@#The NCCN-IPI is more powerful than IPI and aa-IPI in DLBCL patients receiving R-CHOP. aa-IPI is a preferable model in predicting prognosis than IPI and NCCN-IPI in anthracycline-based chemotherapy without rituximab.

Effect of intermediate-dose cytarabine on mobilization of peripheral blood hematopoietic stem cell in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the impact of courses of intermediate-dose cytarabine (ID-Ara-C) chemotherapy on the efficiency of hematopoietic stem cell mobilization in acute myeloid leukemia (AML) patients with autologous hematopoietic stem cell transplantation (auto-HSCT).</p><p><b>METHODS</b>90 patients with de novo AML undergoing auto-HSCT between August 1999 and November 2012 were enrolled. All patients received the mobilization regimen of cytarabine and etoposide chemotherapy in combination with recombinant human granulocyte-colony stimulating factor (rhG-CSF). Stem cell apheresis was scheduled when blood leukocyte count recovered greater than 4.0 × 10⁹/L or the proportion of CD34⁺ cells greater than 1% in peripheral blood. The impact of ID-Ara-C courses on the mobilization efficiency was analyzed retrospectively.</p><p><b>RESULTS</b>According to the ID-Ara-C courses, patients were divided into group A (<2 courses), B (2 courses), and C (>2 courses). The median doses of CD34⁺ cells (×10⁶/kg) in three groups were 4.7, 2.7, 2.3, respectively (P=0.003). Of the available 87 patients who could be evaluated, 61 (70.1%) cases had CD34⁺ cells greater than 2.0 × 10⁶/kg, and 26 (29.9%) cases less than 2.0 × 10⁶/kg. Of the 26 patients without satisfactory mobilization efficiency, 7 (15.2%) were in group A, 10 (47.6%) in group B, and 9 (45.0%) in group C (χ²=10.05, P=0.007). In addition, patients with satisfactory mobilization efficiency (CD34⁺ cells ≥ 2.0×10⁶/kg) in groups C needed more times of collection, more volume of blood processed, and even high-dose and longer course of rhG-CSF (P<0.05). In univariate analysis. The ID-Ara-C courses and the cumulative dose were significant correlate with mobilization efficiency. In multivariate analysis, the ID-Ara-C courses was an independent correlation factor for mobilization efficiency (odd ratio=0.623, 95% confidence interval=0.418-0.926, P=0.019). The sex, age, cytogenetic risk, the standard chemotherapy courses did not correlate with mobilization efficiency.</p><p><b>CONCLUSION</b>The number of ID-Ara-C courses was independent factor for the mobilization efficiency and should be taken seriously in AML patients with auto-HSCT.</p>

Conditioning regimen with or without total body irradiation for allogeneic hematopoietic stem cell transplantation in acute Ieukemia / 中华器官移植杂志

ObjectiveTo investigate the therapeutic effects of the conditioning regimen with or without total body irradiation on allogeneic hematopoietic stem cell transplantation in acute leukemia.Methods We retrospectively evaluated clinical outcomes in 287 allo-HSCT recipients with acute leukemia (ALL- 105,AML-129,and AUL-53) who received myeloablative conditioning regimen with or without total body irradiation from January 2002 to August 2011.Two hundred and six patients obtained complete remission (CR) and 81 non-remission (NR) before transplantation.One hundred and ninety-nine patients received conditioning with total body irradiation (TBI+ Cy group,9 Gy given over 2 days),and 88 patients received busulfan (BuCy group,3.2 mg·kg-1 ·d-1 ),both followed by cyclophosphamide.ResultsThere were no statistically significant differences in hematopoietic reconstitution,regimen-related toxicity (RRT),graft-versus-host disease (GVHD) and relapse between two groups.For patients with AML and AUL,there was no significant difference in the 5-year survival between the two regimens (P＞ 0.05),while for ALL-CR patients,the TBI + Cy regimen had a higher over survival rate (52.0％ vs.31.3％,LogRank=4.249,P＜0.05) and DFS (50.4％ vs.27.8％,LogRank =4.445,P＜0.05) than BuCy.In TBI + Cy group and BuCy group,the proportion of CD19+ B cells at the first month after HSCT was (4.04 ± 1.86)％ and (1.47 ±0.99) ％ (P＜0.05),that of NK cells at 12th month after HSCT was (23.38 ± 12.19) ％ and (13.11± 7.99) ％ (P＜0.05),and that of CD4+ CD45RO+ cells at 9th month after HSCT was (14.63 ±6.17)％ and (9.07 ± 3.12)％ (P＜0.01),respectively.ConclusionUsing TBI-containing regimen was more effective for treating ALL-CR patients than busulphan-containing regimen,but no difference was found for long-term outcomes in patients with AML and AUL between the two regimens.The 9 Gy TBI-based regimens may not affect recipients' thymic function,T-cells reconstitution and immune tolerance,coming out a non-increase of GVHD.

Preventive effect of itraconazole oral solution for invasive fungal infection in neutropenic patients with acute leukemia after chemotherapy / 中华临床感染病杂志

Objective To evaluate the efficacy of itraconazole oral solution for prevention of invasive fungal infection ( IFI ) in neutropenic patients with acute leukemia after chemotherapy.Methods Clinical data of 136 neutropenic patients with acute leukemia after chemotherapy at the Department of Hematology,Nanfang Hospital from January 2008 to December 2010 were retrospectively analyzed.Patients were divided into itraconazole group ( n =67 ) and control group ( n =69).There were 36 patients with acute nonlymphocytic leukemia ( ANLL),31 with acute lymphoblastic leukemia (ALL) in itraconazole group;while in control group,there were 30 patients with ANLL,38 with ALL and 1 with biphenotypic acute leukaemia (BAL).Patients in itraconazole group received intraconazole after chemotherapy until the neutrophil count was increased to 0.5 × 109/L or the body temperature returned to normal and without any imaging evidence of IFI.The incidence of IFI and clinical features were compared between the groups using SPSS 13.0 software.Pearson x2 test was used for nominal variables,for measurement data,t (normal distribution) or Mann-Whitney U (skewed distribution) test were used.Results There were 12 cases ( 17.9％ ) suffering from IFI in itraconazole group and 32 cases (46.4％) in the control group (x2 =12.59,P ＜ 0.01 ).For ANLL patients,the incidence of IFI in itraconazole group was significantly lower than that in control group ( 16.7％ vs.56.7％,x2 =11.53,P ＜0.01 ).In itraconazole group,the incidence of IFI in female patients was significantly lower than that in male patients ( 8.6％ vs.28.1％,x2 =4.35,P ＜0.05 ).And for the female patients,the incidence of IFI in itraconazole group was significantly lower than thatin the control group (8.6％ vs.44.7％,x2 =11.98,P＜0.01).Conclusion Itranconzole oral solution can effectively prevent IFI in neutropenic patients with acute leukemia after chemotherapy,especially for the female patients with ANLL.

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>

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.

A clinical analysis of severe cyclosporine A-related neurotoxicity after allogenic hematopoietic stem cell transplantation / 中华内科杂志

Objective To investigate the morbidity,clinical manifestations,and imageology characteristics,and the influencing factors of severe cyclosporine A(CsA)-related neurotoxicity(SNCT)in the patients after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Finding of SNCT was carried out in 164 allo-HSCT recipients from January 2003 to June 2006.Clinical characteristics were analysed,including precursory symptoms and clinical manifestations.Associations between the onset of SNCT with blood CsA levels,age,transplant types,human leucocyte antigen(HIJA)matching,conditioning regimens,antihuman thymocyte globulin(ATG)used in the prevention and treatment for graft-versus-host disease(GVHD)and intravenous corticosteroid used for acute GVHD were analyzed.Statistical analysis was performed with Binary Logistic Regression using SPSS/PC version 11.0.Results Thirteen patients(7.93%)were identified to have SNCT,including seizures(n=8,4.88%),paralysis(n=6,3.66%),coma(n:2,1.22%),cerebllar ataxia(n=3,1.83%)and chondrioid encephalomyopathy (n=1,0.61%).All the patients had precursory symptoms prior SNCT including headache(n=8),agitation(n=4)and hypertension(n=6).Magnetic resonance imaging(MRI)performed in twelve patients after SNCT showed that eleven patients had signal abnormalities in cerebral cortex and cerebral white matter.Six patients examined with computerized tomography(CT)had no abnormal findings.After extenuation or withdrawal of CsA.ten patients had complete recovery.two had partial recovery and one died of SNCT.Simple effect analysis of Binary Logistic Regression showed that the associations between the onset of SNCT with blood CsA levels.transplanta types.HLA matching.ATG used in the prevention and treatment for GVHD and intravenous corticosteroid used for acute GVHD were of statistical significance.The multiple effect analysis of Binary Logistic Regression showed that the associations of the onset of SNCT with blood CsA levels and ATG used had statistical significance and the odds ratio(OR)was 1.007(P=0.006) and 6.727(P=0.030),respectively.Conclusions 91.67%of the allo-HSCT recipients with SNCT have MRI abnormalities.High blood CsA levels and the use of ATG Call elevate the risk of the occurrence of SNCT.

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.

The clinical significance of interphase fluorescence in situ hybridization monitoring chimeric status after sex-mismatched allogeneic hematopoietic stem cell transplantation for leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the association between chimerism, minimal residual disease (MRD) and relapse after sex-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemia.</p><p><b>METHODS</b>Fifty-seven patients with leukemia received allogeneic hematopoietic stem cell grafts from HLA-matched or partially matched, but sex-mismatched donors. Chimeric status and MRD were detected by dual-color interphase fluorescence in situ hybridization (I-FISH) using X/Y sex chromosome centromere DNA probe and bcr/abl dual fusion DNA probe, respectively, at different time points after transplantation. SPSS software was used to analyse the correlation between chimeric status, MRD and relapse.</p><p><b>RESULTS</b>In comparison with karyotype analysis, I-FISH was of higher sensitivity in detecting sex chromosome and bcr/abl fusion gene. Chimeric status was negatively correlated with MRD (r=-0.9690, P<0.01). In the early times of transplantation (within 3 months), mixed chimerism had higher relapse rate than did complete chimerism. Chimeric status and MRD were correlated with leukemic relapse (r=-8240, P<0.01; r=-0.9040, P<0.01). The decrease in chimeric status occurred before leukemic relapse in hematology.</p><p><b>CONCLUSION</b>I-FISH is a more specific and sensitive test for monitoring MRD after transplantation. The clinical value of sex chromosome is identical to that of the special tumor gene for monitoring MRD after transplantation. Chimeric status is negatively correlated with MRD. Chimeric status and MRD are associated with leukemic relapse. The decrease in chimeric status is considered a mark of leukemic relapse after transplantation.</p>

Application of Problem-based Learning Pattern in Clinical Teaching Urinary Surgery / 中华医学教育探索杂志

For adapting the demands of modern society to medical talents,we applied problem-based learning pattern to urology practice teaching.By breaking the limits of subjects,we enable students to acquire more knowledge of science and problem-solving skills and self-learning skills in the limited time available.The role of teacher shifts from imparting knowledge to leaders.