Mei Wang

State Key Laboratory of Medical Genetics of China, Ch’ang-sha-shih, Hunan, China

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Publications (40)8.11 Total impact

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    ABSTRACT: To explore the impact of interleukin-18 (IL-18) single nucleotide polymorphisms on outcomes of hematologic malignances with HLA-matched sibling donor hematopoietic stem cell transplantation (allo-HSCT). Single- nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis (PCR-SSP) in 93 recipients and their HLA matched sibling donors. Hematopoietic reconstitution, incidences of graft versus host disease (GVHD) and infections, transplant related mortality (TRM), and disease free survival (DFS) were analyzed. In comparison with -137 G/C+C/C donor genotype, patients with -137 G/G donor genotype had shorter duration of neutrophil recovery [15(11-23) days vs 17(11-24) days, P=0.01], higher incidence of extensive chronic GVHD (20.6% vs 3.3%, P=0.029), but no difference in the interval of platelet recovery [20(11-46) days vs 20(7-38) days, P=0.844]. The incidence of extensive chronic GVHD in -607 C/C donor genotype (31.6%) was significantly higher than that (10.8%) in C/A + A/A donor genotype (P=0.024). Recipients with -607 C/C genotype also had higher incidence (33.3%) of extensive chronic GVHD than those with C/A+A/A genotype (10.7%, P=0.016). There were no differences in acute GVHD, TRM, and DFS between different genotypes. IL-18 -137 G homozygous genotype in donor facilitated neutrophil reconstitution, but increased the risk of extensive chronic GVHD in patients with allo-HSCT.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2014; 35(3):215-20.
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    ABSTRACT: Anti-endothelial cell antibody (AECA) is well known to reflect endothelial injury. Graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), is also closely associated with endothelial injury. We hypothesized that AECA may be associated with GVHD. To investigate the clinical significance of AECA in allo-HSCT recipients with GVHD, we detected AECA by cyto-enzyme-linked immunosorbent assay (cyto-ELISA) in allo-HSCT recipients with acute and/or chronic GVHD (aGVHD and cGVHD). Incidences of anti-HMEC-1 AECA (anti-HMEC) and anti-EA.hy926 AECA (anti-EAHY) were significantly higher in patients with grade II-IV than grade 0-I aGVHD (P = 0.049, P = 0.011, respectively). There was no difference in the incidence of AECA between patients with and without cGVHD. Patients with anti-EAHY positive in the early stage post-transplant demonstrated a higher incidence of cGVHD (P = 0.044). In patients with grade 0-I aGVHD, AECA-positive patients had higher overall survival and disease-free survival (P < 0.05), and tended to have lower incidences of relapse and transplant-related mortality. Our data suggest that AECA plays an important role in the pathogenesis of GVHD.
    International journal of hematology 01/2014; · 1.17 Impact Factor
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    ABSTRACT: To investigate the risk factors of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 534 cases of 533 patients undergoing allo-HSCT during Jan 2004 and Sep 2012 were retrospectively analyzed. The effects of donor-recipient HLA mismatching, recipient age, donor age, donor-recipient sex combination, donor-recipient relationship, HSC source, conditioning regimen with or without total body irradiation (TBI) and HLA loci on intestinal aGVHD with different severity were analyzed by Logistic regression. Intestinal aGVHD occurred in 123(23.0%) cases, with 86(16.1%) cases of stage 1 intestinal aGVHD(16.1%) and 37(6.9%) cases of stage 2 to 4 intestinal aGVHD. Multivariate analysis showed that donor-recipient HLA mismatching (OR=2.519, P=0.002), increasing donor age (OR=1.034, P=0.003), female donor for male recipient (OR=1.855, P=0.007) were risk factors for intestinal aGVHD, HLA-B38 (OR=0.256, P=0.032) was its protective factor. Donor-recipient HLA mismatching (OR=2.799, P=0.011), increasing donor age (OR=1.045, P=0.012), HLA-A1 (OR=4.157, P=0.002), A30 (OR=3.143, P=0.005) were risk factors for stage 2 to 4 intestinal aGVHD. Occurrence of intestinal aGVHD and its severity are associated with donor-recipient HLA mismatching, donor age, donor-recipient sex relationships and some HLA loci.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 12/2013; 34(12):1020-3.
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    ABSTRACT: OBJECTIVE: To investigate mesenchymal stem cells (MSCs) immunosuppressive activity in the presence of interferon-gamma (IFN-γ) to reveal synergistic immunomodulatory effects of IFN-γ and MSCs. METHODS: ① MSCs were cultured in the presence or absence of IFN-γ(100 ng/ml), the supernatants were collected for measurements of PGE2、HGF and TGF-β1 by ELISA kits. ② MSCs were cultured in the presence or absence of IFN-γ (100 ng/ml)for 48 h. The cDNA was analysed for the expression of human indoleamine 2, 3-dioxygenase(IDO)mRNA by semiquantitative RT-PCR. ③ Mononuclear cells (MNCs) were extracted from peripheral blood of healthy donors. The T cell proliferation was tested in the co-culture system added with MSCs, recombinant human IFN-γ (100 ng/ml) and anti-IFN-γ mAb (5 μg/ml) by BrdU ELISA kit. RESULTS: ①The immunosuppressive cytokines PGE2、HGF and TGF-β1 were detectable within 24-48 h in the supernatants. Their expressions were significantly up-regulated in the presence of IFN-γ. Concentrations of these cytokines were as of (1715.5±628.6) pg/ml vs (1344.5±709.4) pg/ml (P=0.001);(4031.8±1496.8) pg/ml vs (2452.4±1375.3) pg/ml(P=0.011);(1753.5±413.8) pg/ml vs (1026.6±450.5) pg/ml(P<0.001),respectively. ②The expression of IDO mRNA was undetectable when MSCs were cultured alone. In contrast, The IDO mRNA expression was remarkably enhanced in the presence of IFN-γ. ③Bone marrow-derived MSCs remarkably suppressed allogeneic T cell proliferation in vitro. Addition of exogenous IFN-γ had no significant effect on the inhibitory capacity of MSCs, the inhibitory ratios of T cell proliferation were (40.4±10.9)% vs(36.7±7.4)% (P=0.272). By contrast, the inhibitory ratio of T cell proliferation was significantly decreased in the presence of anti-IFN-γ mAb[(40.4±10.9)% vs (23.9±7.6)%,P=0.002]. CONCLUSION: ①Human MSCs constitutively expressed immunosuppressive concentrations of PGE2, HGF and TGF-β1, and their expressions were significantly up-regulated by IFN-γ. ②IFN-γ-induced expression of IDO on MSCs involved in tryptophan catabolism. ③MSCs notably suppressed allogeneic T cell proliferation in vitro. IFN-γ promoted the immunosuppressive capacity of human MSCs, indicating the synergistic immunomodulatory effect of IFN-γ and MSCs.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2013; 34(3):213-216.
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    ABSTRACT: To explore the impact of IFN-γ + 874 polymorphisms on the outcome in HLA matched sibling HSCT. We used PCR-sequence-specific primer analysis (PCR-SSP) to analyze the polymorphisms of IFN-γ + 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008. Recipients having donors who possessed IFN-γ + 874 A/A genotype had significantly earlier neutrophil recovery compared with those having donors with non-A/A genotype (15 (11 - 27) days vs 18 (12 - 30) days, P = 0.029). And IFN-γ + 874 A/A in both recipients and donors further facilitated neutrophil recovery compared with others (13 (11 - 25) days and 19 (12 - 31) days, P = 0.019). Besides, IFN-γ + 874 A/A in recipients increased the probablity of grade II-IV acute graft vursus disease (aGVHD) and cytomegalo-virus viraemia compared with IFN-γ + 874 T/A or T/T genotype (20% vs 4% P = 0.041, 43.6% vs 16.0% P = 0.032), which lead to increased 5-year transplant-related mortality (TRM) (33.7% ± 6.8% vs 12.0% ± 6.5%, P = 0.050) and decreased 5-year event free survival (EFS) \[(58.2 ± 6.7)% vs (84.0 ± 7.3)%, P = 0.032\] compared with the latter. IFN-γ + 874 A/A in both recipients and donors also significantly increased the probablity of grade II-IV aGVHD and cytomegalovirus viraemia compared with the other (21.7% vs 5.9%, P = 0.050; 45.7% vs 20.6%, P = 0.020), which caused increased 5-year TRM \[(31.6 ± 7.5)% vs (13.6 ± 6.5)%, P = 0.048\] and decreased 5-year EFS \[(56.8 ± 7.3)% vs (79.4 ± 6.9)%, P = 0.037\] compared with the other. In HLA-matched sibling HSCT setting, the presences of IFN-γ + 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade II-IV aGVHD and CMV infection and increased EFS. While IFN-γ + 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 12/2012; 33(12):989-93.
  • Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 01/2012; 20(1):55-7.
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    ABSTRACT: To investigate the incidence, risk factors, prognosis and high risk patients of invasive fungal infections (IFI) in patients with hematological diseases. : Over 2-week hospitalized patients from January 2007 to December 2008 were retrospectively reviewed. Logistic regression was used to analyze the risk factors of IFI, and recursive partitioning to reveal high risk patients. Incidence of IFI was estimated by cumulative incidence function, and the prognosis by Kaplan-Meier method. A total of 1048 assessable treatment cycles were recorded and 93 cases of IFI were diagnosed, with an incidence of 8.87 per 100 treatment cycles. Multivariate logistic regression revealed the following risk factors: age (OR 1.025, 95% CI 1.010-1.041, P = 0.002), duration of neutropenia (OR 1.028, 95% CI 1.014-1.042, P < 0.0001) and uncontrolled underlying diseases (OR 2.620, 95% CI 1.608-4.268, P = 0.0001). Recursive partitioning found two groups of high risk patients: (1) patients with uncontrolled underlying diseases and neutropenia duration > or = 58 days (7/12, 58.3%), (2) patients with uncontrolled underlying diseases and age > or = 33 years (40/208, 19.2%). At the end of follow-up, 111 cases of IFI were recorded in 451 patients, with a 1-year cumulative incidence of 27.1%. In patients with established IFI, overall survival rate and IFI related mortality rate at 12 weeks after diagnosis were 83.4% and 13.5% respectively. Age, duration of neutropenia and uncontrolled underlying diseases are risk factors of IFI; patients with uncontrolled underlying diseases and age > or = 33 years were at high risk of IFI and need major concern. IFI has a better prognosis and a lower related mortality in this study.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 08/2011; 32(8):507-11.
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    ABSTRACT: As an important immune mediator, PGE2 plays an important role in the immune tolerance, autoimmune diseases, immune regulation and tumor immunotolerance. PGE2 is considered to be a promising candidate for the control of the immune diseases. To further understand the immuno-modulating effects of PGE2 on CD4+ T cells, in vitro investigation was conducted in the present study. The results showed that PGE2 inhibited the proliferation of T cells in vitro in a dose-dependent manner. Gene expression profiling showed that 1716 genes were down regulated and 73 genes were up regulated with a change of 1.5 fold. Several signal transduction pathways were involved, such as TNF-α and NF-kB signaling pathway, T cell receptor signaling pathway, IL-2 signaling pathway, and MAPK pathway. The results showed that PGE2 inhibited IFN-γ, TNF-α and IL-4 production by CD4+ T cells 24h after cell culture. A comparison between IFN-γ and IL-4 production showed that PGE2 enhanced the relative ratio of IL-4 to IFN-γ in CD4+ T cells culture, and regulated CD4+ T cells toward Th2 cell development. The results of the present study indicated that PGE2 has the potential to treat Th1-mediated inflammatory diseases by regulating CD4+ T cells toward Th2 cell immune response.
    International immunopharmacology 05/2011; 11(10):1599-605. · 2.21 Impact Factor
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    ABSTRACT: Chronic myeloid leukemia (CML) at advanced and blastic phase is a disease with poor prognosis, for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment choice with curative potential. This study was purposed to investigate the therapeutic efficacy of allo-HSCT and prognosis of advanced CML patients. The 28 cases of CML in accelerated phase or blast crisis received allo-HSCT were analysed retrospectively in terms curative efficacy, basic characteristics before transplant and prognosis, therapeutic strategy before transplant and prognosis, events after transplant and prognosis. The results indicated that 10 out of 28 patients were in complete remission, showing a 3-year overall survival and disease-free survival rate of 34.9% and 35.7% respectively; 18 patients died. Univariate analysis revealed that the clonal evolution and blast amount are baseline risk factor of poor prognosis, and combination of them can be used to predict the outcome of patients; application of imatinib before transplant and achievement of complete hematologic remission could not improve the prognosis; severe aGVHD among post-transplant events was proven to be a negative prognostic factor. It is concluded that for advanced CML patients received allo-HSCT, clonal evolution and blast percentage are prognostic factors, and the pre-transplant use of imatinib did not influence the outcome.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2011; 19(1):149-53.
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    ABSTRACT: Patients undergoing myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) have a higher incidence of acute kidney injury (AKI). RIFLE is a newly developed classification for AKI that includes three grades of severity - AKI-R, AKI-I, AKI-F. The purpose of this study was to analyse retrospectively major risk factors for AKI at the time of myeloablative allo-HSCT and to use the RIFLE criteria to predict mortality in myeloablative allo-HSCT. Renal function was evaluated in 143 patients with allo-HSCT by RIFLE criteria in order to assess the incidence, risk factors and mortality rate of various degrees of AKI. The results of this study showed that patients with hepatic veno-occlusive disease (HVOD) have a higher incidence of AKI-F than those without HVOD (P = 0.002). The incidence of AKI-I and AKI-F in patients with grade III-IV acute graft-versus-host disease (aGVHD) and increased total bilirubin was significantly higher than in those without (P = 0.001, P <0.001). HVOD was an independent risk factor of AKI-F (OR 5.058, 95% CI 1.317-19.424, P = 0.018), and increased total bilirubin was an independent risk factor for AKI-F (OR 5.126, 95% CI 1.403-18.998, P = 0.014). Worsening RIFLE category was associated with increased mortality of the patients in the 100 days post-transplant (P = 0.003). In addition, 180-day survival of patients in different AKI classes was significantly different (P = 0.0095). AKI is common in patients with myeloablative allo-HSCT and is associated with increased risk of death. The RIFLE criteria appear to be an important tool for stratification of these patients on the basis of death risk.
    Schweizerische medizinische Wochenschrift 01/2011; 141:w13225. · 1.88 Impact Factor
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    ABSTRACT: To investigate the efficacy of secondary antifungal prophylaxis (SAP) in patients with hematological diseases, all medical records within two consecutive years were retrospectively reviewed. In all, 57 patients with a history of invasive fungal infections received 149 cycles of further therapy for their underlying hematological diseases. Logistic regression and recursive partitioning were used to discriminate high risk patients for failure of SAP. After a median follow-up period of 120 (12-1,080) days, 11 cases (7.4/100 cycles) experienced failure of SAP, including 5 cases during allo-SCT and 6 cases during chemotherapy, corresponding to cumulative incidence at 24.5%. Multivariate logistic regression revealed two risk factors for failure of SAP: use of high dose corticosteroid (OR 13.5, 95% CI 3.09-58.6, P = 0.0005) and duration of neutropenia ≥ 14 days (OR 7.47, 95% CI 1.69-32.9, P = 0.008). Recursive partitioning found that patients with these two risk factors were in high risk, with SAP failure rate as high as 50.0%. In conclusion, use of high dose corticosteroid and duration of neutropenia ≥ 14 days were risk factors of SAP failure. Patients with the two risk factors concurrently were in high risk and needed special concern.
    International journal of hematology 12/2010; 92(5):725-31. · 1.17 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate the prognosis and hepatitis B serologic marker changes in patients with HBV infection or with HBV infected donors after allogenic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical outcomes of 79 patients receiving allo-HSCT, including 55 with HBV infection and 24 from HBV infected donors were analyzed retrospectively. RESULTS: (1) HBV infection did not interfere with the clinical outcome of allo-HSCT. (2) In 20 HBsAg(+) patients, 13(65.0%) developed HBV reactivation between 0.5 and 10 months after transplantation, 9(45.0%) developed HBV-related hepatitis. (3) For the 35 HBsAg(-) and HBcAb/HBeAb positive patients, 4 (11.4%) occurred HBV seroconversion, 1 of the 4 complicated with severe chronic graft-versus-host disease (cGVHD). (4) There was a significant difference in HBV reactivation rate between the HBsAg(+) and HBsAg-groups (P < 0.01). The incidence of hepatitis occurred within 100 days after HSCT was high in HBsAg(+) patients (P < 0.05). (5) Clearance of HBsAg was observed in 2 HBsAg(+) patients, both of whom received graft from HBsAb positive donors. CONCLUSIONS: Donors or recipients infected with HBV is not considered an absolute contraindication for HSCT, but HBsAg positivity is a high risk factor for HBV reactivation and prophylactic lamivudine treatment may be helpful. For patients with HBcAb/HBeAb positivity, seroconversion can be observed, especially after immunosuppressant withdrawal. Adoptive immunity is effective in clearing HBV in these patients.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 07/2010; 31(7):456-460.
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    ABSTRACT: This study was purposed to investigate the effect of prostaglandin E2 (PGE2) on proliferation of peripheral blood T lymphocytes, and to evaluate the regulatory role of PGE2 on immunological balance between Th1/Th2 and Tc1/Tc2 lymphocytes. The peripheral blood mononuclear cells (PBMNC) were stimulated by anti-human CD3 monoclonal antibody (mAb) and anti-human CD28 mAb, and were cultured in the presence of different concentration of PGE2 for 120 hours. The proliferation of peripheral blood T lymphocytes was assayed according to the manufacture protocol of BrdU Kit; the IFN-gamma and IL-4 levels in supernatants cultured for 24, 48, 72 and 120 hours were detected by ELISA; the ratios of CD4+IL-4+ T cells/CD4+ IFN-gamma+ T cells and CD8+IL-4+ T cell/CD8+IFN-gamma+ T cells were determined by flow cytometry. The cells cultured without PGE2 were used as control. The results indicated that (1) with the raising of concentration of PGE2, the inhibitory rate of T cell proliferation in vitro significantly increased (p=0.001). There was significant positive correlation between inhibitory rate of T cells and PGE2 concentration (correlation coefficient=0.889, p=0.000). (2) the difference between the IFN-gamma concentrations in supernatant cultured for 120 and 72 hours in test groups had no statistical significance (p=0.917). The IFN-gamma concentration increased continually with prolonging of culture time in control group (p=0.046). The IFN-gamma concentrations produced at different times in test group were significantly lower compared with those in control group (p<0.05). The IL-4 concentrations produced at different time had no significant change in test groups (p=0.400). The IL-4 concentration in 24 hours in control group was significantly higher than that at 48, 72 and 120 hours in control group (p=0.007, 0.003 and 0.002). After cultured for 24 hours the IL-4 concentration in test group was significantly lower than that in control group (p=0.037), but after cultured for 48, 72 and 120 hours, the IL-4 concentration in test group did not show statistical difference in comparison with control group (p>0.05). (3) the proportions of CD4+IFN-gamma+T cells in test group and in control group had no significant difference (p=0.767). The proportion of CD4+IL-4+T cells in test group was slightly higher than that in control group (p=0.051). The ratio of CD4+IL-4+T cells to CD4+IFN-gamma+ T cells in test group was significantly higher than that in control group (p=0.011). The proportions of CD8+IFN-gamma+ T cells in test group and in control group had no statistical difference (p=0.441). The proportion of CD8+IL-4+T cells in test group was significantly higher than that in control group (p=0.015). The ratio of CD8+IL-4+ T cells to CD8+IFN-gamma+ T cells in test group were obviously higher than that in control group(p=0.038). It is concluded that the PGE2 inhibits the proliferation of T lymphocytes in vitro. PGE2 influences the production of IFN-gamma and IL-4, and significantly influences peak appearance of IFN-gamma produced by T lymphocyte. PGE2 can continuously inhibit the production of IFN-gamma, but its continuous effect on IL-4 is no significant. PGE2 enhances the ratio of CD4+IL-4+T lymphocytes to CD4+IFN-gamma+T lymphocytes and the ratio of CD8+IL-4+T lymphocytes to CD8+IFN-gamma+T lymphocytes, and regulates development of T cells toward Th2/Tc2 cells.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 04/2010; 18(2):431-5.
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    ABSTRACT: This study was purposed to evaluate the outcome of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in complete remission, and to study the prognostic factors. 75 cases of AML in complete remission receiving allo-HSCT from January 2000 to December 2007 were retrospectively analyzed. Major end points of study included overall survival (OS), disease free survival (DFS), relapse rate and transplantation related mortality (TRM). The results showed that 3-year OS and DFS of the study population reached to 58.4% and 53.9% respectively, and the relapse rate and TRM leaded to 16.9% and 29.9% respectively. Incidence of acute GVHD was 59.6%, with 18.7% II-IV aGVHD. Different prognosis was observed between HSCT recipients of alternative donor and HLA-matched related donor (MRD) (3-year DFS was 34.3% vs 60.0%, p = 0.019), between patients of refractory leukemia and the control (3-year DFS was 35.7% vs 58.2%, p = 0.048), between recipients with and without severe aGVHD (3-year DFS was 35.7% vs 54.4%, p = 0.059). Further analysis revealed significantly high TRM in recipients receiving allo-HSCT of alternative donor (p = 0.033) and high rate of severe aGVHD (p = 0.010). Multivariate analysis revealed three negative prognostic factors: donor availability (alternative vs MRD) (p = 0.049, RR = 2.09, 95%CI 1.01 - 4.36), refractory leukemia (p = 0.038, RR = 2.33, 95%CI 1.05 - 5.20) and severe aGVHD (p = 0.040, RR = 2.33, 95%CI 1.04 - 5.20). It is concluded that allo-HSCT is a choice for the AML case at complete remission and TRM is the major cause of the transplantation failure. Donor availability, refractory leukemia and severe aGVHD are confirmed as risk factors of poor prognosis for allo-HSCT patients with AML in CR.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2010; 18(1):161-6.
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    ABSTRACT: The study was aimed to compare the efficiency of cytomegalovirus (CMV) quantitative PCR and CMV-pp65 antigen test for detection of CMV infection and their clinical significance in patients received allogeneic hematopoietic stem cell transplantation (HSCT). 84 patients received allogeneic HSCT were enrolled in study. Anticoagulant blood samples were obtained from the recipients before and after transplantation and in the convalescence. CMV quantitative PCR and CMV-pp65 antigen test were performed weekly. The results showed that out of 84 patients, 26 cases were positive (30.95%) by CMV quantitative PCR method. Of the 26 cases, 9 cases were CMV antigenemia and 13 cases were CMV disease, the median positive time was 37.1 (7 - 105) days after HSCT. 22 cases were positive (26.19%) by CMV-pp65 antigen test method, the median positive time was 46.6 (10 - 128) days after HSCT. All the 22 positive cases detected by CMV-pp65 antigen test were also positive by CMV quantitative PCR method. Nevertheless, 4 positive cases detected by CMV quantitative PCR but negative detected by CMV-pp65 antigen test method did not develop CMV disease. The CMV disease was found in the cases either with moderate to high copies of CMV quantitative PCR or moderate to high level CMV antigenemia by CMV-pp65 antigen test method. The clearance median time was 17.5 (11 - 28) days by CMV quantitative PCR method after receiving antiviral therapy and was 10.0 (7 - 21) days by CMV-pp65 antigen detection method. It is concluded that both CMV quantitative PCR and CMV-pp65 antigen test can detect the infection of CMV early and effectively in patients received HSCT. CMV quantitative PCR is more sensitive, and CMV-pp65 is more specific. It can be more effective to guide the antiviral treatment and evaluate its efficacy when combining the two methods.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 12/2009; 17(6):1522-6.
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    ABSTRACT: To study the genotype distribution and the effects of killer immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I ligand on related donor hematopoietic stem cell transplantation (HSCT). The genotypes of donor/recipient HLA-Cw and donor KIR were determined by polymerase chain reaction-sequence specific primer (PCR-SSP) in 87 cases of related donor HSCT (40 cases were haploidentical HSCT, and the remaining 47 cases were HLA-identital sibling HSCT). All the donors possessed KIR2DL1, 2DL2/L3, 2DL4, 3DL2, and 3DL3, and 96.6% of donors possessed 3DL1. The rate of activating KIRs varied. 97.7% of the recipients expressed C1, while the rates of C2, Bw4, and HLA-A3/A11 were different. In haploidentical HSCT, KIR-HLA-mismatched group included 34 cases and the matched group included 6 cases. HLA-HLA-mismatched group included 31 cases and the matched group included 9 cases. In matched sibling donor HSCT, KIR-HLA-mismatched group included 42 cases and the matched group included 5 cases. KIR-HLA-mismatched group had higher 2-year disease-free survival (DFS) rate compared with KIR-HLA-matched group [ (71.5 +/- 6.5 ) % vs. (50.0 +/- 10.7)%, P < 0.05]. The rate of activating KIR is lower than inhibitory KIRs. Inhibitory KIR2DL1, 3DL1, and 3DL2 may play key roles in the natural killer cell alloreactivity. The DFS rate is higher in KIR-HLA-mismatched group than in KIR-HLA-matched group in related donor HSCT.
    Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 10/2009; 31(5):533-7.
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    ABSTRACT: This study was purposed to investigate the phenotype, in vitro expansion and cytokine secretion profile of Valpha24(+) NKT cells from cord blood (CB), peripheral blood (PB), and granulocyte colony stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMNCs). Fresh mononuclear cells (MNCs) were isolated by the method of gradient centrifugation and then cultured with alpha-GalCer (100 ng/ml), IL-2 (50 U/ml), IL-15 (50 ng/ml) for 12 days. Valpha24(+) NKT cells were purified by anti-Vbeta11 TCR McAb and goat anti-mouse IgG magnetic beads. The phenotype and purity of Valpha24(+) NKT cells were determined by flow cytometry. Cytokine production was analyzed by ELISA. The results showed that Valpha24(+) NKT cells in CB, PB and G-PBMNCs were expanded by 221.5 (95 - 501), 456.5 (101 - 2207), and 756.38 (82 - 20373)-fold respectively. After stimulation by phorbol-12-myristate-13-acetate (PMA) for 24 hours, IL-4 and IFN-gamma produced by Valpha24(+) NKT cells from CB and PB were 180.33 (144.67 - 2253.48) vs 190.67 (110.07 - 6060.16) ng/ml, 864.33 (401.33 - 3386.67) vs 508.49 (253.82 - 8840.00) ng/ml respectively, with IL-4/IFN-gamma ratio of 0.503 +/- 0.642 vs 0.455 +/- 0.562 respectively. After expansion of Valpha24(+) NKT cells from G-PBMNCs, IL-4 and IFN-gamma produced by Valpha24(+) NKT cells at day 9 and day 12 were 139.08 (7.62 - 606) vs 89.3 (0 - 729.2) ng/ml, 14264.8 (1168 - 18059) vs 14488 (1041 - 18261) ng/ml respectively, with IL-4/IFN-gamma ratio of 0.0531 +/- 0.1081 vs 0.0376 +/- 0.1148 respectively. It is concluded that in presence of IL-2 and IL-15, alpha-GalCer can facilitate the rapid short-term expansion of Valpha24(+) NKT cells from CB, PB, and G-PBMNCs. Valpha24(+) NKT cells from G-PBMNCs show much high potential of expansion in comparison to the counterparts from CB or PB (p < 0.05). The activated Valpha24(+) NKT cells can secrete IFN-gamma and IL-4 in large amounts, with IFN-gamma in particular.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 06/2009; 17(3):633-6.
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    ABSTRACT: This study was purposed to investigate the effects of rat marrow mesenchymal stem cell (rMSC) transplantation on left ventricular (LV) function in a rat myocardial infarction model. Myocardial infarction was performed in male Lewis rats by ligating the proximal left coronary artery. Rats were randomly divided into 3 groups: sham operation group (only thoracotomy, n = 8), AMI group (DF12 injection, n = 10), rMSC group (Dil-Labeled rMSC transplantation). At 8 weeks later, the cardiac functions including left ventricular ejection fraction (LVEF), left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), +dp/dtmax and -dp/dtmax were evaluated by echocardiography and cardiac catheterization. The presence and differentiation of engrafted cells were assessed. CD31 was detected by immunohistochemical staining to demonstrate neovascular formation. The results indicated that the cultured in vitro rMSC expressed CD90, CD44, CD105, CD54; did not express CD34, CD45, CD31, as compared with AMI group, rMSC group showed a significant increase of LVEF, LVESP, +dp/dtmax, -dp/dtmax and a significant decrease of LVEDP. Immunofluorescence demonstrated that some transplanted rMSCs were positive for myosin, suggesting that small number of transplanted rMSCs differentiated into cardiac-like cells. Immunostaining showed marked augmentation of capillary density in the rMSC group than that of AMI group. It is concluded that transplanted rMSCs can differentiate into cardiac-like cells and rMSC transplantation can improve LV function after myocardial infarction in rats.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 05/2009; 17(2):390-4.
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    ABSTRACT: This study was aimed to explore the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients with acute lymphoblastic leukemia and to analyze the related prognostic factors. Clinical data of 114 ALL patients receiving HSCT, including 70 auto-HSCT and 44 allo-HSCT, were retrospectively analyzed. Disease-free-survival (DFS), relapse-rate (RR) and transplantation-related-mortality (TRM) of patients receiving different HSCT were compared. The results showed that the eight-year OS and DFS in a total of 114 adult ALL patients were (40.89+/-5.27)% and (39.50+/-5.22)% respectively. The three-year DFS of ALL patients who received HSCT in phase CR1 and no CR1 were (47.63+/-5.63)% and (17.65+/-9.25)% (p=0.0034). The two-year DFS of patients who received allo-HSCT and had I/II aGVHD was (62.75+/-12.30)%, and the six-month DFS of patients who had III/IV aGVHD was 0, and the two-year DFS of patients without aGVHD was (29.35+/-9.70)% (p=0.005). The three-year DFS of patients with and without maintenance chemotherapy after transplantation were (55.12+/-7.89)% and (33.33+/-11.11)% respectively, there was significant difference between them (p=0.0499). The five-year DFS between patients received auto-HSCT and allo-HSCT in phase CR1 was not significantly different. The RR of patients received allo-HSCT was lower than that of patients received auto-HSCT, but there was no significant difference between them. The TRM of patients received allo-HSCT was higher than of patients received auto-HSCT (p=0.0313). Expression of myeloid antigen and higher LDH level in diagnosis were poor- prognostic factors. It is concluded that auto-HSCT and allo-HSCT completed in phase CR1 may improve prognosis of the patient with ALL as a method for consolidation chemotherapy, but no significant difference exists between the two HSCTs. Patients receiving allo-HSCT and having I/II aGVHD may achieve higher DFS. The maintaining chemotherapy for patients after auto-HSCT may improve therapeutic effect.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2009; 16(6):1325-9.
  • Zheng Zhou, Mei Wang, Yi He
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    ABSTRACT: To study the influence of CD34(+) and T cells doses in grafts on prognosis after HLA-identical sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Sixty-five patients received HLA-identical sibling allo-PBSCT were studied. The numbers of CD34(+), CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) T cells in the grafts were measured by fluorescence-activated cell sorting (FACS). The doses of MNC, and the above cells in grafts were calculated as per kilogram of recipient's body weight. The patients were divided into high-dose (HD) or low-dose (LD) groups according to median dose of those cells, respectively. Hematopoiesis reconstitution, incidence of graft versus host disease (GVHD), transplant-related mortality (TRM), overall survival (OS), and disease-free survival (DFS) were analyzed. HD CD34(+) cells significantly accelerated neutrophil and platelet reconstitution (P < 0.05). There seems a trend toward increasing incidence of grade II approximately IV acute GVHD (aGVHD) in HD CD3(+)CD4(+) and CD3(+)CD8(+) T cells groups compared with those LD groups (P = 0.089 and 0.098, respectively). The TRM rates were significantly higher and OS rates were significantly in HD CD3(+)CD4(+) and CD3(+)CD8(+) T cells groups than in LD groups, respectively (both P < 0.05). Multivariate analyses showed that CD3(+)CD4(+) and CD3(+)CD8(+) T cells doses in grafts were significant risk factors for TRM \[relative risk (RR) were 13.12 and 25.90, respectively, both P < 0.05\] and for OS (RR were 3.71 and 3.01, respectively, both P < 0.05). The DFS rate was significantly lower in HD CD3(+)CD4(+) T cells groups than in LD groups (P < 0.05). Multivariate analyses showed that CD3(+)CD4(+) cells dose in grafts was a significant risk factor for DFS (RR = 6.91, P = 0.011). High dose CD34(+) cells in grafts significantly accelerate hematopoietic reconstitution. Transfusion of high doses CD3(+)CD4(+) and CD3(+)CD8(+) cells increases TRM, but decrease OS or DFS.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 01/2009; 29(12):819-23.

Publication Stats

20 Citations
8.11 Total Impact Points

Institutions

  • 2009–2012
    • State Key Laboratory of Medical Genetics of China
      Ch’ang-sha-shih, Hunan, China
  • 2010–2011
    • Harbin Medical University
      Charbin, Heilongjiang Sheng, China
  • 2004–2011
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 2005–2008
    • China Academy of Chinese Medical Sciences
      • Institute of Hematology
      Peping, Beijing, China