This study was aimed to retrospectively analyze and compare the clinical curative efficacy of patients with hematologic malignancies after G-CSF-mobilized sibling HLA-matched (sm) peripheral blood hematopoietic stem cell transplantation (sm-allo-PBHSCT) and sm-allo-PBHSCT combined with bone marrow transplantation (BMT). 100 patients received sm-allo-HSCT in a single center from October 2001 to October to 2010, included 38 patients received sm-allo-PBHSCT and 62 patients received sm-allo-PBHSCT combined with BMT. The myeloablative or reduced intensity conditioning regimens were chosen according to the condition of patients. All patients received standard cyclosporine (CsA) and mycophenolate mofetil (MMF) as prophylaxis for GVHD. The results showed that the rapid hematopoietic reconstitution was observed in all patients. The median time of ANC ≥ 0.5 × 10(9)/L in both groups were 12 days, the median time of platelet count ≥ 20 × 10(9)/L was 15 days in sm-allo-PBHSCT group and 16 days in sm-allo-PBHSCT + BMT group. The incidence of acute GVHD, acute GVHD of III-IV grade and chronic GVHD in sm-allo-PBHSCT and sm-allo-PBHSCT + BMT groups were 37.1% and 34.2%, 7.89% and 8.06%, 36.11% and 41.38% respectively, there were no statistical differences. The relapse rates were similar in two groups (sm-allo-PBHSCT 13.16% vs sm-allo-PBHSCT + BMT 12.9%). The 3-year disease-free survivals in sm-allo-PBHSC and sm-allo-PBHSCT + BMT groups were 57.1 ± 8.7% and 61.3 ± 6.4% respectively (p = 0.852). The 2-year overall survival of high-risk patients was 41.4 ± 12.8% in sm-allo-PBHSCT group, while 60.9 ± 9.6% in sm-allo-PBHSCT + BMT group (p = 0.071). It is concluded that the rhG-CSF mobilized sibling matched allo-PBHSCT + BMT is superior to the rhG-CSF mobilized sibling matched allo-PBHSCT in increasing the overall survival of high-risk hematologic malignancies.
Adolescent ; Adult ; Aged ; Bone Marrow Transplantation ; Child ; Child, Preschool ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; HLA Antigens ; immunology ; Hematologic Diseases ; immunology ; therapy ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Retrospective Studies ; Siblings ; Tissue Donors ; Young Adult

Adolescent ; Adult ; Female ; Follow-Up Studies ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Treatment Outcome ; Young Adult

The objective of study was to explore the influence of high mobility group box 1 (HMGB1) on migration of cord blood CD34(+) cells and their mechanism of migration. The expressions of receptor for advanced glycation end products (RAGE), toll-like receptor-2 (TLR2) and TLR4 were detected by flow cytometry. The CD34(+) cells in umbilical cord blood (CB) were enriched by MiniMACS and were exposed to various concentration of HMGB1 (10, 50, 100, 1, 000 ng/ml), then the migration effect of HMGB1 on umbilical cord blood (UCB) CD34(+) cell count was determined by microscopy, the chemotactic index was calculated. The CD34(+) cells untreated with HMGB1 were used as control. The results indicated that the purity of the isolated CD34(+) cells was more than 98%. The HMGB1 could promote the migration of CD34(+) cells, and the migration effect of HMGB1 on CD34(+) cells in certain concentrations gradually increased along with raise of concentration, the strongest effect was observed in concentration of 100 ng/ml, there was significant difference as compared with control (p < 0.01). Anti-RAGE antibody partially inhibited the migration effect of HMGB1 on CD34(+) cells. It is concluded that the HMGB1 in certain concentration can enhance migration of CD34(+) cells, which may be mediated through RAGE.
Antigens, CD34 ; Cell Movement ; drug effects ; Cells, Cultured ; Female ; Fetal Blood ; cytology ; drug effects ; HMGB1 Protein ; pharmacology ; Humans ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Signal Transduction

Objective To observe the effect of Guben Kechuan Gran-ules ( GKG ) on expression level of soluble interleukin -2 receptor (sIL-2R) of rats with chronic obstructive pulmonary disease (COPD). Methods Rat models with COPD made by fumigation and dripping li-popolysaccharide.The rtas were randomly divided into 6 groups:normal group, model group, high, middle, low doses ( 2.28, 1.14, 0.57 g? mL-1 ) GKG groups, and Guben Kechuan Tablets group.From the third day of modeling, medicines were administered to rats by means of intragastric administration for consecutive 28 days.Two days after the fin-ishing of intragastric administration,rats were executed and samples were collected.SIL-2 R expression level in rat was tested by means of ABC-ELISA method.Results SIL-2R expression level in low-dose groups of GKG decreased obviously,with a significant difference compared with model group ( P<0.05).Conclusion GKG can enhance immune func-tion and anti infection ability in the airway of rats with experimental COPD by regulating sIL-2R expression level.

Objective To observe the effect of Guben Kechuan Granules ( GKG) on expression level of T lymphocyte subsets in rats with chronic obstructive pulmonary disease ( COPD ) .Methods Rat models with COPD made by fumigation and dripping lipopolysaccharide . The rats were randomly divided into 6 groups:normal group, model group, high, middle,low doses (2.28,1.14,0.57 g? mL-1)GKG groups, and Guben Kechuan Tablets group .From the third day of modeling , medicines were administered to rats by means of intragastric administration for consecu-tive 28 days.Two days after the finishing of intragastric administration , rats were executed and samples were collected .T lymphocyte subsets ex-pression level in rat was tested by means of rapid immunohistochemistry method.Results T lymphocyte subsets expression level in low -dose groups of GKG decreased obviously , with a significant difference com-pared with model group ( P<0.05 ) .Conclusion GKG can enhance immune function in the airway in rats with experimental COPD by regula-ting T lymphocyte subsets expression level .

Objective To observe the effect of Guben Kechuan Gra-nules( GKG) on expression level of thymus index and spleen index of rats with chronic obstructive pulmonary disease ( COPD ).Methods Rats models with COPD made by fumigation and dripping lipopolysaccharide.The rats were randomly divided into 6 groups:normal group, model group, high,middle,low doses (2.28,1.14,0.57 g· mL-1) of GKG groups, and Guben Kechuan tablets group.From the third day of modeling, medicines were administered to rats by means of intragastric administration for consecutive 28 days.Two days after the finishing of in-tragastric administration,rats were executed and samples were collected. And then the spleen index and thymus index were calculated after the spleen and thymus were peeled from rats.Results Thymus index and spleen index expression level in GKG group increased obviously, with a significant difference compared with model group ( P <0.05 ) . Conclusion GKG can enhance immune function in the airway of rats with experimental COPD by regulating thymus index and spleen index expression level.

OBJECTIVESTo investigate the oncologic outcomes of surveillance, retroperitoneal lymph node dissection (RPLND) and primary chemotherapy in patients with clinical stage Ia nonseminomatous germ cell testicular tumors (CS Ia NSGCT) and to analyze risk factors for relapse.

METHODSPatients with CS Ia NSGCT were retrospectively reviewed. Totally 72 patients were enrolled and grouped according to three different treatment after orchiectomy, among them 33 cases in surveillance group, 24 cases in RPLND group and 15 cases in primary chemotherapy group. Disease progressive free survival and disease specific survival were compared using Kaplan-Meier analysis. Cox regression analysis was used to confirm variables those were associated with disease progression.

RESULTSAll 72 patients were followed-up at mean 62 months (12 - 175 months), 6 patients had evidence of relapse. Both the 5-year disease specific survival and 5-year overall survival rate were 100%. For surveillance, chemotherapy and RPLND, cumulative 5-year PFS rates were 84.0%, 93.3% and 100%, respectively. Relapse rate was higher in surveillance group than in RPLND group (17.8% vs. 0, χ² = 3.99, P = 0.04). Patients with the history of cryptorchidism also have higher relapse rate than without (37.5% vs. 4.7%, χ² = 10.02, P = 0.01). In the surveillance cohort, relapse rates were significantly higher in patients with a predominant component of embryonal carcinoma (3/6 vs. 7.4%, χ² = 6.93, P = 0.04) and for those over 13 years of age (23.1% vs. 5.3%, χ² = 4.33, P = 0.04). On multivariate analysis, treatment mode of patients (OR = 0.08, 95% CI: 0.06-0.36, P = 0.03) and patients with a history of cryptorchidism (OR = 25.3, 95% CI: 6.57-78.42, P = 0.04) were independent predictors of relapse.

CONCLUSIONSSurveillance, RPLND and adjuvant chemotherapy could be reliable strategies in compliant stage Ia nonseminoma patients and achieve satisfactory overall survival. Relapse rate is relatively higher for patients with surveillance. Those who are older or have a history of cryptorchidism experience a higher risk of relapse.

Adolescent ; Adult ; Aged ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Humans ; Infant ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Germ Cell and Embryonal ; therapy ; Orchiectomy ; Postoperative Period ; Retrospective Studies ; Risk Factors ; Survival Rate ; Testicular Neoplasms ; therapy ; Treatment Outcome ; Young Adult

This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of umbilical cord blood (UCB) CD34(+) cells and to explore the underlying mechanism. The expression of TLR2 and TLR4 on UCB CD34(+) cells was detected with flow cytometry. The effect of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on the migration and adhesion ability of UCB CD34(+) cells was evaluated with chemotaxis and adhesion assays. The results indicated that expression levels of TLR2 and TLR4 were (14.2 ± 3.8)%, (19.6 ± 4.1)% respectively. Compared with the control group, the migration activity of UCB CD34(+) cells toward SDF-1 decreased significantly in LPS group (p < 0.01). The adhesion activity was not altered significantly in LPS group. However, both the migration activity towards SDF-1 and the adhesion activity of UCB CD34(+) cells were not changed significantly in PAM3CSK4 group. Further study found that LPS did not affect the expression level of CXCR4 on CD34(+) cells, but could inhibit the spontaneous migration ability of CD34(+) cells. It is concluded that TLR4 activation can decrease the chemotaxis function of CD34(+) cells towards SDF-1, which may associate with the decreased spontaneous migration ability of CD34(+) cells.
Antigens, CD34 ; blood ; Cell Movement ; drug effects ; Cells, Cultured ; Chemokine CXCL12 ; Fetal Blood ; cytology ; immunology ; Humans ; Lipopeptides ; pharmacology ; Lipopolysaccharides ; pharmacology ; Toll-Like Receptor 2 ; agonists ; Toll-Like Receptor 4 ; agonists

To investigate the peripheral levels and clinical significance of Th17/Treg cell-associated cytokines in patients with acute graft versus host disease (aGVHD) or chronic GVHD (cGVHD), blood samples were collected from 39 hematopoietic stem-cell transplantation patients and 20 healthy donors. The patients included 10 patients with aGVHD, 13 patients with cGVHD and 16 patients without evidence of GVHD. Th17/Treg cell-associated cytokines such as IFNγ, IL-4, IL-6, IL-10, TGF-β(1), IL-17 and IL-23 were detected by ELISA. The results showed that the plasma levels of IFN-γ, IL-4, IL-6, IL-17 and IL-23 significantly increased in patients with aGVHD or cGVHD, compared with the patients without clinical signs of GVHD and the healthy donors (p < 0.05), while IL-10 and TGF-β(1) were obviously lower than that of them (p < 0.05). After aGVHD and cGVHD patients were treated effectively, the plasma levels of IL-6, IL-17 and IL-23 were significantly decreased, and IL-10, TGF-β(1) were significantly increased, while the levels of IFN-γ and IL-4 did not markedly change. The TGF-β(1) level were negatively correlated with IL-6 (r = -0.36, p < 0.05), IL-17 (r = -0.51, p < 0.05) and IL-23 (r = -0.44, p < 0.05) respectively, while there were positive correlations between IL-6 and IL-17 (r = 0.62, p < 0.05), IL-6 and IL-23 (r = 0.71, p < 0.05), IL-17 and IL-23 (r = 0.93, p < 0.05). It is concluded that Th17/Treg cell-associated cytokines may play an important role in the development of a/cGVHD, which helps to find novel targets for developing new strategies of GVHD treatment.
Adolescent ; Adult ; Case-Control Studies ; Cytokines ; blood ; Female ; Graft vs Host Disease ; blood ; Humans ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Interleukin-23 ; blood ; Interleukin-6 ; blood ; Male ; T-Lymphocytes, Regulatory ; metabolism ; Transforming Growth Factor beta1 ; blood ; Young Adult

OBJECTIVETo study both the release of HMGB1 from irradiation-treated mesenchymal stem cells (MSCs) and the effects of HMGB1 on human cord blood CD34(+) hematopoietic progenitor cell proliferation and differentiation.

METHODSMSCs were obtained from human bone marrow. HMGB1 released by the MSCs after treatment with 12 Gy gamma-ray irradiation was determined by enzyme linked immunosorbent assay (ELISA). CD34(+) cells were positively selected with a MACS CD34 isolation kit. The freshly isolated CD34(+) cells were cultured in the presence of HMGB1 for 6 days. Phenotype of cultured cells surface molecules (CD13, CD14, CD11c, CD41 and CD71) were analyzed by flow cytometry. The proliferation and differentiation capacities of cord blood HSCs were assayed by colony forming cell assay. The receptors of HMGB1 (RAGE, TLR2 and TLR4) on cord blood CD34(+) cells were detected by flow cytometry.

RESULTSHMGB1 level in the supernatant \[(4.3 +/- 0.9) ng/ml\] of the irradiated MSC was significantly higher than that in control \[(0.4 +/- 0.2) ng/ml\] (P < 0.01). Human cord blood CD34(+) cells expressed the HMGB1 receptors RAGE, TLR2 and TLR4. The HMGB1-treated CD34(+) cells contained higher proportions of CD13(+) \[(32.6 +/- 5.9)% vs (18.4 +/- 3.8)%\], CD14(+)\[(25.4 +/- 4.4)% vs (12.6 +/- 2.7)%\], CD11c(+) \[(20.3 +/- 3.9)% vs (9.8 +/- 2.1)%\], CD71(+) \[(47.1 +/- 7.4)% vs (26.6 +/- 4.6)%\] cells compared with control group did. But HMGB1 did not induce the generation of CD41(+) cells \[(1.3 +/- 0.5)% vs (1.1 +/- 0.4)%\]. Furthermore, HMGB1 profoundly induced the growth of BFU-E, CFU-GM and total CFU in a dose-dependent manner, and this effect was partially inhibited by TLR2 and TLR4 antibodies.

CONCLUSIONHuman MSC treated with gamma-ray irradiation can release HMGB1, which can induce the proliferation and differentiation of human cord CD34(+) cells.

Antigens, CD34 ; metabolism ; Cell Differentiation ; Cells, Cultured ; Fetal Blood ; cytology ; HMGB1 Protein ; Hematopoietic Stem Cells ; cytology ; Humans