Weihua Zhai

Interferon-γ mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro.

ABSTRACT Objectives: In the present study, we first confirmed the suppressive function of MSCs in allogeneic T cell proliferation and then examined the underlying mechanisms for MSCs’ immunomodulation and the role of the pro-inflammatory cytokine interferon (IFN)-γ. Methods: Human MSCs were cultured in the presence or absence of IFN-γ. The expression level of prostaglandin E2 (PGE2), hepatocyte growth factor (HGF), transforming growth factor (TGF)-β1 and indoleamine 2,3-dioxygenase (IDO) by MSCs were measured. T lymphocytes were isolated from peripheral blood of healthy donors and then induced to proliferate under the stimulation of anti-human CD3 mAb and anti-human CD28 mAb. In the presence of MSCs, T cell proliferation was examined by BrdU incorporation. In addition, PGE2, HGF, TGF-β1, Kynurenine, recombinant human IFN-γ and anti-IFN-γ mAb were added and cell proliferation was examined. Results: Compared to the controls (MSCs alone), MSCs cocultured with IFN-γ expressed significantly higher concentrations of PGE2, HGF and TGF-β1. The mRNA level of IDO was remarkably increased. Human bone marrow-derived MSCs alone notably suppressed T lymphocytes proliferation in vitro. Addition of exogenous IFN-γ did not ablate the immunosuppressive effects of MSCs. Addition of anti-IFN-γ mAb partially restored suppression of T cell proliferation by MSCs. Conclusions: Human MSCs constitutively expressed immunosuppressive levels of PGE2, HGF and TGF-β1. The proinflammatory cytokine IFN-γ exhibited synergistic effects with MSCs on immunosuppression, possibly by up-regulating PGE2, HGF and TGF-β1 in MSCs and inducting MSCs expression of IDO, involved in tryptophan catabolism.

Combination of cytogenetic classification and MRD status correlates with outcome of autologous versus allogeneic stem cell transplantation in adults with primary acute myeloid leukemia in first remission

Both autologous and allogeneic stem cell transplantation (auto- and allo-SCT) are treatment choice for adults with acute myeloid leukemia (AML) after complete remission (CR). However, the decision-making remains controversial in some situations. To figure out the treatment choice, we retrospectively investigated 172 consecutive patients with primary AML who received auto- (n=46) or allo-SCT (n=126) from a single transplant center. Auto- and allo-SCT group demonstrated comparable overall survival (OS) and disease-free survival (DFS) (P=0.616, P=0.559, respectively). Cytogenetic classification and minimal residual disease (MRD) after one course of consolidation were identified as independent risk factors for DFS (hazard ratio (HR), 1.800; 95% CI, 1.172-2.763; P=0.007; HR, 2.042; 95%CI, 1.003-4.154; P=0.049; respectively). We subsequently found that auto- and allo-SCT offered comparable DFS to patients with favorable or intermediate risk and were tested MRDneg after one course of consolidation (P=0.270) otherwise auto-SCT were inferior due to increased risk of leukemia relapse. Our study indicated that the combination of cytogenetic classification and MRD monitoring correlated with outcome of auto- versus allo-SCT and might help the choice between the two types of SCT for adults with primary AML, which is of significance for patients with expected intermediate prognosis in the current scenario.

A Prospective Observational Study of Antibiotic Therapy in Febrile Neutropenia Patients with Hematological Malignances from Multiple centers in Northeast China.

OBJECTIVES Febrile neutropenia (FN) is a common but lethal complication of chemotherapy in hematological malignance. The aim of this study was to identify the prognostic risk factors for antibiotic treatment outcome in PN patients, and provide the optimal choice for the initial empirical antibiotic treatment. METHODS 227 consecutive FN hematologic malignancies from four hospitals in Northeast China were enrolled. The outcome of antibiotic therapy was investigated until 14 days after the onset of FN. The factors affecting antibiotic therapy outcome were evaluated using Univariate analysis and Multivariate logistic regression analysis. RESULTS Among all patients, 27 patients did not achieve favorable outcome either clinically or bacteriologically. It was shown that the risk factors for poor FN therapy outcome were associated with prolonged duration of neutropenia over 9 days during FN (P=0.019), slow neutrophil recovery (P=0.039), respiratory infection (P=0.005), and that initial monotherapy with drugs recommended by the guidelines indicated better outcome (P=0.009). Additionally, patients with multi-bacterial infection, as well as further ANC decrease after fever, had a poor prognosis. CONCLUSIONS Our results indicate that early application of antibiotics and prevention of respiratory infection as well as good clinical care are able to improve clinical outcomes from empirical antibiotic treatment in FN patients with hematological malignances.

Serum ferritin is a different predictor from transfusion history for allogeneic transplantation outcome in patients with severe aplastic anemia

ABSTRACT Objectives: Severe aplastic anemia (SAA) patients receive more red blood cell (RBC) transfusions as supportive management. We aim to clarify the associations between transfusion history or pre-transplantation serum ferritin (SF) and the overall survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) among SAA patients. Material and methods: We retrospectively investigated 96 SAA patients undergoing allo-HSCT, and grouped them according to pre-transplantation duration. Pre-transplantation SF, transfused units and other iron-related parameters were collected. Comparisons in transplantation outcomes and complications were made in groups with different SF levels and different transfusion histories. Results: Among the 96 SAA patients, 45 patients received transplantation within 2 months after diagnosis (short-term pre-transplantation period), and the rest of the patients had long-term pre-transplantation treatment. Among the patients with short-term pre-transplantation treatment, a higher risk of death was seen in the high-ferritin group (p < 0.05). Elevated SF also predicted a trend in incidence of higher bloodstream infection (p = 0.108). Significant correlations were observed between pre-transplantation SF and infection incidence, as well as transfusion history. However, for patients with longer pre-transplantation duration, transfusion history was associated with worse outcome (p = 0.026), in terms of higher incidence of acute graft versus host disease (p = 0.048). High SF was only significantly associated with prolonged RBC transfusion dependence post-transplantation (p = 0.044). Discussion and conclusions: Transfusion history was a stronger predictor of outcome than SF in patients undergoing transplantation more than 2 months after diagnosis.

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7% ± 5.3% versus 43.4% ± 7.0%, P = .015) and chronic graft-versus- host disease (GVHD; 20.1% ± 5.8% versus 46.0% ± 7.9%, P = .003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1% ± 3.3% versus 84.4% ± 5.7%, P = .235), grades III to IV acute GVHD (3.4% ± 2.4% versus 12.3% ± 4.7%, P = .098), moderate to severe chronic GVHD (12.6% ± 4.9% versus 11.5% ± 4.9%, P = .905), or graft rejection (7.4% ± 3.6% versus 5.5% ± 3.1%, P = .852). There was also no significant difference with regard to the incidence of severe bacterial infection (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P = .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.

Efficacy and safety of posaconazole in hematopoietic stem cell transplantation patients with invasive fungal disease

AIM Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. This study reports real-world efficacy and safety of posaconazole (POS) in HSCT recipients with IFD. PATIENTS & METHODS We performed a retrospective study to investigate the efficacy and safety of POS oral suspension in 45 HSCT patients with IFD from December 2013 to December 2016. RESULTS The success rate at 12 weeks after POS treatment was 57.8%. Multivariate logistic regression analysis showed that persistent neutropenia, severe graft-versus-host disease, high-dose steroid and cytomegalovirus infection were independently associated with inferior responses to POS. POS caused some adverse effects of mild or moderate severity that were of short duration. CONCLUSION This study provides encouraging data regarding the efficacy and safety of POS in HSCT recipients. Neutropenia, graft-versus-host disease, steroid use and cytomegalovirus infection are possibly associated with inferior responses to POS therapy.