Feiyan Wang

Efficacy and safety of thrombopoietin receptor agonists in patients with primary immune thrombocytopenia: A systematic review and meta-analysis.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired platelet production. In this study, we conducted a systematic review and meta-analysis to determine the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in primary ITP patients. Thirteen randomized controlled trials were included in this study, the pooled results of which demonstrated that TPO-RAs significantly increased platelet response (R) and durable response (DR) rates [risk ratio (RR): 2.77, 95% confidence interval (CI): 2.01–3.82, P = 5.9 × 10−10; RR: 7.52, 95% CI: 3.94–14.35, P = 9.2 × 10−10; respectively] and that TPO-RAs significantly reduced the incidences of any or severe bleeding events (RR: 0.80, 95% CI: 0.67–0.95, P = 0.013; RR: 0.52, 95% CI: 0.27–0.99, P = 0.048; respectively). Moreover, our results indicated that there was a significant reduction in the proportion of patients needing rescue medications in the TPO-RA groups compared with the control groups (RR: 0.50, 95% CI: 0.42–0.59, P = 2.0 × 10−15) and that the rates of any or severe adverse events were similar between the TPO-RA and control regimens (RR: 1.01, 95% CI: 0.92–1.10; RR: 0.74, 95% CI: 0.54–1.01; respectively). These findings demonstrate that TPO-RAs are an effective and safe second-line treatment option for primary ITP patients.

Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models

A meta-analysis of animal models was conducted to evaluate the prophylactic effects of mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. A total of 50 studies involving 1848 animals were included. The pooled results showed that MSCs significantly reduced aGVHD-associated mortality (risk ratio = 0.70, 95% confidence interval 0.62 to 0.79, P = 2.73×10−9) and clinical scores (standardized mean difference = −3.60, 95% confidence interval −4.43 to −2.76, P = 3.61×10−17). In addition, MSCs conferred robust favorable prophylactic effects on aGVHD across recipient species, MSC doses, and administration times, but not MSC sources. Our meta-analysis showed that MSCs significantly prevented mortality and alleviated the clinical manifestations of aGVHD in animal models. These data support further clinical trials aimed at evaluating the efficacy of using MSCs to prevent aGVHD.

Comparison of Pipelle sampler with conventional dilatation and curettage (D&C) for Chinese endometrial biopsy

Abstract The aim of this study is to investigate the accuracy and adequacy of the Pipelle endometrial sampler for endometrial biopsy as compared with those of conventional dilatation and curettage (D&C). A total of 245 patients subject to endometrial biopsy were included in this study. We have shown that the failure rates with D&C and Pipelle were 7.75% and 8.98%, respectively, without statistical difference. Additionally, the obtained specimen quality and accurate diagnosis of various diseases using the two methods had no significant statistical differences. Furthermore, patients experienced less pain when Pipelle sampler was used than D&C. Therefore, Pipelle sampler is effective in obtaining adequate endometrial tissue for histodiagnosis, and is applicable in most of the cases for Chinese endometrial biopsy.

Similar outcomes after haploidentical transplantation with post-transplant cyclophosphamide versus HLA-matched transplantation: a meta-analysis of case-control studies

Background Outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PT-Cy) have greatly improved. It remains unknown whether haplo-HCT with PT-Cy was associated with poor outcomes when compared with HLA-matched HCT. To address this issue, we performed a meta-analysis to compare outcomes of haplo-HCT with PT-Cy with those of HLA-matched HCT. Methods A systematic search for case-control studies were performed in PubMed, Embase and Cochrane Library databases. Using a random model, the risk ratios (RRs) and 95% confidence intervals (95% CI) were pooled for the final analysis. Results Nine case-control studies including 2258 patients (827 patients in the haplo-HCT with PT-Cy group, 748 controls from HLA-matched related donors (MRD), and 683 controls from HLA-matched unrelated donors (MUD)) met the inclusion criteria. No differences were found between haplo-HCT with PT-Cy and HLA-matched HCT with regard to acute graft-versus-host-disease (GVHD), non-relapse mortality, relapse, progression free survival and overall survival. However, haplo-HCT with PT-Cy was found to be associated with a lower incidence of moderate to severe chronic GVHD (Haplo vs MRD: RR=0.54; 95% CI=0.39-0.75; Haplo vs MUD: RR=0.70; 95% CI=0.56-0.88). Conclusions The results of this meta-analysis suggest that haplo-HCT with PT-Cy can achieve comparable outcomes with those of HLA-matched HCT. Haploidentical donors can be a feasible and valid alternative when conventional HLA-matched donors are unavailable.BACKGROUND Outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PT-Cy) have greatly improved. It remains unknown whether haplo-HCT with PT-Cy was associated with poor outcomes when compared with HLA-matched HCT. To address this issue, we performed a meta-analysis to compare outcomes of haplo-HCT with PT-Cy with those of HLA-matched HCT. METHODS A systematic search for case-control studies were performed in PubMed, Embase and Cochrane Library databases. Using a random model, the risk ratios (RRs) and 95% confidence intervals (95% CI) were pooled for the final analysis. RESULTS Nine case-control studies including 2258 patients (827 patients in the haplo-HCT with PT-Cy group, 748 controls from HLA-matched related donors (MRD), and 683 controls from HLA-matched unrelated donors (MUD)) met the inclusion criteria. No differences were found between haplo-HCT with PT-Cy and HLA-matched HCT with regard to acute graft-versus-host-disease (GVHD), non-relapse mortality, relapse, progression free survival and overall survival. However, haplo-HCT with PT-Cy was found to be associated with a lower incidence of moderate to severe chronic GVHD (Haplo vs MRD: RR=0.54; 95% CI=0.39-0.75; Haplo vs MUD: RR=0.70; 95% CI=0.56-0.88). CONCLUSIONS The results of this meta-analysis suggest that haplo-HCT with PT-Cy can achieve comparable outcomes with those of HLA-matched HCT. Haploidentical donors can be a feasible and valid alternative when conventional HLA-matched donors are unavailable.

The diagnostic and prognostic value of interleukin-10 in cerebrospinal fluid for central nervous system lymphoma: a meta-analysis

Abstract Central nervous system lymphoma (CNSL) presents diagnostic and prognostic challenges. The aim of this meta-analysis was to evaluate the diagnostic and prognostic value of interleukin (IL)-10 in cerebrospinal fluid (CSF) for CNSL comprehensively. PubMed and Cochrane Library databases were searched through September 2016. Four studies with 212 CNSL patients and 262 control patients were included. The pooled sensitivity and specificity of CSF IL-10 for diagnosing CNSL were 81% (95% CI: 66–91%) and 97% (95% CI: 83–100%), respectively. The summary receiver operating characteristic (SROC) curve indicated that the area under the curve was 0.95 (0.93–0.97). The ROC curve based on extracted individual data showed that the optimal cutoff value was 6.88 pg/ml. Moreover, elevated CSF IL-10 was found to be associated with shorter progression-free survival (hazard ratio: 2.89, 95% CI: 1.13–7.41, p = .027). In conclusion, our meta-analysis showed that CSF IL-10 is an effective diagnostic and prognostic biomarker for CNSL.

Clinical manifestations of pulmonary mucosa-associated lymphoid tissue lymphoma: single-center experience with 18 patients

Purpose Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare entity. To date, the optimal treatment for this disease is still under debate. The aim of this study was to analyze and summarize the clinical manifestations and therapeutic experience of 18 pulmonary MALT lymphoma patients to collect information about the optimal treatment modality. Patients and methods A retrospective analysis was performed in patients who were diagnosed with pulmonary MALT lymphoma at the Chinese People’s Liberation Army General Hospital from April 1995 to April 2016. Results Clinical data of 18 patients were available. The median age was 55 (range, 34–67) years. Also, 61.1% of the patients were male. Only 33.3% had a history of smoking and 27.8% of the patients had tuberculosis. Treatment modalities included surgery alone in 1 patient (5.6%), chemotherapy in 10 patients (55.5%), surgery in combination with chemotherapy in 6 patients (33.3%) and observation in 1 patient (5.6%). Over the median observation period of 93 months, 2 patients died, the median progression-free survival was 6 years, and the estimated 5- and 10-year overall survival rates were 94.1% and 83.7%, respectively. The survival data confirmed the indolent nature of the disease. There was no difference in progression-free survival between the chemotherapy group and the surgery in combination with chemotherapy group. Conclusion Pulmonary MALT lymphoma tended to be an indolent disease. In order to preserve the lung function and reduce the risks associated with surgery, chemotherapy might be an optimal choice for the treatment of pulmonary MALT lymphoma.

Efficacy and safety of mesenchymal stromal cells for the prophylaxis of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials

A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of mesenchymal stromal cells (MSCs) for the prophylaxis of chronic graft-versus-host disease (cGVHD) in patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Six studies involving 365 patients were included. The pooled results showed that MSCs significantly reduced the incidence of cGVHD (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.46 to 0.86, P = 0.004). Favorable prophylactic effects of MSCs on cGVHD were observed with umbilical cord-derived, high-dose, and late-infusion MSCs, while bone marrow-derived, low-dose, and coinfused MSCs did not confer beneficial prophylactic effects. In addition, MSC infusion did not increase the risk of primary disease relapse and infection (RR 1.02, 95% CI 0.70 to 1.50, P = 0.913; RR 0.89, 95% CI 0.44 to 1.81, P = 0.752; respectively). Moreover, there was an apparent trend toward increased overall survival (OS) in the MSC group compared with that in the control group (RR 1.13, 95% CI 0.98 to 1.29, P = 0.084). In conclusion, this meta-analysis demonstrated that MSC infusion is an effective and safe prophylactic strategy for cGVHD in patients with hematological malignancies undergoing allo-HSCT.

G-CSF inhibits LFA-1-mediated CD4 + T cell functions by inhibiting Lck and ZAP-70

In this study, we showed that G-CSF mobilization increased the frequency of T cells, specifically CD3+CD4+ T cells. G-CSF mobilization decreased the secretion of inflammatory cytokines of CD4+ T cells through the LFA-1/ICAM-1 signaling pathway, whereas it did not alter the TH1/TH2 ratio. We found that G-CSF mobilization inhibited LFA-1-mediated CD4+ T cell polarization and motility. In vitro, G-CSF stimulation also attenuated the polarization and adhesiveness of CD4+ T cells through the LFA-1/ICAM-1 interaction. Further investigation revealed that G-CSF mobilization suppressed LFA-1 signaling by down-regulating Lck and ZAP-70 expression in CD4+ T cells, similar results was also confirmed by in-vitro studies. These findings suggested that G-CSF directly suppressed LFA-1-mediated CD4+ T cell functions through the down-regulation of Lck and ZAP-70. The immunosuppressive effect of G-CSF mobilization deepened our understanding about peripheral blood hematopoietic stem cell transplantation. LFA-1/ICMA-1 pathway may become a potential target for graft-versus-host disease prophylaxis.In this study, we showed that G-CSF mobilization increased the frequency of T cells, specifically CD3+CD4+ T cells. G-CSF mobilization decreased the secretion of inflammatory cytokines of CD4+ T cells through the LFA-1/ICAM-1 signaling pathway, whereas it did not alter the TH1/TH2 ratio. We found that G-CSF mobilization inhibited LFA-1-mediated CD4+ T cell polarization and motility. In vitro, G-CSF stimulation also attenuated the polarization and adhesiveness of CD4+ T cells through the LFA-1/ICAM-1 interaction. Further investigation revealed that G-CSF mobilization suppressed LFA-1 signaling by down-regulating Lck and ZAP-70 expression in CD4+ T cells, similar results was also confirmed by in-vitro studies. These findings suggested that G-CSF directly suppressed LFA-1-mediated CD4+ T cell functions through the down-regulation of Lck and ZAP-70. The immunosuppressive effect of G-CSF mobilization deepened our understanding about peripheral blood hematopoietic stem cell transplantation. LFA-1/ICMA-1 pathway may become a potential target for graft-versus-host disease prophylaxis.

Risk Factors for Acute Graft-Versus-Host Disease After Allogeneic Haematopoietic Stem Cell Transplantation: A Single-Center Experience

BACKGROUND Acute graft-versus-host disease (aGVHD) remains the most common and challenging complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). An important obstacle to the therapeutic effect of aGVHD is the inability to identify risk factors for an individual patient at the onset of symptoms. We performed a retrospective study with the aim of defining clinically meaningful pre-transplantation risk factors for grades II-IV aGVHD patients. MATERIAL AND METHODS To identify pre-transplantation risk factors for grades II-IV aGVHD after allo-HSCT, we performed a retrospective study in 292 patients who underwent allo-HSCT at our center from January 2010 to July 2015. RESULTS The cumulative incidence of grades II-IV aGVHD was 36.6±2.8%. The most common target organ of aGVHD was the skin (46.7%), followed by the gastrointestinal tract (29.9%). The risk factors we identified included HLA-mismatched related donors (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.82-5.67) and conditioning regimens containing TBI but no ATG (OR, 2.66; 95% CI, 1.40-5.06). Simultaneously, transplantation with an identical sibling donor (OR, 0.31; 95% CI, 0.18-0.55) and the use of ATG in the conditioning regimen containing TBI (OR 0.37; 95% CI, 0.15-0.93) were two factors found to be associated with a decreased risk of grades II-IV aGVHD. CONCLUSIONS Our study suggests that pre-transplantation characteristics of donor and recipient play an important role in identifying patients at high risk for grades II-IV aGVHD, which provide a direction for the prevention and treatment of aGVHD in the future.