ABSTRACT
<p><b>OBJECTIVE</b>To investigate the value of C-reactive protein (CRP) on transplantation day in predicting early post-transplant infections and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 78 recipients undergoing allo-HSCT. The clinical reference value of CRP on transplantation day was determined, and its sensitivity and specificity for diagnosing bacteremia was analyzed using receiver-operating characteristic curve (ROC). The incidence of transplant-related complications, overall survival, and relapse rate of the patients were analyzed with respect to the CRP level.</p><p><b>RESULTS</b>The clinical reference value of CRP for diagnosing bacteremia was 23.3 mg/L (AUC=0.735 [95% CI: 0.623-0.848], P=0.001), which had a diagnostic sensitivity and specificity of 0.793 and 0.592, respectively. Compared with the patients with low CRP levels, the patients with high CRP levels tended to have delayed neutrophil reconstitution and platelet engraftment by 0.71 days (P=0.237) and 4.09 days (P=0.048), respectively, and had a significantly higher incidence of bacteremia (17.1% vs 53.5%, P=0.001) and CMV viremia (37.1% vs 72.1%, P=0.003) within 100 days following the transplantation; the incidences of EBV viremia, pulmonary invasive fungal infection, or acute graft versus host disease (aGVHD) showed no significant difference between the two groups (41.9% vs 22.9%, P=0.094; 14.0% vs 5.7%, P=0.285; 51.2% vs 45.7, P=0.656, respectively). During the follow-up for a median of 318 (7-773) days in high-CRP group and for 299 (78-747) days in low-CRP group, the high-CRP group showed a significantly lower 2-year overall survival than the low-CRP group (42.5% vs 78.4%, P=0.022), and tended to have a higher 2-year cumulative relapse rate (52.3% vs 19.8%, P=0.235). Logistic multivariate analysis identified a high CRP level on transplantation day as the independent risk factor for post-transplant bacteremia within 100 days (OR=5.090 [95% CI: 1.115 -23.229], P=0.036).</p><p><b>CONCLUSION</b>A high CRP level on transplantation day can be indicative of a high risk of early post-transplant bacteremia and CMV viremia and also a poor prognosis following allo-HSCT.</p>
Subject(s)
Humans , Bacteremia , Diagnosis , C-Reactive Protein , Chemistry , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Incidence , Mycoses , Prognosis , Recurrence , Retrospective Studies , Risk Factors , Sensitivity and Specificity , Viremia , DiagnosisABSTRACT
The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.
ABSTRACT
Herein we reported a case of follicular lymphoma with 50.26% clonal malignant lymphocytes and 50% tumor cells positive for the immunoglobulin heavy chain gene and B-cell lymphoma 2 gene (IGH-BCL2). To determine whether endothelial cells (ECs) within the tumor share the feature of advanced malignancy, we isolated and purified the ECs from the tumor by using the immunomagnetic beads conjugated with a monoclonal antibody against CD34, a surface marker of ECs. Thereafter, we identified ECs according to their morphology and found that ECs presented consistently flat and elongated appearance with a lot of Weibel-Palade bodies in the cytoplasm. Results of flow cytometry confirmed that ECs isolated from the follicular lymphoma expressed high level of both vWF and CD34 and the purity of the ECs fraction was more than 90%. Additionally, we used FISH to check chromosomal aberration in the purified ECs and found that some of the ECs had only one fusion signal for the green IGH probe and the red BCL2 probe in contrast to typical t(14;18)(q32;q21) translocation with two fusion signals. This phenomenon was also observed in the tumor cells. It might be a different breakpoint of IGH in this case, which induced the loss of the fusion signal, indicating t(14;18)(q32;q21) translocation. The positive cells accounted for 18% of the isolated ECs from the tumor, indicating that a proportion of ECs from follicular lymphoma had the same chromosome aberration as the neoplastic cells.
ABSTRACT
Herein we reported a case of follicular lymphoma with 50.26% clonal malignant lymphocytes and 50% tumor cells positive for the immunoglobulin heavy chain gene and B-cell lymphoma 2 gene (IGH-BCL2). To determine whether endothelial cells (ECs) within the tumor share the feature of advanced malignancy, we isolated and purified the ECs from the tumor by using the immunomagnetic beads conjugated with a monoclonal antibody against CD34, a surface marker of ECs. Thereafter, we identified ECs according to their morphology and found that ECs presented consistently flat and elongated appearance with a lot of Weibel-Palade bodies in the cytoplasm. Results of flow cytometry confirmed that ECs isolated from the follicular lymphoma expressed high level of both vWF and CD34 and the purity of the ECs fraction was more than 90%. Additionally, we used FISH to check chromosomal aberration in the purified ECs and found that some of the ECs had only one fusion signal for the green IGH probe and the red BCL2 probe in contrast to typical t(14;18)(q32;q21) translocation with two fusion signals. This phenomenon was also observed in the tumor cells. It might be a different breakpoint of IGH in this case, which induced the loss of the fusion signal, indicating t(14;18)(q32;q21) translocation. The positive cells accounted for 18% of the isolated ECs from the tumor, indicating that a proportion of ECs from follicular lymphoma had the same chromosome aberration as the neoplastic cells.
Subject(s)
Adult , Female , Humans , Cells, Cultured , Chromosomes, Human, Pair 14 , Genetics , Chromosomes, Human, Pair 18 , Genetics , Endothelial Cells , Lymph Nodes , Lymphoma, B-Cell , Genetics , Recombinant Fusion Proteins , Genetics , Translocation, Genetic , GeneticsABSTRACT
The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.