Invasive fungal disease (IFD) is a major infectious complication in patients with hematological malignancies. In this study, we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n = 3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression, which included the following variables: male patients, induction chemotherapy for newly diagnosed or relapsed disease, neutropenia, neutropenia longer than 10 days, hypoalbuminemia, central-venous catheter, and history of IFD. The patients were classified into three groups, which had low (0-10, ~1.2%), intermediate (11-15, 6.4%), and high risk ( > 15, 17.5%) of IFD. In the validation set (n = 1389), the IFD incidences of the groups were ~1.4%, 5.0%, and 21.4%. In addition, we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients, whereas benefits were documented in intermediate (2.1% vs. 6.6%, P = 0.007) and high-risk patients (8.4% vs. 23.3%, P = 0.007). To make the risk score applicable for clinical settings, a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established, and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of IFD. In conclusion, an objective, weighted risk score for IFD was developed, and it may be useful in guiding antifungal prophylaxis.

Objective: To evaluate the effects of endothelial cell-targeted soluble Notch ligand hD1R protein on the proliferation of acute myeloid leukemia (AML) cells. Methods: The expression levels of Notch1, Notch2, Notch3, Notch4, Hes1 in bone marrow CD34⁺ cells from 24 cases of untreated AML (AML group) and 9 healthy controls (control group) were determined by real time quantitative polymerase chain reaction (PCR) . Recombinant hD1R protein was first induced and purified. Bone marrow CD34⁺ cells were co-cultured on human umbilical vein endothelial cells (HUVEC) supplemented with a cocktail containing 5 types of human cytokines (5GF) and soluble hD1R. The cultured cells were tested under different culture conditions including PBS group (PBS replaces HUVEC) , hD1R group, 5GF group, GSI group (hD1R plus GSI) . Proliferation and apoptosis of cultured cells were also analyzed. Real time quantitative PCR was used to test the expression levels of Hes1 and Bcl-2 in cultured cells. Results: The expression levels of Notch1 and Hes1 in primary AML patients were significantly lower, and Notch4 expression was higher compared to the control group (P<0.05) . Cell counting showed a remarkable decrease of AML cells number in the culture with hD1R compared with that in the PBS group[ (0.74±0.13) ×10⁵ vs (2.16±0.21) ×10⁵, P<0.01]. FACS analysis showed that the percentage of AML cells was (18.48±2.51) % in apoptosis, which was higher than that of control cells (3.19±0.58) % after co-culture with hD1R. AML cells in the hD1R group underwent significantly increased apoptosis compared with those in the PBS one (P<0.05) . Moreover, apoptosis of AML cells in the GSI group was lower than that in the hD1R one (P<0.05) . Apoptosis in the PBS group also decreased compared with that in the 5GF one (P<0.05) . Finally, hD1R up-regulated Hes1 expression and inhibited Bcl-2 one in the AML cells. Conclusion hD1R effectively activated Notch signaling and down-regulated Bcl-2 mRNA in AML cells, which lead to cell apoptosis.

Objective To explore the clinical efficacy of low-dose cytarabine and harringtonine (LD-HA) regimen in the induction therapy of acute myeloid leukemia (AML) except M3. Methods 52 AML patients who received LD-HA were analyzed retrospectively. The patients were graded according to molecular biological and cytogenetic risk degree. The clinical efficacy, toxicity of LD-HA and long-term survival followed-up were compared with those of idarubicin and cytarabine (IA) regimen in 49 patients. Results After one cycle, the overall remission (OR) rates of LD-HA group and IA group were 71.2%(37/52) [CR rate 50.0%(26/52), PR rate 21.2%(11/52)] and 53.1%(26/49) [CR rate 44.9%(22/49), PR rate 8.2%(4/49)], respectively, with no statistical significance of OR between the two groups (P= 0.068). OR rates were not statistically significant in either low-risk group or intermediate-risk group between LD-HA group and IA group (P> 0.05), but OR of high-risk group in LD-HA was much higher than that in IA group [100 % (11/11) vs 66.7 % (12/18), P<0.05]. Cardiac toxicity and bone marrow suppression in LD-HA group were much milder than those in IA group. The patients unfit for standard chemotherapy could tolerate to LD-HA regimen. Conclusions LD-HA regimen as induction for high risk AML patients can improve the OR rate, and reduce the side effects, which is beneficial for high-risk AML patients.

Graft vs Host Disease ; therapy ; Humans ; MicroRNAs ; Transplantation, Homologous

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Humans ; Lymphoma, Follicular ; drug therapy ; Rituximab

OBJECTIVEA prospective, multicenter and non-interventional prospective study was conducted to evaluate the clinical features of rituximab combined with chemotherapy (R-Chemo) as first-line treatment on newly diagnosed Chinese patients with diffuse large B-cell lymphoma (DLBCL).

METHODSThis was a single arm, prospective, observational multicenter and phase IV clinical trial for 279 patients, who were newly diagnosed as CD20-positive DLBCL from 24 medical centers in China 2011 and 2012, no special exclusion criteria were used. All patients received rituximab based R-Chemo regimes, such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone) and other regimes as the first-line treatment. The treatment strategies were determined by physicians and patients without detailed description for treatment course, dose, interval time and examination. Clinical response and safety of all patients were investigated in 120 days after completion of last dose of rituximab.

RESULTSOf 279 patients, 258 with stage I-IV who received at least 1 cycle of rituximab treatment and completed at least one time of tumor assessment were enrolled into intention-to-treat analysis, including 148 male and 110 female. The median age of all patients was 57.2(12.8-88.4) years. ECOG performance statuses of 0 or 1 were observed in 91.1% of patients, international prognostic index levels in the low-risk and low-middle-risk groups in 76.4% of patients, the tumor diameters smaller than 7.5 cm in 69.0% of patients. All patients received 6 median cycles of R-Chemo treatment every 24.4 days. R-CHOP treatment was shown to improve the clinical response with overall response rates of 94.2%. Common adverse events included anemia, marrow failure, leukopenia, thrombocytopenia, digestive diseases, infection and liver toxicity. All adverse events are manageable.

CONCLUSIONNon-interventional clinical trial of R-Chemo remains the standard first-line treatment for newly diagnosed patients with DLBCL in real clinical practice, which is consistent with international treatment recommendations for DLBCL patients. R-Chemo can provide the clinical evidence and benefit as the first-line standard treatment for Chinese patients with DLBCL.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; Treatment Outcome

Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; therapy ; Protein-Tyrosine Kinases ; antagonists & inhibitors

OBJECTIVETo evaluate the effects of endothelial cell- targeted soluble Notch ligand hD1R protein on expansion and engraftment of cord blood hematopoietic stem/progenitor cell (CB HSPCs).

METHODSRecombinant hD1R protein was first induced and purified. Human cord blood CD34⁺ cells were co-cultured on human umbilical vein endothelial cells (HUVECs) supplemented with a cocktail containing 5 types of human cytokines including TPO, SCF, FL, IL-6, IL-3 (5GF) and soluble hD1R. The expansion of CD34⁺ cells was tested under different culture conditions including PBS group (PBS replaces HUVEC), hD1R group, sup group (HUVEC supernatant replaces HUVEC), fix group (fixed HUVEC replaces HUVEC), Day 0 group (Control). Cell cycle and apoptosis of cultured cells were also analyzed. Their progeny expanded in PBS or hD1R group were transplanted into sublethally irradiated NOD/SCID mice. The percentages of human CD45⁺ (hCD45⁺) cells in the marrow of recipient mice were determined by FACS 12 weeks later.

RESULTShD1R induced more expansion in the total number of CD34⁺ cells cocultured with HUVECs plus 5GF, which was 87.50-fold increase compared to the Day 0 group, and 7.98-fold increase than that of PBS group. FACS analysis also showed that the percentage of CD34⁺ cells was 77.0% in G0/G1 phase in the hD1R group, which indicated that hD1R enhanced HSPCs expansion and inhibited apoptosis. Moreover, hD1R significantly promoted human HSPC engraftment after BM transplantation in irradiated mice.

CONCLUSIONThe Notch-mediated ex vivo expansion system has been established and hD1R promoted expansion and engraftment of human CB HSPCs, which provided the evidence for further clinical application.

Animals ; Antigens, CD34 ; Cells, Cultured ; Coculture Techniques ; Endothelial Cells ; immunology ; Fetal Blood ; Hematopoietic Stem Cells ; immunology ; Humans ; Membrane Proteins ; immunology ; Mice

Objective To study the calculational method for the radiotherapy facilities of the medical linear accelerator' s useful beam towars its maze.Methods The shielding calculation was made under the relevant national standards for a radiotherapy treatment room and compared with the test results.Results The dose rates at the maze entrance as calculated and measured were 89 and 86 μSv/h inside the maze door,as well as 5.7 and 6.2 μSv/h outside the maze door,respectively.The calculated results were consistent with measured results.Conclusions By comparison of calculated results with measured results,the accuracy of the theoretical calculation method could be verified.

Objective To investigate the influence of the two-dimension computer-aided surgery navigation system to the concordance of lumbar spine pedicle screw fixation on both sides.Methods 1355 patients were undergone lumbar spinal pedicle screw fixation during January 2004 to December 2009.All patients were divided into tow groups:the navigation group (743cases) and the fluoroscopy assistant group (612 cases).All patients got standard A-P and lateral X-ray plate of lumbar spine within seven days after surgery.The X-ray images were analyzed by the software of Image-pro plus 5.0 to evaluate the concordance of lumbar spine pedicle screw fixation on both sides.The angle between axial line of pedicle screw and superior lamina terminals (α angle) and the angle between axial lines of pedicle screw on both sides (γangle) were measured.The position of the pedicle screw was checked weather it was in the lumbar pedicle partially.Results There were no significant differences (P＞0.05) between the α angle on both sides of L1-S5 vertebral body in navigation assistant group (L:3.89°±0.47°,R:3.94°±0.37°).The differences of the α angle on both sides of L2 (L:4.55°±1.27°,R:5.12°±1.87°) and L4 (L:4.22°±1.89°,R:6.62°±1.97°) vertebral body in the fluoroscopy assistant group had statistical significance (P＜0.05).There were no significant differences between the α angle on both sides of other bodies (L:4.32°±1.47°,R:4.37°±1.59°,P＞0.05).The γangle in navigation assistant group (2.32°± 0.27°) was obviously smaller than fluoroscopy assistant group (3.32°±1.51°),the differences had statistical significance (P＜0.05).Accuracy of pedicle screw in navigation assistant group was 91.5％ (3604/3938).Accuracy of pedicle screw in fluoroscopy assistant group was 87.6％ (2426/2768).The difference in accuracy of pedicle screw in both groups had statistical significance (x2=26.913,P＜0.0001).Conclusion The accuracy of pedicle screw and the concordance of pedicle screw on both sides can be significantly improved using the two-dimension perspective computer-aided surgery navigation system.