Tumor lysis syndrome in multiple myeloma treated by daratumumab combined with chemotherapy: report of two cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical safety of daratumumab (DARA) in patients with relapsed/refractory multiple myeloma (MM).Methods:The diagnosis and treatment process of 2 cases of relapsed/refractory MM treated in Huadong Hospital of Fudan University in 2020 were retrospectively analyzed, the related laboratory indicators indexes after using DARA were analyzed, and the related literature was reviewed.Results:After using DARA, the 2 patients rapidly developed tumor lysis syndrome (TLS) such as high potassium, high phosphorus, high uric acid, low calcium and kidney damage, which eventually led to the death of patients.Conclusions:Patients with high tumor load treated by DARA are prone to TLS, which is often life-threatening. Clinicians should be alert to the occurrence of such events.

Efficacy and safety of demethylation drugs in treatment of myelodysplastic syndrome: a Meta-analysis / 白血病·淋巴瘤

Objective:To systematically evaluate the efficacy and safety of demethylation drugs intreatment of myelodysplastic syndrome (MDS), and to provide reliable basis and guidance for clinical application of these drugs.Methods:The randomized controlled trials (RCT) of demethylation drugs for treatment of MDS published in the PubMed, Web of Science, Embase, Cochrane Library, Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM) and VIP database from January 2000 to December 2019 were searched by computer. RevMan 5.3 software was used for Meta-analysis of the efficacy and safety.Results:Seven RCT studies involving 1 172 patients were obtained. Meta-analysis showed that the complete remission rate ( OR = 6.26, 95% CI 1.74-22.49, P = 0.005), partial remission rate ( OR = 4.65, 95% CI 1.51-14.29, P = 0.007), overall response rate ( OR = 14.14, 95% CI 7.27-27.51, P < 0.01), hematology improves ( OR = 3.47, 95% CI 1.44-8.32, P = 0.005) in the demethylation drug treatment group were better than those in the best supportive treatment group. Meanwhile, the overall survival of patients in azacytidine group was improved ( HR = 0.62, 95% CI 0.50-0.77, P < 0.01). In terms of adverse reactions, demethylation drugs increased the incidence of neutropenic fever ( OR = 4.19, 95% CI 2.26-7.76, P < 0.01). However, there was no significant difference in the incidence of neutropenia, thrombocytopenia, anemia, infection, nausea, liver damage and fatigue between the two groups (all P > 0.05). Conclusions:The effect of demethylation drugs in treatment of MDS is obvious, the remission rate can be improved, and azacytidine can prolong the patients' survival, but demethylation drugs increase the incidence of neutropenia fever. In the clinical application of demethylation drugs, it is necessary to further carefully evaluate their clinical safety.

Psychological status of the staff in a general hospital during the outbreak of coronavirus disease 2019 and its influential factors / 中南大学学报(医学版)

OBJECTIVES@#To understand the psychological status of the staff in a general hospital during the coronavirus disease 2019 and its influential factors, and to provide references for the mental health services to hospital staff.@*METHODS@#Using star platform of questionnaire, the staff in the general hospital were investigated via Depression, Anxiety, Stress Scale (DASS-21), Social Support Rating Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ). The influential factors were discussed by descriptive analysis, rank sum test, single factor analysis, correlation analysis and multiple factors binary logistic regression analysis.@*RESULTS@#A total of 2 060 valid questionnaires were collected. The negative emotions of nurses and cleaners were the most obvious. The depression scores, anxiety scores and stress scores for nurses and cleaners were 5.06±7.47, 6.36±7.84, 9.75±8.65, and 6.72±8.84, 4.51±6.56, 9.69±9.56, respectively. Multivariate binary logistic regression analysis showed that staff types, education levels, job status, economic situation and concerns on the supplies of protective goods were the main influential factors for depression; staff types, contacting status with infected patients, economic situation, concerns on the supplies of protective goods, history of disease were the main influential factors for anxiety; contacting status with infected patients, economic situation, concerns on the supplies of protective goods were the main influential factors for stress.@*CONCLUSIONS@#There are differences in psychological characteristics among different groups of staff in the general hospital under the outbreak. Thus psychological protection and intervention measures should be formulated according to different groups and work status.

Infrastructure and sanitation practice of Chinese primary and middle schools canteens / 中国学校卫生

Objective@#To understand the current situation of infrastructure construction and sanitation practice of school canteens in China and to provide a reference for improving food safety in school canteen and sanitation management level.@*Methods@#Stratified sampling method was adopted to select the surveyed schools. Information regarding school canteen infrastructure and sanitation practice was collected through questionnaires. Chi-square test was used to compare the difference in passing rate on the survey indices among different school types.@*Results@#In environmental sanitation, 91.0% of the school canteen was rated as good and in personal hygiene, 92.8% of the employees were rated as good. The overall health level of urban schools was better than that of township schools, and non-boarding schools was better than that of boarding schools, with statistically significant differences(P<0.01). 67.1% of school canteens provided with independent food outlets while 98.7% of school canteens without independent food stores. The qualified rate of washing facilities in the dining area was 94.7%, and the qualified rate of distance between the canteen and the pollution source was 92.5%. Nearly all the employees held canteen catering service license (99.0%) and the health qualification certificate (99.5%). Most of the school canteens (98.7%) established the safety rules and regulations, including the food retention sample system. Nearly 61.5% schools initiated the principal meal program.@*Conclusion@#Sanitation management in the canteens of primary and secondary schools in China is generally satisfactory, with some canteens still fail to meet the standard requirements. More supervision from schools and relevant government departments (market supervision, health and education departments) is needed to provide students with a clean and heathy campus canteen.

Advances in mechanism of immunomodulatory drug resistance in multiple myeloma / 白血病·淋巴瘤

The use of immunomodulators represented by thalidomide and its derivatives in the treatment of multiple myeloma (MM) has made a breakthrough. Cereblon has been identified as a direct target for immunomodulators and plays a significant role in antiproliferation, proapoptotic effects, antiangiogenic activities, enhancement of the activity of T cells and NK cells and intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells. In recent years, majority of the MM patients treated with immunomodulators develop drug resistance. Both upstream and downstream factor expression of cereblon and epigenetic modification may be related to immunomodulatory drugs resistance in MM. This review discusses the mechanism of immunomodulatory drug resistance in MM.

Pretreatment of IL-2 influences the proliferation and polarization of mice splenic lymphocyte following mobilization with G-CSF / 中华微生物学和免疫学杂志

Objective To explore the influence of IL-2 pretreatment on splenic lymphocyte following mobilization with G-CSF, which may provide a new approach to attenuate acute graft-versus-host disease (GVHD). Methods Splenic cells and na(i)ve CD4+T cells from C57BL/6N mice receiving G-CSF-mobilized were pretreated with IL-2(50 U/ml) , and cocultured with the allogeneic antigens from BALB/c mice. The proliferation responses and the polarization of T cells were determined. C57BL/6N mice were randomly divided into 4 groups: G-CSF + IL-2 group, G-CSF group, IL-2 group , control group. Results Compared with the control group, IL-4 increased obviously while IFN-γ decreased significantly in the group of G-CSF + IL-2. The proliferation responses were also suppressed in vitro. Conclusion The proliferation responses of splenic cells and naive CD4 + T cells from C57BI/6N mice receiving G-CSF-mobilized to the allogeneic antigens were significantly abrogated by the pretreatment with IL-2, T cells were polarized toward the production of type-2 cytokines. The combination of G-CSF and IL-2 is potentially synergetic in the induction of T lymphocyte immune tolerance.

Analysis of the distribution characteristics and drug sensitivity of nosocomial infection in patient with hematologic neoplasms / 白血病·淋巴瘤

Objective To investigate clinical distribution and drug sensitivity of infectious pathogens in our wards for hematology malignancies. Methods Drug sensitivity tests of bacteria were performed by Kirby-Bauer method, 56 strains of pathogens were isolated from all detected samples. Results The results showed that the composition ratio of Gram-negtive bacteria, Gram-positive bacteria was 69.64%, 30.36%. In decreasing frequency, Escherichia coli (37.50%), Klebsiella pneumoniae (10.71%). All of staphylococcies were resistant to meticillin, and sensitive to vancomycin. Conclusion This study indicates that Gramnegative bacteria remain the predominant pathogens in microorganisms causing bloodstream infections for hematological malignancies at Huashan Hospital. The incidence of Escherichia coli is the highest. All of staphylococcies were resistant to meticillin.

Glucocorticoid amplifies IL-2 induced the proportion of T regulatory cell to T effector cell and suppress allogeneic antigen reaction / 中华微生物学和免疫学杂志

Objective To established the method of increasihg the proportion of T regulatory cells(Tr) to T effector cells(Te), which could suppresses allogeneic ahtigen reaction, by in vivo of glucocorti-coid (dexamethasone, DXM) combined with IL-2. Methods After combined treatment to male C57BL/6N mice (donor) with DXM(5 mg. kg-1· d-1 ) and IL-2 (300 000 IU · mouse-1·d-1) for 3 d, spleen mono-nuclear cells were made and were carried out by flow cytometry analysis. Using the spleen cells of BALB/c mice as aliogeneic antigen to stimulate the spleen cells of male C57BL/6N mice for 7 d after combined treat-ment of glucoeorticoid and IL-2, the reaction of cell proliferation was detected. Results After the treatrment of DXM and IL-2, CD4+ CD25+ Foxp3+ Tr cells in the spleen of C57BL/6N mice increased abviously. The ratio of CD25+ Foxp3+ Tr to CD4+ T cells was 24.22%±7.60% in the group of DXM combined with IL-2, while the control group was 4.02% ±0. 84% ( P =0. 01 ). Compared with the control group (0. 14±0.01 ), the ratio of Tr to Te increased obviously in the group of DXM combined with IL-2 (0.43±0. 15 ) ( P = 0.01 ). The group of DXM combined with IL-2 also expressed more glucocorticoid-induced tumor necrosis factor receptor(GITR) and alloreaction was suppressed/n vitro obviously ( P < 0. 05 ). Conclusion DXM amplifies IL-2 induced the proportion of Tr to Te, and suppresses the cell proliferation stimulated by alloge-neic antigen.

The polarization and proliferation of TH1 cells inhibited IL-2 through upregulation of SOCS-3 in naive CD4+T cells / 中华微生物学和免疫学杂志

Objective To explore the polarization and proliferation of naive CD4+TT cells after preincubation with interleukin-2. Methods The expression of suppressor of cytokine signal (SOCS)-3 was detected by the real-time PCR in the naive T lymphocytes of DO11.10 TCR transgenic and C57BL/6N mice after they were preincubated by 50 U/ml of IL-2. The naive CD4+T T lymphocytes preincubated for 4 h by IL-2 were stimulated with ovalbumin (OVA) and inactivated BALB/c spleen cells, respectively. After 14 d, IL-12Rβ1, IL-12β2 and cytoplasm IL-4 (cyIL-4) were detected by flow cytometry. Results SOCS-3 in the naive CD4+T lymphocytes of DO11. 10 TCR transgenic and C57BL/6N mice reached the peak after preincu- bated by IL-2 for 6 h. The polarization to TH1 and the proliferation ability of naive CD4+ T lymphocytes stimulated with specific antigen and allogeneic antigen were inhibited conspicuously during the time of the peak of SOCS-3. Conclusion The expression of SOCS-3 in naive CD4+T lymphocytes can be upregulated by IL-2. The upregulation of SOCS-3 can suppress the polarization to TH1and the proliferation ability of naive CD4+T lymphocytes stimulated by specific antigen and allogeneic antigen.

Autogenous peripheral stem cell transplantation combined with interleukin-2 for treatment of 16 patients with lymphoid malignancies / 中国癌症杂志

Purpose:To evaluate the effect of Auto-PBSCT combined with long-time low-dose interleukin-2 (after transplant) for increasing the rate of 5-year disease-free survival of lymphoid malignancies (ALL and NHL).Methods:U- sing chemotherapy combined with low dose G-CSF to mobilize peripheral blood stem cells,we carried out auto-PBSCT in lymphoid malignancies (7 cases CR_1 ALL、1 case CR_2 ALL、3 cases CR_1 NHL、5 cases refractory NHL).After transplant, 15 cases used low dose interleukin-2 at 5.10~5U/d for one year or longer.Results:7 cases CR_1 ALL are still alive,the aver- age disease-free survival is 73 months.Median disease-free survival is 51.5 months.2 of 3 cases CR_1 NHL are still alive. The 6 years disease-free survival in 10 cases CR_1 lymphoid malignancies(CR_1 NHL and CR_1 ALL) is 0.90?0.11,the aver- age disease-free survival is 66.8 months.In another PR (refractory) group of NHL and ALL (CR_2),3 years disease-free survival was 0.33?0.18,and average survival time was 20.66 months,but a chemotherapy-sensitive NHL is still alive (63 months),a case of lymphoblast cell NHL also survived for 46 months and died after relapse.Conclusions:Auto-PBSCT combined with long-turm low dose IL-2(after transplant) could effectively increase the rate of 5-year disease-free survival in CR_1 lymphoid malignancies(ALL and NHL).