Weathering the storm: COVID-19 infection in patients with hematological malignancies / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a matter of months, this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents. In patients with COVID-19, underlying chronic diseases and comorbidities are associated with dismal treatment outcomes. Owing to their immunosuppressive status, patients with hematological malignancies (HMs) are at an increased risk of infection and have a worse prognosis than patients without HMs. Accordingly, intensive attention should be paid to this cohort. In this review, we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs. Furthermore, we briefly describe customized management strategies and interventions for this susceptible cohort. This review is intended to guide clinical practice.

The effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia / 中华血液学杂志

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ(2)=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ(2)=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion: High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Prognostic Value of Model for End-Stage Liver Disease Incorporating with Serum Sodium Score for Development of Acute Kidney Injury after Liver Transplantation / 中华医学杂志(英文版)

<p><b>Background</b>Contribution of model for end-stage liver disease incorporating with serum sodium (MELD-Na) score in predicting acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is yet to be identified. This study assessed the prognostic value of MELD-Na score for the development of AKI following OLT.</p><p><b>Methods</b>Preoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. Postoperative AKI was defined and staged in accordance with the clinical practice guidelines developed by Kidney Disease: Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors for AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI.</p><p><b>Results</b>The prevalence of AKI following OLT was in 206 out of 321 patients (64.2%). Three risk factors for AKI post-OLT were presented, preoperative calculated MELD score (odds ratio [OR] = 1.048, P = 0.021), intraoperative volume of red cell suspension transfusion (OR = 1.001, P = 0.002), and preoperative liver cirrhosis (OR = 2.015, P = 0.012). Two areas under ROC curve (AUCs) of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant (Z = 1.952, P = 0.051). The Spearman's correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 (P = 0.001, 0.001), respectively.</p><p><b>Conclusions</b>We demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of novel MELD-Na score.</p>

Expression of C II TA gene in five human malignant hematological cell lines and its significance / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the role of MHC class II Transactivator (C II TA) in expression of HLA molecules in five human malignant hematological cell lines.</p><p><b>METHODS</b>The expressions of HLA molecules and C II TA protein were detected by immunohistochemistry and flow cytometry. The expression of C II TA gene was detected by RT-PCR. The response of peripheral T cells after stimulation by Jurkat cells was detected by mixed lymphocyte reaction.</p><p><b>RESULT</b>The HLA II-positive tumor cells expressed the C II TA and IFN-gamma induced the expression of HLA I, II in tumor cells, which were able to express C II TA constitutively.</p><p><b>CONCLUSION</b>There is a correlation between the inability of the tumor cells in response to IFN-gamma for HLA expression and the deficiency in the inducible expression of C II TA.</p>

Cytomegalovirus infection of myeloma cell line KM3 and its effect on IL-6 mRNA expression in the cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the infection of myeloma cell line KM3 by cytomegalovirus (CMV) as well as its effect on IL-6 mRNA in the cells.</p><p><b>METHODS</b>RT-PCR assay was used to detect the mRNA expression of CMV immediate early gene (IE), glyceraldehyde phosphate dehydrogenase (GAPDH) and IL-6 of KM3 cells infected by 100-, 10-, 1-folds of median tissue culture infective dose (TCID(50)) of CMV. Flow cytometry was used to detect the expression of pp65 antigen. CMV particles were detected with electron microscope.</p><p><b>RESULTS</b>KM3 cells infected by CMV could express IE mRNA as compared with the uninfected cells. CMV pp65 antigen positive cells were (5.58 +/- 1.55)% and (3.75 +/- 0.85)% respectively when infected by 100 and 10 TCID(50) of CMV, which were significantly higher than that of control group (P < 0.05). CMV particles could be seen in the infected cells. Expression of IL-6 mRNA was increased after the infection.</p><p><b>CONCLUSION</b>CMV can infect myeloma cell line KM3 and replicate in the cells. CMV can increase the expression of IL-6 mRNA.</p>

Human cytomegalovirus protects multiple myeloma cell line KM3 cells from apoptosis induced by growth factor withdrawal / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There is a higher rate of cytomegalovirus (CMV) reactivation in patients with multiple myeloma after an autologous stem cell transplantation, but no attention has been given thus far to a possible pathogenetic interplay between CMV and multiple myeloma. CMV can infect many kinds of cells, and CMV infection has been shown to inhibit apoptotic responses in several cell systems. In this study the authors investigated the alterations in apoptosis in the multiple myeloma cell line KM3 after infection with CMV and proposed a possible mechanism.</p><p><b>METHODS</b>KM3 cells were infected with 100, 10, or 1 TCID50 of CMV and then cultured in serum-free RPMI 1640. An RT-PCR-based assay was used to detect mRNA expression of CMV-IE, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and IL-6 in CMV-infected and mock-infected cells. Flow cytometry was used to detect apoptotic cells. CMV particles and apoptotic cells were also examined with an electron microscope.</p><p><b>RESULTS</b>CMV-infected KM3 cells clearly expressed immediate early (IE) antigen mRNA when compared to uninfected cells, and there were fewer apoptotic cells among cells treated with 100 or 10 TCID50 of CMV after culturing in serum-free RPMI 1640. CMV particles were observable in infected cells under an electron microscope. Expression of IL-6 mRNA increased after infection.</p><p><b>CONCLUSION</b>CMV can infect the multiple myeloma cell line KM3, inhibit the apoptotic response in these cells after apoptosis induction in serum-free culture, and increase the expression of IL-6 mRNA.</p>

Cytotoxic effects of arsenic trioxide in combination with chemotherapeutic drugs on acute non-promyelocytic leukemia cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To provide experimental basis for extending the indications of arsenic trioxide (As(2)O(3)) in clinical application.</p><p><b>METHODS</b>MTT assay was used to detect the cytotoxicity of As(2)O(3) in combination with daunorubicin (DNR), cytosine arabinoside (Ara-C), harringtonine (H) and vincristine (VCR) respectively on leukemic cells from 23 newly diagnosed cases with acute non-promyelocytic leukemia (ANPL) and 16 cases of relapsed, refractory ANPL.</p><p><b>RESULTS</b>(1) As(2)O(3) inhibited the growth of leukemic cells from both newly diagnosed or relapsed and refractory ANPL patients, and there was no statistical difference in cytotoxicity of the patients in the two groups [(12.6 +/-7.7 compared with 10.1 +/-6.2)%, P<0.05]. (2) There was no correlation between the cytotoxicities of As(2)O(3) and Ara-C, H or VCR (P<0.05), but a linear correlation between As(2)O(3)and DNR was found (r=0.432, P<0.05).(3) Additivity and synergism of the cytotoxicity was found in most of the ANPL patients when As(2)O(3) was combined with the four chemotherapy drugs and the combination of As(2)O(3) with DNR or VCR enhanced the cytotoxicity significantly (P<0.05).</p><p><b>CONCLUSION</b>The results indicate that As(2)O(3) might be used in treatment of newly diagnosed or relapsed and refractory ANPL patients;and the combination of As(2)O(3) with DNR or VCR may enhance its therapeutic efficacy.</p>