[Effect of Recombinant Human Thrombopoietin on Platelet Reconstitution after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma].

OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. CONCLUSION: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

Busulfan/Cyclophosphamide Compared with Melphalan as a Conditioning Regimen for Autologous Transplantation of Multiple Myeloma: A Long-Term Assessment.

BACKGROUND: Melphalan was poorly available in mainland China. The aim of this study is to explore the dose-adjusted busulfan/cyclophosphamide (BU/CY) as an alternative regimen in auto stem cell transplantation (ASCT) for multiple myeloma (MM). METHODS: A total of 105 newly diagnosed MM patients undergoing ASCT during May 2012 and August 2017 were retrospectively analyzed. The BU/CY regimen was applied to 64 patients. Busulfan (9.6 mg/kg or 8.0 mg/kg in total) and cyclophosphamide (3.6 g/m2 or 3.0 g/m2 in total) were administered according to the creatinine clearance rate (CCR). A high-dose melphalan (HDMEL) regimen (200 mg/m2) was given to the other 41 patients. RESULTS: At a median follow-up of 65 (1~119) months, estimated overall survival (OS) and progression-free survival (PFS) at 104 months in the BU/CY and HDMEL groups were 35.6% vs. 20.5% (p = 0.263) and 20.2% vs. 2.4% (p = 0.035), respectively. The median overall survival (OS) and PFS of the HDMEL and BU/CY groups were 55 vs. 70.5 months and 26 vs. 46.5 months, respectively. In multivariate analysis, the BU/CY regimen was found to be the only protective factor for PFS. No lethal toxicity was found in the BU/CY group, and treatment-related mortality (TRM) in 100 days was similar to the HDMEL group. CONCLUSIONS: MM patients may also benefit from the dose-adjusted BU/CY regimen.

The prognostic significance of circulating plasma cells in newly diagnosed multiple myeloma patients.

Objective: Multiple myeloma (MM) is a highly characteristic tumor that is influenced by numerous factors that determine its prognosis. Studies indicate that the presence of circulating plasma cells (cPCs) is a detrimental factor that significantly impacts the prognosis of patients with MM. Methods: This study retrospectively analyzed the prognostic value of cPCs quantified by 10-color flow cytometry in 145 newly diagnosed MM (NDMM) cases in the First Affiliated Hospital of Soochow University from November 2018 to February 2021. The study was approved by the Ethics Committee of the hospital (2021 No. 93). Results: Of the 145 patients, 99 (68.2%) were detected cPCs. Through receiver operating characteristics (ROC) analysis, an optimal threshold of 0.165% was identified as a predictor for overall survival (OS). The median progression-free survival (PFS) was 33 months in patients with cPCs ≥0.165%, whereas those with cPCs <0.165% had a PFS of <33 months (p=0.001). The median OS was not reached for two groups; the 3-year OS for patients with cPCs ≥0.165% was 71% compared with 87% for those with cPCs <0.165% (p=0.003). In transplant patients, cPCs ≥0.165% also predicted worse prognosis. Similarly, when considering cytogenetic risk factors in conjunction with cPC levels, comparable results were obtained. To evaluate whether the Revised International Staging System (R-ISS) groups could be further stratified based on different prognostic factors related to cPCs, our study revealed similar median PFS and OS rates in R-ISS II stage patients with cPCs ≥0.165% compared to those in the III stage (p=0.659 and 0.249, respectively). Conclusion: This study demonstrates that a high ratio of cPCs serves as a reliable indicator for predicting a poorer prognosis in MM cases. Furthermore, incorporating the R-ISS system and cytogenetic risk factors alongside the level of cPCs enhances the accuracy of prognostic predictions for patients with MM.

Epidemiology of respiratory syncytial virus in hospitalized children with community-acquired pneumonia in Guangzhou: a 10-year study.

Background: Respiratory syncytial virus (RSV) is one of the most common virus causing community-acquired pneumonia (CAP) in children. To guide the prevention, diagnosis and treatment of RSV, we aimed to analyze the epidemiology of RSV in hospitalized children with CAP. Methods: A total of 9,837 hospitalized children (≤14 years old) with CAP from January 2010 to December 2019 were reviewed. Using the real-time polymerase chain reaction (RT-PCR), the oropharyngeal swab specimens were collected and tested for RSV, influenza virus A (INFA), influenza virus B (INFB), parainfluenza virus (PIV), enterovirus (EV), coronavirus (CoV), human metapneumovirus (HMPV), human bocavirus (HBoV), human rhinovirus (HRV), and adenovirus (ADV) for each patient. Results: The detection rate of RSV was 15.3% (1,507/9,837). From 2010 to 2019, the RSV detection rate showed a wavy change (χ2=166.982, P<0.001), with the highest detection rate in 2011 (158/636, 24.8%). RSV can be detected throughout the year, with the highest detection rate in February (123/482, 25.5%). Children younger than 0.5 years old had the highest detection rate (410/1,671, 24.5%). The detection rate of RSV in male children (1,024/6,226, 16.4%) was higher than that in female children (483/3,611, 13.4%) (P<0.001). A proportion of 17.7% (266/1,507) of RSV positive cases were also co-infected with other viruses, and INFA (41/266, 15.4%) was the most common coinfection virus. After adjusting for potential confounders, the RSV-positive children were associated with increased risk of severe pneumonia [odds ratio (OR) 1.26, 95% confidence interval (CI): 1.04 to 1.53, P=0.019]. Moreover, children with severe pneumonia had significantly lower cycle threshold (CT) values of RSV than those without severe pneumonia (28.88±3.89 vs. 30.42±3.33, P<0.01). Patients with coinfection (38/266, 14.3%) had a higher risk of severe pneumonia than those without coinfection (142/1,241, 11.4%), but the difference was not statistically significant (OR 1.39, 95% CI: 0.94 to 2.05, P=0.101). Conclusions: The detection rate of RSV in CAP hospitalized children changed by years, months, ages, and sexes. CAP hospitalized children with RSV are more likely to develop severe pneumonia than those without RSV. Policy makers and doctors should make timely adjustments to prevention measures, medical resources and treatment options based on these epidemiological characteristics.

Autologous stem cell transplantation in multiple myeloma patients with renal impairment.

Renal impairment (RI) used to exclude multiple myeloma (MM) patients from autologous stem cell transplantation (ASCT) for safety concerns. Here, we retrospectively reviewed 34 consecutively transplanted patients with creatinine clearance < 60 ml/min at ASCT in recent 5 years at our institution. Busulfan/cyclophosphamide and high-dose melphalan were both employed as conditioning regimens. We found 62% grade 1-2 oral mucositis, 12% grade 3 oral mucositis, 48% grade 3 infection, 8% grade ≥ 4 infection, 50% grade 1 transient creatinine increase, 15% cardiac adverse events, and 12% engraftment syndrome. One case of secondary platelet graft failure and 1 case of transplantation-related mortality were observed. Interleukin-6 concentration was elevated among patients with increased body temperature and/or N-terminal pro-brain natriuretic peptide during engraftment, and close monitoring of these markers may help to predict susceptibility to cardiac events and engraftment syndrome. Adverse events occurred frequently, but the majority were manageable in this cohort. ASCT would further deepen the anti-myeloma efficacy and slightly ameliorated renal function. With a median follow-up of 26.2 months post transplantation (range: 1.6-74.8 months), the median progression-free survival (PFS) and overall survival (OS) post-transplantation of patients undergoing first-line transplantation were not reached; the median PFS post-transplantation of patients undergoing rescue transplantation was 19.2 months and the median OS was not reached.

[Clinical Features and Prognostic Factors of Patients with Multiple Myeloma].

OBJECTIVE: To summarize the clinical and Laboratory characteristics of patients with multiple myeloma (MM) and analyze the prognostic factors. METHODS: Two hundred MM patients were retrospectively analyzed for the following parameters, including peripheral blood, bone marrow morphology, cytogenetics, clinical staging, and response to the chemotherapy in order to summarize related factors affecting overall survival (OS). The prognostic factors were also analyzed. RESULTS: 200 patients with MM were divided into 3 groups according to bone marrow plasma cell percentage (BMPC%) in bone marrow smears: ＜10% group (74 cases, 37.0%), 10%-50% group (75 cases, 37.5%), ＞50% group (51 cases, 25.5%). Compared with the other two groups, patients in BMPC%<10% group were characterized by lower clinical staging levels, lower rates of 13q14 deletion and t(11;14) positive, better response to chemotherapy and favorable three-year OS rate. The univariate analysis showed that prognostic factors indicating favorable outcome as evaluated by OS included age≤55 years old, BMPC%＜10%, WBC＜7.5×109/L, Hb≥68 g/L, PLT≥150×109/L, ß2-MG＜5.5 mg/L, LDH≤230 U/L, Durie-Salmon staging A, achievement of VGPR or better outcome after the first chemotherapy, achievement VGPR or better outcome after the fourth chemotherapy, and presence of autologous hematopoietic stem cell transplantation(auto-HSCT)(P<0.05). The multivariate analysis showed that prognostic factors indicating favorable outcome as evaluated by OS included age≤55 years old, BMPC%≤50%, WBC＜7.5×109/L, Hb≥68 g/L, achievement of VGPR or better outcome after the fourth chemotherapy (P<0.05). CONCLUSION: The clinical characteristics are different among MM patients with different BMPC% in bone marrow smears at initial diagnosis, and prognostic analysis shows that the BMPC% in bone marrow smears has an effect on OS rate. BMPC% in bone marrow smears at initial diagnosis, age, WBC, Hb, response to the fourth chemotherapy are also the main factors impacting the prognosis of patients.

Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence.

Reprogramming of human somatic cells into pluripotent cells (iPSCs) by defined transcription factors is an extremely inefficient process. Treatment with the histone deacetylase inhibitor valproic acid (VPA) during reprogramming can improve the induction of iPSCs. To examine the specific mechanism underlying the role of VPA in reprogramming, we transfected human bone marrow-derived cells (HSC-J2 and HSC-L1) with lentiviruses carrying defined factors (OCT4, SOX2, KLF4, and c-MYC, OSKM) in the presence of VPA. We found that, OSKM lentiviruses caused significant senescence in transfected cells. Administration of VPA, however, significantly suppressed this reprogramming-induced stress. Notably, VPA treatment improved cell proliferation in the early stages of reprogramming, and this was related to the down-regulation of the activated p16/p21 pathway. In addition, VPA also released the G2/M phase blockade in lentivirus-transfected cells. This study demonstrates a new mechanistic role of the histone deacetylase inhibitor in enhancing the induction of pluripotency. J. Cell. Physiol. 231: 1719-1727, 2016. © 2015 Wiley Periodicals, Inc.

[Protection effect of amentoflavone in Selaginella tamariscina against TNF-alpha-induced vascular injury of endothelial cells].

This study is to observe the protection effect of amentoflavone (AMT) in Selaginella tamariscina against TNF-alpha-induced vascular inflammation injury of endothelial cells. On the basis of TNF-alpha induced human umbilical vein endothelial cell, observe the influence of AMT on endothelial active factor, the contents of SOD and MDA, the protein expression of vascular endothelial adhesion molecules and inflammatory factor; study the effect of its common related signal pathways such as NF-kappaB; research the effect of AMT against TNF-a induced human umbilical vein endothelial cell injury by means of MTT, ELISA, Western blotting and the cell immunofluorescence. The results showed that AMT could increase the content of NO and decrease the levels of VCAM-1, E-selectin, IL-6, IL-8 and ET-1; enhance the activity of SOD, reduce the content of MDA; downregulate the protein expressions of VCAM-1, E-selectin, NF-kappaBp65 and up-regulate IkappaBalpha, attenuate the NF-kappaBp65 transfer to cell nucleus. AMT has the effect of protect vascular endothelial and maybe via the signal pathway of NF-kappaB to down-regulate the inflammation factor and oxidative damage factor of downstream.