Background: Recently, improvement in overall survival (OS) was demonstrated in elderly patients with multiple myeloma (MM). Our aim here was to analyze treatment outcomes in elderly Chinese patients with MM in real-world practice. Material/Methods: This retrospective study enrolled 122 newly diagnosed MM patients ages 65-84 between January 2007 and December 2015 in a single hematology department. Results: The median age of patients was 70.5 years. The median OS period of the entire cohort was 33 months; the 5-year OS estimate was 30.4%. The median OS of the 65-69, 70-74, and 75 years old groups were 43, 36, and 6 months, respectively. Female patients had better OS than male patients (40 and 28 months, P=0.026). Patients who received short-course bortezomib-containing regimens during their course of disease had a significantly longer median OS of 37 months compared with 28 months for patients without bortezomib treatment (P=0.029). Patients with age-adjusted Charlson comorbidity index (aaCCI) <5 showed longer median OS compared to those with aaCCI >= 5 (45 months vs. 23 months, P<0.001). Multivariate analysis revealed that male sex, high aaCCI, and LDH were independent prognostic factor for OS. Conclusions: The marked survival improvement in the elderly patients was associated with the increased use of short-course bortezomib. CCI and LDH are important clinical prognostic factors for survival in elderly MM patients.
BACKGROUND: Red blood cell distribution width (RDW) has been reported as an inflammatory biomarker and a predictor of prognosis in different types of cancer. However, the role of RDW at diagnosis in patients with multiple myeloma ( MM) has been less explored. OBJECTIVE: We aimed to investigate the association between RDW and the response to treatment and overall survival (OS) in patients with MM. METHODS: We retrospectively analyzed the data for 196 MM patients between January 1, 2007 and December 31, 2015. Kaplan-Meier analysis and Cox regression model were used. RESULTS: High RDW values were associated with lower platelet count, lower hemoglobin levels, lower albumin levels, and higher lactate dehydrogenase (LDH) level. Among the entire cohort, the overall response rates (ORR) and complete response (CR) rate of initial therapy were markedly higher in the low-RDW group compared to the high-RDW group. RDW was significant lower in CR in comparison to Non-CR groups in patients treated with bortezomib-based regimens as induction therapy. The patients with low-RDW at diagnosis had better OS when compared to those with high-RDW. CONCLUSIONS: Elevated RDW was associated with worse survival in patients with MM and could predict treatment responses. Further larger and prospective studies are required.
We present the optical characterization of quantum dot cascade laser (QDCL) structures using photoluminescence. In this work, two InAs/AlAs quantum dot structures are investigated with different GaAs QW thicknesses. Low temperature photoluminescence measurements show peaks at 1.03 eV, 1.28 eV, and 1.51 eV for QDCL1, and 1.07 eV, 1.27 eV, and 1.47 eV for sample QDCL2, corresponding to ee-hh transition in both QD and QW. A three dimensional QD-QW model in Nextnano is developed to simulate the energy states, wave functions, and transition rates between conduction and valence bands using a typical QD size obtained from atomic force microscope measurements. The simulation results agree well with the experimental data. This allows us not only to understand the optical characteristics of the QD- QW structure, but also to optimize the QDCL structure design.
Since two genome-wide association studies identified the same susceptible region at ARID5B and IKZF1 for acute leukemia in Caucasians in the same time, several research groups have confirmed the similar results in different ethnicities and of different acute leukemia subtypes (ALL and AML). However, the causal variants of these two genes were not identified. In this study, we systematically screened 6 potentially functional SNPs in ARID5B and IKZF1 genes, and conducted a case-control study including 660 AML cases and 1034 cancer-free controls to investigate the associations between these SNPs and AML risk. We found that the variant alleles of rs4509706 and rs11761922 could significantly increase the risk of AML (rs4509706: OR = 1.35, 95%CI = 1.12–1.62 in additive model; rs11761922: OR = 1.29, 95%CI = 1.02–1.62 in recessive model). Luciferase reporter assay showed that both rs11761922-G and rs4509706-C significantly increased the luciferase levels as compared with rs11761922-C and rs4509706-T in K562 cells (P < 0.05 for rs11761922 and P < 0.001 for rs4509706). Our results indicated that rs4509706 and rs11761922 may play important roles in AML development in Chinese population.
A wafer fused GaP/GaAs waveguide was developed for THz QCLs to achieve high confinement factor benefiting from its lower refractive index in THz regime. The modal simulation of several waveguide structures using COMSOL showed an increase of confinement factor up to 2 as compared to regular waveguide; however it also resulted in high losses. Experimental results showed good electric characteristics but poor optical performance, which is mainly due to the degradation of crystal quality after high temperature process, confirmed by stress analysis and XRD. Therefore, a low temperature fusion process is necessary to fabricate GaP/GaAs THz waveguide.
There is increasing evidence that the human lissencephaly-1 gene, LIS1, plays an important role in carcinogenesis of several malignancies including leukemia. However, little is known about the relationship between single nucleotide polymorphisms (SNPs) in LIS1 and the susceptibility to myeloid leukemia. In the present study, we systematically screened 5 potentially functional polymorphisms in LIS1, and conducted a case-control study including 660 acute myeloid leukemia (AML) patients and 1034 cancer-free controls in a Chinese population, to assess the association between these SNPs and AML risk. We found that the variant alleles of rs4790348, rs4790353, and rs7209748 could significantly increase the AML risk (rs4790348: adjusted OR=1.31, 95%CI=1.13-1.53 in additive model; rs4790353: adjusted OR=4.97, 95%CI=1.59-15.50 in recessive model; rs7209748: adjusted OR=2.34, 95%CI=1.11-4.94 in recessive model). These findings indicated that genetic variants in LIS1 may contribute to AML risk in Chinese population.
In this study, we investigated the anti-tumor activity both in vitro and in vivo of a polysaccharide obtained from Ganoderma lucidum on HL-60 acute myeloid leukemia cells, and focused on its targeting effect on mitogen-activated protein kinase (MAPK) pathways. It was found by the methods such as western blot and flow cytometry (FCM), that G. lucidum polysaccharide (GLP) blocked the extracellular signal-regulated kinase/MAPK signaling pathway, simultaneously activated p38 and JNK MAPK pathways, and therefore regulated their downstream genes and proteins, including p53, c-myc, c-fos, c-jun, Bcl-2, Bax, cleaved caspase-3 and cyclin D1. As a result, cycle arrest and apoptosis of HL-60 cells were induced. Therefore, GLP exerted anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.
目的 探讨诱导疗法对急性髓系白血病患者临床疗效及生活质量的影响.方法 选取2012年1月至2015年12月间在无锡市人民医院进行治疗的80例急性髓系白血病患者,回顾性分析患者采用标准剂量伊达比星联合阿糖胞苷诱导治疗的不良反应、疗效及复发情况.结果 标准剂量伊达比星联合阿糖胞苷方案诱导治疗对造血系统的毒性为92.5%,对感染、脱发、胃肠道反应也有一定毒性影响.80例患者中,预后良好24例,预后中等50例,预后不良6例.预后良好患者在第1个疗程完全缓解率为54.2%,好于预后中等患者和预后不良患者,预后良好患者在各个疗程2年生存(0S)率以及2年无复发生存期(DFS)均明显高于预后中等患者.结论 伊达比星联合阿糖胞苷诱导方案治疗急性髓系白血病患者生存状况明显优于常规治疗,有利于提高患者DFS和OS率,值得推广应用.
Two genome-wide association studies (GWASs) have identified several new acute leukemia susceptibility loci in populations of European descent. However, the roles of these loci in the development of acute leukemia in other populations are largely unknown.
OBJECTIVES:Our aim was to retrospectively investigate the real-world outcome and healthcare costs associated with the treatment of patients with relapsed or refractory multiple myeloma (RRMM) in a Chinese single center.METHODS:A retrospective study was conducted for 93 patients between January 2008 and December 2013 in a Chinese hematology department. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-based treatment regimens.RESULTS:Mean total cost per patient-month ($1139.85) varied depending on the sequence of therapy (range: mean $51.63-$6600.96). Drugs and hospital visit were the most and the least consumed resource (65.48% and 2.87%, respectively). Mean total monthly costs were $2071.96 (range: $679.73-$6600.96) and $551.14 (range: $51.63-$1698.59) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Differences between the two groups were significant for drugs; drugs costs were higher for patients treated with bortezomib. Kaplan-Meier curves showed a longer overall survival (mean [median] 31.43 [25] vs. 21.93 [18] months) for patients treated with bortezomib.CONCLUSION:Real-world costs during treatment of RRMM varied greatly. Total costs during bortezomib-based regimens are significantly higher compared with non-bortezomib regimens. Further multi-center studies are needed to assess the cost-effectiveness of bortezomib for the treatment of RRMM in China.
OBJECTIVE:To investigate the relationship between RAD51-G135C and XRCC3-C241T single nucleotide polymorphisms and onset of acute myeloid leukemia (AML).METHODS:The study was performed in 2 groups: AML patient group and normal person group as control group. Genomic DNA was extracted from peripheral blood cells of 545 AML patients and 1 034 normal persons. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by TaqMan probe technology and the ralatienship between RAD51-G135C/XRCC3-C241T polymorphisms and onset of acute myeloid leukemia was investigated.RESULTS:Compared with the control group, RAD51-G135C homozygous mutant (CC) could significantly increase the risk of AML patients (OR=3.07), and there was no statistical relationship between heterozygous mutant (GC) of RAD51-G135C and onset of AML. There was no statistical relationship between homozygous mutant (TT) of XRCC3-C241T and onset of AML, and the XRCC3-C241T heterozygous mutation type (CT) increased the risk of AML patients (OR=0.66).CONCLUSION:RAD51-G135C homozygous mutant and XRCC3-C241T heterozygous mutation significantly increase the risk of the AML onset, which can provide more predictive value for incidence of AML.
T cell abnormalities have been reported to play an important role in pathogenesis of immune thrombocytopenia (ITP) besides specific autoantibodies towards platelet. The aim of this study was to explore the clinical importance of T lymphocyte subsets in adult patients with newly diagnosed ITP before and after first-line treatment. Elderly ITP patients were also studied and we tried to analyze the relationships between these items and therapeutic outcomes. The patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids and therapeutic responses were evaluated. As a result, compared with the controls, absolute lymphocyte counts in ITP patients decreased significantly before treatment. After treatment, lymphocyte counts restored to control level regardless of their treatment outcomes. In addition, we observed increased IgG and CD19(+) cell expression and decreased CD4(+)/CD8(+) cell ratio in both whole ITP group and elderly group before treatment. After treatment, the increased IgG and CD19(+) cell expression could be reduced in both respond and non-respond group regardless of patient age, while CD4(+)/CD8(+) cell ratio could not be corrected in non-respond ITP patients. In non-respond ITP patients, increased CD8(+) cell expression was noticed and could not be corrected by first-line treatment. Furthermore, even lower NK cell expression was found in non-respond elderly patients after treatment when compared with that in controls. Our findings suggest that ITP patients usually had less numbers of peripheral lymphocytes and patients with higher levels of CD8(+) cells or lower levels of CD4(+)/CD8(+) cell ratio were less likely to respond to first-line treatment. Lower levels of NK cells made therapies in elderly ITP patients even more difficult.
This paper introduces the continuously tunable THz radiation through sideband generation of a free running and solidnitrogen- cooled THz quantum cascade laser. The 2.324 THz QCL operating in a single longitudinal mode (SLM) in continuous-wave (cw) was mixed with a swept synthesized microwave signal by a THz Schottky-diode-balanced mixer. Through sideband generation, two frequency branches were observed at low and high frequency, characterized with a Fourier-transform spectrometer. At low frequency, the sideband generates frequencies from -50 GHz to +50 GHz. At high frequency, it generates sideband frequencies from 70 GHz to 115 GHz. The total ±100 GHz tuning range can be further expanded with higher frequency millimeter wave amplifier/multiplier source. The sideband generates total 1 μW of output power at both upper and lower frequency with 200 μW of driven power from the THz QCL, showing a power conversion efficiency of 5 × 10-3. The demonstration of this SM, continuously tunable THz source enables its applications where SM, spatially coherent beam is required.
A compact, tunable, ultranarrow band terahertz source, Delta nu similar to 1 MHz, is demonstrated by upconversion of a 2.324 THz, free-running quantum cascade laser with a THz Schottky-diode-balanced mixer using a swept, synthesized microwave source to drive the nonlinearity. Continuously tunable radiation of 1 mu W power is demonstrated in two frequency regions: nu(Laser) +/- 0 to 50 GHz and nu(Laser) +/- 70 to 115 GHz. The sideband spectra were characterized with a Fourier-transform spectrometer, and the radiation was tuned through CO, HDO, and D2O rotational transitions. (C) 2014 Optical Society of America
OBJECTIVE To evaluate the impact of Fc gamma receptor IIIa (FcγR IIIa) polymorphisms on the efficacy of rituximab (RTX) combined chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). METHODS FcγRIIIa polymorphisms were analyzed by PCR in 122 patients and 100 healthy controls. All patients received 8(4-12) cycles of RTX combined chemotherapy. RESULTS 78(63.93%) patients with F/F, 5(4.10%) with V/V, and 39(31.97%) with V/F were identified, which were not different compared to controls. Patients with different FcγRIIIa genotypes did not have any difference in terms of gender, age, molecular subtypes, lactate dehydrogenase (LDH) or international prognostic index (IPI). The overall response rate (ORR) was 89.35% with a complete response (CR) of 80.33% and a partial response (PR) of 9.02%. The ORR was 83.33%, 100.00% and 100.00% in F/F, V/V and V/F, respectively. A higher response rate was observed in V/V and V/F as compared with F/F (P<0.05). With a median follow-up of 35 months (range: 12-62 months), 46(37.71%) patients had relapsed and 40 (32.79%) cases progressed and ended in death. The 3-year progress-free survival (PFS) rate was 41.03%, 100.00%, 100.00% in F/F, V/V and V/F, respectively. The 3-year overall survival (OS) rate was 48.72%, 100.00% and 100.00% in patients with three genotypes. The PFS and OS rate were significantly higher in V/V and V/F as compared with F/F (P<0.05). CONCLUSION FcγR III a polymorphisms could predict response and prognosis of RTX combined chemotherapy for patients with DLBCL.
Objective To investigate the association between systemic lupus erythematosus (SLE) and multi-ple myeloma (MM) .Methods Clinical data of one 68-year-old woman with diagnosis of SLE combined with MM was analyzed .Clinical characteristics of SLE combined with MM were analyzed in 15 cases ,reported in articles of recent 35 years ,retrieved from PubMed database .Results In these 15 cases ,the proportion of female was higher than male (male∶female=1∶14) .The median age at diagnosis of MM was 49 ,which was obviously earlier than the age at di-agnosis of MM in general population .The incidence rates of main symptoms of SLE in patens combined with SLE and MM,including arthritis/arthralgia ,erythema/light sensitivity rashes and blood system damage ,were 80 .0% ,60 .0%and 66 .7% ,which were not different with patients single with SLE .Five cases were at stable stage of SLE or with negative serological changes ,when they were diagnosed with MM.Mprotein could be detected in 12 cases . Conclusion Monoclonal gammopathy of undetermined significance could be exist in SLE patients ,which might in-crease the onset risk of MM.
目的 观察地西他滨联合CAG方案治疗骨髓增生异常综合征(MDS)与急性髓系白血病(AML)的临床疗效与安全性.方法 2010年1月11日至2013年8月2日诊治并应用地西他滨治疗的MDS与AML共13例,观察疗效与不良反应.结果 13例患者中,完全缓解(CR)5例,其中2例治疗1个疗程即获得CR,另外3例治疗2个疗程获得CR.部分缓解(PR)2例,血液学改善(HI)3例.结论 地西他滨联合半量CAG方案可有效治疗MDS和AML,且患者如果第1个疗程血小板反应良好,则容易获得CR,但对于经过多种化疗的MDS和AML均疗效不佳。
The interleukin-23 (IL-23) and its receptor (IL-23R) mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C) have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML) patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.01-1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01-1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.
Childhood acute lymphoblastic leukemia (C-ALL) is the most common pediatric cancer. Although its etiology remains poorly understood, the hypothesis of ALL correlated with a genetic basis was examined through association studies based on candidate genes. Recently, two independent large-scale genome-wide association studies reported that the five single nucleotide polymorphisms (rs7073837; rs10821936; rs10994982; rs7089424; rs10740055) in the gene AT rich interactive domain 5B (ARID5B) at 10q21.2, were associated with the high incidence risk of C-ALL, especially with hyperdiploid lymphoblastic leukemia. Variations in these single nucleotide polymorphisms influence the risk of specific disease subtypes, and also possess race- and sex-differences in leukemia incidence. Further elucidation of the mechanisms through which ARID5B variants are involved in C-ALL not only has a great diagnostic value, but also a guidance for the clinical therapy, ultimately improving the prognosis of disease. Therefore, the related studies of ARID5B with C-ALL were summarized briefly in this review.
Frequency stabilization of a THz quantum cascade laser (QCL) to the harmonic of a microwave source has been accomplished using a Schottky diode waveguide mixer designed for harmonic mixing. The 2.32 THz, 1.0 milliwatt CW QCL is coupled into the signal port of the mixer and a 110 GHz signal, derived from a harmonic of a microwave synthesizer, is coupled into the IF port. The difference frequency between the 21st harmonic of 110 GHz and the QCL is used in a discriminator to adjust the QCL bias current to stabilize the frequency. The short-term frequency jitter is reduced from 550 kHz to 4.5 kHz (FWHM) and the long-term frequency drift is eliminated. This performance is compared to that of several other THz QCL frequency stabilization techniques.