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  • 1
    Online Resource
    Online Resource
    American Thoracic Society ; 2022
    In:  American Journal of Respiratory and Critical Care Medicine Vol. 205, No. 4 ( 2022-02-15), p. 450-458
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 205, No. 4 ( 2022-02-15), p. 450-458
    Type of Medium: Online Resource
    ISSN: 1073-449X , 1535-4970
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    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2022
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  • 2
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4603-4603
    Abstract: Background Graft-versus-host disease (GVHD) is an important complication after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Antithymocyteglobulin (ATG) has been widely used for GVHD prophylaxis. However, the delay of T-cell reconstitution causes by ATG may increase the risk of opportunistic infections. In this multicenter prospective study, we compared the outcomes of the patients undergoing haplo-HSCT who received 7.5 mg/kg ATG or 10 mg/kg ATG as GVHD prophylaxis. Methods A total of 368 consecutive patients undergoing haplo-HSCT were randomized in 5 hospitals between May 2013 and March 2016. ATG with a total dosage of 7.5 mg/kg were administered in 184 patients and 10 mg/kg ATG were administered in 181 for GVHD prophylaxis. Three patients did not received allocated intervention and transplantation due to leukemia relapse before transplant or toxicity of conditioning regimens. The primary endpoint was the incidence of acute GVHD grade II to IV on day 100. Noninferiority of 7.5mg/kg ATG against 10mg/kg ATG was established if the difference of the 95% confidence interval (CI) in acute GVHD grade II to IV between the two groups was within 15%. Results The incidences of acute GVHD grade II to IV on day 100 were 31.5% and 28.2% in 7.5 mg/kg and 10 mg/kg ATG (P=0.485), respectively. The difference between these two groups was 3.3% with 95% CI of -6.1% to 12.7%, which indicated that 7.5 mg/kg ATG was not inferior to 10 mg/kg ATG. The incidences of acute GVHD grade III to IV were similar in the two groups (8.2% in 7.5 mg/kg group vs. 5.0% in 10 mg/kg group, P=0.220). No difference in chronic GVHD was found in the two groups (21.2% in 7.5 mg/kg arm vs. 19.8% in 10 mg/kg arm, P=0.748). More patients developed EBV viremia in 10 mg/kg group (37.5±3.8%) than those in 7.5 mg/kg group (25.2±3.3%, P=0.018). The 2-years overall survival were 69.5±4.3% and 66.7±4.0% for 7.5 mg/kg and 10 mg/kg group (P=0.356). And the 2-year disease-free survival were also comparative in the two groups (66.3±5.7% in 7.5 mg/kg arm vs. 66.6±3.8% in 10 mg/kg arm, P=0.288). Conclusion Compared with 10 mg/kg ATG, the 7.5mg/kg ATG applied in haplo-HSCT appears not to increase GVHD and might reduce the risk of EBV infection after transplantation. Disclosures Lin: National Natural Science Foundation of China 81400141: Research Funding; National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 3
    In: Genomics, Elsevier BV, Vol. 113, No. 6 ( 2021-11), p. 3696-3704
    Type of Medium: Online Resource
    ISSN: 0888-7543
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1468023-3
    SSG: 12
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  • 4
    In: Clinical Pharmacology & Therapeutics, Wiley, Vol. 112, No. 6 ( 2022-12), p. 1236-1242
    Abstract: Thiopurine dose optimization by thiopurine‐S‐methyltransferase ( TPMT ) or nudix hydrolase‐15 ( NUDT15 ) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence ( 〉  2 months). Although laboratory monitoring of 6‐thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA‐thioguanine nucleotides (DNA‐TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA‐TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells  〈  3.5 × 10 9 /L) were observed in 43 patients (14.0%), who had significantly higher DNA‐TG concentration than those without leucopenia ( P  = 4.1 × 10 –9 , 423.3 (~ 342.2 to 565.7) vs. 270.5 (~ 188.1 to 394.3) fmol/μg DNA). No difference in 6TGN concentrations between leucopenia and non‐leucopenia was found. With a DNA‐TG threshold of 340.1 fmol/μg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed that DNA‐TG was an independent risk factor for late leucopenia. Quantification of DNA‐TG, rather than 6TGN, can be applied to gauge thiopurine therapy after NUDT15 screening in Chinese patients with IBD.
    Type of Medium: Online Resource
    ISSN: 0009-9236 , 1532-6535
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2022
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    SSG: 15,3
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  • 5
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 825-825
    Abstract: Background: Antithymocyteglobulin (ATG), used as conditioning regimen, can reduce graft-versus-host disease (GVHD) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Notwithstanding, immunosuppressive effect of ATG may increase the risk of viral infections after HSCT. To evaluate the effect of different doses of ATG on post-transplant viral infection, we conducted a multicenter prospective study to compare EBV and CMV infection in haplo-HSCT recipients receiving 7.5 mg/kg or 10 mg/kg ATG. Methods Between May 2013 and November 2015, 350 consecutive patients with hematological malignancies undergoing haplo-HSCT were randomized in 5 hospitals. One hundred and seventy-two patients received ATG with a total dosage of 7.5 mg/kg and 175 received 10 mg/kg ATG. Three patients did not received allocated intervention and transplantation due to leukemia relapse before transplant or toxicity of conditioning regimens. Results The cumulative incidence of EBV viremia on day 180 was 23.3±3.2% in 7.5 mg/kg ATG arm which was lower than that in 10 mg/kg arm (34.6±3.7%, P=0.037). CMV viremia were comparable in the two arms (7.5 mg/kg arm: 79.0±3.1% vs. 10 mg/kg arm: 76.9±3.2%, P=0.950). The incidences of CMV diseases were 0.6±0.6% and 2.4±1.2% in 7.5 mg/kg and 10 mg/kg arms, respectively (P=0.093). No difference in the incidence of post-transplant lymphoproliferative disorder (PTLD) was found between the two arms (2.4±1.2% in 7.5 mg/kg arm vs. 5.4±1.8% in 10 mg/kg arm, P=0.150). Besides, acute GVHD grade II to IV within 100 days occurred in 55 recipients with the incidence of 31.4% in 7.5mg/kg ATG arms and 45 recipients in 10 mg/kg arms with the incidence of 26.2% (P=0.279). The incidences of aGVHD grade III to IV were similar in the two arms (8.0% in 7.5 mg/kg arm: vs. 4.7% in 10 mg/kg arm, P=0.196). The 2-years overall survival were 69.5±4.7% and 69.4±3.9% for 7.5 mg/kg and 10 mg/kg group (P=0.540). Conclusion Compared with 10 mg/kg of ATG, the application of 7.5 mg/kg might reduce the risk of EBV infection after haplo-HSCT and not increase aGVHD. Disclosures Lin: National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding; National Natural Science Foundation of China 81400141: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: The Lancet, Elsevier BV, Vol. 394, No. 10196 ( 2019-08), p. 407-418
    Type of Medium: Online Resource
    ISSN: 0140-6736
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 7
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 2610-2610
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 2610-2610
    Abstract: Introduction: Early detection is critical to improving cancer patient survival and quality of life. Cell-free DNA (cfDNA) methylation profiling is a promising diagnostic approach for early detection of cancer, even before symptoms appear. We previously reported a non-invasive and cost-effective methylation test, Aurora, which is able to detect three major cancer types with high specificity and sensitivity especially at early stages (I/II), including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC). We have improved this test to include two additional major cancer types, gastric cancer (GC) and esophageal cancer (EC). Taking together, these five cancer types represent 56% of new cancer cases and 60% of cancer-related deaths in China. Methods: We developed a novel high-throughput targeted methylation profiling platform, Aurora 2.0 (an improved version of Aurora 1.0, as presented in AACR 2020), to efficiently enrich and capture cancer-specific DNA methylation markers in plasma, prior to analysis via next-generation sequencing on a MiSeqDx system. About 100 cases each for GC and EC patients (mostly at Stage I/II), together with ~200 healthy controls, have been analyzed by using Aurora 2.0 and used for model development and validation. Results and Discussion: cfDNA methylation profiles have been obtained from 409 plasma samples, comprising 206 healthy controls, 98 GC and 105 EC patients. Logistic regression model has been developed with the Area Under Curve (AUC) of 94.0% and 93.5% for GC and EC, respectively. Overall, the performance (AUC) of Aurora 2.0 for LC/BC/CRC/GC/EC are 97.3%, 96.2%, 92%, 94% and 93.5%, respectively. An independent cohort (~2,000 plasma samples, five cancer types including lung, breast, colorectal, gastric and esophageal cancers with healthy controls) study is undergoing to further validate this test prospectively. The superior performance and cost-effectiveness (~$100) of the test could make early cancer screening of multiple major cancers in symptom-free and average-risk populations more achievable. Citation Format: Linhao Xu, Jun Wang, Weifeng Ma, Xin Liu, Ting Yang, Sihui Li, Qian Hu, Jinsheng Tao, Zhujia Ye, Zhiwei Chen, Jian-Bing Fan. A high performance blood test for multiple cancer early screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2610.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    detail.hit.zdb_id: 410466-3
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  • 8
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 4601-4601
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 4601-4601
    Abstract: Introduction: Early cancer detection remains a critical challenge to improve patients' survival rate and clinical outcomes. Alterations in DNA methylation play a key role in tumor initiation, development, progression and metastasis. Cell-free DNA (cfDNA) methylation analysis on liquid biopsies (e.g., blood and urine) holds a great promise for early detection of cancers even without symptoms. In this context, we are developing a non-invasive, cost-effective test that can detect several major cancer types, including lung (LnC), breast (BrC), colorectal (CRC), gastric (GC), esophageal (EC) and liver (LvC) cancers with high specificity (Sp) and sensitivity (Sn). These six cancer types represent two third of the newly diagnosed cancer patients and 72% of cancer deaths every year in China. Methods: In order to identify highly effective DNA methylation markers for early detection, we have conducted genome-wide methylation profiling on more than 2,000 benign and malignant tissue samples, including large number of early stage (Stage I/II) tumors and pre-cancerous lesions from lung, breast, colorectum, liver, stomach and esophagus. We then developed a high performance assay, Aurora, to capture cancer-specific DNA methylation signatures in plasma. Specifically, cfDNA was extracted from each of the plasma samples, bisulfite-converted, and analyzed by NGS on Illumina MiSeq system. Results and Discussion: To date, methylation profiles of plasma samples derived from, 1) 58 normal and 106 malignant pulmonary nodule patients, 2) 31 normal and 85 malignant CRC patients, and 3) 81 normal and 78 malignant breast nodule patients, were analyzed. Overall performances (Area Under Curve, AUC) of the Aurora test are 90%, 98% and 92% for LnC, BrC and CRC, respectively. Further clinical validation and evaluation are being conducted in larger independent cohorts of these three types of cancers as well as additional cohorts for the other cancers (GC, EC and LvC). The superior performance and low cost (~$100) make the Aurora test very promising for simultaneous screening of multiple major cancers in symptom-free, average risk populations. Citation Format: Linhao Xu, Jun Wang, Ting Yang, Jinsheng Tao, Xin Liu, Zhujia Ye, Dezhi Zhao, Zeyu Jiang, Zhiwei Chen, Jian-Bing Fan. Toward the development of a $100 screening test for 6 major cancer types [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4601.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 11 ( 2021-12-06), p. e3949-e3955
    Abstract: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18–59 years. Methods In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. Results A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. Conclusions Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. Clinical Trials Registration NCT04412538.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2002229-3
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 10561-10561
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 10561-10561
    Abstract: 10561 Background: Early detection at the localized stage is pivotal for the successful treatment of various cancer types. Although several cancers already have routine screening approaches, the comprehensive utilities are impeded for various reasons, e.g., low accuracy, high cost, limited availability of required facilities, especially in the developing countries. Therefore, an accurate, cost-effective, and non-invasive test for multiple major cancer screening is in high demand. We previously reported a cfDNA methylation test, which can detect five major cancer types with high specificity and sensitivity, especially at the early stage (stage I). These five major cancers, including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and esophageal cancer (EC), account for 56% of new cancer cases and 60% of cancer-related deaths yearly in China. Here, we report the result in an independent cohort as a further validation of this multi-cancer screening test. Methods: The high-throughput targeted methylation profiling platform, Aurora, was used to analyze the plasma samples from an independent retrospective cohort containing 505 healthy controls and ̃200 cases for each cancer type. A locked model based on our previous pilot study (reported in AACR 2020 and 2021) was applied to this data set to assess the overall performance. Results: The Area Under Curves (AUC) of the classifier for LC, BC, CRC, GC and EC are 97.3%, 96.2%, 92.0%, 94.0% and 93.5%, respectively. At a fixed specificity of 99%, the sensitivities for LC, BC, CRC, GC and EC are 84%, 75%, 82%, 85% and 78%, respectively. Conclusions: A methylation blood test for five major cancer screening has been validated in a large retrospective cohort. Its high sensitivity for each cancer type, especially at the early stage (stage I), and easy to use suggests it can be implemented in real clinical world. A large prospective clinical trial is undergoing to further validate this test in asymptomatic populations.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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