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Workshop proceedings: GWAS summary statistics standards and sharing

Cell Genomics 2021年第1期1卷 100004-100004页

作者： MacArthur, Jacqueline A.L. Buniello, Annalisa Harris, Laura W. Hayhurst, James McMahon, Aoife Sollis, Elliot Cerezo, Maria Hall, Peggy Lewis, Elizabeth Whetzel, Patricia L. Bahcall, Orli G. Barroso, Inês Carroll, Robert J. Inouye, Michael Manolio, Teri A. Rich, Stephen S. Hindorff, Lucia A. Wiley, Ken Parkinson, Helen European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Genome Campus Hinxton United Kingdom BHF Data Science Centre Health Data Research UK London United Kingdom Division of Genomic Medicine National Human Genome Research Institute National Institutes of Health Bethesda 20892 MD United States Cell Genomics Cell Press 50 Hampshire St. 5th Floor Cambridge 02139 MA United States Exeter Centre of Excellence in Diabetes (EXCEED) University of Exeter Medical School Exeter United Kingdom Department of Biomedical Informatics Vanderbilt University Medical Center Nashville TN United States Cambridge Baker Systems Genomics Initiative Department of Public Health and Primary Care University of Cambridge Cambridge CB1 8RN United Kingdom Cambridge Baker Systems Genomics Initiative Baker Heart and Diabetes Institute 75 Commercial Rd. Melbourne 3004 VIC Australia The Alan Turing Institute London United Kingdom Center for Public Health Genomics University of Virginia Charlottesville 22908 VA United States

Genome-wide association studies (GWASs) have enabled robust mapping of complex traits in humans. The open sharing of GWAS summary statistics (SumStats) is essential in facilitating the larger meta-analyses needed for increased power in resolving the genetic basis of disease. However, most GWAS SumStats are not readily accessible because of limited sharing and a lack of defined standards. With the aim of increasing the availability, quality, and utility of GWAS SumStats, the National Human Genome Research Institute-European bioinformatics Institute (NHGRI-EBI) GWAS Catalog organized a community workshop to address the standards, infrastructure, and incentives required to promote and enable sharing. We evaluated the barriers to SumStats sharing, both technological and sociological, and developed an action plan to address those challenges and ensure that SumStats and study metadata are findable, accessible, interoperable, and reusable (FAIR). We encourage early deposition of datasets in the GWAS Catalog as the recognized central repository. We recommend standard requirements for reporting elements and formats for SumStats and accompanying metadata as guidelines for community standards and a basis for submission to the GWAS Catalog. Finally, we provide recommendations to enable, promote, and incentivize broader data sharing, standards and FAIRness in order to advance genomic medicine. © 2022 The Authors

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The real-world adherence of the first-line anti-osteoporosis medications in Taiwan: Visualize the gap between reality and expectations

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Journal of the Formosan Medical Association 2023年第Sup1期122卷 S55-S64页

作者： Lee, Chia-Che Fu, Shau-Huai Chen, Ho-Min Lin, Jou-Wei Hsu, Chih-Cheng Lin, Sheng-Chieh Hwang, Jawl-Shan Yang, Rong-Sen Wu, Chih-Hsing Wang, Chen-Yu Department of Orthopedic Surgery National Taiwan University Hospital Taipei Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Department of Orthopedics National Taiwan University Hospital Yunlin Branch Yunlin Taiwan Department of Public Health College of Medicine National Cheng Kung University Tainan Taiwan Health Data Research Center National Taiwan University Taipei Taiwan Department of Medicine College of Medicine National Taiwan University Taipei Taiwan Department of Internal Medicine National Taiwan University Hospital Yunlin Branch Yunlin County Douliu Taiwan Institute of Population Health Sciences National Health Research Institutes Miaoli County Taiwan Department of Orthopedic Surgery Chung Shan Medical University Hospital Taichung Taiwan Department of Orthopaedics College of Medicine National Taiwan University Taipei Taiwan Institute of Gerontology College of Medicine National Cheng Kung University Tainan Taiwan Department of Family Medicine College of Medicine National Cheng Kung University Tainan Taiwan Department of Family Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan National Center for Geriatrics and Welfare Research National Health Research Institutes Yunlin County Taiwan Department of Pharmacy National Taiwan University Hospital Yunlin Branch Yunlin Taiwan Division of Endocrinology and Metabolism Department of Internal Medicine Chang Gung Memorial Hospital Chang Gung University Taoyuan Taiwan

Background: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. Methods: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. Results: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. Conclusion: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study. © 2023 Formosan Medical Association

关键词： Adherence Antiosteoporosis medication Denosumab Medication possession ratio Zoledronate

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Blockchain-Based Incentive Announcement System for Internet of Vehicles

Blockchain-Based Incentive Announcement System for Internet ...

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IEEE International Conference on Big data and Cloud Computing (BdCloud)

作者： Yang Yang Jialiang Chen Xianghan Zheng Ximeng Liu Wenzhong Guo Hairong Lv College of Mathematics and Computer Science Fuzhou University Fuzhou China Guangxi Key Laboratory of Cryptography and Information Security Guangnxi China Guangdong Provincial Key Laboratory of Data Security and Privacy Protection Guangzhou China Fujian Provincial Key Laboratory of Information Processing and Intelligent Control (Minjiang University) Fuzhou China Ministry of Education Key Laboratory of Bioinformatics Bioinformatics Division and Center for Synthetic and Systems Biology Beijing National Research Center for Information Science and TechnologyDepartment of Automation Tsinghua University Beijing China

ISBN: (数字)9781728143286

ISBN: (纸本)9781728143293

With the rapid development of computation and communication technologies, the traditional vehicle ad hoc networks (VANETs) are changing to Internet of vehicle (IoV). Vehicular announcement networks in IoV have been widely used in the communication of vehicles. Generally, we need to solve two problems while establishing a vehicular announcement system. First, we need to protect user's privacy when broadcasting the message. Second, participants usually lack the enthusiasm to reply to the announcement. To solve these two problems, we propose a novel blockchain-based incentive announcement system that not only allows participants to anonymously announce their message on the blockchain in a non-trusted environment, but also motivates witnesses to respond to the request of the traffic information with incentive mechanism. Meanwhile, traffic messages and signatures in our system are tamper-resistant, which are recorded on the blockchain. According to the security and performance analysis, it shows that our system is privacy-preserving and efficient in computation cost.

关键词： Blockchain Privacy Smart contracts Authentication Internet Remuneration Hash functions

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Estimation of Lead Time via Low-Dose CT in the National Lung Screening Trial

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Journal of Healthcare Informatics Research 2018年第4期2卷 353-366页

作者： Liu, Ruiqi Pérez, Adriana Wu, Dongfeng Department of Bioinformatics and Biostatistics School of Public Health and Information Sciences University of Louisville Louisville 40202 KY United States Department of Biostatistics and Data Science The University of Texas Health Science Center at Houston-UTHealth School of Public Health Austin Campus Austin 78701 TX United States

Based on recent reports from the National Lung Screening Trial (NLST), smokers who were screened by low-dose computer tomography (LDCT) had a 20% lower chance of dying from lung cancer than those screened by chest X-rays. However, due to the complexities of lead time bias and over diagnosis, no formal test has been shown to reduce lung cancer mortality. To correctly evaluate survival benefit due to early detection, it is critical to estimate lead time, the length of time that detection of a disease is advanced by screening. We applied a recently developed probability method to estimate lead time, using the LDCT data from NLST, where human lifetime was treated as random and derived from the actuarial life table of the US Social Security Administration. Using Bayesian posterior samples of key parameters extracted from the NLST-LDCT data, simulations on lead time were carried out on 16 hypothetical cohorts with four initial ages (55, 60, 65, and 70) and four future screening intervals (12, 18, 24, and 30 months). For each scenario, the estimated lead time for both screen-detected and interval cases is reported. Results show that the probability of no-early-detection (interval cases) increases monotonically when the screening interval increases for both genders. A male heavy smoker with an initial screening age at 60 has 11.65% (female 6.76%) chance of no-early-detection with annual screenings. This probability increases to 36.35% (female 28.26%) if the screenings were biennial. The mean lead time appears longer for women than for men. The mean lead time decreases when the screening interval increases, but it appears stable across different initial age groups. These results lay a foundation to evaluate survival benefit accurately with LDCT and to schedule future screening exams. © 2018, Springer International Publishing AG, part of Springer Nature.

关键词： Cancer screening Low-dose computed tomography National Lung Screening Trial No-early-detection

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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Phylogeny, ancestral ranges and reclassification of sand dollars

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Scientific Reports 2023年第1期13卷 1-12页

作者： Lee, Hsin Lee, Kwen-Shen Hsu, Chia-Hsin Lee, Chen-Wei Li, Ching-En Wang, Jia-Kang Tseng, Chien-Chia Chen, Wei-Jen Horng, Ching-Chang Ford, Colby T. Kroh, Andreas Bronstein, Omri Tanaka, Hayate Oji, Tatsuo Lin, Jih-Pai Janies, Daniel National Museum of Marine Biology and Aquarium Pingtung 944401 Taiwan Department of Geosciences National Taiwan University Taipei 10617 Taiwan Institute of Oceanography National Taiwan University Taipei 10617 Taiwan Biology Department National Museum of Natural Science Taichung 40453 Taiwan Tuple LLC 2413 Commonwealth Ave Charlotte 28205 NC United States School of Data Science University of North Carolina at Charlotte 9201 University City Blvd Charlotte 28223 NC United States Department of Bioinformatics and Genomics University of North Carolina at Charlotte 9201 University City Blvd Charlotte 28223 NC United States Center for Computational Intelligence to Predict Health and Environmental Risks (CIPHER) University of North Carolina at Charlotte 9201 University City Blvd Charlotte 28223 NC United States Department of Geology and Palaeontology Natural History Museum Vienna Vienna 1010 Austria School of Zoology Faculty of Life Sciences Tel Aviv University Tel Aviv 6997801 Israel Steinhardt Museum of Natural History Tel Aviv University Tel Aviv 6997801 Israel Department of Biological Sciences Graduate School of Science University of Tokyo Tokyo 113-0033 Japan University Museum Nagoya University Furo-cho Nagoya 464-8601 Japan

Classification of the Class Echinoidea is under significant revision in light of emerging molecular phylogenetic evidence. In particular, the sister-group relationships within the superorder Luminacea (Echinoidea: Irregularia) have been considerably updated. However, the placement of many families remains largely unresolved due to a series of incongruent evidence obtained from morphological, paleontological, and genetic data for the majority of extant representatives. In this study, we investigated the phylogenetic relationships of 25 taxa, belonging to eleven luminacean families. We proposed three new superfamilies: Astriclypeoidea, Mellitoidea, and Taiwanasteroidea (including Dendrasteridae, Taiwanasteridae, Scutellidae, and Echinarachniidae), instead of the currently recognized superfamily Scutelloidea Gray, 1825. In light of the new data obtained from ten additional species, the historical biogeography reconstructed shows that the tropical western Pacific and eastern Indian Oceans are the cradle for early sand dollar diversification. Hothouse conditions during the late Cretaceous and early Paleogene were coupled with diversification events of major clades of sand dollars. We also demonstrate that Taiwan fauna can play a key role in terms of understanding the major Cenozoic migration and dispersal events in the evolutionary history of Luminacea. © 2023, The Author(s).

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Thiazide diuretics versus loop diuretics in stage 3-5 CKD: impact on cardiorenal outcomes

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Postgraduate medicine 2024年第7期136卷 738-748页

作者： Li-Chin Sung Hui-Wen Chiu Samuel Mon-Wei Yu Liam Li-An Tsou Yung-Ho Hsu Mai-Szu Wu Cheng-Li Lin Fuu-Jen Tsai Chu-Lin Chou Division of Cardiology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Division of Cardiology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan. Department of General Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Taipei Heart Institute Taipei Medical University Taipei Taiwan. Research Center of Urology and Kidney Taipei Medical University Taipei Taiwan. Division of Nephrology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Medical Research Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan. Division of Nephrology Department of Medicine Icahn School of Medicine at Mount Sinai New York NY USA. Biochemistry Department of Chemistry Hofstra University Hempstead NY USA. Division of Nephrology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan. Division of Nephrology Department of Internal Medicine Hsin Kuo Min Hospital Taipei Medical University Taoyuan Taiwan. Management Office for Health Data China Medical University Hospital Taichung Taiwan. College of Medicine China Medical University Taichung Taiwan. School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan. Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan. Division of Medical Genetics China Medical University Children's Hospital Taichung Taiwan. Department of Biotechnology and Bioinformatics Asia University Taichung Taiwan.

OBJECTIVES:The association between diuretic use and cardiorenal outcomes remains limited in patients with stage 3-5 chronic kidney disease (CKD) and hypertension. To address this gap, we aim to investigate the long-term clinical impact of diuretic use with its pharmacological classification in Taiwanese patients with stage 3-5 CKD and hypertension who were concurrently received angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). METHODS:Using data from the National Health Insurance Research database (January 2008 to December 2019), we focused on individuals with stage 3-5 CKD receiving ACEIs/ARBs between 2010 and 2018. We categorized the cohort into non-diuretic, loop diuretic (furosemide), thiazide diuretic, and combination diuretic groups. We used a Cox proportional hazards regression model with propensity score matching to analyze the influence of diuretics on all-cause mortality, cardiovascular (CV) death, and cardiorenal adverse outcomes. RESULTS:The study included 59,719 patients, with 17,585 in the non-diuretic group and 42,134 in the diuretic group. Diuretics including furosemide use was significantly associated the risks of hospitalization for decompensated congestive heart failure (CHF), acute renal failure (ARF), end-stage renal disease (ESRD) requiring dialysis, CV mortality, and all-cause mortality (-value <0.001). Thiazide diuretics showed no such adverse outcomes associations. The group receiving both thiazide and furosemide was more associated with all-cause mortality than the nondiuretic, thiazide, and furosemide monotherapy groups (all -value <0.001). CONCLUSION:Among stage 3-5 CKD patients on ACEIs/ARBs, loop diuretics exposure was associated with increased mortality and hospitalization for cardiorenal events, while thiazide diuretics exposure in isolation had no such associations. In the present data, we cannot evaluate the relationship between furosemide-associated adverse outcomes and worse renal functio

关键词： Adverse clinical outcomes Mortality chronic kidney disease cohort study diuretics

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Gvhd and Relapse Free Survival (GRFS) after Allogeneic Transplantation for Idiopathic Severe Aplastic Anemia: An Analysis from the Saawp data Quality Initiative Program of EBMT

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BLOOD 2020年 136卷 3-4页

作者： Devillier, Raynier Eikema, Dirk-Jan Bosman, Paul Dufour, Carlo Aljurf, Mahmoud Wu, Depei Maschan, Alexey Afanasyev, Boris V. Halkes, Constantijn Collin, Matthew P. Snowden, John A. Bertrand, Yves Ganser, Arnold Sykora, Karl-Walter Gibson, Brenda Maertens, Johan Itala-Remes, Maija Paola, Corti Cornelissen, Jan J. Bornhauser, Martin Colorado, Mercedes Ozdogu, Hakan Risitano, Antonio De Latour, Regis Peffault Institut Paoli Calmettes Marseille France CRCM / INSERM U1068 Marseille France Aix Marseille University Medicine Faculty Marseille France EBMT Data Office Leiden Department of Medical Statistics and Bioinformatics Leiden University Medical Center Leiden Netherlands EBMT Data Office Leiden Netherlands Severe Aplastic Anemia Working Party European Group for Blood and Marrow Transplantation (EBMT) Leiden Netherlands Hematology Unit IRCCS Istituto Giannina Gaslini Genova Italy King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia The First Affiliated Hosp. of Soochow University Suzhou China Dmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology Moscow Russian Federation RM Gorbacheva Research Institute Pavlov University Saint-Petersburg Russian Federation Department of Hematology Leiden University Medical Center Leiden Netherlands Newcastle University Newcastle Upon Tyne United Kingdom Sheffield Teaching Hospitals NHS Trust Sheffield United Kingdom Institute of Pediatric Hematology and Oncology Civil Hospital of Lyon Claude Bernard University Lyon France Klinik für Hämatologie Hämostaseologie Onkologie und Stammzelltransplantation Medizinische Hochschule Hannover Hannover Germany Pediatric Hematology and Oncology Hannover Medical School Hanover Germany Department of Hematology Royal Hospital for Children Glasgow GBR University Hospital Gasthuisberg Leuven Belgium Turku University Hospital Stem cell transplantation unit Turku Finland Ematologia Pediatrica Ospedale San Gerardo Monza Italy Department of Hematology Erasmus MC Cancer Institute Rotterdam Netherlands Department of Hematology and Oncology University Hospital Carl Gustav Carus Dresden Dresden Germany French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria Assistance Publique - Hôpitaux de Paris Université de Paris Paris France Severe Aplastic Anemia Working Party European Group for Blood and Marrow Trans

Background Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved over past 20 years, approaching 75% at 5 years. However, beyond survival, a SAA-adapted composite endpoint GVHD and relapse free survival (GRFS) may more accurately assess patient outcomes, becoming a meaningful study endpoint. We analyzed GRFS aiming to identify risk factors and specific causes of GRFS failure. Methods This retrospective analysis from the SAAWP data Quality Initiative (DQI registry database) program of EBMT included patients with: diagnosis of idiopathic SAA; first Allo-HSCT from 2005 to 2016; and matched related (MRD) or unrelated donor (UD) (no cord blood). Relevant events for Kaplan-Meier calculation of GRFS were: relapse (including primary and secondary graft failure); grade 3-4 acute GVHD; extensive chronic GVHD; and death. In addition, we used a competing-risk model to analyze cumulative incidences of specific causes of GRFS failure. Results We analyzed 580 patients (385 adults and 195 younger than 18 years), with a median age of 23 years (<0.1-77). Donor was matched related and unrelated in 337 and 243 patients, respectively. Median time from diagnosis to Allo-HSCT was 6 months (IQR: 2-15) and 310 (53%) patients underwent Allo-HSCT without prior treatment. GRFS at 5 years was 69% (65-73) in the whole cohort. Median follow up was 61 months (95%CI: 56-67). Multivariate cox model including age (continuous), graft source, conditioning intensity, sex mismatch, CMV-serostatus, donor type, time from diagnosis to Allo-HSCT (< vs. > 6 months) and previous treatment before Allo-HSCT showed that age (HR=1.02, [1.01-1.03], p<0.001) and CMV serostatus other than negative-donor to negative-recipient [D-/R-] (HR=1.51, [1.02-2.23], p=0.041) were the only independent factors associated with worse GRFS. Using cause specific cox model, we analyzed the risk of the different causes of GRFS failure and found that CMV-serostatus other than D-/R- was associated with higher

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Author Correction: Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

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Nature genetics 2023年第3期55卷 519-520页

作者： Ceres Fernandez-Rozadilla Maria Timofeeva Zhishan Chen Philip Law Minta Thomas Stephanie Schmit Virginia Díez-Obrero Li Hsu Juan Fernandez-Tajes Claire Palles Kitty Sherwood Sarah Briggs Victoria Svinti Kevin Donnelly Susan Farrington James Blackmur Peter Vaughan-Shaw Xiao-Ou Shu Jirong Long Qiuyin Cai Xingyi Guo Yingchang Lu Peter Broderick James Studd Jeroen Huyghe Tabitha Harrison David Conti Christopher Dampier Mathew Devall Fredrick Schumacher Marilena Melas Gad Rennert Mireia Obón-Santacana Vicente Martín-Sánchez Ferran Moratalla-Navarro Jae Hwan Oh Jeongseon Kim Sun Ha Jee Keum Ji Jung Sun-Seog Kweon Min-Ho Shin Aesun Shin Yoon-Ok Ahn Dong-Hyun Kim Isao Oze Wanqing Wen Keitaro Matsuo Koichi Matsuda Chizu Tanikawa Zefang Ren Yu-Tang Gao Wei-Hua Jia John Hopper Mark Jenkins Aung Ko Win Rish Pai Jane Figueiredo Robert Haile Steven Gallinger Michael Woods Polly Newcomb David Duggan Jeremy Cheadle Richard Kaplan Timothy Maughan Rachel Kerr David Kerr Iva Kirac Jan Böhm Lukka-Pekka Mecklin Pekka Jousilahti Paul Knekt Lauri Aaltonen Harri Rissanen Eero Pukkala Johan Eriksson Tatiana Cajuso Ulrika Hänninen Johanna Kondelin Kimmo Palin Tomas Tanskanen Laura Renkonen-Sinisalo Brent Zanke Satu Männistö Demetrius Albanes Stephanie Weinstein Edward Ruiz-Narvaez Julie Palmer Daniel Buchanan Elizabeth Platz Kala Visvanathan Cornelia Ulrich Erin Siegel Stefanie Brezina Andrea Gsur Peter Campbell Jenny Chang-Claude Michael Hoffmeister Hermann Brenner Martha Slattery John Potter Konstantinos Tsilidis Matthias Schulze Marc Gunter Neil Murphy Antoni Castells Sergi Castellví-Bel Leticia Moreira Volker Arndt Anna Shcherbina Mariana Stern Bens Pardamean Timothy Bishop Graham Giles Melissa Southey Gregory Idos Kevin McDonnell Zomoroda Abu-Ful Joel Greenson Katerina Shulman Flavio Lejbkowicz Kenneth Offit Yu-Ru Su Robert Steinfelder Temitope Keku Bethany van Guelpen Thomas Hudson Heather Hampel Rachel Pearlman Sonja Berndt Richard Hayes Marie Elena Martinez Sushma Thomas Douglas Corley Paul Pharoah Susanna Larsson Yun Yen Heinz-Jo Edinburgh Cancer Research Centre Institute of Genomics and Cancer University of Edinburgh Edinburgh UK. Genomic Medicine Group Instituto de Investigacion Sanitaria de Santiago Santiago de Compostela Spain. Colon Cancer Genetics Group Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK. Danish Institute for Advanced Study Department of Public Health University of Southern Denmark Odense Denmark. Division of Epidemiology Department of Medicine Vanderbilt-Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University Medical Center Nashville TN USA. Division of Genetics and Epidemiology Institute of Cancer Research London UK. Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA. Genomic Medicine Institute Cleveland Clinic Cleveland OH USA. Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland OH USA. Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute Barcelona Spain. Oncology Data Analytics Program Catalan Institute of Oncology Barcelona Spain. Consortium for Biomedical Research in Epidemiology and Public Health Madrid Madrid Spain. Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain. Department of Biostatistics School of Public Health University of Washington Seattle WA USA. Institute of Cancer and Genomic Sciences College of Medical and Dental Sciences University of Birmingham Birmingham UK. Department of Public Health Richard Doll Building University of Oxford Oxford UK. Department of Biomedical Informatics Vanderbilt University School of Medicine Nashville TN USA. Department of Preventive Medicine USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA. Center for Public Health Genomics Department of Public Health Sciences University of Virginia Charlottesville VA USA. De

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Does a Change in IPSS-R between Diagnosis and Transplant Have an Impact on Transplant Outcome in Patients with MDS? a Retrospective Analysis from the EBMT Chronic Malignancies Working Party

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BLOOD 2020年 136卷 39-40页

作者： Scheid, Christof Eikema, Dirk-Jan Niittyvuopio, Riitta Maertens, Johan Passweg, Jakob Blaise, Didier Byrne, Jennifer Kroger, Nicolaus Bornhauser, Martin Chevallier, Patrice Bourhis, Jean-Henri Cornelissen, Jan J. Sengeloev, Henrik Finke, Jurgen, Sr. Snowden, John A. Gedde-Dahl, Tobias Guyotat, Denis Schanz, Urs Patel, Amit Koster, Linda de Wreede, Liesbeth C. Hayden, Patrick J. Onida, Francesco Robin, Marie Yakoub-Agha, Ibrahim Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn University of Cologne Cologne Germany EBMT Data Office Leiden Department of Medical Statistics and Bioinformatics Leiden University Medical Center Leiden Netherlands Helsinki Hospital HELSINKI FIN University Hospital Gasthuisberg Leuven Belgium Hematology University Hospital Basel Basel Switzerland Institut Paoli Calmettes Marseille France Centre for Clinical Haematology Nottingham University Hospitals Trust Nottingham United Kingdom University Hospital Eppendorf Hamburg Germany University Cancer Center (UCC) University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany Hematology Clinic CHU Nantes Nantes France Gustave Roussy Villejuif France Department of Hematology Erasmus MC Cancer Institute Rotterdam Netherlands Rigshospitalet Copenhagen Denmark University of Freiburg Freiburg Germany Dept. of Hematology Oncology and Stem Cell Transplantation Freiburg Germany Department of Haematology Sheffield Teaching Hospitals NHS Foundation Trust Sheffield United Kingdom Department of Hematology Oslo University Hospital Rikshospitalet and Institute of Clinical Medicine University of Oslo Oslo Norway Hematology department Lucien Neuwirth Cancer Institute Saint-Priest-en-Jarez France Department of Medical Oncology and Hematology University Hospital Zurich Zurich Switzerland Zurich Switzerland The Christie NHS Foundation Trust Manchester UK Manchester United Kingdom Univ Lille CHU de Lille INFINITE INSERM U1286 59000 Lille LILLE France

IPSS-R is a well established prognostic factor for transplant outcome in patients with MDS, irrespective whether it is assessed at diagnosis or at transplant. However it is unclear how a change in IPSS-R, e.g. by reducing bone marrow blasts through therapy, would potentially affect transplant results. In particular the decision to treat patients before transplant or perform an upfront allogeneic transplantation can so far not be based on evidence. We did a registry search based in the MDS quality initiative conducted by EBMT to identify transplanted patients with MDS and sufficient data to calculate IPSS-R at diagnosis and before transplant. The search was limited to patients reveiving a first allogeneic stem cell transplantation in the period 2005 -2018. 1482 patients were identified. Median age at alloHCT was 59 (interquartile range 51-64) years, 60% were male. Donors were related in 36%, graft source was PBSC in 85% of cases. Conditioning was standard dose in 33% and reduced intensity in 67%. IPSS-R both at diagnosis and at transplant had a significant impact on OS and RFS after alloHCT. To investigate the effect of a change in IPSS-R between diagnosis and transplant we constructed 3 subgroups: stable IPSS-R, improved IPSS-R, worsened IPSS-R. A change in IPSS-R was noted in 77.5% of patients with prior chemotherapy, 72% with prior HMA and 59.8% of untreated patients. Univariate analysis showed no significant difference in OS or RFS in patients with stable IPSS-R compared to improved or worsened IPSS-R. In patients treated with chemotherapy before transplant OS and RFS was significantly worse with worsened IPSS-R, while this effect was not found in patient treated with hypomethylating agents (HMA) or untreated patients. The same analysis was performed regarding the difference in bone marrow blasts and the cytogenetics score: OS and RFS after transplant were significantly worse with increased blasts (p=0.04 and p=0.001) and a worsened cytogenetic score before trans

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