Myelodysplastic Syndromes
October 2017 Issue

Nearly every major medical breakthrough over the past 50 years can be attributed to new discoveries that were made possible through meticulous biomedical research. Many diseases and conditions that previously took a heavy toll on patients in terms of both morbidity and mortality are now either treatable or preventable thanks in large part to painstaking research that expanded the frontiers of scientific knowledge and moved the most promising basic research developments into tangible health benefits through human clinical trails. Ongoing research is also the key that will open the door to additional major medical advances and breakthroughs in the future.

Our staff at Medifocus is committed to keeping our subscribers to the Medifocus Digest Alert on Myelodysplastic Syndromes abreast of the latest new research developments that have recently been published in the medical literature for this condition. In this issue of the Digest Alert, you will find a focused list of hand-picked journal article references that represent the latest advances in basic and clinical research for Myelodysplastic Syndromes. These articles represent the current state-of-the-art of the research that will hopefully lead to additional major advances and breakthroughs in the clinical management of Myelodysplastic Syndromes. You can access the summaries of each article referenced below by simply clicking on the article Title.

We will continue to update you with the latest scientific and clinical developments through the Medifocus Digest Alert on Myelodysplastic Syndromes every 3 months. Thank you for your ongoing subscription to this publication.

Elliot Jacob, Ph.D.
Vice-President - Content, Inc.

1:A call for action: Increasing enrollment of untreated patients with higher-risk myelodysplastic syndromes in first-line clinical trials.
Authors:Zeidan AM, Stahl M, Sekeres MA, Steensma DP, Komrokji RS, Gore SD
Institution:Department of Hematology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut.
Journal:Cancer. 2017 Oct 1;123(19):3662-3672. doi: 10.1002/cncr.30903. Epub 2017 Jul 31.

2:A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes.
Authors:Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J, Slama B, Badre S, Gasal E, Mehta B, Franklin J
Institution:University Hospital Carl Gustav Carus Dresden, Medizinische Klinik und Poliklinik I, Dresden, Germany. Medical School, Patras, Greece. Calabria, Italy. Switzerland. Leuven, Leuven, Belgium. and Faculty of Medicine, Masaryk University, Brno, Czech Republic. Avignon, France.
Journal:Leukemia. 2017 Sep;31(9):1944-1950. doi: 10.1038/leu.2017.192. Epub 2017 Jun 19.

3:Role of serum ferritin level on overall survival in patients with myelodysplastic syndromes: Results of a meta-analysis of observational studies.
Authors:Pileggi C, Di Sanzo M, Mascaro V, Marafioti MG, Costanzo FS, Pavia M
Institution:Department of Health Sciences, University of Catanzaro 'Magna Graecia', Catanzaro, Italy.; Department of Experimental and Clinical Medicine, University of Catanzaro 'Magna Graecia', Catanzaro, Italy.
Journal:PLoS One. 2017 Jun 16;12(6):e0179016. doi: 10.1371/journal.pone.0179016. eCollection 2017.

4:Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group.
Authors:Ramos F, Robledo C, Pereira A, Pedro C, Benito R, de Paz R, Del Rey M, Insunza A, Tormo M, Diez-Campelo M, Xicoy B, Salido E, Sanchez-Del-Real J, Arenillas L, Florensa L, Luno E, Del Canizo C, Sanz GF, Maria Hernandez-Rivas J
Institution:Department of Hematology, Hospital Universitario de Leon, Leon, Spain.; Institute of Biomedicine (IBIOMED, Leon), Leon, Spain.; Unidad de Diagnostico Molecular y Celular del Cancer, IBSAL, IBMCC-Centro de Investigacion del Cancer (USAL-CSIC), Salamanca, Spain.; Department of Blood Transfusion, Hospital Clinic i Provincial, Barcelona, Spain.; Department of Hematology, Hospital del Mar, Barcelona, Spain.
Journal:Am J Hematol. 2017 Sep;92(9):E534-E541. doi: 10.1002/ajh.24813. Epub 2017 Jul 19.

5:Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation.
Authors:Heuser M, Gabdoulline R, Loffeld P, Dobbernack V, Kreimeyer H, Pankratz M, Flintrop M, Liebich A, Klesse S, Panagiota V, Stadler M, Wichmann M, Shahswar R, Platzbecker U, Thiede C, Schroeder T, Kobbe G, Geffers R, Schlegelberger B, Gohring G, Kreipe HH, Germing U, Ganser A, Kroger N, Koenecke C, Thol F
Institution:Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Germany.; Medizinische Klinik und Poliklinik I, Universtitatsklinikum Carl Gustav Carus, Dresden, Germany.; Klinik fur Hamatologie, Onkologie und Klinische Immunologie, Heinrich Heine University, Dusseldorf, Germany.; Helmholtz Centre for Infection Research, Braunschweig, Germany.; Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
Journal:Ann Hematol. 2017 Aug;96(8):1361-1372. doi: 10.1007/s00277-017-3027-5. Epub 2017 Jun 13.

6:Success in bone marrow failure? Novel therapeutic directions based on the immune environment of myelodysplastic syndromes.
Authors:Cull AH, Rauh MJ
Institution:Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada. Ontario, Canada
Journal:J Leukoc Biol. 2017 Aug;102(2):209-219. doi: 10.1189/jlb.5RI0317-083R. Epub 2017 Jun 8.

7:Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117.
Authors:Sekeres MA, Othus M, List AF, Odenike O, Stone RM, Gore SD, Litzow MR, Buckstein R, Fang M, Roulston D, Bloomfield CD, Moseley A, Nazha A, Zhang Y, Velasco MR, Gaur R, Atallah E, Attar EC, Cook EK, Cull AH, Rauh MJ, Appelbaum FR, Erba HP
Institution:Mikkael A. Sekeres and Aziz Nazha, Cleveland Clinic, Cleveland; Clara D. Bloomfield, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Megan Othus and Anna Moseley, SWOG Statistical Center; Min Fang and Frederick R. Appelbaum, Fred Hutchinson Cancer Research Center, Seattle, WA; Alan F. List, H. Lee Moffitt Cancer Center, Tampa, FL; Olatoyosi Odenike, University of Chicago, Chicago; Mario R. Velasco, Heartland NCORP/Cancer Care Specialists of Central Illinois, Decatur, IL; Richard M. Stone, Dana Farber Cancer Institute; Eyal C. Attar, Massachusetts General Hospital, Boston, MA; Steven D. Gore, Yale University, New Haven, CT; Mark R. Litzow, Mayo Clinic, Rochester, MN; Rena Buckstein, Sunnybrook Health Sciences Centre, Toronto; Elina K. Cook, Alyssa H. Cull, and Michael J. Rauh, Queen's University, Kingston, Ontario, Canada; Diane Roulston, University of Michigan, Ann Arbor, MI; Yanming Zhang, Memorial Sloan-Kettering Cancer Center, New York, NY; Rakesh Gaur, Kansas City National Cancer Institute Community Oncology Research Program, Prairie Village, KS; Ehab Atallah, Medical College of Wisconsin, Milwaukee, WI; and Harry P. Erba, University of Alabama, Birmingham, AL.
Journal:J Clin Oncol. 2017 Aug 20;35(24):2745-2753. doi: 10.1200/JCO.2015.66.2510. Epub 2017 May 9.

8:Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial).
Authors:Kroger N, Iacobelli S, Franke GN, Platzbecker U, Uddin R, Hubel K, Scheid C, Weber T, Robin M, Stelljes M, Afanasyev B, Heim D, Deliliers GL, Onida F, Dreger P, Pini M, Guidi S, Volin L, Gunther A, Bethge W, Poire X, Kobbe G, van Os M, Brand R, de Witte T
Institution:Nicolaus Kroger, University Medical Center Hamburg-Eppendorf, Hamburg; Georg-Nikolaus Franke, University Hospital Leipzig, Leipzig; Uwe Platzbecker, University Hospital Dresden, Dresden; Kai Hubel and Christof Scheid, University of Cologne, Cologne; Thomas Weber, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Halle; Matthias Stelljes, University of Munster, Munster; Peter Dreger, University of Heidelberg, Heidelberg; Andreas Gunther, University Hospital Schleswig Holstein Campus Kiel, Kiel; Wolfgang Bethge, University Hospital Tubingen, Tubingen; Guido Kobbe, Heinrich Heine University, Dusseldorf, Germany; Simona Iacobelli, Universita Tor Vergata, Rome; Giorgio Lambertenghi Deliliers and Francesco Onida, Fondazione IRCC Ca' Granda Ospedale Maggiore Policlinico, University of Milano, Milan; Massimo Pini, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria; Stefano Guidi, Azienda Ospedaliera Universitaria Careggi, Florence, Italy; Ruzena Uddin, Guy's Hospital, London, United Kingdom; Marie Robin, Hopital Saint Louis, Assistance Publique Hopitaux Paris, France; Boris Afanasyev, SPB Pavlov Medical University, St Petersburg, Russia; Dominik Heim, University Hospital Basel, Basel Switzerland; Liisa Volin, Helsinki University Hospital, Helsiniki, Finland; Xavier Poire, Cliniques Universitaires St-Luc, Brussels, Belgium; Marleen van Os, European Group of Blood and Marrow Transplantation Clinical Trials Office; Ronald Brand, Leiden University Medical Center, Leiden; and Theo de Witte, Radboud University Medical Center, Nijmegen, the Netherlands.
Journal:J Clin Oncol. 2017 Jul 1;35(19):2157-2164. doi: 10.1200/JCO.2016.70.7349. Epub 2017 May 2.

9:Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk myelodysplastic syndromes: a retrospective, multicentre study.
Authors:Musto P, Maurillo L, Simeon V, Poloni A, Finelli C, Balleari E, Ricco A, Rivellini F, Cortelezzi A, Tarantini G, Villani O, Mansueto G, Milella MR, Scapicchio D, Marziano G, Breccia M, Niscola P, Sanna A, Clissa C, Voso MT, Fenu S, Venditti A, Santini V, Angelucci E, Levis A
Institution:Scientific Direction, IRCCS-CROB, 'Referral Cancer Centre of Basilicata', Rionero In Vulture (Pz), Italy.; Haematology, Department of Biomedicine and Prevention, 'Tor Vergata' University, Rome, Italy.; Laboratory of Pre-clinical and Translational Research, IRCCS-CROB, 'Referral Cancer Centre of Basilicata', Rionero In Vulture (Pz), Italy.; Haematology Clinic, Department of Clinic and Molecular Sciences, 'Universita Politecnica delle Marche', Ancona, Italy.; 'Seragnoli Institute of Haematology', University School of Medicine, Bologna, Italy.
Journal:Br J Haematol. 2017 Jun;177(5):741-750. doi: 10.1111/bjh.14621. Epub 2017 Apr 17.

10:A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study (POE 10-03).
Authors:Cooper TM, Sison EAR, Baker SD, Li L, Ahmed A, Trippett T, Gore L, Macy ME, Narendran A, August K, Absalon MJ, Boklan J, Pollard J, Magoon D, Brown PA
Institution:Seattle Children's Cancer and Blood Disorders Center, University of Washington, Seattle, Washington. Houston, Texas. University School of Medicine, Baltimore, Maryland. University School of Medicine, Baltimore, Maryland.
Journal:Pediatr Blood Cancer. 2017 Aug;64(8). doi: 10.1002/pbc.26414. Epub 2017 Apr 14.

11:An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromes.
Authors:Daher M, Hidalgo Lopez JE, Randhawa JK, Jabbar KJ, Wei Y, Pemmaraju N, Borthakur G, Kadia T, Konopleva M, Kantarjian HM, Hearn K, Estrov Z, Reyes S, Bueso-Ramos CE, Garcia-Manero G
Institution:Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Texas, USA.; Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Texas, USA.; Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Texas, USA.
Journal:Am J Hematol. 2017 Jul;92(7):674-682. doi: 10.1002/ajh.24746. Epub 2017 Jun 9.

12:Cytogenetics and comorbidity predict outcomes in older myelodysplastic syndrome patients after allogeneic stem cell transplantation using reduced intensity conditioning.
Authors:Yucel OK, Saliba RM, Rondon G, Ahmed S, Alousi A, Bashir Q, Ciurea SO, Popat U, Khouri I, Marin D, Rezvani K, Kebriaei P, Shpall EJ, Champlin RE, Oran B
Institution:Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Journal:Cancer. 2017 Jul 15;123(14):2661-2670. doi: 10.1002/cncr.30632. Epub 2017 Mar 21.

13:Iron chelation therapy in low risk myelodysplastic syndrome.
Authors:Killick SB
Institution:Department of Haematology, Royal Bournemouth Hospital NHS Foundation Trust, Bournemouth, UK.
Journal:Br J Haematol. 2017 May;177(3):375-387. doi: 10.1111/bjh.14602. Epub 2017 Mar 16.

14:Relation between chelation and clinical outcomes in lower-risk patients with myelodysplastic syndromes: Registry analysis at 5 years.
Authors:Lyons RM, Marek BJ, Paley C, Esposito J, McNamara K, Richards PD, DiBella N, Garcia-Manero G
Institution:Texas Oncology and US Oncology Research, 4411 Medical Drive, San Antonio, TX 78229, United States. Electronic address: 78503, United States. Electronic address: United States. Electronic address: United States. Electronic address: United States. Electronic address: 24153, United States. Electronic address: Street, Aurora, CO 80012, United States. Electronic address: TX 77030, United States. Electronic address:
Journal:Leuk Res. 2017 May;56:88-95. doi: 10.1016/j.leukres.2017.01.033. Epub 2017 Jan 31.

15:Lenalidomide use in myelodysplastic syndromes: Insights into the biologic mechanisms and clinical applications.
Authors:Stahl M, Zeidan AM
Institution:Yale Cancer Center, New Haven, Connecticut. Haven, Connecticut. Haven, Connecticut.
Journal:Cancer. 2017 May 15;123(10):1703-1713. doi: 10.1002/cncr.30585. Epub 2017 Feb 13.

16:Over-expression of CD200 predicts poor prognosis in MDS.
Authors:Chen JX, Mei LP, Chen BG, Wang DL, Luo WD, Luo LF, Lu R, Zheng R, Zhang L
Institution:Department of Clinical Laboratory, Enze Hospital of Zhejiang Province, Luqiao, Taizhou, 317050, China. Taizhou, 317000, China. Taizhou, 317000, China. Electronic address: Taizhou, 317050, China. 317000, China. Taizhou, 317050, China. Taizhou, 317050, China. Taizhou, 317000, China. 317000, China.
Journal:Leuk Res. 2017 May;56:1-6. doi: 10.1016/j.leukres.2017.01.021. Epub 2017 Jan 15.

17:New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study.
Authors:Taher AT, Origa R, Perrotta S, Kourakli A, Ruffo GB, Kattamis A, Goh AS, Cortoos A, Huang V, Weill M, Merino Herranz R, Porter JB
Institution:American University of Beirut Medical Center, Beirut, Lebanon. Italy. Medical School, Patras, Greece. Italy.
Journal:Am J Hematol. 2017 May;92(5):420-428. doi: 10.1002/ajh.24668. Epub 2017 Feb 18.

18:Phase 2, randomized, double-blind study of pracinostat in combination with azacitidine in patients with untreated, higher-risk myelodysplastic syndromes.
Authors:Garcia-Manero G, Montalban-Bravo G, Berdeja JG, Abaza Y, Jabbour E, Essell J, Lyons RM, Ravandi F, Maris M, Heller B, DeZern AE, Babu S, Wright D, Anz B, Boccia R, Komrokji RS, Kuriakose P, Reeves J, Sekeres MA, Kantarjian HM, Ghalie R, Roboz GJ
Institution:Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas. Houston, Texas. Houston, Texas. Houston, Texas. Houston, Texas. Maryland. Hospital, Detroit, Michigan. Houston, Texas.
Journal:Cancer. 2017 May 15;123(6):994-1002. doi: 10.1002/cncr.30533. Epub 2017 Jan 17.

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