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Publisher: Elsevier   (Total: 3177 journals)

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Showing 1 - 200 of 3177 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 30, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 86, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 35, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 386, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 242, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 7)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 132, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 29, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 14)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 43, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 53, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 15, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 384, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 9, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 337, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 10, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 435, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 51, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 42, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 196, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 62, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 14)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 168, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)

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Journal Cover Leukemia Research
  [SJR: 1.043]   [H-I: 70]   [8 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0145-2126 - ISSN (Online) 0145-2126
   Published by Elsevier Homepage  [3177 journals]
  • Lifetime physical inactivity is associated with increased risk for Hodgkin
           and non-Hodgkin lymphoma: A case-control study
    • Authors: John Lewis Etter; Rikki Cannioto; Kah Teong Soh; Emad Alquassim; Hani Almohanna; Zachary Dunbar; Janine M. Joseph; Sophia Balderman; Francisco Hernandez-Ilizaliturri; Kirsten B. Moysich
      Pages: 7 - 11
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): John Lewis Etter, Rikki Cannioto, Kah Teong Soh, Emad Alquassim, Hani Almohanna, Zachary Dunbar, Janine M. Joseph, Sophia Balderman, Francisco Hernandez-Ilizaliturri, Kirsten B. Moysich
      Background Although physical activity is a well-established risk factor for several cancer types, studies evaluating its association with lymphoma have yielded inconclusive results. In such cases where physical activity is not clearly associated with cancer risk in a dose-dependent manner, investigators have begun examining physical inactivity as an independent exposure of interest. Methods Associations of self-reported, lifetime physical inactivity with risk of developing Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a hospital-based case control study using data from the Patient Epidemiology Data System at Roswell Park Comprehensive Cancer Center. Participants included 87 patients with HL and 236 patients with NHL as well as 348 and 952 cancer-free controls, respectively. Multivariable-adjusted logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) estimating the association between physical inactivity and lymphoma risk. Results We observed significant, positive associations between lifetime recreational physical inactivity and risk of both HL (OR = 1.90, 95% CI: 1.15–3.15) and NHL (OR = 1.35, 95% CI: 1.01–1.82). Conclusions The current analysis provides evidence for a positive association between physical inactivity and risk of both HL and NHL. These results add to a growing body of research suggesting that lifetime physical inactivity may be an important independent, modifiable behavioral risk factor for cancer.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.014
      Issue No: Vol. 69 (2018)
       
  • Lenalidomide treatment in lower risk myelodysplastic syndromes—The
           experience of a Czech hematology center. (Positive effect of
           erythropoietin ± prednisone addition to lenalidomide in refractory or
           relapsed patients)
    • Authors: Anna Jonasova; Radana Neuwirtova; Helena Polackova; Magda Siskova; Tomas Stopka; Eduard Cmunt; Monika Belickova; Alena Moudra; Lubomir Minarik; Ota Fuchs; Kyra Michalova; Zuzana Zemanova
      Pages: 12 - 17
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): Anna Jonasova, Radana Neuwirtova, Helena Polackova, Magda Siskova, Tomas Stopka, Eduard Cmunt, Monika Belickova, Alena Moudra, Lubomir Minarik, Ota Fuchs, Kyra Michalova, Zuzana Zemanova
      Lenalidomide therapy represents meaningful progress in the treatment of anemic patients with myelodysplastic syndromes with del(5q). We present our initial lenalidomide experience and the positive effect of combining erythropoietin and steroids with lenalidomide in refractory and relapsed patients. We treated by lenalidomide 55 (42 female; 13 male; median age 69) chronically transfused lower risk MDS patients with del(5q) (45) and non-del(5q) (10). Response, meaning transfusion independence (TI) lasting ≥ eight weeks, was achieved in 38 (90%) of analyzed patients with del(5q), of whom three achieved TI only by adding erythropoietin ± prednisone. Another five patients responded well to this combination when their anemia relapsed later during the treatment. In the non-del(5q) group only one patient with RARS-T reached TI. Cytogenetic response was reached in 64% (32% complete, 32% partial response). The TP53 mutation was detected in 7 (18%) patients; four patients progressed to higher grade MDS or acute myeloid leukemia (AML). All seven RAEB-1 patients cleared bone marrow blasts during lenalidomide treatment and reached complete remission (CR); however, three later progressed to higher grade MDS or AML. Lenalidomide represents effective treatment for del(5q) group and combination with prednisone and erythropoietin may be used for non-responders or therapy failures.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.015
      Issue No: Vol. 69 (2018)
       
  • Prognostic factors for thrombosis-free survival and overall survival in
           polycythemia vera: A retrospective analysis of 623 PTS With long follow-up
           
    • Authors: Ambra Di Veroli; Francesco Buccisano; Alessandro Andriani; Marco Montanaro; Roberto Latagliata; Cristina Santoro; Massimo Breccia; Francesca Spirito; Michele Cedrone; Barbara Anaclerico; Sabrina Leonetti Crescenzi; Raffaele Porrini; Marianna De Muro; Giuseppe Avvisati; Agostino Tafuri; Giuseppe Cimino; Antonio Spadea
      Pages: 18 - 23
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): Ambra Di Veroli, Francesco Buccisano, Alessandro Andriani, Marco Montanaro, Roberto Latagliata, Cristina Santoro, Massimo Breccia, Francesca Spirito, Michele Cedrone, Barbara Anaclerico, Sabrina Leonetti Crescenzi, Raffaele Porrini, Marianna De Muro, Giuseppe Avvisati, Agostino Tafuri, Giuseppe Cimino, Antonio Spadea


      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.016
      Issue No: Vol. 69 (2018)
       
  • Secreted Wnt antagonists in leukemia: A road yet to be paved
    • Authors: Melek Pehlivan; Ceyda Çalışkan; Zeynep Yüce; Hakki Ogun Sercan
      Pages: 24 - 30
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): Melek Pehlivan, Ceyda Çalışkan, Zeynep Yüce, Hakki Ogun Sercan
      Wnt signaling has been a topic of research for many years for its diverse and fundamental functions in physiological (such as embryogenesis, organogenesis, proliferation, tissue repair and cellular differentiation) and pathological (carcinogenesis, congenital/genetic diseases, and tissue degeneration) processes. Wnt signaling pathway aberrations are associated with both solid tumors and hematological malignancies. Unregulated Wnt signaling observed in malignancies may be due to a wide spectrum of abnormalities, from mutations in the genes of key players to epigenetic modifications of Wnt antagonists. Of these, Wnt antagonists are gaining significant attention for their potential of being targets for treatment and inhibition of Wnt signaling. In this review, we discuss and summarize the significance of Wnt signaling antagonists in the pathogenesis and treatment of hematological malignancies.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.011
      Issue No: Vol. 69 (2018)
       
  • Inhibition of NAMPT sensitizes MOLT4 leukemia cells for etoposide
           treatment through the SIRT2-p53 pathway
    • Authors: Theresa Grohmann; Melanie Penke; Stefanie Petzold-Quinque; Susanne Schuster; Sandy Richter; Wieland Kiess; Antje Garten
      Pages: 39 - 46
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): Theresa Grohmann, Melanie Penke, Stefanie Petzold-Quinque, Susanne Schuster, Sandy Richter, Wieland Kiess, Antje Garten
      NAMPT (Nicotinamide phosphoribosyltransferase) catalyses the rate-limiting step in the NAD biosynthesis from nicotinamide and thereby regulates the activity of NAD-dependent enzymes. Cancer cells are highly dependent on NAD for energy and DNA repair processes and are assumed to be more susceptible to an inhibition of NAD synthesis than non-transformed cells. We aimed to investigate whether or not inhibition of NAMPT with its specific inhibitor FK866 can sensitize leukemia cells for chemotherapeutic agents. NAMPT protein abundance, enzymatic activity and NAD concentrations were significantly higher in Jurkat and Molt-4 leukemia cell lines compared to normal peripheral blood mononuclear cells. Combination of etoposide and FK866 caused increased cell death in leukemia cell lines compared to etoposide alone. Etoposide decreased protein abundance of NAD-dependent deacetylases SIRTUIN1. After combining etoposide and FK866 treatment SIRTUIN2 was further decreased and accumulation and acetylation of the downstream target p53 was further enhanced in MOLT4 cells. Concomitantly, protein abundance of p21 and cleaved BAX was increased. Targeting NAMPT could be a novel therapeutic strategy to enhance the efficacy of chemotherapeutic agents such as etoposide against leukemia.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.04.004
      Issue No: Vol. 69 (2018)
       
  • New rapid method to detect BCR-ABL fusion genes with multiplex RT-qPCR in
           one-tube at a time
    • Authors: Yong-Qing Tong; Zhi-Jun Zhao; Bei Liu; An-Yu Bao; Hong-Yun Zheng; Jian Gu; Ying Xia; Mary McGrath; Sinisa Dovat; Chun-Hua Song; Yan Li
      Pages: 47 - 53
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): Yong-Qing Tong, Zhi-Jun Zhao, Bei Liu, An-Yu Bao, Hong-Yun Zheng, Jian Gu, Ying Xia, Mary McGrath, Sinisa Dovat, Chun-Hua Song, Yan Li
      Fast identification of BCR-ABL fusion genes is critical for precise diagnosis, risk stratification and therapy scheme selection in leukemia. More convenient methods are needed for quickly detection of the BCR-ABL fusion genes. Multiplex fluorescent reverse transcription quantitative real-time PCR (Multiplex RT-qPCR) methods are developed for detection of the at least 14 subtypes of BCR-ABL fusion genes in one tube at a time by using patients’ bone marrow samples. The new Multiplex RT-qPCR method could quickly detect BCR-ABL fusion genes with sensitivity up to 10–106 copies. It can detect the fusion genes in patients’ bone marrow samples containing any subtypes of the major bcr (M-bcr) e13a2, e14a2, e13a3 and e14a3, the minor bcr (m-bcr) e1a2 and e1a3, the micro bcr (μ-bcr) e19a2 and e19a3, and the nano bcr (n-bcr) e6a2 and e6a3. The specificity is comparable to the FISH methods. The cutoff for clinical diagnosis of BCR-ABL(+) is also determined by testing in clinical chronic myeloid leukemia samples. This is a new fast method with high sensitivity and specificity for clinical detection of BCR-ABL fusion genes. It will benefit the precise diagnosis, targeted therapy and minimal residual disease (MRD) monitoring in leukemia.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.04.001
      Issue No: Vol. 69 (2018)
       
  • Inter-observer variance and the need for standardization in the
           morphological classification of myelodysplastic syndrome
    • Authors: Keiko Sasada; Noriko Yamamoto; Hiroki Masuda; Yoko Tanaka; Ayako Ishihara; Yasushi Takamatsu; Yutaka Yatomi; Waichiro Katsuda; Issei Sato; Hirotaka Matsui
      Pages: 54 - 59
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): Keiko Sasada, Noriko Yamamoto, Hiroki Masuda, Yoko Tanaka, Ayako Ishihara, Yasushi Takamatsu, Yutaka Yatomi, Waichiro Katsuda, Issei Sato, Hirotaka Matsui
      In this era of genome medicine, the sub-classification of myeloid neoplasms, including myelodysplastic syndrome (MDS), is now supported by genetic testing in selected cases. However, as the initial suspicion and primary diagnosis of the disease still largely relies on morphological features and numbers of hematopoietic cells, the establishment of a uniform diagnostic basis, especially for cell morphology, is essential. In this study, we collected nearly 100,000 hematopoietic cell images from 499 peripheral blood smear specimens from patients with MDS and used these to evaluate the standardization of morphological classification by medical technologists. The observers in this study ranged between two to eleven for each image, and the images were classified according to MDS criteria through a web-based system. We found considerable inter-observer variance in the assessment of dysplastic features. Observers did not recognize cytoplasmic hypo–granularity unless almost all granules in neutrophils were absent. Pseudo Pelger–Huët anomalies were also often overlooked, except for cells with a very typical “pince-nez” appearance. Taken together, this study suggests a requirement for further standardization in terms of morphological cell classification, and a need for the development of automatic cell classification–supporting devices for the accurate diagnosis of MDS.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.04.003
      Issue No: Vol. 69 (2018)
       
  • Effect of absolute monocyte count post-transplant on the outcome of
           patients with acute myeloid leukemia undergoing myeloablative allogeneic
           hematopoietic stem cell transplant with busulfan and cyclophosphamide
           conditioning
    • Authors: Liyuan Tang; Na Wang; Chongyun Xing; Qiang Zhuang; Bin Liang; Lan Sun; Yi Chen; Yan Qian; Zhijian Shen; Songfu Jiang; Kang Yu; Jianhua Feng
      Pages: 60 - 65
      Abstract: Publication date: June 2018
      Source:Leukemia Research, Volume 69
      Author(s): Liyuan Tang, Na Wang, Chongyun Xing, Qiang Zhuang, Bin Liang, Lan Sun, Yi Chen, Yan Qian, Zhijian Shen, Songfu Jiang, Kang Yu, Jianhua Feng
      Peripheral monocytes have recently been evaluated as a prognostic factor in different types of hematological malignancies. This study assessed the prognostic value of absolute monocyte count (AMC) post-transplant on the clinical outcomes of 59 patients with acute myeloid leukemia (AML) who had undergone myeloablative conditioning (MAC) allogeneic hematopoietic stem cell transplant (allo-HSCT) with busulfan and cyclophosphamide (Bu/Cy). Kaplan-Meier analysis showed that patients with a high AMC (≥ 0.57 × 109/L) on post-transplant day (PTD) 15 had a significantly worse overall survival (OS) compared to patients with a low AMC (< 0.57 × 109/L) on PTD 15 (P = .0049). Univariate Cox proportional hazard analyses revealed that only high AMC on PTD 15 was a poor prognostic factor for OS (P = .008) and post-relapse survival (P = .030). We conclude that AMC ≥ 0.57 × 109/L on PTD 15 is associated with more deaths in patients with AML who have undergone MAC allo-HSCT with Bu/Cy.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.04.006
      Issue No: Vol. 69 (2018)
       
  • Enhanced perforin expression associated with dasatinib therapy in natural
           killer cells
    • Authors: Noriyoshi Iriyama; Hiromichi Takahashi; Katsuhiro Miura; Yoshihito Uchino; Masaru Nakagawa; Yoshihiro Hatta; Masami Takei
      Pages: 1 - 8
      Abstract: Publication date: Available online 24 February 2018
      Source:Leukemia Research
      Author(s): Noriyoshi Iriyama, Hiromichi Takahashi, Katsuhiro Miura, Yoshihito Uchino, Masaru Nakagawa, Yoshihiro Hatta, Masami Takei
      We investigated the effects of dasatinib on natural killer (NK) cell-induced signaling protein and perforin expression as well as plasma cytokine levels by analyzing blood samples from patients with well-controlled chronic myeloid leukemia receiving tyrosine kinase inhibitor (TKI) therapy. Perforin expression and phosphorylation of signal transducer and activator of transcription (STAT) 1, STAT3, Janus kinase (JAK) 1, and JAK2 in NK cells were evaluated by flow cytometry, and the levels of plasma cytokines, including interferon (IFN)-γ and interleukin (IL)-2, were determined by enzyme-linked immunosorbent assays in 40 patients (dasatinib, n = 23; imatinib, n = 11; and nilotinib, n = 6). Perforin levels in NK cells were higher in dasatinib-treated patients before TKI treatment; phospho (p)-STAT1 levels were closely correlated with pJAK1 and perforin levels, and pSTAT3 levels were correlated with pJAK2 and perforin levels. The correlation between pJAK1 and pSTAT1 was apparent in dasatinib-treated patients but not in other TKI-treated patients, and the correlation between pJAK2 and pSTAT3 was apparent in patients treated with other TKIs. Constitutive expression of IFN-γ was higher in patients treated with dasatinib or with other TKIs than in those who were in treatment-free remission (TFR). In contrast, constitutive expression of IL-2 was lower in patients treated with other TKIs than in those treated with dasatinib or in those who were in TFR. These results provided insights into the effects of dasatinib on JAK/STAT signaling in NK cells in vivo and the mechanisms underlying NK cell activation induced by dasatinib therapy.

      PubDate: 2018-02-25T22:28:30Z
      DOI: 10.1016/j.leukres.2018.02.014
      Issue No: Vol. 68 (2018)
       
  • ZFP36L2, a novel AML1 target gene, induces AML cells apoptosis and
           inhibits cell proliferation
    • Authors: Jia Liu; Wenting Lu; Shuang Liu; Ying Wang; Saisai Li; Yingxi Xu; Haiyan Xing; Kejing Tang; Zheng Tian; Qing Rao; Min Wang; Jianxiang Wang
      Pages: 15 - 21
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Jia Liu, Wenting Lu, Shuang Liu, Ying Wang, Saisai Li, Yingxi Xu, Haiyan Xing, Kejing Tang, Zheng Tian, Qing Rao, Min Wang, Jianxiang Wang
      The t(8;21)(q22;q22) translocation generated the fusion protein AML1-ETO. AML1-ETO recruits histone deacetylase (HDAC) complex via its ETO part to repress AML1-mediated transactivation. Our previous study demonstrated that HDAC inhibitor phenylbutyrate (PB) could induce AML1-ETO positive leukemia cell line Kasumi-1 cells to undergo differentiation and apoptosis accompanied by significant changes in gene expression profile. ZFP36L2 was one of the up-regulated genes in Kasumi-1 cells induced by PB treatment. In this study, ZFP36L2 was found to express at a lower level in acute myeloid leukemia (AML) patients with t(8;21) compared to AML patients without t(8;21). In order to investigate the correlation between the expression of ZFP36L2 and AML1 or AML1-ETO, the putative AML1 binding sites in the enhancer/promoter region of ZFP36L2 gene were predicted through the bioinformatics analysis. And the biological function of ZFP36L2 in leukemic cells was further investigated. The results demonstrated that AML1 could transactivate ZFP36L2 significantly by binding on specific site of the ZFP36L2 promoter sequence. And overexpression of ZFP36L2 in leukemia cells could inhibit the cell proliferation, promote cell-cycle arrest in G0/G1 phase and induce the cell apoptosis. In conclusion, ZFP36L2 could be transactivated by AML1, which subsequently induced cell-cycle arrest and apoptosis of leukemia cells.

      PubDate: 2018-03-07T13:58:48Z
      DOI: 10.1016/j.leukres.2018.02.017
      Issue No: Vol. 68 (2018)
       
  • Early preemptive ICU admission for newly diagnosed high-risk acute myeloid
           leukemia patients
    • Authors: Colombe Saillard; Elodie Elkaim; Jerome Rey; Evelyne d’Incan; Aude Charbonnier; Anne Etienne; Antoine Sannini; Laurent Chow-Chine; Magali Bisbal; Norbert Vey; Djamel Mokart
      Pages: 29 - 31
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Colombe Saillard, Elodie Elkaim, Jerome Rey, Evelyne d’Incan, Aude Charbonnier, Anne Etienne, Antoine Sannini, Laurent Chow-Chine, Magali Bisbal, Norbert Vey, Djamel Mokart


      PubDate: 2018-03-07T13:58:48Z
      DOI: 10.1016/j.leukres.2018.02.015
      Issue No: Vol. 68 (2018)
       
  • An autologous tumor vaccine for CLL
    • Authors: Fang Zhu; Ismat Khatri; David Spaner; Reginald M. Gorczynski
      Pages: 40 - 47
      Abstract: Publication date: Available online 2 March 2018
      Source:Leukemia Research
      Author(s): Fang Zhu, Ismat Khatri, David Spaner, Reginald M. Gorczynski
      Chronic Lymphocytic Leukemia B cells (CLL) are malignant cells which retain at least some functions of normal B cells. Paramount amongst the latter is that when such cells are appropriately stimulated, they are able to present antigens, including any potential tumor antigens, making them excellent choices as a candidate tumor vaccine. We show that following stimulation of CLL cells with Phorbol myristic acetate, IL-2, the TLR7 agonist imiquimod (P2I) and ionomycin (P2Iio), markedly increased expression of CD54 and CD83 was seen, indicative of B cell activation and a transition to antigen-presenting cells. However, this occurred in the context of augmented expression of the known immunoregulatory molecule, CD200. Accordingly we explored the effect of stimulation of CLL cells with P2Iio, followed by coating of cells with a non-depleting anti-CD200mAb, on the ability of those cells to immunize PBL in vitro to become cytotoxic to CLL cells, or to protect NOD-SCIDγcnull (NSG) mice from subsequent CLL tumor challenge. Our data indicate that this protocol is effective in inducing CD8+ CTL able to lyse CLL cells in vitro, and decrease tumor burden in vivo in spleen and marrow of mice injected with CLL cells. Pre-treatment of mice with a CD8 depleting antibody before vaccination with P2Iio/anti-CD200 coated cells abolished any protection seen. These data suggest a potential role for blockade of CD200 expression on CLL cells as a component of a tumor vaccination strategy.

      PubDate: 2018-03-07T13:58:48Z
      DOI: 10.1016/j.leukres.2018.03.002
      Issue No: Vol. 68 (2018)
       
  • Comparison of anthracyclines used for induction chemotherapy in patients
           with FLT3-ITD-mutated acute myeloid leukemia
    • Authors: Eun-Ji Choi; Je-Hwan Lee; Jung-Hee Lee; Han-Seung Park; Sun-Hye Ko; Eun-Hye Hur; Juhyun Moon; Bon-Kwan Goo; Yeonhee Kim; Miee Seol; Young-Shin Lee; Young-Ah Kang; Mijin Jeon; Ji Min Woo; Kyoo-Hyung Lee
      Pages: 51 - 56
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Eun-Ji Choi, Je-Hwan Lee, Jung-Hee Lee, Han-Seung Park, Sun-Hye Ko, Eun-Hye Hur, Juhyun Moon, Bon-Kwan Goo, Yeonhee Kim, Miee Seol, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Ji Min Woo, Kyoo-Hyung Lee
      This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90 mg/m2/d × 3d; n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m2/d × 3d; n = 51), or idarubicin (IDA; 12 mg/m2/d × 3d; n = 33) in combination with cytarabine (100–200 mg/m2/d × 7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2 days of daunorubicin (45 mg/m2/d) or IDA (8 or 12 mg/m2/d) in addition to 5 days of cytarabine. Complete remission (CR) rates were 77.3%, 56.9%, and 69.7% for HD-DN, SD-DN, and IDA, respectively (P = 0.101; HD-DN vs. SD-DN, P = 0.036; HD-DN vs. IDA, P = 0.453; IDA vs. SD-DN, P = 0.237). The HD-DN showed higher overall survival (OS) and event-free survival (EFS) than SD-DN and IDA: the differences between HD-DN and SD-DN (P = 0.009 for OS and P = 0.010 for EFS) were statistically significant. Results of in vitro studies using FLT3-ITD-mutated cell lines supported these findings. In conclusion, HD-DN improved the CR rate, OS, and EFS of FLT3-ITD-mutated AML patients. HD-DN also tended to yield better outcomes than IDA, though the difference was not significant. The superiority of HD-DN over IDA should be confirmed in future studies.

      PubDate: 2018-03-19T14:51:36Z
      DOI: 10.1016/j.leukres.2018.03.006
      Issue No: Vol. 68 (2018)
       
  • Safety and efficacy of the CD95-ligand inhibitor asunercept in
           transfusion-dependent patients with low and intermediate risk MDS
    • Authors: Tobias Boch; Thomas Luft; Georgia Metzgeroth; Maximilian Mossner; Johann-Christoph Jann; Daniel Nowak; Franziska La Meir; Christiane Schumann; Jennifer Klemmer; Susanne Brendel; Harald Fricke; Claudia Kunz; Christel Weiß; Wolf-Karsten Hofmann; Florian Nolte
      Pages: 62 - 69
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Tobias Boch, Thomas Luft, Georgia Metzgeroth, Maximilian Mossner, Johann-Christoph Jann, Daniel Nowak, Franziska La Meir, Christiane Schumann, Jennifer Klemmer, Susanne Brendel, Harald Fricke, Claudia Kunz, Christel Weiß, Wolf-Karsten Hofmann, Florian Nolte
      In low risk MDS, increased apoptosis of erythroid progenitors mediated via CD95 (Fas) activation has been described to result in peripheral cytopenia. Blockade of the CD95 system can improve erythropoiesis in MDS. Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1 blocking the interaction between CD95 and its ligand. Here we report on results from a phase I study in 20 transfusion-dependent low and intermediate risk MDS patients treated with intravenous asunercept (EudraCT 2012-003027-37). Primary objectives were safety and tolerability as well as pharmacodynamic effects. Secondary objectives were hematologic improvement, incidence and time to leukemic progression as well as overall survival. Frequency and severity of adverse events were in range of what could be expected in a patient cohort comprising of elderly MDS patients. Two patients experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low. In the 20 patients a decrease of the transfusion need from a mean of 10,8 (±5,1) pRBCs during the 12 weeks treatment phase to a mean of 10,0 (±4,2) pRBCs at the end of the study was observed. In conclusion, asunercept was well tolerated and showed efficacy in transfusion-dependent low and intermediate risk MDS patients. Further clinical investigation is warranted, particularly in combination with erythropoiesis stimulating agents (ESAs).

      PubDate: 2018-03-19T14:51:36Z
      DOI: 10.1016/j.leukres.2018.03.007
      Issue No: Vol. 68 (2018)
       
  • Comparison of intensive, pediatric-inspired therapy with non-intensive
           therapy in older adults aged 55–65 years with Philadelphia
           chromosome-negative acute lymphoblastic leukemia
    • Authors: Josep-Maria Ribera; Olga García; Cristina Gil; Santiago Mercadal; Irene García-Cadenas; Pau Montesinos; Pere Barba; Susana Vives; José González-Campos; Mar Tormo; Jordi Esteve; Aurelio López; María José Moreno; Jordi Ribera; Natalia Alonso; Arancha Bermúdez; María Luz Amigo; Eulàlia Genescà; Daniel García; Ferran Vall-Llovera; Juan Miguel Bergua; Ramon Guàrdia; María Carmen Monteserín; Teresa Bernal; María Calbacho; María Pilar Martínez; Evarist Feliu
      Pages: 79 - 84
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Josep-Maria Ribera, Olga García, Cristina Gil, Santiago Mercadal, Irene García-Cadenas, Pau Montesinos, Pere Barba, Susana Vives, José González-Campos, Mar Tormo, Jordi Esteve, Aurelio López, María José Moreno, Jordi Ribera, Natalia Alonso, Arancha Bermúdez, María Luz Amigo, Eulàlia Genescà, Daniel García, Ferran Vall-Llovera, Juan Miguel Bergua, Ramon Guàrdia, María Carmen Monteserín, Teresa Bernal, María Calbacho, María Pilar Martínez, Evarist Feliu
      Background and objective The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55–65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients. Patients and methods The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07). Results Baseline patient and ALL characteristics were similar in both groups, except for a younger median age in the intensive group (medians: 58 vs. 62 years). Patients treated intensively had a higher complete remission rate (85% vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% [95%CI, 25% to 52%] vs. 60% [95%CI, 38% to 77%], p = .003), a similar cumulative incidence of treatment-related mortality (28% [95% CI, 18%, 40%] vs. 21% [95% CI, 10%, 34%]) and superior event-free survival at 2 years (37% [95%CI, 25%–49%) vs. 21% [8%-34%], p = 0.002). On multivariable analysis the type of protocol was the only variable with independent significance for event-free survival (HR [95% CI]: 2 [1.3, 3], p = .002). Conclusions Compared with less intensive chemotherapy, pediatric-inspired intensive chemotherapy significantly improves the outcome of older adults with Ph-negative ALL in the age range of 55–65 years.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.010
      Issue No: Vol. 68 (2018)
       
  • High frequency of dicentric chromosomes detected by multi-centromeric FISH
           in patients with acute myeloid leukemia and complex karyotype
    • Authors: Iveta Sarova; Jana Brezinova; Zuzana Zemanova; Sarka Ransdorfova; Karla Svobodova; Silvia Izakova; Lenka Pavlistova; Libuse Lizcova; Adela Berkova; Karolina Skipalova; Lucie Hodanova; Cyril Salek; Anna Jonasova; Kyra Michalova
      Pages: 85 - 89
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Iveta Sarova, Jana Brezinova, Zuzana Zemanova, Sarka Ransdorfova, Karla Svobodova, Silvia Izakova, Lenka Pavlistova, Libuse Lizcova, Adela Berkova, Karolina Skipalova, Lucie Hodanova, Cyril Salek, Anna Jonasova, Kyra Michalova
      Dicentric chromosomes (DCs) are considered markers of cancer in various malignancies. However, they can be overlooked when conventional analysis or multicolor fluorescence in situ hybridization (mFISH) is used to detect complex karyotypes. We analyzed the karyotypes of 114 patients with acute myeloid leukemia (AML) and complex karyotypes and verified the presence of monosomies by FISH using multi-centromeric probes. Monosomy was detected in 63% of patients by G-banding/mFISH and confirmed in 55% of patients by centromeric FISH. FISH analysis indicated a high frequency of DCs that were previously considered monosomies. In some cases, it was apparent that the derivative monocentric chromosome was a primary DC. DCs were formed mostly by chromosomes 17 and 20. In conclusion, chromosome loss and unbalanced translocation suggest the presence of a hidden DC or its previous existence. DCs undergo several stabilizing changes and can induce other chromosomal aberrations and/or the formation of new DCs. This can result in the clonal evolution of abnormal cells, which is considered an independent prognostic marker of an unfavorable disease course and short survival.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.009
      Issue No: Vol. 68 (2018)
       
  • New synergistic combinations of differentiation-inducing agents in the
           treatment of acute promyelocytic leukemia cells
    • Authors: Amir Amanzadeh; Vahid Molla-kazemiha; Saeed Samani; Mahdi Habibi-Anbouhi; Kayhan Azadmanesh; Mohsen Abolhassani; Mohammad Ali Shokrgozar
      Pages: 98 - 104
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Amir Amanzadeh, Vahid Molla-kazemiha, Saeed Samani, Mahdi Habibi-Anbouhi, Kayhan Azadmanesh, Mohsen Abolhassani, Mohammad Ali Shokrgozar
      Acute promyelocytic leukemia (APL) was considered to be one of the most lethal forms of leukemia in adults before the introduction of the vitamin A metabolite all-trans retinoic acid (ATRA). Surprisingly, it has been confirmed that FICZ (6-Formylindolo (3, 2-b) carbazole) enhances ATRA-induced differentiation. Moreover, a number of studies have demonstrated that anti CD44 monoclonal antibody (mAb) induces to bring back differentiation blockage the leukemic stem cells. The level of differentiation markers including CD11b and CD11c in NB4 cells was assessed by flow cytometry. The induction of apoptosis was also evaluated. We estimated the induction potential of a triple compound of ATRA-FICZ, anti-CD44 maps. The cells showed the gradually increased expression levels of CD11b and CD11c. A mixture of a “CD44 mAb, ATRA and FICZ effectively promoted granulocytic maturation resulting in increased rates of apoptosis. The differences in expression of CD11b and CD11c at 5 μg/ml and 10 μg/ml were significant. These phenomena were highest at 10 μg/ml CD44 mAb concentrations. Synergistic induction differentiation and apoptosis of APL cells by using a co-treatment with novel triple compound are more effective for eradicating blasts and controlling the metastasis. Our results show that the addition of anti-CD44 mAb improves “ATRA-FICZ”-induced differentiation and has potential to reduce usual chemotherapy based treatments. Taken together, this compound may lead to novel clinical applications of differentiation-based approaches for APL and other types of leukemia. Further clinical studies would be recommended to clarify the clinical efficacy.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.01.007
      Issue No: Vol. 68 (2018)
       
  • Reactive oxygen species activate differentiation gene transcription of
           acute myeloid leukemia cells via the JNK/c-JUN signaling pathway
    • Authors: Chung Fan Lam; Hoi Ting Yeung; Yuk Man Lam; Ray Kit Ng
      Pages: 112 - 119
      Abstract: Publication date: May 2018
      Source:Leukemia Research, Volume 68
      Author(s): Chung Fan Lam, Hoi Ting Yeung, Yuk Man Lam, Ray Kit Ng
      Reactive oxygen species (ROS) and altered cellular redox status are associated with many malignancies. Acute myeloid leukemia (AML) cells are maintained at immature state by differentiation blockade, which involves deregulation of transcription factors in myeloid differentiation. AML cells can be induced to differentiate by phorbol-12-myristate-13-acetate (PMA), which possesses pro-oxidative activity. However, the signaling events mediated by ROS in the activation of transcriptional program during AML differentiation has not been fully elucidated. Here, we investigated AML cell differentiation by treatment with PMA and ROS scavenger N-acetyl-l-cysteine (NAC). We observed elevation of intracellular ROS level in the PMA-treated AML cells, which correlated with differentiated cell morphology and increased CD11b+ mature cell population. The effect of PMA can be abolished by NAC co-treatment, supporting the involvement of ROS in the process. Moreover, we demonstrated that short ROS elevation mediated cell cycle arrest, but failed to activate myeloid gene transcription; whereas prolonged ROS elevation activated JNK/c-JUN signaling pathway. Inhibition of JNK suppressed the expression of key myeloid transcriptional regulators c-JUN, SPI-1 and MAFB, and prevented AML cells from undergoing terminal differentiation. These findings provide new insights into the crucial role of JNK/c-Jun signaling pathway in the activation of transcriptional program during ROS-mediated AML differentiation.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.012
      Issue No: Vol. 68 (2018)
       
  • Allogeneic hematopoietic cell transplantation in T-cell prolymphocytic
           leukemia: A single-center experience
    • Authors: Bhagirathbhai R. Dholaria; Ernesto Ayala; Lubomir Sokol; Taiga Nishihori; Julio C. Chavez; Mohammad Hussaini; Ambuj Kumar; Mohamed A. Kharfan-Dabaja
      Pages: 1 - 5
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Bhagirathbhai R. Dholaria, Ernesto Ayala, Lubomir Sokol, Taiga Nishihori, Julio C. Chavez, Mohammad Hussaini, Ambuj Kumar, Mohamed A. Kharfan-Dabaja
      Background T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and improve survival, but data is limited. Patients and methods We evaluated clinical outcomes of 11 patients, median age of 56 (range, 43–71) years who underwent allo-HCT for T-PLL. The majority of cases were in the first complete remission (CR1 = 9, CR2 = 1, second partial response PR2 = 1) at time of allo-HCT. Myeloablative conditioning was the most commonly prescribed preparative regimen (n = 8, 73%) and tacrolimus plus sirolimus was most commonly prescribed regimen for graft-versus-host disease prophylaxis (n = 5, 46%). Results The median follow-up for surviving patients was 48 (range, 6–123) months. The 4-year progression-free survival (PFS) and overall survival (OS) were 45% (95% confidence interval (CI) = 13–78%) and 56% (95% CI = 24–89%), respectively. Cumulative incidence of non-relapse mortality (NRM) at 4-year post-transplantation was 34% (95%CI = 14–85%). The 4-year cumulative incidence of relapse/progression was 21% (95% CI = 6–71%). Conclusion Allo-HCT is an effective treatment for T-PLL. Patients must be evaluated for their candidacy for allo-HCT as soon as the diagnosis is confirmed. Efforts are needed to decrease NRM and relapse.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.01.009
      Issue No: Vol. 67 (2018)
       
  • Prognostic significance of The Wilms’ Tumor-1 (WT1) rs16754 polymorphism
           in acute myeloid leukemia
    • Authors: Jessica Petiti; Valentina Rosso; Marco Lo Iacono; Chiara Calabrese; Elisabetta Signorino; Valentina Gaidano; Massimo Berger; Giuseppe Saglio; Daniela Cilloni
      Pages: 6 - 11
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Jessica Petiti, Valentina Rosso, Marco Lo Iacono, Chiara Calabrese, Elisabetta Signorino, Valentina Gaidano, Massimo Berger, Giuseppe Saglio, Daniela Cilloni
      Acute myeloid leukemia is a genetically heterogeneous disease characterized by the accumulation of mutations in hematopoietic progenitor cells. For its heterogeneity, prognostic markers are very useful for therapeutic choice. The most important prognostic markers are age, white blood cell count, chromosomal alterations and gene mutations. Recent works have studied the prognostic significance of WT1 polymorphisms and mutations, highlighting the role of SNP rs16754 as a positive prognostic factor in AML patients. Nevertheless, the data are still unclear. To investigate the role of WT1 rs16754 polymorphism in AML, we designed a new tool for the detection using PNA directed PCR Clamping technology. Our data were able to establish a correlation between SNP rs16754 and the clinical outcome. Our results support the hypothesis that rs16754 polymorphism is an independent positive prognostic molecular marker that could be useful for therapeutic choice. In view of this, we described a novel assay faster, more sensitive and cheaper than DNA sequencing. The assay allows evaluating WT1 rs16754 polymorphism in diagnostic routine to improve prognostic information faster and without over-costing for diagnostic laboratories.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.01.016
      Issue No: Vol. 67 (2018)
       
  • Report of the relapsed/refractory cohort of SWOG S0919: A phase 2 study of
           idarubicin and cytarabine in combination with pravastatin for acute
           myelogenous leukemia (AML)
    • Authors: Anjali S. Advani; Hongli Li; Laura C. Michaelis; Bruno C. Medeiros; Michaela Liedtke; Alan F. List; Kristen O’Dwyer; Megan Othus; Harry P. Erba; Frederick R. Appelbaum
      Pages: 17 - 20
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Anjali S. Advani, Hongli Li, Laura C. Michaelis, Bruno C. Medeiros, Michaela Liedtke, Alan F. List, Kristen O’Dwyer, Megan Othus, Harry P. Erba, Frederick R. Appelbaum
      Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukemia (AML) blasts to chemotherapy. A Phase 2 study of high dose pravastatin given in combination with idarubicin and cytarabine demonstrated an impressive response rate [75% complete remission (CR), CR with incomplete count recovery (CRi)]. However, this population was a favorable risk group as eligible patients had to have a CR/CRi lasting ≥3 months following their most recent chemotherapy. Therefore, the study was amended to treat patients with poor risk disease including those with CR/CRi <6 months following their last induction regimen or with refractory disease. Here, we present results in this poor risk group. This trial included a significant number of patients with poor risk cytogenetics (43%) and poor risk molecular mutations. The response rate was 30% and approximately one-fourth of patients were able to proceed to allogeneic hematopoietic stem cell transplant (HSCT). The median overall survival for patients proceeding to allogeneic HSCT is 27.1 months. Although this trial did not meet criteria for a positive study based on the response rate (p = .062), these results are encouraging given the poor risk population and suggest that targeting the cholesterol pathway may have therapeutic benefit in AML.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.01.021
      Issue No: Vol. 67 (2018)
       
  • Prognostic impact of a suboptimal number of analyzed metaphases in normal
           karyotype lower-risk MDS
    • Authors: Louise de Swart; Alex Smith; Detlef Haase; Pierre Fenaux; Argiris Symeonidis; Jaroslav Cermak; Guillermo Sanz; Reinhard Stauder; Moshe Mittelman; Eva Hellström-Lindberg; Luca Malcovati; Saskia Langemeijer; Mette Skov-Holm; Krzysztof Mądry; Ulrich Germing; Antonio Medina Almeida; Aurelia Tatic; Aleksandar Savic; Njetočka Gredelj Šimec; Corine van Marrewijk; Agnes Guerci-Bresler; Laurence Sanhes; Elisa Luño; Dominic Culligan; Odile Beyne-Rauzy; Sonja Burgstaller; Nicole Blijlevens; David Bowen; Theo de Witte
      Pages: 21 - 26
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Louise de Swart, Alex Smith, Detlef Haase, Pierre Fenaux, Argiris Symeonidis, Jaroslav Cermak, Guillermo Sanz, Reinhard Stauder, Moshe Mittelman, Eva Hellström-Lindberg, Luca Malcovati, Saskia Langemeijer, Mette Skov-Holm, Krzysztof Mądry, Ulrich Germing, Antonio Medina Almeida, Aurelia Tatic, Aleksandar Savic, Njetočka Gredelj Šimec, Corine van Marrewijk, Agnes Guerci-Bresler, Laurence Sanhes, Elisa Luño, Dominic Culligan, Odile Beyne-Rauzy, Sonja Burgstaller, Nicole Blijlevens, David Bowen, Theo de Witte
      Conventional karyotype is one of the most relevant prognostic factors in MDS. However, about 50% of patients with MDS have a normal karyotype. Usually, 20–25 normal metaphases (nMP) are considered to be optimal to exclude small abnormal clones which might be associated with poor prognosis. This study evaluated the impact of examining a suboptimal number of metaphases in patients recruited to the EUMDS Registry with low and intermediate-1 risk according to IPSS. Only 179/1049 (17%) of patients with a normal karyotype had a suboptimal number of nMP, defined as less than 20 metaphases analyzed. The outcome (overall survival and progression-free survival) of patients with suboptimal nMP was not inferior to those with higher numbers of analyzed MP both in univariate and multivariate analyses. For patients with an abnormal karyotype, 224/649 (35%) had a suboptimal number of MP assessed, but this did not impact on outcome. For patients with a normal karyotype and suboptimal numbers of analyzable metaphases standard evaluation might be acceptable for general practice, but we recommend additional FISH-analyses or molecular techniques, especially in candidates for intensive interventions.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.01.022
      Issue No: Vol. 67 (2018)
       
  • Prognostic significance of SOX2, SOX3, SOX11, SOX14 and SOX18 gene
           expression in adult de novo acute myeloid leukemia
    • Authors: Natasa Tosic; Isidora Petrovic; Natasa Kovacevic Grujicic; Slobodan Davidovic; Marijana Virijevic; Nada Suvajdzic Vukovic; Sonja Pavlovic; Milena Stevanovic
      Pages: 32 - 38
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Natasa Tosic, Isidora Petrovic, Natasa Kovacevic Grujicic, Slobodan Davidovic, Marijana Virijevic, Nada Suvajdzic Vukovic, Sonja Pavlovic, Milena Stevanovic
      Aberrant expression of different SOX (SRY-related high mobility group (HMG) box) genes has been observed in number of tumors but, little is known about their expression patterns in hematological malignancies, especially in acute myeloid leukemia (AML). In this study we investigated SOX2, SOX3, SOX11, SOX14 and SOX18 gene expression in 50 de novo adult AML patients and correlated our findings with known clinical and molecular prognostic markers of the disease. We have found that these genes are overexpressed in 10–22% of patients and preliminary findings suggest that high expression level of these genes may have prognostic significance in AML patients. This is the first study focused on examining the expression level of SOX2, SOX3, SOX11, SOX14 and SOX18 genes in AML patients. Although this is a relatively limited study, initial findings indicate the need for further investigation of these genes, their potential roles in leukemia pathogenesis as well as prognosis in AML patients.

      PubDate: 2018-02-25T22:28:30Z
      DOI: 10.1016/j.leukres.2018.02.001
      Issue No: Vol. 67 (2018)
       
  • Pulmonary Langerhans cell histiocytosis, acute myeloid leukemia, and
           myelofibrosis in a large family and review of the literature
    • Authors: Matthew P. Blakley; Janice P. Dutcher; Peter H. Wiernik
      Pages: 39 - 44
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Matthew P. Blakley, Janice P. Dutcher, Peter H. Wiernik
      Background There is mounting evidence that Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are hematopoietic neoplasms that arise from the same myeloid precursor cell. In addition, studies suggest a relationship between LCH and primary idiopathic myelofibrosis (MF). Furthermore familial LCH, AML, and MF have each been reported. Methods We examined more than 750 pedigrees of familial hematologic malignancies for evidence of familial LCH, AML, and/or MF and identified one family with all three neoplasms, which is presented here. Findings In four generations of this large family there are five cases of AML in three generations, two cases of LCH in two generations and three cases of MF in two generations. Anticipation of −18 and −6 years was present in the patients with MF, and −8 years in the patients with LCH. Anticipation was also identified between one AML patient pair in generations III and IV (−18 years) and three patients with AML in generations II, III, and IV (−5 years and −10 years). Interpretation This is the first report of familial LCH, AML, and MF in one family. The pedigree suggests a common basis for these entities, which is further suggested by the presence of anticipation in the pedigree.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.01.011
      Issue No: Vol. 67 (2018)
       
  • PD-1 /PD-L1 checkpoint in hematological malignancies
    • Authors: O. Annibali; A. Crescenzi; V. Tomarchio; A. Pagano; A. Bianchi; A. Grifoni; G. Avvisati
      Pages: 45 - 55
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): O. Annibali, A. Crescenzi, V. Tomarchio, A. Pagano, A. Bianchi, A. Grifoni, G. Avvisati
      Programmed cell death protein 1 (PD-1), is a cell surface receptor with an important role in down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. PD-1/PDL1 axis represents a checkpoint to control immune responses and it is often used as a mechanism of immune escaping by cancers and infectious diseases. Many data demonstrate its important role in solid tumors and report emerging evidences in lymphoproliferative disorders. In this review, we summarized the available data on the role of PD-1/PD-L1 checkpoint in lymphoproliferative diseases and the therapeutics use of monoclonal blocking antibodies.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.01.014
      Issue No: Vol. 67 (2018)
       
  • Association of red cell distribution width with clinical outcomes in
           myelodysplastic syndrome
    • Authors: Yuta Baba; Bungo Saito; Shotaro Shimada; Yohei Sasaki; So Murai; Maasa Abe; Shun Fujiwara; Nana Arai; Yukiko Kawaguchi; Nobuyuki Kabasawa; Hiroyuki Tsukamoto; Yui Uto; Hirotsugu Ariizumi; Kouji Yanagisawa; Norimichi Hattori; Hiroshi Harada; Tsuyoshi Nakamaki
      Pages: 56 - 59
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Yuta Baba, Bungo Saito, Shotaro Shimada, Yohei Sasaki, So Murai, Maasa Abe, Shun Fujiwara, Nana Arai, Yukiko Kawaguchi, Nobuyuki Kabasawa, Hiroyuki Tsukamoto, Yui Uto, Hirotsugu Ariizumi, Kouji Yanagisawa, Norimichi Hattori, Hiroshi Harada, Tsuyoshi Nakamaki
      Studies showed red cell distribution width (RDW) can improve the detection of morphological changes in red blood cells and the understanding of their contribution to dyserythropoiesis in myelodysplastic syndrome (MDS). The purpose of the study was to evaluate dyserythropoiesis in MDS by RDW analysis and to explore the utility of RDW in clinical practice. We retrospectively analyzed laboratory and clinical data of 101 patients (59 patients was refractory anemia (RA) according to the French-American-British (FAB) classification). In patients with RA, RDW was showed weak inverse correlation with both hemoglobin concentration (Hb) (rs  = −0.37, P = 0.0035) and mean corpuscular hemoglobin concentration (MCHC) (rs  = −0.36, P = 0.0047). On the other hand, RDW was showed weak correlation with the number of ringed sideroblasts in bone marrow (rs  = 0.31, P = 0.023). The increased RDW (≥15.0%) was associated with shorter overall survival (OS) (P = 0.0086). In patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-t), effect of RDW on OS was less evident. These results suggested that increased RDW might reflect dyserythropoiesis, associated with deregulated hemoglobin synthesis and iron metabolism in MDS. Furthermore, increased RDW may have potential to be a prognostic significance in RA.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.02.004
      Issue No: Vol. 67 (2018)
       
  • The impact of the neutrophil:lymphocyte ratio in response and survival of
           patients with de novo diffuse large B-cell lymphoma
    • Authors: Brady E. Beltrán; Sally Paredes; Esther Cotrina; Eduardo M. Sotomayor; Jorge J. Castillo
      Pages: 82 - 85
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Brady E. Beltrán, Sally Paredes, Esther Cotrina, Eduardo M. Sotomayor, Jorge J. Castillo
      The neutrophil:lymphocyte ratio (NLR) has emerged as prognostic in patients with hematological malignancies. We aimed at evaluating the NLR as predictive for complete response (CR) and prognostic for progression-free (PFS) and overall survival (OS) in a study cohort of 121 Peruvian patients with diffuse large B-cell lymphoma (DLCBL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Patients with an NLR ≥6 (n = 28) were more likely to have a performance status ECOG ≥2 (74% vs. 23%; p < 0.001). NLR ≥6 was associated with lower CR rate to R-CHOP (46% vs. 74%; p = 0.02) and there was a trend towards significance in multivariate regression analyses (OR 0.36, 95% CI 0.11–1.00; p = 0.05). Patients with NLR ≥6 had lower 5-year PFS rate (39% vs. 72%; p < 0.001) and lower 5-year OS rate (46% vs. 75%; p = 0.001) than patients with NLR <6 and was an independent adverse factor for PFS (HR 2.43, 95% CI 1.21–4.87; p = 0.01) and OS (HR 2.68, 95% CI 1.31–5.47; p = 0.007) in multivariate Cox regression analyses. NLR ≥6 was prognostic of PFS and OS after adjusting for the International Prognostic Index and the NCCN-IPI scores. In conclusion, the NLR could add predictive and prognostic value to well established prognostic tools in DLBCL.

      PubDate: 2018-02-25T22:28:30Z
      DOI: 10.1016/j.leukres.2018.02.011
      Issue No: Vol. 67 (2018)
       
  • Knockdown of the Wnt receptor Frizzled-1 (FZD1) reduces
           MDR1/P-glycoprotein expression in multidrug resistant leukemic cells and
           inhibits leukemic cell proliferation
    • Authors: Yan-Hua Wang; Yoichi Imai; Masayuki Shiseki; Junji Tanaka; Toshiko Motoji
      Pages: 99 - 108
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Yan-Hua Wang, Yoichi Imai, Masayuki Shiseki, Junji Tanaka, Toshiko Motoji
      Multidrug resistance (MDR) is a major obstacle to leukemia treatment. The Frizzled-1 (FZD1) Wnt receptor is involved in MDR in some solid cancers, but has rarely been reported to act in acute myeloid leukemia (AML). We investigated whether the knockdown of FZD1 affects MDR1 expression and P-glycoprotein (P-gp) function in multidrug resistant leukemic cell lines, as well as FZD1 and MDR1/P-gp expression in leukemic cells taken from patients with AML (n = 112). FZD1 knockdown significantly reduced MDR1 expression through the Wnt/β-catenin pathway, disrupted the P-gp efflux function, induced the recovery of sensitivity to chemotherapeutic agents, and hindered cell proliferation in cell lines. FZD1 expression in leukemic cells was significantly higher in patients experiencing relapse (n = 34) than in those with no relapse (n = 44, P = .003). Leukemic cells unable to achieve complete response (CR) showed an increased expression of MDR1 and P-gp, compared to patients who achieved CR. Obtaining CR in patients with higher FZD1 expression at diagnosis is difficult. Moreover, they tend to present instances of relapse, suggesting that AML cells with increased FZD1 expression are resistant to chemotherapy. We conclude that the activated FZD1 observed in leukemic cells likely confers acquired drug resistance, whereas FZD1 silencing may be more effective in reversing MDR.

      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.01.020
      Issue No: Vol. 67 (2018)
       
  • Corrigendum to: Comparison of Induction Therapy in Non-high Risk Acute
           Promyelocytic Leukemia with Arsenic Trioxide or in Combination with ATRA
           Leukemia Research 66 (2018) 85–88
    • Authors: Ardeshir Ghavamzadeh; Mahdi Jalili; Sharbanoo Rostami; Marjan Yaghmaie; Leyla Sharifi Aliabadi; Seyed Asadollah Mousavi; Mohammad Vaezi; Hossein Kamranzadeh Fumani; Mohammad Jahani; Kamran Alimoghaddam
      First page: 116
      Abstract: Publication date: April 2018
      Source:Leukemia Research, Volume 67
      Author(s): Ardeshir Ghavamzadeh, Mahdi Jalili, Sharbanoo Rostami, Marjan Yaghmaie, Leyla Sharifi Aliabadi, Seyed Asadollah Mousavi, Mohammad Vaezi, Hossein Kamranzadeh Fumani, Mohammad Jahani, Kamran Alimoghaddam


      PubDate: 2018-04-15T17:10:39Z
      DOI: 10.1016/j.leukres.2018.03.003
      Issue No: Vol. 67 (2018)
       
  • Lenalidomide plus dexamethasone for patients with relapsed or refractory
           multiple myeloma: Final results of a non-interventional study and
           comparison with the pivotal phase 3 clinical trials
    • Authors: Wolfgang Knauf; Ali Aldaoud; Christoph Losem; Johann Mittermueller; Michael Neise; Beate Niemeier; Johanna Harde; Tanja Trarbach; Karin Potthoff
      Abstract: Publication date: Available online 14 March 2018
      Source:Leukemia Research
      Author(s): Wolfgang Knauf, Ali Aldaoud, Christoph Losem, Johann Mittermueller, Michael Neise, Beate Niemeier, Johanna Harde, Tanja Trarbach, Karin Potthoff
      Lenalidomide (LEN) is an immunomodulatory drug with significant clinical activity against relapsed and refractory multiple myeloma (r/r MM). Based on the pivotal phase 3 trials MM-009 and MM-010, LEN in combination with dexamethasone (DEX) is approved for treatment of patients with MM who have received at least one prior therapy. LEN monotherapy is also approved in first line treatment. Here, we evaluated LEN/DEX combination therapy in a non-interventional study in patients with r/r MM in routine clinical practice. Patients received LEN/DEX as per Summary of Product Characteristics. Ninety-eight patients were treated with at least 1 cycle of LEN/DEX (median age 71 years; range, 42–88), forty-eight patients with at least 6 cycles. The Kaplan-Meier estimate for overall median time to progression was 12.0 months, 13.9 months for patients receiving second-line therapy and 10.3 months for third-line or higher-line therapy. The overall response rate was 60.2%. The median overall survival was 24.3 months. The most common adverse events were anemia (32.7%), thrombocytopenia (27.6%) and leukopenia (24.5%). Seven (7.1%) patients developed thromboembolic events despite prophylaxis. In conclusion, the combination of LEN/DEX administered to patients with r/r MM in routine clinical practice showed similar effectiveness and safety as demonstrated in the registration trials.

      PubDate: 2018-03-19T14:51:36Z
      DOI: 10.1016/j.leukres.2018.03.008
       
  • Acute Myeloid Leukemia Induction with Cladribine: Outcomes by Age and
           Leukemia Risk
    • Authors: Martin W. Schoen; Susan K. Woelich; James T. Braun; Dhinesh V. Reddy; Mark J. Fesler; Paul J. Petruska; Carl E. Freter; Jack M. Lionberger
      Abstract: Publication date: Available online 6 March 2018
      Source:Leukemia Research
      Author(s): Martin W. Schoen, Susan K. Woelich, James T. Braun, Dhinesh V. Reddy, Mark J. Fesler, Paul J. Petruska, Carl E. Freter, Jack M. Lionberger
      Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7 + 3). Because of evidence of increased efficacy of cladribine combined with this regimen, we conducted a retrospective analysis of 107 AML patients treated with idarubicin, cytarabine and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old and 72% (36/50) in those <60 (Relative Risk [RR] 1.9, 95% CI 1.2-3.2). Median overall survival was 17.3 months in all patients and Cox proportional hazard ratio (HR) for death was 2.2 (95% CI 1.3-3.6) for age ≥60 years compared to <60 years. One year survival was 100% among favorable NCCN risk patients versus 64% in intermediate-risk and 35% in poor-risk patients (p < 0.001). HR for death in intermediate- risk (4.2, 95% CI 1.5-12) and poor-risk (8.4, 95% CI 3.0-24) compared to favorable risk AML was higher than that associated with age ≥60 years (HR 2.2). We conclude that IAC is an effective AML induction regimen, NCCN leukemia risk predicts survival better than age in our population, and high intensity regimens can be justified in selected older patients.

      PubDate: 2018-03-19T14:51:36Z
      DOI: 10.1016/j.leukres.2018.03.005
       
  • Targeting histone demethylases KDM5A and KDM5B in AML cancer cells: A
           comparative view
    • Authors: Gelareh Shokri; Shaghayegh Doudi; Mehrnoosh Fathi-Roudsari; Fatemeh Kouhkan; Mohammad-Hossein Sanati
      Abstract: Publication date: Available online 7 February 2018
      Source:Leukemia Research
      Author(s): Gelareh Shokri, Shaghayegh Doudi, Mehrnoosh Fathi-Roudsari, Fatemeh Kouhkan, Mohammad-Hossein Sanati
      Epigenetic modifications play an important role in initiation and progression of cancers including acute myeloid leukemia. Among different epigenetic modifiers, lysine specific demethylases have been noticed as potential therapeutic targets. KDM5 family of histone demethylases which removes methyl marks from lysine residues of H3, are frequently found in the promoter region of transcriptionally active genes resulting in repression of expression. Here we have compared the effects of KDM5A and KDM5 B downregulation on HL-60 cell line behavior. KDM5A/5 B knockdown resulted in lower viability of HL-60 cells in addition to modified cell cycle distribution and sub-G1 accumulation. Induction of apoptosis was observed in both knockdown cells. But in spite of similarity in their role, downregulation of KDM5A showed more efficient anti-leukemic effects in comparison to KDM5B. Cells showed higher accumulation in sub-G1 and apoptosis occurred significantly higher and also earlier after KDM5A reduction. Expression analysis confirmed almost 5 and 4 fold increased expression for bax and caspase-3 after downregulation of KDM5A in comparison to KDM5B. Due to the present study we propose KDM5A as a potential target for therapeutic aspects of acute myeloid leukemia although further investigations are needed.

      PubDate: 2018-03-19T14:51:36Z
      DOI: 10.1016/j.leukres.2018.02.003
       
  • Arsenic Trioxide Inhibits Proliferation and Induced apoptosis of Leukemia
           Stem Cells with Drug Resistance
    • Authors: Chunxia Liu; Hulai Wei; Xiaojian Yao; Bei Liu; Yaming Xi; Li Zhao
      Abstract: Publication date: Available online 2 March 2018
      Source:Leukemia Research
      Author(s): Chunxia Liu, Hulai Wei, Xiaojian Yao, Bei Liu, Yaming Xi, Li Zhao
      Acute myeloid leukemia (AML) patients show high relapse rates and some develop conventional chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main player for AML relapses and drug resistance. K562/ADM cell, a leukemia resistant cell subtype, was used as leukemia multidrug resistant model to explore drug resistance of leukemia cells. We found that CD34+CD38−, CD34+CD38−CD123+, cell surface markers of LSCs were significantly high expressed in K562/ADM cell, not in K562 cell with less drug resistance; compared with LSCs from K562, multidrug resistance protein P-gp and BCRP expression were significantly higher in K562/ADM cell. Compared to the patients with primary leukemia, the subpopulation of LSCs from patients with AML relapses and drug resistance is significantly increased. Arsenic trioxide (As2O3) as an inhibitor markedly inhibited proliferation and induced apoptosis of LSCs from K562/ADM cell in a dose dependent way. The results of colony formation assay showed that As2O3 obviously inhibited colony formation of LSCs from K562/ADM cell. Collectively, our study showed that LSCs take an important role in the drug resistance of leukemia therapies. As2O3, as an inhibition agent, may be a potential drug targeting LSCs for improving the cure rate.

      PubDate: 2018-03-07T13:58:48Z
      DOI: 10.1016/j.leukres.2018.02.016
       
  • It is not just the number of metaphases that matters
    • Authors: Marília Braga Costa; Daniela de Paula Borges; Mayara Magna de Lima Melo; Silvia Maria Meira Magalhães; Ronald Feitosa Pinheiro
      Abstract: Publication date: Available online 1 March 2018
      Source:Leukemia Research
      Author(s): Marília Braga Costa, Daniela de Paula Borges, Mayara Magna de Lima Melo, Silvia Maria Meira Magalhães, Ronald Feitosa Pinheiro


      PubDate: 2018-03-07T13:58:48Z
      DOI: 10.1016/j.leukres.2018.02.018
       
  • Efficacy and safety of nilotinib 300 mg twice daily in patients with
           chronic myeloid leukemia in chronic phase who are intolerant to prior
           tyrosine kinase inhibitors: Results from the Phase IIIb ENESTswift study
    • Authors: Devendra Hiwase; Peter Tan; James D’Rozario; John Taper; Anthony Powell; Ian Irving; Matthew Wright; Susan Branford; David T. Yeung; Luke Anderson; Othon Gervasio; Carly Levetan; Will Roberts; Ann Solterbeck; Robert Traficante; Timothy Hughes
      Abstract: Publication date: Available online 21 February 2018
      Source:Leukemia Research
      Author(s): Devendra Hiwase, Peter Tan, James D’Rozario, John Taper, Anthony Powell, Ian Irving, Matthew Wright, Susan Branford, David T. Yeung, Luke Anderson, Othon Gervasio, Carly Levetan, Will Roberts, Ann Solterbeck, Robert Traficante, Timothy Hughes
      Background Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. Methods This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months. Results Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300 mg bid. Conclusion Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.

      PubDate: 2018-02-25T22:28:30Z
      DOI: 10.1016/j.leukres.2018.02.013
       
  • AML refractory to primary induction with Ida-FLAG has a poor clinical
           outcome
    • Authors: Simon Kavanagh; Emily Heath; Rose Hurren; Marcela Gronda; Samir H. Barghout; Sanduni U. Liyanage; Thirushi P. Siriwardena; Jaime Claudio; Tong Zhang; Mahadeo Sukhai; Tracy L. Stockley; Suzanne Kamel-Reid; Amr Rostom; Andrzej Lutynski; Dina Khalaf; Anna Rydlewski; Steven M. Chan; Vikas Gupta; Dawn Maze; Hassan Sibai; Andre C. Schuh; Karen Yee; Mark D. Minden; Aaron D. Schimmer
      Abstract: Publication date: Available online 20 February 2018
      Source:Leukemia Research
      Author(s): Simon Kavanagh, Emily Heath, Rose Hurren, Marcela Gronda, Samir H. Barghout, Sanduni U. Liyanage, Thirushi P. Siriwardena, Jaime Claudio, Tong Zhang, Mahadeo Sukhai, Tracy L. Stockley, Suzanne Kamel-Reid, Amr Rostom, Andrzej Lutynski, Dina Khalaf, Anna Rydlewski, Steven M. Chan, Vikas Gupta, Dawn Maze, Hassan Sibai, Andre C. Schuh, Karen Yee, Mark D. Minden, Aaron D. Schimmer
      We evaluated outcomes of 100 patients with high risk AML treated with Ida-FLAG induction as first-line therapy. 72 achieved remission with one cycle; 19 did not. High risk cytogenetics and TP53 mutations were associated with failure to achieve remission. In those reaching remission, allogeneic bone marrow transplantation was associated with better relapse-free and overall survival. Those not achieving remission with induction therapy were extremely unlikely to reach remission with further therapy and had a dismal prognosis. Exploratory molecular analysis confirmed persistence of the dominant genetic mutations identified at diagnosis. Ex vivo chemosensitivity did not demonstrate significant differences between responders and non-responders. Thus, Ida-FLAG induction has a high chance of inducing remission in patients with high risk AML. Those achieving remission require allogeneic transplantation to achieve cure; those not achieving remission rarely respond to salvage chemotherapy and have a dismal outcome. Alternatives to conventional chemotherapy must be considered in this group.

      PubDate: 2018-02-25T22:28:30Z
      DOI: 10.1016/j.leukres.2018.02.012
       
  • The Importance of Meaningful Activity in People Living with Acute Myeloid
           Leukemia
    • Authors: Amy L. Deckert; Galina Gheihman; Rinat Nissim; Cynthia Chung; Aaron Schimmer; Camilla Zimmermann; Gary Rodin
      Abstract: Publication date: Available online 15 February 2018
      Source:Leukemia Research
      Author(s): Amy L. Deckert, Galina Gheihman, Rinat Nissim, Cynthia Chung, Aaron Schimmer, Camilla Zimmermann, Gary Rodin
      Purpose The symptom burden of acute myeloid leukemia (AML) and its treatment can accelerate physical deconditioning and impair mobility and quality of life. In the present study, we explore the subjective experience of functional capacity in people living with AML. Methods A secondary qualitative analysis was performed on a subset of interviews (n = 21) obtained from an observational cohort study of people with acute leukemia. Conventional content analysis was employed to identify key themes and concepts. Results Participants valued their physical function to the extent that it was required to pursue valued activities and interests. We identified Meaningful Activity as an overarching goal of participants. Three interrelated themes captured the obstacles participants reported facing when attempting to realize this goal: Compromised Body, Threatened Identity, and Shrinking World. Adaptation was common across themes, representing the strategies employed to overcome such challenges. Themes were consistent across participants, despite the variability in disease states at the time of the interview. Conclusions Dynamic interactions between physical, psychological, and environmental factors affect the pursuit and achievement of meaningful activity among people living with AML. It may be important to consider personal incentives when designing interventions for physical rehabilitation in this patient population.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.02.009
       
  • Helios Expression in Regulatory T cells Promotes Immunosuppression,
           Angiogenesis and the growth of leukemia cells in Pediatric Acute
           Lymphoblastic Leukemia
    • Authors: Xue Li; Dong Li; Xiaoyang Huang; Panpan Zhou; Qing Shi; Bing Zhang; Xiuli Ju
      Abstract: Publication date: Available online 14 February 2018
      Source:Leukemia Research
      Author(s): Xue Li, Dong Li, Xiaoyang Huang, Panpan Zhou, Qing Shi, Bing Zhang, Xiuli Ju
      Regulatory T cells (Tregs) characterized by the transcription factor forkhead box P3 (FoxP3) are crucial for maintaining immune tolerance and preventing autoimmunity. However, FoxP3 does not function alone and Helios is considered a potential candidate for defining Treg subsets. In this study, we investigated the expression and function of Helios for identifying Tregs in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that patients with pre-B ALL had a higher percentage of Helios+ FoxP3+ CD4+ Tregs. And there was a positive correlation between the expression of Helios and the suppressive function of Tregs, the risk gradation of ALL. Helios in combination with CD4 and FoxP3 may be an effective way to detect functional Tregs in pre-B ALL by promoting the secretion of transforming growth factor (TGF)-β1. Furthermore, Helios+ Tregs could regulate angiogenesis in the BM niche of pre-B ALL via the VEGFA/VEGFR2 pathway. We also found Helios+ Tregs decreased apoptosis rate of nalm-6 cells by up-regulating the expression of anti-apoptosis protein Bcl-2. In summary, these data strongly imply the physiological importance of Helios expression in Tregs, and suggest that the manipulation of Helios may serve as a novel strategy for cancer immunotherapy.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.02.007
       
  • Widespread use of measurable residual disease in acute myeloid leukemia
           practice
    • Authors: Zachary D. Epstein-Peterson; Sean M. Devlin; Eytan M. Stein; Elihu Estey; Martin S. Tallman
      Abstract: Publication date: Available online 13 February 2018
      Source:Leukemia Research
      Author(s): Zachary D. Epstein-Peterson, Sean M. Devlin, Eytan M. Stein, Elihu Estey, Martin S. Tallman
      Purpose Measurable residual disease (MRD) has prognostic importance for patients with acute myeloid leukemia (AML). How leukemia providers incorporate MRD into routine practice remains undefined. Patients and methods A survey was developed and distributed to a large sample of leukemia physicians. Demographic information was collected along with details concerning MRD practices. A multivariable logistic regression model evaluated provider characteristics predictive of MRD utilization. Results 268 responses were received (response rate of 41%). 69% of providers reported routine use of MRD in management of AML, most commonly (90%) for its role in guiding therapy; providers who did not use MRD routinely most frequently cited inadequate resources (58%). Providers utilized flow cytometry- more than polymerase chain reaction-based assays with nucleophosmin-1 being the most common target with the latter. We found substantial variability in how MRD affected clinical decision making, particularly in pre- and post-transplant scenarios. Conclusions MRD was frequently used in making treatment decisions and in estimating prognosis. However, there was lack of uniformity in these practices. Standardization of assays, adoption of requisite technology, and dissemination of data about the value of MRD use would likely increase usage of MRD in the care of patients with AML.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.02.006
       
  • Iron Overload in Lower International Prognostic Scoring System Risk
           Patients with Myelodysplastic Syndrome Receiving Red Blood Cell
           Transfusions: Relation to Infections and Possible Benefit of Iron
           Chelation Therapy
    • Authors: Colleen A.C. Wong; Shannon A.Y. Wong; Heather A. Leitch
      Abstract: Publication date: Available online 10 February 2018
      Source:Leukemia Research
      Author(s): Colleen A.C. Wong, Shannon A.Y. Wong, Heather A. Leitch
      Background An increased incidence of infections and infectious mortality has been reported in myelodysplastic syndromes (MDS) patients receiving red blood cell (RBC) transfusions. Methods We examined incidence of infections requiring antibiotics, antifungal or antiviral medications in transfused lower International Prognostic Scoring System (IPSS) risk MDS patients and whether this differed with iron chelation therapy (ICT). Results 138 transfused MDS patients were lower IPSS risk. 59 received ICT; median duration was 13 months. There was no significant difference between groups in neutrophil count at first RBC transfusion or first infection. Infections included: bacterial, n = 88; viral; fungal; and mycobacterial; n = 2 each. In ICT and non-ICT patients, respectively, infections were (number [%]): patients, 23 (40.0%) and 22 (27.8%); episodes (median [range]), 2 (1–6) and 2 (1–5); hospitalizations, 16 (27.1%) and 8 (10.1%); and deaths, 0 (0%) and 1 (1.3%), p = NS for all. Median overall survival (OS) from first RBC transfusion was superior in ICT patients, p = 0.01, and remained significant in a multivariate analysis (MVA), p = 0.003. Median time to first infection (TTI) was 27 and 7.8 months, respectively, p < 0.0001, and ICT remained significant for TTI in an MVA, p = 0.02, hazard ratio 0.3. For ICT patients with blast count <5%, TTI was significantly superior (p = 0.004). Conclusions In this retrospective analysis, for lower IPSS risk MDS patients receiving RBC transfusions, though number and type of infections were similar between groups and despite similar neutrophil counts, time to first infection was significantly longer in ICT patients (p < 0.0001). These results should be confirmed in larger, prospective analyses.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.02.005
       
  • Interpretation of clinical endpoints in trials of acute myeloid leukemia
    • Authors: Bruno C. Medeiros
      Abstract: Publication date: Available online 7 February 2018
      Source:Leukemia Research
      Author(s): Bruno C. Medeiros
      Treatment regimens for acute myeloid leukemia (AML) have remained largely unchanged until recently. Molecular advances have opened the door to targeted therapies, many of which are in late-phase clinical trials. As new therapeutic opportunities arise, it is appropriate to review key aspects of clinical trial design, statistical interpretation of outcomes, and methods of data reporting. Complete remission and overall survival (OS) are common primary endpoints in early-phase AML clinical trials. OS and event-free survival are frequent primary endpoints in phase 3 trials. Clinical trials are designed to address the primary endpoint using prespecified α and power levels. Interpretation of additional endpoints (eg, secondary endpoints and subgroup analyses) must be viewed in light of a trial’s statistical design. Furthermore, variations in reporting of endpoints must be considered in order to understand trial outcomes. Time-to-event endpoints are typically reported using Kaplan-Meier curves, which are visually informative. Statistical data derived from these curves can be complex, and a variety of factors may impact interpretation. The purpose of this review is to discuss the nuances of common AML trial endpoints and their data presentation to better inform evaluation and understanding of clinical trial data.

      PubDate: 2018-02-15T21:53:19Z
      DOI: 10.1016/j.leukres.2018.02.002
       
  • Abnormal CD25 expression on hematopoietic cells in myelodysplastic
           syndromes
    • Authors: Pei Liu; Huijuan Jiang; Mengting Che; Rong Fu; Huaquan Wang; Lijuan Li; Wei Zhang; Jinglian Tao; Shan Gao; Zonghong Shao
      Abstract: Publication date: Available online 15 December 2017
      Source:Leukemia Research
      Author(s): Pei Liu, Huijuan Jiang, Mengting Che, Rong Fu, Huaquan Wang, Lijuan Li, Wei Zhang, Jinglian Tao, Shan Gao, Zonghong Shao
      Objective To investigate the frequencies and biological characteristics of CD25 positive hematopoietic stem cells (HSC) in myelodysplastic syndromes. Methods The expression of CD25 on HSC in bone marrow derived from patients with untreated MDS patients, untreated AML patients and normal controls were accessed by flow cytometry (FCM). The correlation analysis was done between CD25+ HSC and clinical parameters in MDS patients. Results The expression of CD25 on HSC (CD34+CD38− cells) in MDS patients (28.81%) was significantly higher than that in normal controls (9.41%, P = 0.020), which similar to that in AML patients (32.54%, P = 0.410). The CD25 expression on HSC was positively correlated with the CD123 expression on HSC (r = 0.602, P = 0.008). The expression of CD25 on HSC in high-risk MDS group (53.27%) based on IPSS score was significantly higher than that in low-risk MDS group (18.66%, P = 0.003). In MDS patients, CD25+ HSC were negatively correlated with the counts of neutrophils (r = −0.684, P = 0.002) and platelets (r = −0.561, P = 0.015), while positively correlated with the percentage of blasts in bone marrow (r = 0.596, P = 0.009). The CD25 expression on erythroblasts had a significant positive correlation with red blood cell counts in MDS patients (r = 0.536, P = 0.012). Conclusions CD25 was over-expressed on HSC in MDS patients, especially in high-risk MDS patients. Increased CD25+ HSC was correlated with progression of MDS. Low-expression of CD25 on erythroblasts might correlate with anemia in MDS patients. CD25 could be a specific marker of LSC in MDS, and could involve in the mechanisms of development and progression of MDS.

      PubDate: 2017-12-21T18:29:17Z
      DOI: 10.1016/j.leukres.2017.11.010
       
 
 
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