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Publisher: John Wiley and Sons   (Total: 1583 journals)

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Showing 1 - 200 of 1583 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 54, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 44, SJR: 0.547, h-index: 30)
ACEP NOW     Free  
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 50, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 141, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 54, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 7, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 5, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 2)
Addiction     Hybrid Journal   (Followers: 32, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 11, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 24, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 25, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 49, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 253, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 4)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 14, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 9, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 29, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 49, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 128, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 91, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 28, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 31, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Orthopsychiatry     Hybrid Journal   (Followers: 4, SJR: 0.756, h-index: 69)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 36, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 248, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 15, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 115, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 11, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 155)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 211, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 34, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 8, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 43, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 16, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 14)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 93, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 44, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 6, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 67, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 137, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 13, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 34, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 14, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 215, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 49, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 28, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 14)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 311, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 3, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 13, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 12, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 43, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 22, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 13, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 17, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 381, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 66, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 31, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 3, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 8, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 14, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 36, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 137, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 18, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 10, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 34, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)

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Journal Cover American Journal of Hematology
  [SJR: 1.761]   [H-I: 77]   [31 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0361-8609 - ISSN (Online) 1096-8652
   Published by John Wiley and Sons Homepage  [1583 journals]
  • Prevalence and Predictors of Anemia in Hereditary Hemorrhagic
    • Authors: Raj S. Kasthuri; Megan Montifar, Jeffrey Nelson, Helen Kim, Michael T. Lawton, Marie E. Faughnan,
      PubDate: 2017-06-22T02:20:55.898227-05:
      DOI: 10.1002/ajh.24832
  • Bone Marrow Hematons: An Access Point to the Human Hematopoietic Niche
    • Authors: Alexandre Janel; Juliette Berger, Céline Bourgne, Richard Lemal, Nathalie Boiret-Dupré, Frédérique Dubois-Galopin, Pierre Déchelotte, Charlotte Bothorel, Eric Hermet, Sara Chabi, Jacques-Olivier Bay, Céline Lambert, Bruno Pereira, Françoise Pflumio, Rima Haddad, Marc G. Berger
      Abstract: To understand the complex interactions between hematopoietic stem cells and the bone marrow niche, a human experimental model is needed. Our hypothesis is that hematons are an appropriate ex vivo model of human bone marrow.We analyzed the hierarchical hematopoietic cell content and the tissue organization of single hematons from healthy donors.Most (>90%) hematons contained precursors of all cell lineages, myeloid progenitors, and LTC-ICs without preferential commitment. Approximately half of the hematons could generate significant levels of lympho-myeloid hematopoiesis after transplantation in an NSG mouse model, despite the low absolute numbers of transplanted CD34+ cells. Mesenchymal STRO-1+ and/or CD271+ cells formed a critical network that preserved hematon cohesion, and STRO-1+ cells co-localized with most hematopoietic CD34+ cells (68%). We observed an influence of age and gender.These structures represent a particularly attractive model for studying the homeostasis of the bone marrow niche and pathological changes that occur during diseases. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-22T02:20:52.458237-05:
      DOI: 10.1002/ajh.24830
  • Acute leukemic transformation of myelodysplastic syndrome – is
           cytochemistry still relevant'
    • Authors: Imogen Caldwell; Anna Ruskova, Nicola Eaddy, Barbara J. Bain
      PubDate: 2017-06-22T02:15:48.738401-05:
      DOI: 10.1002/ajh.24831
  • Early Mortality in Patients with Acute Myelogenous Leukemia Treated in
           Teaching versus Non-teaching Hospitals: A Large Database Analysis
    • Authors: Adam Levin; Ariel Kleman, Lisa Rein, Sergey Tarima, Laura C. Michaelis, Karen Sue Carlson, Mehdi Hamadani, Timothy S. Fenske, Parameswaran Hari, Ehab Atallah, Binod Dhakal
      PubDate: 2017-06-20T01:10:25.439226-05:
      DOI: 10.1002/ajh.24825
  • Missing HLA C group 1 ligand in patients with AML and MDS is associated
           with reduced risk of relapse and better survival after allogeneic stem
           cell transplantation with fludarabine and treosulfan reduced toxicity
    • Authors: Avichai Shimoni; Luca Vago, Massimo Bernardi, Ronit Yerushalmi, Jacopo Peccatori, Raffaella Greco, Noga Shem-Tov, Alessandro Lo Russo, Ivetta Danylesko, Arie Apel, Chiara Bonini, Maria Teresa Lupo Stanghellini, Arnon Nagler, Fabio Ciceri
      Abstract: Reduced-toxicity conditioning with fludarabine and treosulfan is a dose-intensive regimen with enhanced anti-leukemia effect and acceptable toxicity in AML/MDS. HLA-C regulates natural-killer (NK) cell function by inhibiting Killer immunoglobulin-like receptors (KIR) and is divided into C1 and C2 epitopes. The missing-ligand theory suggests that missing recipient KIR ligands drives NK-alloreactivity after SCT, in the absence of HLA-mismatch by activating unlicensed donor NK cells. We analyzed SCT outcomes in 203 patients with AML/MDS, median age 58 years, given SCT from matched-siblings (n=97) or matched-unrelated donors (n=106), using two treosulfan doses (total 36 or 42 gr/m2). 34% expressed one HLA-C group 1 allele (C1C1), 19% one HLA-C group 2 allele (C2C2) and 48% both KIR ligands (C1C2). Median follow-up was 48 months. 5-year relapse, non-relapse mortality (NRM) and leukemia-free survival (LFS) rates were 38%, 27% and 36%, respectively. Relapse rates were 43%, 45% and 26% in patients expressing C1C1, C1C2 and C2C2 ligands, respectively (P=0.03). Multivariate-analysis identified chemo-refractory disease (HR 3.1, P=0.003), poor cytogenetics (HR 1.7, P=0.08), female donor to male recipient (HR 0.4, P=0.01) and C2C2 ligands (HR 0.4, P=0.04) as independent factors predicting relapse. HLA-C ligands were not associated with GVHD or NRM. LFS was 33%, 30% and 46%, respectively (P=0.07). Chemo-refractory disease (HR 3.1, P=0.0004) and C2C2 group ligand (HR 0.6, P=0.06) independently predicted LFS. Treosulfan dose did not predict any SCT outcome. In conclusion, missing HLA-C group 1 ligand is associated with reduced relapse risk, similar NRM and improved LFS, after HLA-matched SCT with treosulfan conditioning in AML/MDS. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-19T22:35:27.243302-05:
      DOI: 10.1002/ajh.24827
  • High prevalence of osteonecrosis among the HLH population: Single
           institution 10 year retrospective data review
    • Authors: Paul Craig; Shelly Marette, Jutta Ellermann, Surbhi Shah, Takashi Takahashi
      PubDate: 2017-06-19T22:20:28.32516-05:0
      DOI: 10.1002/ajh.24828
  • Platelet counts in women with normal pregnancies: A systematic review
    • Authors: Jessica A. Reese; Jennifer D. Peck, Jennifer J. McIntosh, Sara K. Vesely, James N. George
      Abstract: The occurrence of thrombocytopenia in 5% of pregnant women at delivery, described as gestational thrombocytopenia, is well documented. A commonly believed concept is that gestational thrombocytopenia is the result of gradually decreasing platelet counts in all women during pregnancy. The goal of our study was to evaluate the data supporting this concept. To learn what is known about platelet counts throughout normal pregnancies, we systematically reviewed all publications describing platelet counts during pregnancy. We identified 3039 studies; 46 reporting ≥30 women with normal pregnancies were included in our analyses. The combined mean platelet counts from all studies supported the concept that platelet counts decrease during pregnancy and increase postpartum: first trimester, 251,000/µL (95% CI, 238,000-264,000/µL); second trimester, 238,000/µL (95% CI, 222,000-253,000/µL); third trimester, 224,000/µL (95% CI, 213,000-235,000/µL); delivery, 237,000/µL (95% CI, 209,000-264,000/µL); 4-8 weeks postpartum, 247,000/µL (95% CI, 207,000-287,000/µL). However, individual studies were inconsistent. Eleven longitudinal studies compared platelet counts on the same women at different times during gestation: seven reported a decrease; four reported no change. Ten cross-sectional studies compared platelet counts of different women at different times during gestation: five reported a decrease; five reported no change. Five studies compared platelet counts of pregnant to nonpregnant women: three reported that platelet counts were lower in pregnant women; one reported no difference; one reported that platelet counts were higher in pregnant women. These inconsistent data emphasize the need to accurately describe platelet counts throughout normal pregnancies. Accurate data are essential for evaluating the clinical importance of thrombocytopenia during pregnancy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-19T22:20:24.723942-05:
      DOI: 10.1002/ajh.24829
  • Effect of velaglucerase alfa enzyme replacement therapy on red blood cell
           properties in Gaucher disease
    • Authors: Melanie Franco; Nelly Reihani, Mickael Marin, Marine De Person, Thierry Billette de Villemeur, Christian Rose, Yves Colin, Fathi Moussa, Nadia Belmatoug, Caroline Le Van Kim
      PubDate: 2017-06-16T09:50:37.919709-05:
      DOI: 10.1002/ajh.24816
  • Long-term Follow-up of Chemoimmunotherapy with Rituximab, Oxaliplatin,
           Cytosine Arabinoside, Dexamethasone (ROAD) in Patients With Relapsed CD20+
           B–Cell Non-Hodgkin Lymphoma: Results of a study of the Mayo Clinic
           Cancer Research Consortium (MCCRC) MC0485 now known as Academic and
           Community Cancer Research United (ACCRU)
    • Authors: Thomas E. Witzig; Patrick B. Johnston, Betsy R. LaPlant, Paul J. Kurtin, Levi D. Pederson, Dennis F. Moore, Nassim H. Nabbout, Daniel A. Nikcevich, Kendrith M. Rowland, Axel Grothey
      Abstract: Patients with relapsed aggressive non-Hodgkin lymphoma (NHL) are often treated with platinum-based chemoimmunotherapy regimens in preparation for autologous stem cell transplant. We sought to reduce toxicity and maintain efficacy by using oxaliplatin with rituximab, cytarabine and dexamethasone (ROAD) in a phase II clinical trial in patients who had relapsed after one prior regimen. ROAD was delivered q21 days and consisted of rituximab 375 mg/m2 IV weekly x 4 doses (cycle 1 only); dexamethasone 40 mg PO/IV d2 – 5; oxaliplatin 130 mg/m2 IV d2; cytarabine 2000 mg/m2 IV x two doses on days 2 – 3; and pegfilgrastim 6 mg SC on d4. Forty-five eligible patients were accrued between 2006- 2008. Patient characteristics were a median age of 69 years; 96% had received prior rituximab; 53% were within one year of diagnosis. The median number of cycles received was 2 (range, 1-6). Forty-four % received ROAD as an outpatient. The overall response rate was 71% with 27% (12/45) CR and 44% (20/45) PR. Forty-four % (20/45) of all patients and 69% (18/26) of patients whom responded after 2 cycles proceeded to transplant. Median overall survival was 26 mos (95% CI: 7.3 mos – not reached) and median progression-free survival was 11 mos (95% CI: 6 – 104 mos). There was no grade 3/4 nephrotoxicity; the rate of grade 3/4 neuropathy was 4%. Forty-two percent of all patients and 69% of patients transplanted remain alive at 5 years. ROAD represents an acceptable salvage therapeutic option for patients with relapsed aggressive NHL. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-14T17:57:15.426988-05:
      DOI: 10.1002/ajh.24824
  • Deformability of Transfused Red Blood Cells is a Potent Effector of
           Transfusion-Induced Hemoglobin Increment: A Study with β-Thalassemia
           Major Patients
    • Authors: Gregory Barshtein; Neta Goldschmidt, Axel R Pries, Orly Zelig, Dan Arbell, Saul Yedgar
      PubDate: 2017-06-14T17:57:14.124802-05:
      DOI: 10.1002/ajh.24821
  • Thiotepa-based conditioning versus total body irradiation as myeloablative
           conditioning prior to allogeneic stem cell transplantation for acute
           lymphoblastic leukemia: A matched-pair analysis from the Acute Leukemia
           Working Party of the European Society for Blood and Marrow Transplantation
    • Authors: Sandra Eder; Jonathan Canaani, Eric Beohou, Myriam Labopin, Miguel A. Sanz, William Arcese, Reuven Or, Juergen Finke, Agostino Cortelezzi, Dietrich Beelen, Jakob Passweg, Gerard Socié, Gunhan Gurman, Mahmoud Aljurf, Matthias Stelljes, Sebastian Giebel, Mohamad Mohty, Arnon Nagler,
      Abstract: The optimal conditioning regimen to employ before hematopoieitic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while Cy/TBI is the most commonly used myeloablative regimen, there are concerns regarding long term toxicity for patients conditioned with this regimen. Thiotepa based conditioning is an emerging radiation free regimen with recent publications indicative of comparable clinical outcomes to TBI based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched-pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa-based conditioning (n=180) with those receiving Cy/TBI conditioning (n=540). The 2 year leukemia-free survival and overall survival rates of both conditioning regimens were comparable, 33% for thiotepa [95% confidence interval (CI): 26.4 - 42.8] versus 39% for Cy/TBI (95% CI: 34.8 - 44.5] (P=0.33) and 46.5% [95% CI: 38.6 - 56.1] versus 48.8% [95% CI: 44.2 - 54] (P=0.9), respectively. There was no significant difference between the two regimens in the incidence of either acute graft versus host disease (GVHD) or chronic GVHD.Multivariate analysis demonstrated increased relapse incidence for thiotepa conditioning compared to Cy/TBI (HR=1.78, 95% CI, 1.07-2.95; P=0.03) which did not affect overall survival. Our results indicate that thiotepa based conditioning may not be inferior to Cy/TBI for adult ALL patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-14T17:57:11.32836-05:0
      DOI: 10.1002/ajh.24823
  • A comparative analysis of biosimilar vs originator filgrastim in
           combination with plerixafor for stem cell mobilization in lymphoma and
           multiple myeloma; a propensity-score weighted multicenter approach
    • Authors: F Lanza; F Saraceni, A Pezzi, M Martino, A Bosi, N Cascavilla, P Musto, E Zuffa, M Tani, C Cellini, D Laszlo, F Bonifazi,
      PubDate: 2017-06-13T19:20:26.779766-05:
      DOI: 10.1002/ajh.24817
  • Day 14 bone marrow examination in the management of acute myeloid leukemia
    • Authors: Christopher M Terry; Rory M Shallis, Elihu Estey, Seah H Lim
      Abstract: The National Comprehensive Cancer Network (NCCN) recommends that a repeat bone marrow evaluation is carried out seven to ten days following completion of induction therapy so that if a patient's day 14 bone marrow shows residual blast cell counts of>10%, the patient would proceed early to a second cycle of induction therapy. Although blast cell counts of 5% on day 14 bone marrow would still attain a complete remission of the disease without any further chemotherapy. Clinical decision based on day 14 bone marrow will result in some of these patients being given a second induction therapy unnecessarily. A second cycle of chemotherapy is associated with not only higher risk for treatment-related mortality but also increased use of hospital resources such as increased intravenous antimicrobials use, longer hospital stay, and higher demand for blood products. In this paper, we examined the utility, discussed the shortfalls, and re-appraised the values of day 14 bone marrow in the management of patients with AML. Based on our review, we suggest that the practice of day 14 bone marrow examination should be re-evaluated and should probably only be carried out in the setting of clinical trials with clear questions to address its role in predicting outcome of the therapeutic intervention. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:20:24.832926-05:
      DOI: 10.1002/ajh.24818
  • Impact of Comorbidities on Outcomes of Elderly Patients with Diffuse Large
           B-cell Lymphoma
    • Authors: Caner Saygin; Xuefei Jia, Brian Hill, Robert Dean, Brad Pohlman, Mitchell R. Smith, Deepa Jagadeesh
      Abstract: International prognostic index (IPI) has remained the primary prognostic tool in diffuse large B cell lymphoma (DLBCL) for more than 20 years. Even though the disease is more common in older population, the impact of comorbidities, dose reductions, and treatment-related adverse events (TAEs) on the outcome in elderly DLBCL patients has not been well established. We studied 413 consecutive patients aged ≥ 60 years who were treated at the Cleveland Clinic. The median age at diagnosis was 69 years, 58% of patients had high IPI score, and 85% had low Charlson comorbidity index (CCI). Forty percent of patients required dose reductions during treatment, 78% achieved CR, and 70% experienced at least one grade II-IV TAE. High IPI score, high CCI, reduced dose chemotherapy, TAE, and hospitalization were significant predictors of death and relapse. In multivariable analysis, high IPI and CCI were independent predictors of overall and progression free survival. A simple model combining IPI and CCI could reliably distinguish three prognostically separate risk groups. Our results suggest that incorporation of CCI in current prognostic models can improve prognostication of older DLBCL patients and CCI might be a valuable tool in evaluating the eligibility of older patients for clinical trial enrollment. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:20:22.784329-05:
      DOI: 10.1002/ajh.24819
  • Genetic Determinants of HbF in Saudi Arabian and African Benin Haplotype
           Sickle Cell Anemia
    • Authors: Elmutaz M. Shaikho; John J. Farrell, Abdulrahman Alsultan, Paola Sebastiani, Martin H. Steinberg
      PubDate: 2017-06-13T19:20:20.655602-05:
      DOI: 10.1002/ajh.24822
  • Juvenile myelomonocytic leukemia in an infant with congenital HIV and CMV
    • Authors: Jessica Bazin; Leena Karnik, Gareth Tudor-Williams, Anne M. Kelly, Barbara J. Bain
      PubDate: 2017-06-13T19:20:18.751115-05:
      DOI: 10.1002/ajh.24815
  • Iron deficiency across chronic inflammatory conditions: International
           expert opinion on definition, diagnosis and management
    • Authors: Maria Domenica Cappellini; Josep Comin-Colet, Angel de Francisco, Axel Dignass, Wolfram Doehner, Carolyn SP Lam, Iain C Macdougall, Gerhard Rogler, Clara Camaschella, Rezan Kadir, Nicholas J Kassebaum, Donat R Spahn, Ali T Taher, Khaled M Musallam,
      Abstract: Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines.In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease-specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:15:24.454116-05:
      DOI: 10.1002/ajh.24820
  • Multidimensional assessment of patient condition and mutational analysis
           in peripheral blood, as tools to improve outcome prediction in
           myelodysplastic syndromes: A prospective study of the Spanish MDS Group
    • Authors: Fernando Ramos; Cristina Robledo, Arturo Pereira, Carmen Pedro, Rocío Benito, Raquel de Paz, Mónica del Rey, Andrés Insunza, Mar Tormo, María Díez-Campelo, Blanca Xicoy, Eduardo Salido, Javier Sánchez-del-Real, Leonor Arenillas, Lourdes Florensa, Elisa Luño, Consuelo del Cañizo, Guillermo F. Sanz, Jesús María Hernández-Rivas,
      Abstract: The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS-R, for estimating overall survival and the risk of leukemic transformation in patients with MDS.A prospective cohort (2006-2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS-R. Patients were further stratified according to patient condition (assessed using the multidimensional Lee index for older adults) and genetic mutations (peripheral blood samples screened using next-generation sequencing). The change in likelihood-ratio was tested in Cox models after adding individual covariates.The addition of the Lee index to the IPSS-R significantly improved prediction of overall survival [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.96–4.66, p
      PubDate: 2017-06-13T19:15:22.462678-05:
      DOI: 10.1002/ajh.24813
  • Transplantation Related Toxicity and Mortality in Older Autologous
           Hematopoietic Cell Transplantation Recipients
    • Authors: Hewan Belete; Linda J Burns, Ryan Shanley, Manju Nayar, Brian McClune, Aleksandr Lazaryan, Veronika Bachanova, Nelli Bejanyan, Celalettin Ustun, Claudio Brunstein, Daniel J Weisdorf, Mukta Arora
      Abstract: With advances in supportive care, autologous hematopoietic cell transplant (AHCT) is increasingly being performed for patients older than 60 years. We analyzed patients receiving an AHCT for multiple myeloma or lymphoma in a contemporary cohort (2010-2012), with consistent treatment and supportive care and compared outcomes [CTCAE grade 3-5 toxicities, non-relapse mortality (NRM) and overall-survival (OS)] of younger (40-59 years, n=77) versus older (≥ 60 years, n=67) recipients. The proportion of patients with neutropenic infections was higher in the older group (64% vs. 44%; p=0.02). The proportion of patients with any grade 3-5 toxicity was also higher in the older group (84% vs. 67%, p=0.03). In multivariate analysis, older age was significantly associated with higher odds (OR: 2.57, 95% CI:1.09-6.05) of grade 3-5 toxicity. The NRM was 3% (older) vs. 0% (younger) at one-year. The probability of OS at 2-years was lower in the older group (76% vs. 90%, p=0.04). Though AHCT can be performed safely in older recipients, the higher toxicity and slightly higher NRM in this population needs attention. Studies focusing on risk-stratification in older patients would further help predict toxicity. Further studies addressing enhanced supportive care needs for older patients who are most likely to benefit are indicated. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:15:20.309524-05:
      DOI: 10.1002/ajh.24814
  • Cross-altitude analysis suggests a turning point at the elevation of
           4,500m for polycythemia prevalence in Tibetans
    • Authors: Hui Zhang; Yaoxi He, Chaoying Cui, Ouzhuluobu, Baimakangzhuo, Duojizhuoma, Dejiquzong, Bianba, Gonggalanzi, Yongyue Pan, Qula, Kangmin, Cirenyangji, Baimayangji, Caijuan Bai, Wei Guo, Yangla, Yi Peng, Xiaoming Zhang, Kun Xiang, Zhaohui Yang, Shiming Liu, Xiang Tao, Gengdeng, Wangshan Zheng, Yongbo Guo, Tianyi Wu, Xuebin Qi, Bing Su
      PubDate: 2017-06-07T03:50:23.669209-05:
      DOI: 10.1002/ajh.24809
  • Losartan for the Nephropathy of Sickle Cell Anemia: A Phase-2,
           Multi-Center Trial
    • Authors: Charles T. Quinn; Santosh L. Saraf, Victor R. Gordeuk, Courtney D. Fitzhugh, Susan E. Creary, Prasad Bodas, Alex George, Ashok B. Raj, Alecia C. Nero, Catherine E. Terrell, Lisa McCord, Adam Lane, Hans C. Ackerman, Yu Yang, Omar Niss, Michael D. Taylor, Prasad Devarajan, Punam Malik
      Abstract: Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase-2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA=14, MicroA=12, MacroA=6). The primary endpoint was met in 83% of the MacroA group (P50% (0.2➝0.3 mg/dL), N=1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase-3, randomized, placebo-controlled trial of losartan for the nephropathy of SCA. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-07T03:30:30.099014-05:
      DOI: 10.1002/ajh.24810
  • Safety and Efficacy of Recombinant Activated Coagulation Factor VII in
           Congenital Hemophilia with Inhibitors in the Home Treatment Setting: A
           Review of Clinical Studies and Registries
    • Authors: Guy Young; Miguel A. Escobar, Steven W. Pipe, David L. Cooper
      Abstract: Self-administration of factor and bypassing agents by persons with hemophilia in the home setting is recommended to facilitate earlier intervention after bleeding episodes. The objective of this review was to summarize recombinant activated coagulation factor VII (rFVIIa) safety and efficacy data from clinical trials and patient registries documenting use in the home treatment setting in people with congenital hemophilia with inhibitors (CHwI). A total of 16 studies and registries were identified for inclusion; 14 evaluated on-demand treatment of acute bleeding episodes (865 patients, 9024 bleeding episodes) and 2 evaluated use for secondary prophylaxis (108 patients, 42,861 prophylaxis days). In the on-demand studies, efficacy was consistently high (81%-96%), and thrombotic events were uncommon (n=3). In the secondary prophylaxis studies, rFVIIa was associated with a 45% to 59% reduction in bleeding episodes and no thrombotic events. These data support the clinical practice of administering rFVIIa in patients in the home treatment setting after initiation under a physician's care. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-07T03:30:22.938194-05:
      DOI: 10.1002/ajh.24811
  • IGHV Mutational Status Testing in Chronic Lymphocytic Leukemia
    • Authors: Jennifer Crombie; Matthew S. Davids
      Abstract: As the therapeutic landscape for chronic lymphocytic leukemia (CLL) continues to expand, biological predictors of response to therapy are becoming increasingly important. One such predictive biomarker is the mutational status of the variable region of the immunoglobulin heavy chain (IGHV) gene, which is a powerful predictor of duration of response and overall survival with chemoimmunotherapy (CIT). As this test may influence choice of therapy between CIT and novel agents, it is critical that providers understand how mutational status is determined and the limitations of testing. Here, we describe the details of IGHV mutational status testing, highlighting the appropriate way to interpret this information and best apply it to the care of patients with CLL. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-07T03:30:21.785173-05:
      DOI: 10.1002/ajh.24808
  • Developmentally-Faithful and Effective Human Erythropoiesis in
           Immunodeficient and Kit Mutant Mice
    • Authors: Claudia Fiorini; Nour J. Abdulhay, Sean K. McFarland, Mathias Munschauer, Jacob C. Ulirsch, Roberto Chiarle, Vijay G. Sankaran
      Abstract: Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis from various human developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-31T20:00:28.196168-05:
      DOI: 10.1002/ajh.24805
  • Allogeneic hematopoietic cell transplantation in morphologic leukemia-free
           aplastic state
    • Authors: Armin Rashidi; Alaa M. Ali, Kiran R. Vij, Ryan Shanley, Rizwan Romee, Sarah A Cooley, Peter Westervelt, John F. DiPersio, Jeffrey S. Miller, Daniel J. Weisdorf, Celalettin Ustun
      PubDate: 2017-05-31T19:55:26.432032-05:
      DOI: 10.1002/ajh.24804
  • Transformation in Pre-treatment Manifestations of Gaucher Disease Type 1
           during Two Decades of Alglucerase/Imiglucerase Enzyme Replacement Therapy
           in the International Collaborative Gaucher Group (ICGG) Registry
    • Authors: Pramod K. Mistry; Julie L. Batista, Hans C. Andersson, Manisha Balwani, Thomas Andrew Burrow, Joel Charrow, Paige Kaplan, Aneal Khan, Priya S. Kishnani, Edwin H. Kolodny, Barry Rosenbloom, C. Ronald Scott, Neal Weinreb
      Abstract: This study tests the hypothesis that the prevalence of severe clinical manifestations in Gaucher disease type 1 (GD1) patients at the time of treatment initiation has changed since alglucerase/imiglucerase enzyme replacement therapy (ERT) was approved in the United States (US) in 1991. US alglucerase/imiglucerase-treated GD1 patients from the International Collaborative Gaucher Group Gaucher Registry were stratified by age at ERT initiation (
      PubDate: 2017-05-31T19:55:25.595721-05:
      DOI: 10.1002/ajh.24801
  • The Prognostic Significance of Polyclonal Bone Marrow Plasma Cells in
           Patients with Relapsing Multiple Myeloma
    • Authors: Toshi Ghosh; Wilson I. Gonsalves, Dragan Jevremovic, Angela Dispenzieri, David Dingli, Michael M. Timm, William G. Morice, Prashant Kapoor, Taxiarchis V. Kourelis, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, Nelson Leung, Ronald S. Go, Yi Lin, Stephen J. Russell, John A. Lust, Steven R. Zeldenrust, Rahma Warsame, Yi L. Hwa, Robert A. Kyle, Morie A. Gertz, S. Vincent Rajkumar, Shaji K. Kumar
      Abstract: Prior studies have revealed that the presence of increasing number of polyclonal plasma cells (pPCs) in the bone marrow (BM) are associated with better outcomes in newly diagnosed multiple myeloma (MM) patients. This effect has not been studied in patients with MM at the time of disease relapse. We determined the prognostic value of depletion of pPCs in the BM by 7-color multiparameter flow cytometry in a series of 174 relapsing MM patients. The time to next therapy (TTNT) in those with
      PubDate: 2017-05-31T19:55:24.188635-05:
      DOI: 10.1002/ajh.24807
  • Autoimmune neutropenia of childhood secondary to other autoimmune
           disorders: data from the Italian Neutropenia Registry
    • Authors: Piero Farruggia; Giuseppe Puccio, Francesca Fioredda, Tiziana Lanza, Laura Porretti, Ugo Ramenghi, Angelica Barone, Sonia Bonanomi, Andrea Finocchi, Roberta Ghilardi, Saverio Ladogana, Nicoletta Marra, Baldassare Martire, Lucia Dora Notarangelo, Daniela Onofrillo, Marta Pillon, Giovanna Russo, Laura Lo Valvo, Jessica Serafinelli, Fabio Tucci, Fiammetta Zunica, Federico Verzegnassi, Carlo Dufour
      PubDate: 2017-05-31T19:55:23.056964-05:
      DOI: 10.1002/ajh.24803
  • A follow-up on Desiderosmia (olfactory craving), a novel symptom
           associated with iron deficiency anemia
    • Authors: Bryar R. Hansen; Wayne A. Bottner, Aishwarya Ravindran, Ramona DeJesus, Ronald S. Go
      PubDate: 2017-05-31T19:55:21.926608-05:
      DOI: 10.1002/ajh.24806
  • Cardiac Tamponade in Myelofibrosis: A Mayo Clinic Series of 9 Consecutive
    • Authors: Sravanthi Lavu; Ayalew Tefferi
      PubDate: 2017-05-31T19:50:23.527121-05:
      DOI: 10.1002/ajh.24800
  • Factors associated with risk of central nervous system relapse in patients
           with non-core binding factor acute myeloid leukemia
    • Authors: Elias Jabbour; Naval Guastad Daver, Nicholas James Short, Xuelin Huang, Hsiang-Chun Chen, Abhishek Maiti, Farhad Ravandi, Jorge Cortes, Simon Abi Aad, Guillermo Garcia-Manero, Zeev Estrov, Tapan Kadia, Susan O'Brien, Bouthaina Dabaja, Carlos Bueso-Ramos, Paolo Strati, Carol Bivins, Sherry Pierce, Hagop Kantarjian
      Abstract: Central nervous system (CNS) relapse is uncommon in patients with acute myeloid leukemia (AML) with the use of high-dose cytarabine containing chemotherapy regimens. The clinical and molecular features associated with a higher risk of CNS relapse are not well defined. We assessed the incidence and outcome of CNS relapses among 1245 patients with relapsed/refractory AML referred to our institution between 2000 and 2014. CNS leukemia relapse was observed in 51 patients (4.1%). Using a multivariate regression model and after adjusting for age, FLT3-ITD mutation (OR=2.33; p=0.02) and elevated LDH (>1000 IU/L, OR=1.99; p=0.04) were independent predictive factors for CNS relapse. Patients under 64 years of age with 0, 1, or 2 baseline adverse features had a probability of 3.8%, 7.0-8.0%, and 13.9% for developing CNS disease, respectively. Our study identifies patients with AML at higher risk for CNS relapse in whom prophylactic CNS therapy may be warranted. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-27T02:55:23.5782-05:00
      DOI: 10.1002/ajh.24799
  • Recognition of early mortality in multiple myeloma by a prediction matrix
    • Authors: Howard Terebelo; Shankar Srinivasan, Mohit Narang, Rafat Abonour, Cristina Gasparetto, Kathleen Toomey, James W. Hardin, Gail Larkins, Amani Kitali, Robert M. Rifkin, Jatin J. Shah
      Abstract: Early mortality (EM; death ≤ 6 months from diagnosis) has been reported in several newly diagnosed multiple myeloma (NDMM) trials. Before the era of novel agents, the incidence was 10%-14%. Causes of death included infections/pneumonia, renal failure, refractory disease, and cardiac events. Staging systems, such as the revised International Staging System (r-ISS), and prognostic factors including cytogenetics, lactate dehydrogenase levels, and myeloma-specific factors, are useful to assess overall prognosis; however, they cannot predict EM. We evaluated patients treated with novel agents in the Connect MM® Registry and identified risk factors of the EM cohort. Eligible patients were enrolled in the registry within 60 days of diagnosis. Univariate and multivariate analyses were conducted to evaluate associations between baseline characteristics and EM. Prediction matrices for EM were constructed from a logistic model. Between September 2009 and December 2011, 1493 patients were enrolled in the registry and had adequate follow-up. Of these patients, 102 (6.8%) had EM and 1391 (93.2%) survived for > 180 days. Baseline factors significantly associated with increased EM risk included age > 75 years, higher Eastern Cooperative Oncology Group performance status, lower EuroQol-5D mobility score, higher ISS stage, lower platelet count, and prior hypertension. Renal insufficiency trended toward increased EM risk. These risk factors were incorporated into a prediction matrix for EM. The EM prediction matrix uses differential weighting of risk factors to calculate EM risk in patients with NDMM. Identifying patients at risk for EM may provide new opportunities to implement patient-specific treatment strategies to improve outcomes. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-24T18:05:29.57664-05:0
      DOI: 10.1002/ajh.24796
  • Multicenter analysis of the use of transjugular intrahepatic portosystemic
           shunt (TIPS) for management of MPN-associated portal hypertension
    • Authors: Christopher R. Reilly; Daria V. Babushok, Karlyn Martin, Jerry L. Spivak, Michael Streiff, Ranjeeta Bahirwani, Jeffrey Mondschein, Brady Stein, Alison Moliterno, Elizabeth O. Hexner
      Abstract: BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders defined by proliferation of one or more myeloid lineages, and carry an increased risk of vascular events and progression to myelofibrosis and leukemia. Portal hypertension (pHTN) occurs in 7-18% of MPN patients via both thrombotic and nonthrombotic mechanisms and portends a poor prognosis. Transjugular intrahepatic portosystemic shunt (TIPS) has been used in the management of MPN-associated pHTN; however, data on long-term outcomes of TIPS in this setting is limited and the optimal management of medically refractory MPN-associated pHTN is not known. In order to assess the efficacy and long-term outcomes of TIPS in MPN-associated pHTN, we performed a retrospective analysis of 29 MPN patients who underwent TIPS at three academic medical centers between 1997 and 2016. The majority of patients experienced complete clinical resolution of pHTN and its clinical sequelae following TIPS. One, two, three, and four-year overall survival post-TIPS was 96.4%, 92.3%, 84.6%, and 71.4%, respectively. However, despite therapeutic anticoagulation, in-stent thrombosis occurred in 31.0% of patients after TIPS, necessitating additional interventions. In conclusion, TIPS can be an effective intervention for MPN-associated pHTN regardless of etiology. However, TIPS thrombosis is a frequent complication in the MPN population and indefinite anticoagulation post-TIPS should be considered. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-24T18:00:28.229997-05:
      DOI: 10.1002/ajh.24798
  • Ibrutinib Therapy for Lymphoplasmacytic Lymphoma
    • Authors: Margaret J. Helber; Jeremiah E. Moore, AnnaLynn M. Williams, Philip J. Meacham, Paul G. Rothberg, Clive S. Zent
      PubDate: 2017-05-24T18:00:25.166102-05:
      DOI: 10.1002/ajh.24795
  • Clinical impact of pre-transplant use of multiple tyrosine kinase
           inhibitors on the outcome of allo-HSCT for CML
    • Authors: Takeshi Kondo; Tokiko Nagamura-Inoue, Arinobu Tojo, Fumitaka Nagamura, Naoyuki Uchida, Hirohisa Nakamae, Takahiro Fukuda, Takehiko Mori, Shingo Yano, Mineo Kurokawa, Hironori Ueno, Heiwa Kanamori, Hisako Hashimoto, Makoto Onizuka, Minoko Takanashi, Tatsuo Ichinohe, Yoshiko Atsuta, Kazuteru Ohashi,
      Abstract: Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with chronic myelogenous leukemia in the chronic phase (CML-CP), and outcomes of TKI treatment for patients with CML-CP have been excellent. Since multiple TKIs are currently available, second-line or third-line TKI therapy is considered for patients who are intolerant of or resistant to the previous TKI treatment. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered only for patients with disease progression or for patients after treatment failure with multiple TKIs. To reflect the current clinical situation of patients with CML-CP, we tried to clarify whether prior TKI treatment affects the outcome of allo-HSCT. Data from 237 patients for whom the number of pre-transplant TKIs varied from one to three were used for analysis. Before allo-HSCT, 153 patients were treated with one TKI, 49 patients were treated with two TKIs and 35 patients were treated with three TKIs. In addition to conventional risk factors, i.e., disease status at transplantation and patient's age, the use of three TKIs before transplantation was identified as a significant adverse factor for prognosis. Non-relapse mortality rate was higher in patients treated with three TKIs than in patients treated with one or two TKIs. Our results suggest that allo-HSCT could be considered for young patients with CML-CP who manifest resistance to second-line TKI therapy and who have an appropriate donor. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-20T03:30:30.848038-05:
      DOI: 10.1002/ajh.24793
  • Chimeric Antigen Receptor Modified T cells That Target Chemokine Receptor
           CCR4 as a Therapeutic Modality for T-cell Malignancies
    • Authors: Liyanage P. Perera; Meili Zhang, Masao Nakagawa, Michael N. Petrus, Michiyuki Maeda, Marshall E. Kadin, Thomas A. Waldmann, Pin-Yu Perera
      PubDate: 2017-05-20T03:30:26.803875-05:
      DOI: 10.1002/ajh.24794
  • Pre-fibrotic/early primary myelofibrosis vs. WHO-defined essential
           thrombocythemia: The impact of minor clinical diagnostic criteria on the
           outcome of the disease
    • Authors: Georg Jeryczynski; Juergen Thiele, Bettina Gisslinger, Albert Wölfler, Martin Schalling, Andreas Gleiß, Sonja Burgstaller, Veronika Buxhofer-Ausch, Thamer Sliwa, Ernst Schlögl, Klaus Geissler, Maria-Theresa Krauth, Alexander Nader, Michael Vesely, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Christine Beham-Schmid, Heinz Gisslinger
      Abstract: The 2016 revised WHO criteria for the diagnosis of pre-fibrotic/early primary myelofibrosis (pre-PMF) require at least one of the following four borderline expressed minor clinical criteria: anemia, leukocytosis, elevated lactate dehydrogenase and splenomegaly. In this study, we evaluated the relative frequency of these four criteria in a group of 170 pre-PMF patients and compared them to 225 ET cases. More than 91% of pre-PMF cases showed one or more of these features required for diagnosis, by contrast with only 48.0% of ET patients. According to clinical data the cumulative risk of progression to advanced/overt PMF in pre-PMF was 36.9% after 15 years. After fitting cox regression models to analyze the impact of the minor criteria on overall survival, only leukocytosis remained as a significant predictor of survival in both pre-PMF and ET.Molecular characterization showed differences in survival in pre-PMF but not ET, with CALR being a more favorable mutation than JAK2. The different outcome of pre-PMF versus ET and associated molecular genetic data supports the concept of two different entities, rather than a continuum of the same disease.Although slightly less than 50% of ET patients also show one or more minor clinical criteria, accurate distinction between ET and pre-PMF is possible by following an integrated approach including histomorphological diagnosis and presence of minor clinical criteria. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-20T02:45:24.354158-05:
      DOI: 10.1002/ajh.24788
  • The aggressive peripheral T-cell lymphomas: 2017
    • Authors: James O. Armitage
      PubDate: 2017-05-18T00:35:39.687236-05:
      DOI: 10.1002/ajh.24791
  • Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing
           after autologous stem cell transplant in the current era of novel
           therapeutics: A retrospective analysis
    • Authors: SM Bair; L Strelec, SJ Nagle, SD Nasta, DJ Landsburg, AR Mato, AW Loren, SJ Schuster, EA Stadtmauer, J Svoboda
      Abstract: Patients with relapsed/refractory Hodgkin lymphoma (RR-HL) who progress or relapse following autologous stem cell transplantation (ASCT) have historically had a poor prognosis. Several novel agents, particularly brentuximab vedotin, have shown efficacy in this setting. However, there remains a paucity of data characterizing outcomes outside of clinical trials and how these novel agents impacted prognosis in general population of patients with RR-HL. Here, we conducted a retrospective analysis to evaluate outcomes in 87 patients with RR-HL with relapse post-ASCT. Treatment with novel agents (including brentuximab vedotin) was associated with significant improvement in median overall survival (OS) compared to patients who did not receive novel agents (85.6 vs 17.1 months; p
      PubDate: 2017-05-16T21:00:30.546864-05:
      DOI: 10.1002/ajh.24792
  • A hit to current ‘HIT' wisdom: A century later, it's time for a
    • Authors: Francesco Rodeghiero
      PubDate: 2017-05-16T20:46:00.904929-05:
      DOI: 10.1002/ajh.24789
  • Implementation of Multi-Disciplinary Care Reduces Maternal Mortality in
           Women with Sickle Cell Disease Living in Low-resource Setting
    • Authors: Eugenia Vicky Asare; Edeghonghon Olayemi, Theodore Boafor, Yvonne Dei-Adomakoh, Enoch Mensah, Harriet Ghansah, Yvonne Osei-Bonsu, Selina Crabbe, Latif Musah, Charles Hayfron-Benjamin, Brittany Covert, Adetola A. Kassim, Andra James, Mark Rodeghier, Michael R. DeBaun, Samuel A. Oppong
      Abstract: Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Intervention consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10,791 per 100,000 live births at pre-intervention to 1,176 per 100,000 at post-intervention, representing a risk reduction of 89.1% (p = 0.007). Perinatal mortality decreased from 60.8 per 1,000 total births at pre-intervention to 23.0 per 1,000 at post-intervention, representing a risk reduction of 62.2% (p = 0.20).A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-16T20:45:56.902867-05:
      DOI: 10.1002/ajh.24790
  • Look Into My Eyes: An Unusual First Presentation of Sickle Cell Disease
    • Authors: Rupali Sood; Kim Jiramongkolchai, Michael Streiff, Christopher Gonzalez, Satish Shanbhag, Sophie Lanzkron, J. Fernando Arevalo, Rakhi Naik
      PubDate: 2017-05-11T18:55:24.824436-05:
      DOI: 10.1002/ajh.24787
  • Urinary Prednisolone Excretion is a Determinant of Serum Hepcidin Levels
           in Renal Transplant Recipients
    • Authors: Michele F. Eisenga; Robin P. F. Dullaart, Stefan P. Berger, Daan J. Touw, Stephan J.L. Bakker, Carlo A.J.M. Gaillard
      PubDate: 2017-05-11T18:45:51.138627-05:
      DOI: 10.1002/ajh.24785
  • Characterization of TP53 mutations in clonal cytopenia of undetermined
    • Authors: Wei Wang; Mark J. Routbort, Chi Young OK, Keyur P. Patel, Yi Sun, Rashmi Kanagal-Shamanna, L. Jeffrey Medeiros, Sa A. Wang
      PubDate: 2017-05-11T18:45:48.338495-05:
      DOI: 10.1002/ajh.24786
  • Minimal Residual Disease Eradication with Epigenetic Therapy in Core
           Binding Factor Acute Myeloid Leukemia
    • Authors: Brittany Knick Ragon; Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
      Abstract: Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival. Real-time quantitative (RTPCR) trends were reviewed in 23 patients (median age 53 years) with CBF-AML that received HMA therapy following induction/consolidation with fludarabine, cytarabine and G-CSF (FLAG) with low dose gemtuzumab or idarubicin (NCT00801489). Of the 23 patients evaluated, 17 had a detectable RTPCR at HMA initiation. Five patients had progressive disease and a notable increase in RTPCR values over 1 to 2 cycles of HMA therapy. Twelve patients did not fail HMA and had a median RTPCR at HMA initiation of 0.06 (range, 0.01-0.91). Unlike the HMA failure subset, 11 of these patients had a reduction in RTPCR after the first or second cycle of HMA. Our data suggests that CBF-AML patients with low levels of RTPCR (between 0.01 and 0.05) at the conclusion of induction/consolidation chemotherapy benefit most from maintenance HMA, particularly those that have a reduction in the RTPCR within the first 2 cycles of HMA therapy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T18:45:45.280492-05:
      DOI: 10.1002/ajh.24782
  • Estimates of total body iron indicate 19 mg and 38 mg oral iron are
           equivalent for the mitigation of iron deficiency in individuals
           experiencing repeated phlebotomy
    • Authors: Walter Bialkowski; Joseph E. Kiss, David J. Wright, Ritchard Cable, Rebecca Birch, Pam D'Andrea, Barbara J. Bryant, Bryan R. Spencer, Alan E. Mast
      Abstract: Iron deficiency anemia is a common clinical condition often treated with tablets containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side effects lowering patient compliance. Oral iron supplements also increase hepcidin production causing decreased fractional absorption of subsequent doses. Frequent blood donors often become iron deficient. Therefore, they were enrolled in a two-year study involving continued blood donations and randomization to receive no pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI) did not change for the subset of donors in the no pill and placebo groups who completed both enrollment and final visits (p=0.21 and p=0.28, respectively). However, repeated measures regression analysis on the complete dataset estimated a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (p=0.001). The effects of 19 and 38 mg iron supplementation on TBI were indistinguishable (p=0.54). TBI increased by 229 mg after the initial 60 days of iron supplementation (p
      PubDate: 2017-05-11T18:45:37.334668-05:
      DOI: 10.1002/ajh.24784
  • Correlates of resistance and relapse during blinatumomab therapy for
           relapsed/refractory acute lymphoblastic leukemia
    • Authors: Ibrahim Aldoss; Joo Song, Tracey Stiller, Tina Nguyen, Joycelynne Palmer, Margaret O'Donnell, Anthony S Stein, Guido Marcucci, Stephen Forman, Vinod Pullarkat
      Abstract: We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM-ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts>50%) (P=0.02), history of prior EM-ALL (P=0.005), and active EM-ALL at the time of initiating blinatumomab (P=0.05) predicted lower CR rate. Among refractory cases, 13 (41%) had evidence of EM-ALL progression, and CD19 expression was negative or dim in 18% and 23%, respectively. Among responders, 20 (61%) subsequently relapsed among whom EM-ALL relapse occurred in 8 (40%) patients, and CD19 expression was negative or dim in 35% and 6% of evaluable cases, respectively. Pre-treatment moderate/strong CD19 expression (P=0.01) and history of prior EM-ALL during ALL course (P=0.04) were risk factors for developing EM-ALL at progression/relapse. However, no pretreatment factors predicted progression/relapse with CD19-negative ALL. Overall-survival (OS) and even-free survival were improved for patients underwent allogeneic HCT compared to responders who did not. Furthermore, OS was superior for patients responded to blinatumomab compared to those who did not. Extramedullary and CD19-negative disease are common during blinatumomab failure in r/r ALL. In addition to high leukemia burden, concurrent or prior history EM-ALL were associated with lower response to blinatumomab. Higher CD19 expression as well as prior history of EM-ALL were associated with EM-ALL at the time of blinatumomab failure. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T18:45:30.512175-05:
      DOI: 10.1002/ajh.24783
  • Outcome of Elderly Patients after Failure to Hypomethylating Agents Given
           as Frontline Therapy for Acute Myeloid Leukemia (AML): Single Institution
    • Authors: Rama Nanah; Kristen McCullough, William Hogan, Kebede Begna, Mrinal Patnaik, Michelle Elliott, Mark Litzow, Aref Al-Kali
      Abstract: Outcomes of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy is challenging. Hypomethylating agents (HMAs) can be effective in these patients but responses are usually short-lived. The majority of patients will either have stable disease or progress through therapy. We hereby describe the outcome of these patients at our institution after they fail HMAs. The data on 56 AML patients at Mayo Clinic, Rochester were reviewed. Patients were considered for our study if they received HMA as frontline therapy for their AML. Out of 56 patients, 15 (27%) patients received azacitidine (AZA) and 41 (73%) received decitabine. Complete remission was found in 10 (18%), with overall response of 28% and median response duration of 10 months. Thirteen (81%) out of 16 responders relapsed. Therefore 53 patients were included in the primary or secondary failure analysis with a median overall survival (OS) of two months after the date of failure. Out of 53 patients, 12 (23%) received subsequent treatments. None of the 12 patients who got first salvage therapy achieved remission. Five out of the 12 patients received second salvage therapy, 2 (40%) of which achieved CR. Median OS for patients who received subsequent salvage therapies was better than those who did not receive any subsequent therapy after failing HMA (9.5 vs 2 months, p = 0.0009). Outcome for patients who have primary or secondary failure is very poor. Our study provides important historical data for future novel therapies, which are sorely needed for these patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:18:46.445914-05:
      DOI: 10.1002/ajh.24780
  • Chronic lymphocytic leukemia in Brazil: A retrospective analysis of 1903
    • Authors: Matheus Vescovi Gonçalves; Celso Arrais Rodrigues, Irene Gyongyver Heidemarie Lorand Metze, Marcelo Pitombeira Lacerda, Alita Azevedo, Cintia Machado, Carlos Sérgio Chiattone, Sérgio Fortier, Leila Perobelli, Maura Rosane Valerio Ikoma, Nelma Clementino, Nelson Hamerschlak, Inara Lucia Arce, Vivia Machado Stehl, Larissa Veloso Mendes Ommati, Danielle Leão Cordeiro Farias, Fernando Barroso Duarte, Valeria Buccheri, Ana Paula Azambuja, Denise Ramos Almeida, Vera Lucia Piratininga Figueiredo, Mihoko Yamamoto,
      PubDate: 2017-05-05T06:14:05.836186-05:
      DOI: 10.1002/ajh.24779
  • Daratumumab Monotherapy Compared With Historical Control Data in Heavily
           Pretreated and Highly Refractory Patients With Multiple Myeloma: An
           Adjusted Treatment Comparison
    • Authors: Saad Z Usmani; Joris Diels, Tetsuro Ito, Maneesha Mehra, Imran Khan, Annette Lam
      Abstract: Daratumumab is a human CD38-directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison. Patient-level data were pooled from 2 daratumumab monotherapy studies (16 mg/kg; GEN501 and SIRIUS) and 2 independent US databases (IMS LifeLink and OPTUM), which reflect treatments used in real-world patients with MM who received ≥3 prior LOTs or were double refractory to a PI and an IMiD. Using a multivariate proportional hazards regression model, the relative treatment effect of daratumumab versus historical controls was estimated, adjusting for imbalances in characteristics between cohorts. Baseline characteristics that differed between patients treated with daratumumab (N=148) and historical control (N=658) were prior treatment with pomalidomide (55% vs 15%) or carfilzomib (41% vs 28%) and triple/quadruple refractory status (64% vs 14%). The adjusted overall survival–hazard ratio (OS-HR) for daratumumab versus historical control was 0.33 (95% confidence interval, 0.24-0.46) compared with 0.46 (0.35-0.59) for unadjusted HR. Impact of adjustment was mainly driven by refractory status and prior pomalidomide/carfilzomib exposure. This adjusted treatment comparison suggests that daratumumab demonstrates improved OS compared with historical control data in heavily pretreated and highly refractory MM patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:13:57.327007-05:
      DOI: 10.1002/ajh.24781
  • A novel in vivo model for studying conditional dual loss of BLIMP-1 and
           p53 in B-cells, leading to tumor transformation
    • Authors: Antonio Sacco; Yawara Kawano, Michele Moschetta, Oksana Zavidij, Daisy Huynh, Michaela Reagan, Yuji Mishima, Salomon Manier, Jihye Park, Elizabeth Morgan, Satoshi Takagi, Kwok K Wong, Ruben Carrasco, Irene M. Ghobrial, Aldo M. Roccaro
      Abstract: The tumor suppressors B-Lymphocyte-Induced Maturation Protein-1 (BLIMP-1) and p53 play a crucial role in B-cell lymphomas, and their inactivation contributes to the pathogenesis of a wide spectrum of lymphoid malignancies, including diffuse large B-cell lymphomas (DLBCLs). Patients with activated B-cell-like (ABC) DLBCL may present with loss of BLIMP-1, c-Myc over-expression, decreased p53, and poor prognosis. Nevertheless, there is a lack of in vivo models recapitulating the biology of high-grade ABC DLBCL. We therefore aimed to develop an in vivo model aiming to recapitulate the phenotype observed in this cohort of patients.A Cre-Lox approach was used to achieve inactivation of both p53 and BLIMP-1 in murine B-cells. Contextual ablation of BLIMP-1 and p53 led to development of IgM-positive B-cell lymphoma with an aggressive phenotype, supported by c-Myc up-regulation, and accumulation of somatic mutations, as demonstrated by whole exome sequencing. Sensitivity of B-tumor cells to BTK inhibition was demonstrated. This model mirrors what reported in patients with ABC DLBLC, and therefore represents a novel model for studying the biology of ABC-DLBCL harboring the dual loss of BLIMP-1/p53 and c-Myc over-expression. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:07:33.690921-05:
      DOI: 10.1002/ajh.24778
  • Acquired hemophilia A: Updated review of evidence and treatment guidance
    • Authors: Rebecca Kruse-Jarres; Christine L. Kempton, Francesco Baudo, Peter W. Collins, Paul Knoebl, Cindy A. Leissinger, Andreas Tiede, Craig M. Kessler
      Abstract: Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies (inhibitors) against endogenous factor VIII (FVIII) that leads to bleeding, which is often spontaneous and severe. AHA tends to occur in elderly patients with comorbidities and is associated with high mortality risk from underlying comorbidities, bleeding, or treatment complications. Treatment, which consists of hemostatic management and eradication of the inhibitors, can be challenging to manage.Few data are available to guide the management of AHA-related bleeding and eradication of the disease-causing antibodies. An extensive literature review was conducted with the aim to build on and complement already existing guidelines since the emergence of a newly approved hemostatic agent for this condition.An international panel of 8 experts in AHA was convened in 2015. A comprehensive literature search of PubMed and Embase was conducted; duplicate records and single-patient case studies were removed; and outputs were evaluated by at least 2 reviewers. Key questions were identified and analyzed; evidence was weighted; and consensus was formed. The resulting guidance for the management of AHA, presented here, was endorsed by the Hemostasis and Thrombosis Research Society of North America.AHA is rarely encountered by most physicians, and is likely to be underdiagnosed and misdiagnosed in real-world clinical practice. Data for AHA are limited and mainly restricted to registries, case reports, and clinical expertise. Recommendations for the management of AHA are summarized here based on the available data, integrated with the clinical experience of panel participants. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-03T18:20:57.713249-05:
      DOI: 10.1002/ajh.24777
  • The BCR-ABL1 transcript type influences response and outcome in
           Philadelphia chromosome-positive chronic myeloid leukemia patients treated
           frontline with imatinib
    • Authors: Fausto Castagnetti; Gabriele Gugliotta, Massimo Breccia, Alessandra Iurlo, Luciano Levato, Francesco Albano, Paolo Vigneri, Elisabetta Abruzzese, Giuseppe Rossi, Serena Rupoli, Francesco Cavazzini, Bruno Martino, Ester Orlandi, Patrizia Pregno, Mario Annunziata, Emilio Usala, Mario Tiribelli, Simona Sica, Massimiliano Bonifacio, Carmen Fava, Filippo Gherlinzoni, Monica Bocchia, Simona Soverini, Maria Teresa Bochicchio, Michele Cavo, Giovanni Martinelli, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Gianantonio Rosti,
      Abstract: The most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed. A qualitative PCR was performed at baseline: 52% patients had a e14a2 transcript, 37% a e13a2 transcript, 11% co-expressed both transcripts and 1% had other rare transcripts. The median follow-up was 76 months (95% of the patients had at least a 5-year observation). The complete cytogenetic response rates were comparable in e14a2 and e13a2 patients. The median time to MR3.0 (6 and 12 months) and MR4.0 (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR3.0 (88% and 83%, p
      PubDate: 2017-05-02T19:15:34.068537-05:
      DOI: 10.1002/ajh.24774
  • Validation of the 2016 Revisions to the WHO Classification in Lower-Risk
           Myelodysplastic Syndrome
    • Authors: Rashmi Kanagal-Shamanna; Juliana E. Hidalgo Lopez, Denái R. Milton, Hye Ryoun Kim, Chong Zhao, Zhuang Zuo, Michelle Janania Martinez, Francesco Stingo, John Lee, Rajyalakshmi Luthra, Elias J. Jabbour, Guillermo Garcia-Manero, L. Jeffrey Medeiros, Carlos E. Bueso-Ramos
      PubDate: 2017-04-29T10:24:27.890231-05:
      DOI: 10.1002/ajh.24776
  • A life-threatening ruxolitinib discontinuation syndrome
    • Authors: Giacomo Coltro; Francesco Mannelli, Paola Guglielmelli, Annalisa Pacilli, Alberto Bosi, Alessandro Maria Vannucchi
      PubDate: 2017-04-29T10:24:23.269551-05:
      DOI: 10.1002/ajh.24775
  • Clinical Outcomes in a Cohort of Patients with Heparin-induced
    • Authors: David J. Kuter; Barbara A. Konkle, Taye H. Hamza, Lynne Uhl, Susan F. Assmann, Joseph E. Kiss, Richard M. Kaufman, Nigel S. Key, Bruce S. Sachais, John R. Hess, Paul Ness, Keith R. McCrae, Cindy Leissinger, Ronald G. Strauss, Janice G. McFarland, Ellis Neufeld, James B. Bussel, Thomas L. Ortel
      Abstract: BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder usually prompting treatment with non-heparin anticoagulants. The benefits and risks of such treatments have not been fully assessed.METHODS: We analyzed data for 442 patients having a positive heparin-platelet factor 4 antibody test and recent heparin exposure. The primary outcome was a composite endpoint (death, limb amputation/gangrene, or new thrombosis). Secondary outcomes included bleeding and the effect of anticoagulation.FINDINGS: Seventy-one patients (16%) had HIT with thrombosis (HIT-T); 284 (64%) had HIT without thrombosis (isolated HIT); 87 (20%) did not have HIT. An intermediate or high “4T” score was found in 85%, 58%, and 8% of the three respective groups. Non-heparin anticoagulation was begun in 80%, 56% and 45%. The composite endpoint occurred in 48%, 36% and 17% (P=0.01) of which 61%, 38% and 40% were receiving non-heparin anticoagulation. Compared with the no HIT group, the composite endpoint was significantly more likely in HIT-T [HR 2.48 (1.35-4.55), P=0.003)] and marginally more likely in isolated HIT [HR 1.66 (0.96-2.85), P=0.071]. Importantly, risk increased (HR 1.77, P=0.02) after platelet transfusion. Major bleeding occurred in 48%, 36%, and 16% of the three groups (P=0.005). Non-heparin anticoagulation was not associated with a reduction in composite endpoint events in either HIT group.INTERPRETATION: HIT patients have high risks of death, limb amputation/gangrene, thrombosis, and bleeding. Non-heparin anticoagulant treatment may not benefit all patients and should be considered only after careful assessment of the relative risks of thrombosis and bleeding in individual patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-26T01:11:02.38029-05:0
      DOI: 10.1002/ajh.24759
  • Real-world results of ibrutinib in relapsed/refractory CLL in France:
           Early results on a large series of 428 patients
    • Authors: Loic Ysebaert; Thérèse Aurran-Schleinitz, Caroline Dartigeas, Marie-Sarah Dilhuydy, Pierre Feugier, Anne-Sophie Michallet, Olivier Tournilhac, Jehan Dupuis, Pierre Sinet, Claire Albrecht, Florence Cymbalista
      PubDate: 2017-04-25T03:51:30.806815-05:
      DOI: 10.1002/ajh.24773
  • ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic
           cell transplantation for acute myeloid leukemia - a report from the acute
           leukemia working party of the EBMT
    • Authors: Jonathan Canaani; Bipin N Savani, Myriam Labopin, Mauricette Michallet, Charles Craddock, Gerard Socié, Lisa Volin, Johan A Maertens, Charles Crawley, Didier Blaise, Per T Ljungman, Jan Cornelissen, Nigel Russell, Frédéric Baron, Norbert Gorin, Jordi Esteve, Fabio Ciceri, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
      Abstract: ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P=0.32], and non-relapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P=0.2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P=0.35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P=0.87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching [Hazard ratio (HR) of 0.7, 95% CI, 0.5-1; P = 0.049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T03:51:08.59011-05:0
      DOI: 10.1002/ajh.24771
  • Botryoid nuclei resulting from cocaine abuse
    • Authors: Maurizio Fumi; Ylenia Pancione, Silvia Sale, Vincenzo Rocco, Barbara J. Bain
      PubDate: 2017-04-25T03:50:53.475352-05:
      DOI: 10.1002/ajh.24769
  • Feasibility Trial for Primary Stroke Prevention in Children with Sickle
           Cell Anemia in Nigeria (SPIN Trial)
    • Authors: Najibah Galadanci; Shehu Umar Abdullahi, Leah D. Vance, Abdulkadir Musa Tabari, Shehi Ali, Raymond Belonwu, Auwal Salihu, Aisha Amal Galadanci, Binta Wudil Jibir, Halima Bello-Manga, Kathleen Neville, Fenella J. Kirkham, Yu Shyr, Sharon Phillips, Brittany V. Covert, Adetola A. Kassim, Lori C. Jordan, Muktar H. Aliyu, Michael R. DeBaun
      Abstract: The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥ 200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements 
      PubDate: 2017-04-25T03:50:29.092133-05:
      DOI: 10.1002/ajh.24770
  • The utility of MASS-FIX to detect and monitor monoclonal proteins in the
    • Authors: Paolo Milani; David L. Murray, David R. Barnidge, Mindy C. Kohlhagen, John R. Mills, Giampaolo Merlini, Surendra Dasari, Angela Dispenzieri
      Abstract: The detection and quantification of monoclonal-proteins (M-proteins) are necessary for the diagnosis and evaluation of response in plasma cell dyscrasias. Immunoglobulin enrichment-coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MASS-FIX) is a simple and inexpensive method to identify M-proteins, but its clinical generalizability has not yet been elucidated. We compared MASS-FIX to protein electrophoresis (PEL), serum/urine immunofixation-electrophoresis (IFE) and quantitative serum free-light chain (FLC) for the identification of M-proteins in different clinical diagnoses. Paired serum and urine samples from 257 patients were tested. There were six patients for whom s-IFE and FLC ratio were positive and serum MASS-FIX was negative, but when serum and urine MASS-FIX results were combined, only one patient with light chain-MGUS was missed. Serum/urine-MASS-FIX detected M-proteins in 18 patients with negative serum/urine-PEL/IFE and serum-FLC, 10 of whom had multiple myeloma or AL amyloidosis, who were mistakenly thought to have complete hematologic response by serum/urine-PEL/IFE and serum-FLC. Nearly half of the AL amyloidosis patients had atypical spectra, which may prove to be a clue to the diagnosis and pathogenesis of the disease. In conclusion, MASS-FIX has a comparable sensitivity with PEL/IFE/FLC methods and can help inform the clinical diagnosis. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T03:50:13.45982-05:0
      DOI: 10.1002/ajh.24772
  • High prevalence of monoclonal gammopathy among patients with warm
           autoimmune hemolytic anemia
    • Authors: Aishwarya Ravindran; Janani Sankaran, Eapen K. Jacob, Justin D. Kreuter, C. Christopher Hook, Morie A. Gertz, Timothy G. Call, Rajiv K. Pruthi, Mark R. Litzow, Alexandra P. Wolanskyj, William J. Hogan, Aneel A. Ashrani, Kebede H. Begna, Ariela L. Marshall, Robert A. Kyle, Neil E. Kay, Ronald S. Go
      PubDate: 2017-04-24T18:15:57.947054-05:
      DOI: 10.1002/ajh.24765
  • Clinical Significance of IgE in a Large Cohort of Patients with Moderate
           or Severe Chronic Graft-versus-Host Disease
    • Authors: Sencer Goklemez; Filip Pirsl, Lauren M. Curtis, Seth M. Steinberg, Edward W. Cowen, Jacqueline W. Mays, Meg Kenyon, Judy Baruffaldi, Fran T. Hakim, Steven Z. Pavletic
      PubDate: 2017-04-24T18:15:56.853007-05:
      DOI: 10.1002/ajh.24768
  • Early Mortality and Overall Survival of Acute Myeloid Leukemia Based on
           Facility Type
    • Authors: Vijaya R. Bhatt; Valerie Shostrom, Smith Giri, Krishna Gundabolu, K.M. Monirul Islam, Frederick R. Appelbaum, Lori J. Maness
      Abstract: Cancer health disparities may exist based on the facility type. We aimed to determine the association between the academic status of centers and outcomes of patients with acute myeloid leukemia (AML). Using the National Cancer Data Base, we compared one-month mortality and longer-term overall survival (OS) of 60,738 patients with AML, who received first course treatment between 2003-2011 at academic or non-academic centers (community cancer program, comprehensive community cancer program, and others). Multivariate analysis was done using logistic regression for one-month mortality and Cox regression with backward elimination approach for OS. Patients treated at academic centers differed from those at non-academic centers in that they were younger with a median age of 62 versus 70 years (p
      PubDate: 2017-04-24T18:15:54.775481-05:
      DOI: 10.1002/ajh.24767
  • The impact of sample site and storage on thromboelastography values
    • Authors: Mari Tuovila; Tiina Erkinaro, Eeva-Riitta Savolainen, Paivi Laurila, Pasi Ohtonen, Tero Ala-Kokko
      PubDate: 2017-04-24T18:15:52.356242-05:
      DOI: 10.1002/ajh.24766
  • Heterogeneity of neutrophil spontaneous death
    • Authors: Yan Teng; Hongbo R Luo, Hiroto Kambara
      PubDate: 2017-04-24T18:15:51.635813-05:
      DOI: 10.1002/ajh.24764
  • Mitotic figure in the peripheral blood smear
    • Authors: Sebastian Hörber; Ingo Rettig, Andreas Peter
      Abstract: A previously healthy 19-year-old man presented with fever, sore throat and strong feeling of illness. Physical examination showed strong swelling of throat tonsils and moderate hepatosplenomegaly. The laboratory values were as following: a total white blood count of 10.9 x 109/L, hemoglobin 14.1 g/dL and a platelet count of 109 x 109/L. Total bilirubin was 1.4 mg/dL and CRP was 1.32 mg/dL. The serological analyses revealed IgG and IgM antibodies against EBV-VCA consistent with an acute Epstein-Barr virus infection. The peripheral blood smear revealed 80.0% lymphocytes, 12.4% neutrophils, 6.9% monocytes, 0.4% eosinophils and 0.3% basophils. In it a mitotic figure was found (see illustration). Mitotic figures are an extremely uncommon finding as they are usually seen in patients with acute leukemia or rarer in EBV infections. Symptomatic therapy led to complete resolution of the symptoms. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-12T12:15:38.164844-05:
      DOI: 10.1002/ajh.24761
  • CD105 expression in early erythroid precursors
    • Authors: José Antonio García-Vela; Isaac Martin Rubio, Juan Marquet, Miguel Angel Alvarez Juarez
      PubDate: 2017-04-12T12:15:34.44241-05:0
      DOI: 10.1002/ajh.24763
  • Akt inhibitor MK-2206 in combination with Bendamustine and Rituximab in
           Relapsed or Refractory Chronic Lymphocytic Leukemia: Results from the
           N1087 Alliance Study
    • Authors: Jeremy T. Larsen; Tait D. Shanafelt, Jose F. Leis, Betsy LaPlant, Tim Call, Adam Pettinger, Curtis Hanson, Charles Erlichman, Thomas Matthew Habermann, Craig Reeder, Daniel Nikcevich, Deborah Bowen, Michael Conte, Justin Boysen, Charla Secreto, Connie Lesnick, Renee Tschumper, Diane Jelinek, Neil E. Kay, Wei Ding
      Abstract: Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single-agent MK-2206 (weekly dosed) was administered one-week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2-6. Phase II employed the MTD of MK-2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6-cycle of therapy. The maximum tolerated dose of MK-2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-12T10:37:23.271765-05:
      DOI: 10.1002/ajh.24762
  • A Somatic Mosaicism in the G6PD Gene Inducing a Late Onset Chronic non
           Spherocytic Hemolytic Anemia
    • Authors: Lucile Couronné; Gérard Tertian, Audrey Boutron, Véronique Picard, Patricia Hughes, Olivier Hermine, Claude Préhu, Gil Tchernia, Loïc Garçon
      PubDate: 2017-04-10T11:32:23.924921-05:
      DOI: 10.1002/ajh.24760
  • Associations between Elevated Pre-treatment Serum Cytokines and Peripheral
           Blood Cellular Markers of Immunosuppression in Patients with Lymphoma
    • Authors: Moritz Binder; Megan M. O'Byrne, Matthew J. Maurer, Stephen Ansell, Andrew L. Feldman, James Cerhan, Anne Novak, Luis Francisco Porrata, Svetomir Markovic, Brian K. Link, Thomas E. Witzig
      Abstract: Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n=390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r=-0.36), IL-12 (r=-0.17), IP-10 (r=-0.23), and MIG (r=-0.32) concentrations (p
      PubDate: 2017-04-06T05:40:23.785406-05:
      DOI: 10.1002/ajh.24758
  • Chronic lymphocytic leukemia (CLL) and prognostic models: A bridge between
           clinical and biological markers
    • Authors: Gianluigi Reda; Ramona Cassin, Bruno Fattizzo, Diana Giannarelli, Veronica Mattiello, Wilma Barcellini, Agostino Cortelezzi
      PubDate: 2017-04-06T05:35:31.651583-05:
      DOI: 10.1002/ajh.24755
  • IgM Myeloma: A Multicenter Retrospective Study of 134 Patients
    • Authors: Jorge J. Castillo; Artur Jurczyszyn, Lucie Brozova, Edvan Crusoe, Jacek Czepiel, Julio Davila, Angela Dispenzieri, Marion Eveillard, Mark A. Fiala, Irene M. Ghobrial, Alessandro Gozzetti, Joshua N. Gustine, Roman Hajek, Vania Hungria, Jiri Jarkovsky, David Jayabalan, Jacob P. Laubach, Barbara Lewicka, Vladimir Maisnar, Elisabet E. Manasanch, Philippe Moreau, Elizabeth A. Morgan, Hareth Nahi, Ruben Niesvizky, Claudia Paba-Prada, Tomas Pika, Ludek Pour, John L. Reagan, Paul G. Richardson, Jatin Shah, Ivan Spicka, Ravi Vij, Anna Waszczuk-Gajda, Morie A. Gertz
      Abstract: IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37%, 43%, 19% and 70%, respectively. The median serum IgM level was 2,895 mg/dl with 19% of patients presenting with levels >6,000 mg/dl. International Staging System (ISS) stages 1, 2 and 3 were seen in 40 (33%), 54 (44%) and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (p=0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-06T05:35:27.756816-05:
      DOI: 10.1002/ajh.24753
  • Clinical characteristics and prognostic factors in multiple myeloma
           patients with light chain deposition disease
    • Authors: Meera Mohan; Amy Buros, Pankaj Mathur, Neriman Gokden, Manisha Singh, Sandra Susanibar, Jorge Jo Kamimoto, Shadiqul Hoque, Muthukumar Radhakrishnan, Aasiya Matin, Cynthia Davis, Monica Grazziutti, Sharmilan Thanendrarajan, Frits van Rhee, Maurizio Zangari, Faith Davies, Gareth Morgan, Joshua Epstein, Bart Barlogie, Carolina Schinke
      Abstract: Light chain deposition disease (LCDD) is characterized by monotypic immunoglobulin depositions which will eventually lead to loss of organ function if left untreated. While the kidney is almost always affected, the presence and degree of LCDD in other organs vary. Ten to 30% of LCDD patients have underlying Multiple Myeloma (MM), yet outcome and prognostic markers in this particular patient group are still lacking. Here, we analyzed 69 patients with MM and biopsy proven LCDD and report on renal and extra-renal involvement and its impact on prognosis as well as renal response depending on hematologic response. Coexisting light chain diseases such as AL amyloid and cast nephropathy were found in 30% of patients; those with LCDD and concurrent amyloid tended to have shorter survival. Cardiac involvement by LCDD was seen in one-third of our patients and was associated with shorter overall survival; such patients also had a significantly higher risk of treatment related mortality (TRM) after stem cell transplant (SCT) compared to LCDD patients without cardiac involvement. This study highlights that MM patients with LCDD present with different clinical features compared to previously reported LCDD cohorts. Rapid initiation of treatment is necessary to prevent progressive renal disease and worse outcome. Coexisting light chain diseases and cardiac involvement are more common than previously reported and confer worse clinical outcome, emphasizing the need for careful patient careful patient evaluation and treatment selection. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-06T05:35:13.223541-05:
      DOI: 10.1002/ajh.24756
  • Monosomal karyotype in chronic lymphocytic leukemia: association with
           clinical and biological features and potential prognostic significance
    • Authors: Maria Joao Baptista; Isabel Granada, Mireia Morgades, María-José Calasanz, Jordi Canals, Diego Robles De Castro, Elisa Luño, Neus Ruiz-Xivillé, Inés Rodríguez-Hernández, Teresa González, María-José Terol, Alberto Valiente, Francisco Ortuño, María-Dolores Garcia-Malo, María-Ángeles Piñan, Ana Carla Oliveira, Maria Talavera, Ismael Buño, Ana Batlle-López, Carol Moreno, Christelle Ferra, Francesc Solé
      PubDate: 2017-04-06T05:35:03.476211-05:
      DOI: 10.1002/ajh.24754
  • "Anemia is present years before myelodysplastic syndrome diagnosis –
           results from the pre-diagnostic period"
    • Authors: Jakob Werner Hansen; Håkon Sandholdt, Volkert Siersma, Andreas Due Ørskov, Staffan Holmberg, Ole Weis Bjerrum, Hans Carl Hasselbalch, Niels F Olivarius, Kirsten Groenbaek, Christen Andersen
      PubDate: 2017-04-06T05:34:43.05235-05:0
      DOI: 10.1002/ajh.24757
  • The 2016 WHO diagnostic criteria for polycythemia vera renders an accurate
           diagnosis to a broader range of patients including masked polycythemia
           vera: comparison with the 2008 WHO diagnostic criteria
    • Authors: Kyohei Misawa; Hajime Yasuda, Marito Araki, Tomonori Ochiai, Soji Morishita, Mai Nudejima, Yumi Hironaka, Shuichi Shirane, Yoko Edahiro, Akihiko Gotoh, Akimichi Ohsaka, Norio Komatsu
      PubDate: 2017-04-04T18:05:43.919383-05:
      DOI: 10.1002/ajh.24752
  • A multicenter prospective study on efficacy and safety of imatinib
           generics; a report from Polish Adult Leukemia Group imatinib generics
    • Authors: T. Sacha; J. Góra-Tybor, M. Szarejko, G. Bober, O. Grzybowska-Izydorczyk, J. Niesiobędzka-Krężel, M. Dudziński, E. Wasilewska, K. Myśliwiec, J. Gil, M. Gniot, I. Pietkun, E. Mędraś, J. Hołojda, J. Wącław, K. Giannopoulos
      Abstract: The efficacy and safety of imatinib generics were not studied and reported on larger cohort of patients yet. We report on efficacy and safety of imatinib generics in 726 chronic myeloid leukemia patients in chronic phase who completed one-year observation, prospectively assessed within Polish Adult Leukemia Group imatinib generics registry. In 99 previously untreated patients the rate of early molecular response achieved at 3 months and major molecular response achieved at 12 months was 65.7% and 53.4% respectively. Complete cytogenetic response at 6 months was achieved in 55.4% of patients. In 627 patients switched from branded to generic imatinib the molecular response was sustained in 64.8%, worsened in 15% and improved in 19% of them. Complete cytogenetic response, major molecular response and MR4,5 were lost in 0.3%, 1.3% and 10.3%, respectively. Hematologic toxicity (grade 3 or 4) and non-hematologic toxicity (any grade) occurred in 3% and 40% of 99 previously untreated patients and in 0.2% and 14.4% of "switched" patients, respectively. In one-year observation the efficacy and safety of tested imatinib generics are not inferior to branded imatinib. No increased switching rate from first to second generation tyrosine kinase inhibitors was noticed This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-04T18:05:40.870471-05:
      DOI: 10.1002/ajh.24748
  • A puzzling case of methemoglobinemia
    • Authors: Audrey Morris; Barbara J. Bain, Maria Atta, D. Mark Layton
      PubDate: 2017-03-31T18:10:27.877779-05:
      DOI: 10.1002/ajh.24747
  • NPM1 mutation but not RUNX1 mutation or multilineage dysplasia defines a
           prognostic subgroup within de novo acute myeloid leukemia lacking
           recurrent cytogenetic abnormalities in the revised 2016 WHO Classification
    • Authors: Olga K. Weinberg; Christopher J. Gibson, Traci M. Blonquist, Donna Neuberg, Olga Pozdnyakova, Frank Kuo, Benjamin L. Ebert, Robert P. Hasserjian
      PubDate: 2017-03-28T10:50:38.067097-05:
      DOI: 10.1002/ajh.24739
  • Secondary CNS Involvement of ALK-Negative Anaplastic Large Cell Lymphoma
    • Authors: Ajay Major; Zenggang Pan, Manali Kamdar
      PubDate: 2017-03-28T10:50:34.806914-05:
      DOI: 10.1002/ajh.24733
  • Cutaneous septic emboli from Candida glabrata in a haematological patient
    • Authors: Andrea Lombardi; Giorgio Alberto Croci, Valeria Brazzelli, Marco Vecchia, Valentina Zuccaro, Marco Sciarra, Raffaele Bruno
      PubDate: 2017-03-23T18:33:38.977836-05:
      DOI: 10.1002/ajh.24729
  • A Centrocyte Blood Count of a Quarter Million
    • Authors: Matthew Behrens; Rajasree P. Chowdry, Saliba Saba, Nakhle S. Saba
      PubDate: 2017-03-01T00:51:01.588441-05:
      DOI: 10.1002/ajh.24708
  • Plasmodium knowlesi
    • Authors: Peter Chiodini; Barbara J. Bain
      PubDate: 2017-02-23T07:25:54.80021-05:0
      DOI: 10.1002/ajh.24697
  • Identification of renal infiltration based on urinary findings in a child
           with burkitt leukemia/lymphoma
    • Authors: Zühre Kaya; Nurettin Alıcı, Özlem Ezgi Özmen, Meltem Akgül, Büşra Topuz, Emine Akkuzu
      PubDate: 2017-02-22T03:45:26.542078-05:
      DOI: 10.1002/ajh.24694
  • The distinctive cytological features of T-cell prolymphocytic leukemia
    • Authors: Vishal Jayakar; Kan Cheung, Eva Yebra-Fernandez, Barbara J. Bain
      PubDate: 2017-02-21T00:26:12.320801-05:
      DOI: 10.1002/ajh.24659
  • The significance of irregularly contracted cells and hemighosts in sickle
           cell disease
    • Authors: Wenchee Siow; Francis Matthey, Barbara J. Bain
      PubDate: 2017-02-21T00:26:07.934864-05:
      DOI: 10.1002/ajh.24658
  • DAT-positive Plasmodium ovale malaria presenting in a child with sickle
           cell anemia
    • Authors: Nicholas S. Whipple; Jason R. Schwartz, Kerri A. Nottage
      PubDate: 2017-02-17T03:25:24.73837-05:0
      DOI: 10.1002/ajh.24691
  • Issue Information – Table of Contents
    • Pages: 595 - 597
      PubDate: 2017-06-13T05:06:25.029202-05:
      DOI: 10.1002/ajh.24514
  • Natural history of chronic myelomonocytic leukemia treated with
           hypomethylating agents
    • Authors: Ana Alfonso; Guillermo Montalban-Bravo, Koichi Takahashi, Elias J. Jabbour, Tapan Kadia, Farhad Ravandi, Jorge Cortes, Zeev Estrov, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos Bueso-Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
      First page: 599
      Abstract: Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n=151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow-up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20-28) and event-free survival 14 months (95%CI: 11-17). By multivariate analysis, age 
      PubDate: 2017-03-28T10:35:31.932396-05:
      DOI: 10.1002/ajh.24735
  • Pediatric patients undergoing hematopoietic stem cell transplantation can
           greatly benefit from a novel once-daily intravenous busulfan dosing
    • Authors: Su-jin Rhee; Ji Won Lee, Kyung-Sang Yu, Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Kyung Duk Park, Hee Young Shin, Sang Hoon Song, Hyoung Jin Kang, Howard Lee
      First page: 607
      Abstract: Busulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aims of this study were to derive a novel once-daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2,183 busulfan concentrations in 137 pediatric patients (age: 0.6 - 22.2 years), who received IV busulfan once-daily for 4 days before undergoing HSCT. Based on the final population PK model, an optimal once-daily IV busulfan dosing nomogram was derived. The percentage of simulated patients achieving the daily target area under the concentration-time curve (AUC) by the new nomogram was compared with that by other busulfan dosing regimens including the FDA regimen, the EMA regimen, and the empirical once-daily regimen without TDM. A one-compartment open linear PK model incorporating patient's body surface area, age, dosing day, and aspartate aminotransferase as a significant covariate adequately described the concentration–time profiles of busulfan. An optimal dosing nomogram based on the PK model performed significantly better than the other dosing regimens, resulting in >60% of patients achieving the target AUC while the percentage of patients exceeding the toxic AUC level was kept
      PubDate: 2017-03-28T10:35:41.097009-05:
      DOI: 10.1002/ajh.24734
  • Enumerating Bone Marrow Blasts from Nonerythroid Cellularity Improves
           Outcome Prediction in Myelodysplastic Syndromes and Permits a Better
           Definition of the Intermediate Risk Category of the Revised International
           Prognostic Scoring System (IPSS-R)
    • Authors: Xavier Calvo; Leonor Arenillas, Elisa Luño, Leonor Senent, Montserrat Arnan, Fernando Ramos, Carme Pedro, Mar Tormo, Julia Montoro, María Díez-Campelo, María Laura Blanco, Beatriz Arrizabalaga, Blanca Xicoy, Santiago Bonanad, Andrés Jerez, Meritxell Nomdedeu, Ana Ferrer, Guillermo F Sanz, Lourdes Florensa,
      First page: 614
      Abstract: The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3,924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. 24% patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS
      PubDate: 2017-03-28T10:35:52.510098-05:
      DOI: 10.1002/ajh.24732
  • Inhaled Steroids Reduce Pain and sVCAM Levels in Individuals with Sickle
           Cell Disease: A Triple-Blind, Randomized Trial
    • Authors: Jeffrey Glassberg; Caterina Minnitti, Caroline Cromwell, Lawrence Cytryn, Thomas Kraus, Gwen S. Skloot, Jason T. Connor, Adeeb H. Rahman, William J. Meurer
      First page: 622
      Abstract: Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance and hyperreactivity) is an intrinsic component of SCD and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 non-asthmatic individuals with SCD. Participants received once daily mometasone furoate 220 mcg dry powder inhalation or placebo for 16 weeks. The primary outcome was feasibility (the number who complete the trial divided by the total number enrolled) with pre-specified efficacy outcomes including daily pain score over time (patient reported) and change in soluble vascular cell adhesion molecule (sVCAM) levels between entry and 8-weeks. For the primary outcome of feasibility, the result was 96% (52 of 54, 95% CI 87% - 99%) for the intent-to-treat analysis and 83% (45 of 54, 95% CI 71% - 91%) for the per-protocol analysis. The adjusted treatment effect of mometasone was a reduction in daily pain score of 1.42 points (95%CI 0.61 - 2.21, p = 0.001). Mometasone was associated with a reduction in sVCAM levels of 526.94 ng/mL more than placebo (95% CI 50.66 - 1,003.23, p = 0.03). These results support further study of ICS in SCD including multi-center trials and longer durations of treatment. (NCT02061202) This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:35:56.217691-05:
      DOI: 10.1002/ajh.24742
  • Renal Outcomes in Patients with AL Amyloidosis: Prognostic Factors, Renal
           response and the Impact of Therapy
    • Authors: Efstathios Kastritis; Maria Gavriatopoulou, Maria Roussou, Magdalini Migkou, Despina Fotiou, Dimitrios C. Ziogas, Nikos Kanellias, Evangelos Eleutherakis-Papaiakovou, Ioannis Panagiotidis, Stavroula Giannouli, Erasmia Psimenou, Smaragdi Marinaki, Theofanis Apostolou, Hariklia Gakiopoulou, Anna Tasidou, Ioannis Papassotiriou, Evangelos Terpos, Meletios A. Dimopoulos
      First page: 632
      Abstract: A staging system for patients with renal AL amyloidosis, based on eGFR (
      PubDate: 2017-03-28T10:50:23.837826-05:
      DOI: 10.1002/ajh.24738
  • Monocytosis in Polycythemia Vera: Clinical and Molecular Correlates
    • Authors: Daniela Barraco; Sonia Cerquozzi, Naseema Gangat, Mrinal M Patnaik, Terra Lasho, Christy Finke, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani, Ayalew Tefferi
      First page: 640
      Abstract: Monocytosis (absolute monocyte count, AMC ≥1 x 109/L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)-defined PV, 55 (21%) patients displayed an AMC of ≥1 x 109/L and 18 (7%) an AMC of ≥1.5 x 109/L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs 50% at AMC ≥1 x 109/L) and TET2/SRSF2 mutations (57%/29% vs 19%/1% at AMC≥1.5 x 109/L). In univariate analysis, AMC ≥1.5 x 109/L adversely affected overall (OS; p=0.004; HR 2.6, 95% CI 1.4-4.8) and myelofibrosis-free (MFFS; p=0.02; HR 4.4, 95% CI 1.3-15.1) survival; during multivariable analysis, significance was borderline sustained for OS (p=0.05) and MFFS (p=0.06). Other independent risk factors for OS included unfavorable karyotype (p=0.02, HR 3.39, 95% CI 1.17-9.79), older age (p
      PubDate: 2017-03-28T10:50:28.504525-05:
      DOI: 10.1002/ajh.24740
  • Independent Adjudicator Assessments of Platelet Refractoriness and rFVIIa
           Efficacy in Bleeding Episodes and Surgeries from the Multinational
           Glanzmann's Thrombasthenia Registry
    • Authors: Michael Recht; Madhvi Rajpurkar, Meera Chitlur, Roseline d'Oiron, Rainer Zotz, Giovanni Di Minno, David L. Cooper, Man-Chiu Poon
      First page: 646
      Abstract: Glanzmann's thrombasthenia (GT) is a rare congenital bleeding disorder associated with decreased platelet aggregation due to qualitative/quantitative deficiencies of the fibrinogen receptor. Severe bleeding episodes and perioperative bleeding are typically managed with platelet transfusions, although patients can develop anti-platelet antibodies or experience clinical refractoriness. The GT Registry (GTR) was established to collect efficacy/safety data on hemostatic treatments for GT, including recombinant factor VIIa (rFVIIa). At the request of the United States Food and Drug Administration, three hematology experts evaluated platelet refractoriness, antibody status, and rFVIIa efficacy data on a case-by-case basis to support a potential indication for rFVIIa in GT. Adjudication included 195 patients with 810 events (619 severe bleeding episodes, 192 surgeries), and a consensus algorithm was developed to describe adjudicators' coding of refractoriness and antibody status based on treatment patterns over time. Most rFVIIa-treated events were in patients without refractoriness or antibodies. Adjudicators rated most rFVIIa-treated bleeding episodes as successful (251/266, 94.4%; rFVIIa only, 101/109, 92.7%; rFVIIa ± platelets ± other agents, 150/157, 95.5%); efficacy was consistent in patients with platelet refractoriness ± antibodies (75/79, 94.9%), antibodies only (10/10, 100.0%), and neither/unknown (166/177, 93.8%). Adjudicators also rated most rFVIIa-treated surgeries as successful (159/160, 99.4%; rFVIIa only, 65/66, 98.5%; rFVIIa ± platelets ± other agents, 94/94, 100.0%); efficacy was consistent in patients with platelet refractoriness ± antibodies (69/70, 98.6%), antibodies only (24/24, 100.0%), and neither/unknown (66/66, 100.0%). Unblinding the adjudicators to investigator efficacy ratings changed few assessments. Doses of rFVIIa were narrowly distributed, regardless of other hemostatic agents used. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:50:30.411683-05:
      DOI: 10.1002/ajh.24741
  • Long term impact of hyperleukocytosis in newly diagnosed acute myeloid
           leukemia patients undergoing allogeneic stem cell transplantation: an
           analysis from the acute leukemia working party of the EBMT
    • Authors: Jonathan Canaani; Myriam Labopin, Gerard Socié, Anne Nihtinen, Anne Huynh, Jan Cornelissen, Eric Deconinck, Tobias Gedde-Dahl, Edouard Forcade, Patrice Chevallier, Jean Henri Bourhis, Didier Blaise, Mohamad Mohty, Arnon Nagler
      First page: 653
      Abstract: Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the EBMT. A cohort of 357 patients with hyperleukocytosis (159 patients with WBC 50K-100K, 198 patients with WBC≥100K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14 - 2.12; p=0.004), decreased leukemia-free survival (HR of 1.38, 95% CI, 1.07 - 1.78; p=0.013), and inferior overall survival (HR of 1.4, 95% CI, 1.07 - 1.84; p=0.013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:50:33.397973-05:
      DOI: 10.1002/ajh.24737
  • A Phase 1 Study of AMG 900, an Orally Administered Pan-Aurora Kinase
           Inhibitor, in Adult Patients With Acute Myeloid Leukemia
    • Authors: Hagop M. Kantarjian; Michael W. Schuster, Nitin Jain, Anjali Advani, Elias Jabbour, Erick Gamelin, Erik Rasmussen, Gloria Juan, Abraham Anderson, Vincent F. Chow, Greg Friberg, Florian D. Vogl, Mikkael A. Sekeres
      First page: 660
      Abstract: Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small-molecule inhibitor of both Aurora kinase A and B, in patients with AML. Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every-2-week dose-escalation schedules using a modified 3 + 3+3 design were used: AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule). Thirty-five patients were enrolled at 9 different dose levels: 22 patients on the 4/10 schedule (doses from 15 to 100 mg daily), and 13 patients on the 7/7 schedule (doses from 30 to 50 mg daily). Both schedules were tolerated; nausea (31%), diarrhea (29%), febrile neutropenia (29%), and fatigue (23%) were the most common treatment-related adverse events. Three patients (9%) achieved complete response with incomplete count recovery. Patients with higher baseline expression of a set of specific pathway-related genes (BIRC5, AURKA, TTK, CDC2, and CCNB1) were more likely to respond in an exploratory biomarker analysis. AMG 900 was tolerated in a general AML population, and pathway-specific biomarkers identified a potential target population. Future research efforts will be directed toward further exploration of biomarkers of response and combination of AMG 900 with other anticancer agents. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:50:41.602061-05:
      DOI: 10.1002/ajh.24736
  • Clinical Presentation and Outcomes of Patients with Type 1 Monoclonal
    • Authors: Surbhi Sidana; S. Vincent Rajkumar, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, David Dingli, Prashant Kapoor, Wilson I. Gonsalves, Ronald S. Go, Yi Lisa Hwa, Nelson Leung, Amie L. Fonder, Miriam A. Hobbs, Steven R. Zeldenrust, Stephen J. Russell, John A. Lust, Robert A. Kyle, Shaji K. Kumar
      First page: 668
      Abstract: We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n=43, 42%) and ulcers/gangrene (n=35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n=24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS – 39, myeloma – 20, lymphoplasmacytic lymphoma – 21 and others – 14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia-related symptoms in 57. Treatment regimens consisted of: steroids +/- alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab +/- steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n=47) or stabilization (n=16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one-half. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-29T12:19:13.806616-05:
      DOI: 10.1002/ajh.24745
  • An exploratory clinical trial of bortezomib in patients with lower risk
           myelodysplastic syndromes
    • Authors: May Daher; Juliana Elisa Hidalgo Lopez, Jasleen K. Randhawa, Kausar Jabeen Jabbar, Yue Wei, Naveen Pemmaraju, Gautam Borthakur, Tapan Kadia, Marina Konopleva, Hagop M. Kantarjian, Katherine Hearn, Zeev Estrov, Steven Reyes, Carlos E. Bueso-Ramos, Guillermo Garcia-Manero
      First page: 674
      Abstract: Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis and an increased risk of transformation. Few effective therapies are available for lower risk MDS patients, especially after the failure of hypomethylating agents. MDS progenitor cells are dependent on the nuclear factor-κB (NF-κB) for survival, which makes it an attractive therapeutic target. As a proteosomal inhibitor, bortezomib is thought to have inhibitory activity against NF-κB. We designed a proof-of-principle study of subcutaneous (SC) bortezomib in lower risk MDS patients with evidence of NF-κB activation in their bone marrow. Fifteen patients were treated, their median age was 71 (range 56-87), 33% were low and 67% int-1 by IPSS, median number of prior therapies was 2, all patients were transfusion dependent. Baseline median pp65 percentage was 31% and 11 patients had evidence of ring sideroblasts. SC bortezomib was safe, well tolerated with no excess toxicity. Three patients out of the 15 (20%) had evidence of response with hematologic improvement (HI-E). Bortezomib caused a decrease in pp65 levels in 7 out of 13 evaluable patients (54%, p=0.025). Of interest, unexpectedly, we observed a significant decrease in ring sideroblasts in 7 out of 10 (70%) evaluable patients during treatment. In conclusion, this study suggests that NF-κB activation, measured by pp65 levels, may be a useful biomarker in MDS. Bortezomib is safe in this patient population but has modest clinical activity. The role of the proteasome in the genesis of ring sideroblasts needs further study. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-31T18:20:35.062261-05:
      DOI: 10.1002/ajh.24746
  • The Association of Histologic Grade with Acute Graft-versus-Host Disease
           Response and Outcomes
    • Authors: Mayur Narkhede; Lisa Rybicki, Donna Abounader CCRP, Brian Bolwell, Robert Dean, Aaron T. Gerds, Rabi Hanna, Brian Hill, Deepa Jagadeesh, Matt Kalaycio, Hien D Liu, Brad Pohlman, Ronald Sobecks, Navneet S Majhail, Betty Ky Hamilton
      First page: 683
      Abstract: Consensus criteria are routinely used to clinically grade acute graft-versus-host disease (GVHD). A histologic grading system for acute GVHD is available, but there are limited data on its correlation with clinical grade and hematopoietic cell transplantation (HCT) outcomes. Among 503 patients who underwent allogeneic HCT from 2005-2013, we identified 300 biopsy episodes of the skin and gastrointestinal (GI) tract in 231 patients. Histologic grade was correlated with clinical grade of GVHD, day 28 treatment response, and outcome. Both skin (R=0.32) and GI (R=0.61) histologic grade correlated with clinical grade (p
      PubDate: 2017-04-04T18:05:48.240779-05:
      DOI: 10.1002/ajh.24749
  • Global hypomethylation is an independent prognostic factor in diffuse
           large B cell lymphoma
    • Authors: Eileen Wedge; Jakob Werner Hansen, Christian Garde, Fazila Asmar, Dorte Tholstrup, Søren Sommer Kristensen, Helga D. Munch-Petersen, Elisabeth Ralfkiaer, Peter Brown, Kirsten Grønbæk, Lasse Sommer Kristensen
      First page: 689
      Abstract: Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure for global methylation, was measured in DNA from 67 tumor biopsies. Additionally, cell-free circulating DNA (cfDNA) in plasma samples from 74 patients was tested to assess the feasibility of global hypomethylation as a biomarker in liquid biopsies. LINE1 methylation was assessed using a commercially available kit, based on pyrosequencing of PCR amplified bisulfite-treated DNA. Global hypomethylation was detected in a subset of cases and was associated with poor overall survival in both tumor biopsies (P=0.001) and cfDNA (P=0.009). It was the strongest risk factor in multivariate analysis in both biopsies (HR: 10.65, CI: 2.03-55.81, P=0.005) and cfDNA (HR: 11.87, CI: 2.80-50.20, P=0.001), outperforming conventional clinical risk factors. Finally, hierarchical cluster analyses were performed for the cfDNA samples using previously published gene-specific methylation data. This analysis shows that global hypomethylation co-occurs with other epigenetic abnormalities, including DAPK1 promoter hypermethylation. In conclusion, we have shown that global hypomethylation is strongly associated with poor survival in DLBCL both when present in tumor biopsy DNA and when detected in plasma cfDNA, and has potential for clinical application as a prognostic biomarker. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-03T08:55:25.703539-05:
      DOI: 10.1002/ajh.24751
  • Neonatal Anemia: Revisiting the Enigmatic Pyknocyte
    • Authors: Michele L. Nassin; Jo-Anne Vergilio, Matthew M. Heeney, James L. LaBelle
      First page: 717
      PubDate: 2017-03-23T18:38:35.327392-05:
      DOI: 10.1002/ajh.24731
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