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Publisher: John Wiley and Sons   (Total: 1579 journals)

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Showing 1 - 200 of 1579 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: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 46, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 51, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 153, 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: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, 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: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 13, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 50, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 258, 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: 5)
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: 34, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 10, 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: 15, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 30, 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: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 50, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 140, 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: 90, 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: 33, 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: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 271, 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: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 131, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, 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: 169)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 216, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 38, 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: 7, 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: 47, 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: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
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: 91, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 47, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 7, 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: 69, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 176, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, 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: 14, 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: 36, 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: 15, 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: 238, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 51, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, 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: 15)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 314, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, 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: 4, 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: 4, 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: 5, 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: 12, 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: 14, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, 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: 46, 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: 7, 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: 29, 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: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 406, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 71, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 32, 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: 5, 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: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, 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: 16, 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: 179, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 37, 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)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 234, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Hematology
  [SJR: 1.761]   [H-I: 77]   [33 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  [1579 journals]
  • Severe Thrombocytopenia in a Patient Following Liver Transplantation
           Caused by HPA-1a Antibodies Produced by the Liver Donor
    • Authors: Paul F. Lindholm; Hau C. Kwaan, Glenn Ramsey, Brian R. Curtis, Jonathan Fryer
      PubDate: 2017-10-16T21:56:01.167175-05:
      DOI: 10.1002/ajh.24944
       
  • Prognostic significance of additional chromosomal abnormalities at the
           time of diagnosis in patients with chronic myeloid leukemia treated with
           frontline tyrosine kinase inhibitors
    • Authors: Ahmad Alhuraiji; Hagop Kantarjian, Prajwal Boddu, Farhad Ravandi, Gautam Borthakur, Courtney DiNardo, Naval Daver, Tapan Kadia, Naveen Pemmaraju, Sherry Pierce, Guillermo Garcia-Manero, William Wierda, Srdan Verstovsek, Elias Jabbour, Jorge Cortes
      Abstract: Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148 (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with ponatinib. There was a significantly higher rate of complete cytogenetic response (CCyR) at 6 months in patients without ACA (P = 0.02). However cumulative CCyR and major molecular response (MMR) rates were not different. Similarly, MR4.0 and MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5 for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact transformation-free, failure-free, event-free, or overall survival expectations. Acknowledging small sample size estimates, response rates and survival outcomes were comparable in CP with ACA irrespective of whether chromosomal abnormalities were ‘major route' or other. The presence of ACA at diagnosis does not confer worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA at diagnosis should not alter treatment strategies in these patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-13T01:50:24.142094-05:
      DOI: 10.1002/ajh.24943
       
  • Revisiting the need for bone marrow examination in chronic myeloid
           leukemia
    • Authors: Ayalew Tefferi; Curtis A. Hanson, Rhett P. Ketterling
      PubDate: 2017-10-13T01:50:19.417156-05:
      DOI: 10.1002/ajh.24942
       
  • The athlete's hematological response to hypoxia: A meta-analysis on the
           influence of altitude exposure on key biomarkers of erythropoiesis
    • Authors: Louisa M. Lobigs; Ken Sharpe, Laura A. Garvican-Lewis, Christopher J. Gore, Peter Peeling, Brian Dawson, Yorck O. Schumacher
      PubDate: 2017-10-13T01:46:28.887101-05:
      DOI: 10.1002/ajh.24941
       
  • Lymphoplasmacytoid cytology in plasma cell leukemia
    • Authors: Ahmad Khoder; Magda Al Obaidi, Natasha Wiles, Elisabet Nadal-Melsio, Barbara J. Bain
      PubDate: 2017-10-13T01:45:20.555896-05:
      DOI: 10.1002/ajh.24940
       
  • Program Expansion of a Day Hospital Dedicated to Manage Sickle Cell Pain
    • Authors: Jin Han; Santosh L. Saraf, Laura Kavoliunaite, Shivi Jain, Johara Hassan, Lewis L Hsu, Robert E. Molokie, Victor R. Gordeuk, Michel Gowhari
      PubDate: 2017-10-11T03:00:36.143758-05:
      DOI: 10.1002/ajh.24938
       
  • Therapy Related-Chronic Myelomonocytic Leukemia (CMML): Molecular,
           Cytogenetic and Clinical Distinctions from de novo CMML
    • Authors: Mrinal M. Patnaik; Rangit Vallapureddy, Fevzi F. Yalniz, Curtis A. Hanson, Rhett P. Ketterling, Terra L Lasho, Christy Finke, Aref Al-Kali, Naseema Gangat, Ayalew Tefferi
      Abstract: Therapy related myeloid neoplasms (t-MN) including therapy related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are associated with aggressive disease biologies and poor outcomes. In this large (n=497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t-CMML. T-CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t-CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t-MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (
      PubDate: 2017-10-11T03:00:22.154306-05:
      DOI: 10.1002/ajh.24939
       
  • Impact of screening and exclusion of high anti-A titer donors on the risk
           of hemolytic anemia with intravenous immunoglobulin treatment – a
           hospital-based cohort study in the US
    • Authors: Carlos Martinez; Douglas J Watson, Amgad Shebl, Christopher Wallenhorst, Alphonse Hubsch, Toby L Simon
      PubDate: 2017-10-06T03:40:34.970531-05:
      DOI: 10.1002/ajh.24931
       
  • Alternate use of thrombopoietin receptor agonists in adult primary immune
           thrombocytopenia patients: A retrospective collaborative survey from
           italian hematology centers
    • Authors: Silvia Cantoni; Monica Carpenedo, Maria Gabriella Mazzucconi, Valerio De Stefano, Valentina Carrai, Marco Ruggeri, Giorgina Specchia, Nicola Vianelli, Fabrizio Pane, Ugo Consoli, Andrea Artoni, Francesco Zaja, Mariella D'Adda, Andrea Visentin, Felicetto Ferrara, Wilma Barcellini, Domenica Caramazza, Erminia Baldacci, Elena Rossi, Alessandra Ricco, Angela Ciminello, Francesco Rodeghiero, Michele Nichelatti, Roberto Cairoli
      PubDate: 2017-10-06T03:40:28.026415-05:
      DOI: 10.1002/ajh.24935
       
  • Improved prognosis with additional medium-dose VP16 to CY/TBI in
           allogeneic transplantation for high risk ALL in adults
    • Authors: Yasuyuki Arai; Tadakazu Kondo, Akio Shigematsu, Junji Tanaka, Kazuteru Ohashi, Takahiro Fukuda, Michihiro Hidaka, Naoki Kobayashi, Koji Iwato, Toru Sakura, Makoto Onizuka, Yukiyasu Ozawa, Tetsuya Eto, Mineo Kurokawa, Kaoru Kahata, Naoyuki Uchida, Yoshiko Atsuta, Shuichi Mizuta, Shinichi Kako,
      Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium-dose etoposide (VP16, 30 – 40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30–40 mg/kg) (N=376) and CY/TBI (N=1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56–1.00; p = 0.05) with a corresponding improvement in leukemia-free survival (hazard ratio [HR], 0.76; 95%CI, 0.62–0.93; p = 0.01), particularly in patients transplanted at CR1 with advanced-risk (positive minimal residual disease, presence of poor-risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56–1.00; p = 0.05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39–0.88; p = 0.01). The addition of VP16 did not increase post-transplant complications or non-relapse mortality (HR, 0.88; 95%CI, 0.65 – 1.18; p = 0.38). This study was the first to reveal the efficacy of the addition of medium-dose VP16 to CY/TBI in high-risk ALL. To establish new myeloablative conditioning regimens including VP16, a large-scale prospective study is necessary. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-06T03:31:13.267166-05:
      DOI: 10.1002/ajh.24933
       
  • Transformation of MDS/MPN-RS-T to AML – Trisomy 13, Resistant
           Thrombocytosis and Transient Disease Control with Oral Busulfan Therapy
    • Authors: A. Barrett; M. Catherwood, P. Thornton, P. Murphy, J. Quinn
      PubDate: 2017-10-06T03:31:10.712926-05:
      DOI: 10.1002/ajh.24934
       
  • Correcting the cut-off point of hemoglobin at high altitude favors
           misclassification of anemia, erythrocytosis and excessive erythrocytosis
    • Authors: Gustavo F. Gonzales; Verónica Rubín de Celis, José Begazo, María del Rosario Hinojosa, Sandra Yucra, Alisson Zevallos, Vilma Tapia
      PubDate: 2017-10-06T03:31:09.295066-05:
      DOI: 10.1002/ajh.24932
       
  • Revised Prevalence Estimate of Possible Hereditary Xerocytosis as Derived
           from a Large U.S. Laboratory Database
    • Authors: Harvey W. Kaufman; Justin K. Niles, Denis R. Gallagher, Alicia Rivera, Seth L. Alper, Carlo Brugnara, L. Michael Snyder
      PubDate: 2017-10-03T03:40:42.000351-05:
      DOI: 10.1002/ajh.24923
       
  • Cardiovascular Evaluation and Management of Iron Overload Cardiomyopathy
           in Sickle Cell Disease
    • Authors: Mahazarin Ginwalla; Abdullah AlMasoud, David Tofovic, Tara Alin, Sadeer Al-Kindi, Guilherme Oliveira, Sanjay Rajagopalan, Robert Schilz, Jane Little
      PubDate: 2017-10-03T03:35:48.084081-05:
      DOI: 10.1002/ajh.24924
       
  • Current paradigms in the management of Philadelphia chromosome positive
           acute lymphoblastic leukemia in adults
    • Authors: Riad El Fakih; Elias Jabbour, Farhad Ravandi, Mona Hassanein, Farhan Anjum, Syed Ahmed, Hagop Kantarjian
      Abstract: Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) is a biologically, clinically, and genetically distinct subtype of precursor-B ALL. The Ph chromosome, results from a reciprocal translocation of the ABL1 kinase gene on chromosome 9 to the breakpoint cluster region (BCR) gene on chromosome 22. Depending on the translocation breakpoint, typically a p210 BCR-ABL1 or a p190 BCR- ABL onc protein are generated; both are constitutively active tyrosine kinases that play a central role to alter signaling pathways of cell proliferation, survival, and self-renewal, leading to leukemogenesis. In Ph-positive ALL, the p190-BCR-ABL (minor [m]-bcr) subtype is more frequent than the p210-BCR-ABL (major [M]-bcr) subtype, commonly found in chronic myeloid leukemia 1,2. The Philadelphia chromosome is the most frequent recurrent cytogenetic abnormality in elderly patients with ALL. Its incidence increases with age, reaching approximately 50% in patients with ALL aged 60 years and over 1. Patients traditionally had a very poor outcome with chemotherapy, particularly if they do not undergo allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1). With the availability of multiple tyrosine kinase inhibitors (TKI), the therapeutic armamentarium is expanding quickly. However, there is no consensus on how to best treat Ph-positive ALL. With modern therapy, improved outcomes have led to the emergence of a number of controversies, including the need for intensive chemotherapy, the ideal TKI, and whether all eligible patients should receive an allo-HSCT, and if so, what type. Here we discuss these controversies in light of the available literature. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-03T03:35:46.405937-05:
      DOI: 10.1002/ajh.24926
       
  • High dose chemotherapy and autologous stem cell transplantation in nodular
           lymphocyte-predominant Hodgkin lymphoma: A retrospective study by the
           European Society for Blood and Marrow Transplantation (EBMT)-Lymphoma
           Working Party
    • Authors: Saad Akhtar; Silvia Montoto, Ariane Boumendil, Herve Finel, Tamas Masszi, Pavel Jindra, Damir Nemet, Stephan Fuhrmann, Yves Beguin, Luca Castagna, Felicetto Ferrara, Saveria Capria, Ram Malladi, Jose Maria Moraleda, Adrian Bloor, Hervé Ghesquières, Julia Meissner, Anna Sureda, Peter Dreger
      Abstract: Whilst autologous stem cell transplantation (auto-SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto-SCT in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto-SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003-2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto-SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13-58), and the median number of prior treatment lines was 2 (range 1-5), including rituximab in 63% of the patients. At auto-SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. 72% of the patients received BEAM as high-dose therapy. With a median follow-up of 56 months (range 3-105), 5-year progression-free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto-SCT (vs PR, p=0.049) for OS. Auto-SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long-term survival independent of the time interval between diagnosis and transplant. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-03T03:35:41.859486-05:
      DOI: 10.1002/ajh.24927
       
  • Hereditary Stomatocytosis: An underdiagnosed condition
    • Authors: Immacolata Andolfo; Roberta Russo, Antonella Gambale, Achille Iolascon
      Abstract: Hereditary stomatocytoses are a wide class of hemolytic anemias characterized by alterations of ionic flux with increased cation permeability that results in inappropriate shrinkage or swelling of the erythrocytes, and water lost or gained osmotically.The last few years have been crucial for new acquisitions in this field in terms of identifying new causative genes and of studying their pathogenetic mechanisms.This review summarizes the main features of erythrocyte membrane transport diseases, dividing them into forms with either isolated erythroid phenotype (non-syndromic) or extra-hematological manifestations (syndromic), and focusing particularly on the most recent advances regarding dehydrated forms of hereditary stomatocytosis and familial pseudohyperkalemia. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-03T03:35:39.752302-05:
      DOI: 10.1002/ajh.24929
       
  • Vanin 1 (VNN1) levels predict poor outcome in acute myeloid leukemia
    • Authors: Valerio Izzi; Juho Lakkala, Raman Devarajan, Eeva-Riitta Savolainen, Pirjo Koistinen, Ritva Heljasvaara, Taina Pihlajaniemi
      PubDate: 2017-10-03T03:35:33.936867-05:
      DOI: 10.1002/ajh.24925
       
  • Relatively favourable outcome after allogeneic stem cell transplantation
           for BCR-ABL1-positive AML: A survey from the Acute Leukemia Working Party
           of the European Society for Blood and Marrow Transplantation (EBMT)
    • Authors: Vladimir Lj Lazarevic; Myriam Labopin, Depei Wu, Ibrahim Yakoub-Agha, Anne Huynh, Per Ljungman, Nicolaas Schaap, Jan J. Cornelissen, Natacha Maillard, Pietro Pioltelli, Tobias Gedde-Dahl, Stig Lenhoff, Mohamed Houhou, Jordi Esteve, Mohamad Mohty, Arnon Nagler
      Abstract: The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR-ABL1-positive acute myeloid leukemia (AML). Fifty-seven patients (median age, 48 years, range: 19-67) with BCR-ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR-ABL1/ABL
      PubDate: 2017-10-03T03:35:22.178269-05:
      DOI: 10.1002/ajh.24928
       
  • Late infections and secondary malignancies after bendamustine/rituximab or
           RCHOP/RCVP chemotherapy for B-cell lymphomas
    • Authors: Adam J Olszewski; John L Reagan, Jorge J Castillo
      PubDate: 2017-09-29T10:54:03.359619-05:
      DOI: 10.1002/ajh.24921
       
  • Urological complications associated with adult allogeneic stem cell
           transplantation
    • Authors: Laila Schneidewind; Thomas Neumann, Kathrin Zimmermann, Christian Andreas Schmidt, William Krüger
      PubDate: 2017-09-29T10:51:49.196623-05:
      DOI: 10.1002/ajh.24920
       
  • Residual disease detection using targeted parallel sequencing predicts
           relapse in cytogenetically normal acute myeloid leukemia
    • Authors: Lukas Gaksch; Karl Kashofer, Ellen Heitzer, Franz Quehenberger, Shruti Daga, Sybille Hofer, Iris Halbwedl, Ricarda Graf, Nina Krisper, Gerald Hoefler, Armin Zebisch, Heinz Sill, Albert Wölfler
      Abstract: Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform. Furthermore, the variant allelic frequency of distinct mutations was validated by digital PCR and sequencing using a barcoding approach. Twenty-seven out of 34 patients could be analyzed for mutation clearance. We identified 68 somatic mutations at diagnosis (median, 3 mutations per patient; range 1-5) and 22 of these were still detected in 16 patients after consolidation therapy with a reliable sensitivity of 0.5% (median, 1 mutation; range 0-3). The most frequent non-cleared mutations were found in DNMT3A. However, as persistence of these mutations has recently been shown to be without any impact on relapse risk, we performed survival and relapse risk analysis excluding DNMT3A mutations. Importantly, persistence of non-DNMT3A mutations was associated with a higher risk of AML relapse (7/8 pts versus 6/19 pts; p=0.013) and with a shorter relapse-free survival (333 days vs. not reached; log-rank p=0.0219). Detection of residual disease by routine targeted parallel sequencing proved feasible and effective as persistence of somatic mutations other than DNMT3A were prognostic for relapse in CN AML. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-29T10:51:18.620427-05:
      DOI: 10.1002/ajh.24922
       
  • Timing and deepness of response to tyrosine kinase inhibitors as a measure
           of potential treatment discontinuation in chronic myeloid leukemia
           patients managed in the real-life
    • Authors: Massimo Breccia; Gioia Colafigli, Matteo Molica, Emilia Scalzulli, Daniela Diverio, Roberto Latagliata, Anna Guarini, Robin Foà
      PubDate: 2017-09-28T03:15:19.538768-05:
      DOI: 10.1002/ajh.24916
       
  • Utility and limitations of exome sequencing in the molecular diagnosis of
           pediatric inherited platelet disorders
    • Authors: Edward J. Romasko; Batsal Devkota, Sawona Biswas, Vijayakumar Jayaraman, Ramakrishnan Rajagopalan, Matthew C. Dulik, Christopher S. Thom, Jiwon Choi, Sowmya Jairam, Maria I. Scarano, Ian D. Krantz, Nancy B. Spinner, Laura K. Conlin, Michele P. Lambert
      Abstract: Inherited platelet disorders (IPD) are a heterogeneous group of rare disorders that affect platelet number and function and often predispose to other significant medical complications. In spite of the identification of over 50 IPD disease-associated genes, a molecular diagnosis is only identified in a minority (10%) of affected patients without a clinically suspected etiology. We studied a cohort of 21 pediatric patients with suspected IPDs by exome sequencing (ES) to: 1) examine the performance of the exome test for IPD genes, 2) determine if this exome-wide diagnostic test provided a higher diagnostic yield than has been previously reported, 3) to evaluate the frequency of variants of uncertain significance identified, and 4) to identify candidate variants for functional evaluation in patients with an uncertain or negative diagnosis. We established a high priority gene list of 53 genes, evaluated exome capture kit performance, and determined the coverage for these genes and disease-related variants. We identified likely disease causing variants in 5 of the 21 probands (23.8%) and variants of uncertain significance in 52% of patients studied. In conclusion, ES has the potential to molecularly diagnose causes of IPD, and to identify candidate genes for functional evaluation. Robust exome sequencing also requires that coverage of genes known to be associated with clinical findings of interest need to be carefully examined and supplemented if necessary. Clinicians who undertake ES should understand the limitations of the test and the full significance of results that may be returned. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T03:46:57.906647-05:
      DOI: 10.1002/ajh.24917
       
  • Impact of involved free light chain (FLC) levels in patients achieving
           normal FLC ratio after initial therapy in light chain amyloidosis (AL)
    • Authors: Nidhi Tandon; Surbhi Sidana, Angela Dispenzieri, Morie A. Gertz, Martha Q. Lacy, David Dingli, Francis K. Buadi, Amie L. Fonder, Suzanne R. Hayman, Yi Lisa Hwa, Miriam A. Hobbs, Prashant Kapoor, Wilson I. Gonsalves, Nelson Leung, Ronald S. Go, John A. Lust, Stephen J. Russell, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
      Abstract: Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n=166; 48.1%) were compared to those who did not (n=179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; p=0.002) and patients in advanced Mayo stage (42.9 vs 32.2%; p=0.04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; p=0.0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; p
      PubDate: 2017-09-27T03:46:36.600115-05:
      DOI: 10.1002/ajh.24919
       
  • Non-invasive monitoring of liver fibrosis in Sickle Cell Disease:
           Longitudinal observation of a cohort of adult patients
    • Authors: Valeria Pinto; Barbara Gianesin, Manuela Balocco, Lorenzo Bacigalupo, Gian Luca Forni
      PubDate: 2017-09-27T03:35:21.443398-05:
      DOI: 10.1002/ajh.24918
       
  • Diagnostic value of targeted next-generation sequencing (NGS) in suspected
           hemochromatosis patients with a single copy of the HFE p.Cys282Tyr
           causative allele
    • Authors: Kevin Uguen; Virginie Scotet, Chandran Ka, Isabelle Gourlaouen, Carine L'Hostis, Marie-Christine Merour, Tania Cuppens, Claude Ferec, Gerald Le Gac
      PubDate: 2017-09-22T03:31:18.200795-05:
      DOI: 10.1002/ajh.24912
       
  • Liver Dysfunction in Chronic Lymphocytic Leukemia: Prevalence, Outcomes,
           and Pathological Findings
    • Authors: Paul J. Hampel; Kari G. Chaffee, Rebecca L. King, Douglas Simonetto, Melissa C. Larson, Sara Achenbach, Timothy G. Call, Wei Ding, Saad S. Kenderian, Jose F. Leis, Asher A. Chanan-Khan, Deborah A. Bowen, Michael J. Conte, Susan M. Schwager, Curtis A. Hanson, Susan L. Slager, Neil E. Kay, Tait D. Shanafelt, Sameer A. Parikh
      Abstract: The prevalence of liver dysfunction and its association with outcomes in patients with previously untreated chronic lymphocytic leukemia (CLL) is unknown. Newly diagnosed (
      PubDate: 2017-09-22T03:31:13.832602-05:
      DOI: 10.1002/ajh.24915
       
  • Safety and Pharmacokinetics of the Oral Iron Chelator SP-420 in
           β-thalassemia
    • Authors: Ali T Taher; Antoine N Saliba, Kevin H Kuo, Patricia J Giardina, Alan R Cohen, Ellis J Neufeld, Yesim Aydinok, Janet L Kwiatkowski, Brenda I Jeglinski, Keith Pietropaolo, Gregory Berk, Vip Viprakasit
      Abstract: Our Phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n=3), 3 (n=3), 6 (n=3), 12 (n=3), and 24 (n=6) mg/kg or as a twice-daily dose of 9 mg/kg (n=6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for Cmax and AUC0-τ over the dose range evaluated. The median tmax ranged from 0.5 – 2.25 h and was not dose-dependent. The study was prematurely terminated by the sponsor due to renal adverse events including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal adverse events observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-22T03:30:43.099362-05:
      DOI: 10.1002/ajh.24914
       
  • The eutos long-term survival score (elts) accurately predicts the risk of
           death in chronic myeloid leukaemia patients treated outside of clinical
           trials
    • Authors: Matteo Molica; Martina Canichella, Danilo Alunni Fegatelli, Gioia Colafigli, Fulvio Massaro, Roberto Latagliata, Robin Foà, Massimo Breccia
      PubDate: 2017-09-22T03:30:19.070855-05:
      DOI: 10.1002/ajh.24913
       
  • Effects of Pre- and Post-transplantation Minimal Residual Disease on
           Outcomes in Pediatric Patients with Acute Myeloid Leukemia Receiving Human
           Leukocyte Antigen-matched or Mismatched Related Donor Allografts
    • Authors: Ying-Jun Chang; Xiao-Su Zhao, Yu Wang, Yan-Rong Liu, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Wei- Han, Yu-Qian Sun, Chen-Hua Yan, Xiao-Dong Mo, Kai-Yan Liu, Xiao-Jun Huang
      PubDate: 2017-09-20T03:30:37.341556-05:
      DOI: 10.1002/ajh.24910
       
  • Treatment of hepatitis C virus infection with direct-acting antiviral
           drugs is safe and effective in patients with hemoglobinopathies
    • Authors: Raffaella Origa; Maria Laura Ponti, Aldo Filosa, Alfonso Galeota Lanza, Antonio Piga, Giorgio Maria Saracco, Valeria Pinto, Antonino Picciotto, Paolo Rigano, Salvatore Madonia, Rosamaria Rosso, Domenico D'Ascola, Maria Domenica Cappellini, Roberta D'Ambrosio, Immacolata Tartaglione, Lucia De Franceschi, Barbara Gianesin, Vito Di Marco, Gian Luca Forni,
      Abstract: Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis. Between March 2015 and December 2016, 139 patients received DAAs and completed 12 weeks of follow up after the end of treatment for the evaluation of sustained virological response (12SVR). The 12SVR (93.5%) was comparable with that typically observed in cirrhotic patients without hemoglobinopathies. Three patients died during the period of observation of causes unrelated to DAAs. One patient did not achieve a virological response and five (3.6%) relapsed during 12 weeks of follow-up after the end of therapy. In addition, patients showed significant reductions in serum ferritin at 12 weeks to levels similar to those observed in a control group of 39 patients with thalassemia major without HCV infection, who adhered to chelation therapy and had no overt iron overload. In conclusion, the use of DAAs appears to be safe and effective in patients with hemoglobinopathies and advanced liver disease due to HCV. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-20T03:30:26.85827-05:0
      DOI: 10.1002/ajh.24911
       
  • Bone marrow xanthomas associated with hypertriglyceridemia
    • Authors: Nelson CN Chan; Chak-Chung Chan, Natalie PH Chan
      PubDate: 2017-09-19T01:25:24.071253-05:
      DOI: 10.1002/ajh.24909
       
  • Incidence and predictive score for delayed hemolytic transfusion reaction
           in adult patients with sickle cell disease
    • Authors: David Narbey; Anoosha Habibi, Philippe Chadebech, Armand Mekontso-Dessap, Mehdi Khellaf, Jean-Daniel Lelièvre, Bertrand Godeau, Marc Michel, Frédéric Galactéros, Rachid Djoudi, Pablo Bartolucci, France Pirenne
      Abstract: Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those of vaso-occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI [2.6; 6.9]) and 6.8% per patient during the 30 months of the study (95% CI [4.2; 11.3]). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR-predictive score had an area under the ROC curve of 0.850 [95% CI: 0.780-0.930], a negative-predictive value of 98.4% and a positive-predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-19T01:25:19.710199-05:
      DOI: 10.1002/ajh.24908
       
  • A Clinically Meaningful Fetal Hemoglobin Threshold for Children with
           Sickle Cell Anemia During Hydroxyurea Therapy
    • Authors: Jeremie H. Estepp; Matthew P. Smeltzer, Guolian Kang, Chen Li, Winfred C. Wang, Christina Abrams, Banu Aygun, Russell E. Ware, Kerri Nottage, Jane S. Hankins
      Abstract: Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose-dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long-term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA. In 230 children, providing 610 patient-years of follow up, the mean attained HbF% at MTD was>20% for up to 4 years of follow-up. When HbF% values were ≤20%, children had twice the odds of hospitalization for any reason (p
      PubDate: 2017-09-14T20:35:54.964598-05:
      DOI: 10.1002/ajh.24906
       
  • A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter
           retrospective study)
    • Authors: Takashi Kobayashi; Yasuhito Nannya, Motoshi Ichikawa, Kenji Oritani, Yuzuru Kanakura, Akihiro Tomita, Hitoshi Kiyoi, Masayoshi Kobune, Junji Kato, Hiroshi Kawabata, Motohiro Shindo, Yoshihiro Torimoto, Yuji Yonemura, Nobuyoshi Hanaoka, Hideki Nakakuma, Daisuke Hasegawa, Atsushi Manabe, Naohito Fujishima, Nobuharu Fujii, Mitsune Tanimoto, Yasuyoshi Morita, Akira Matsuda, Atsushi Fujieda, Naoyuki Katayama, Haruhiko Ohashi, Hirokazu Nagai, Yoshiki Terada, Masayuki Hino, Ken Sato, Naoshi Obara, Shigeru Chiba, Kensuke Usuki, Masatsugu Ohta, Osamu Imataki, Makiko Uemura, Tomoiku Takaku, Norio Komatsu, Akira Kitanaka, Kazuya Shimoda, Kenichiro Watanabe, Kaoru Tohyama, Akifumi Takaori-Kondo, Hideo Harigae, Shunya Arai, Yasushi Miyazaki, Keiya Ozawa, Mineo Kurokawa,
      Abstract: Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences. The overall survival (OS) and AML progression-free survival (AML-PFS) of hMDS were higher than those of non-hMDS, especially in patients at age ≥50 and of lower risk in Revised International Prognostic Scoring System (IPSS-R). In competing risks analysis, hMDS exhibited decreased risk of AML-progression in lower IPSS or IPSS-R risk patients, and higher risk of death from BMF in patients at age ≥50. Poor performance status (PS ≥2) and high karyotype risks in IPSS-R (high and very high) were significant risk factors of death and AML-progression in Cox proportional hazards analysis. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-11T03:46:36.003793-05:
      DOI: 10.1002/ajh.24905
       
  • Unrelated matched versus autologous transplantation in adult patients with
           good and intermediate risk acute myelogenous leukemia in first molecular
           remission
    • Authors: Norbert-Claude Gorin; Myriam Labopin, Thomas Pabst, Peter Remenyi, Depei Wu, Anne Huynh, Liisa Volin, Jean Yves Cahn, Ibrahim Yakoub-Agha, Melanie Mercier, Mohamed Houhou, Mohamad Mohty, Arnon Nagler,
      Abstract: Patients with Acute Myelogenous Leukemia have a better outcome if reaching molecular remission.We compared the outcome of 373 patients autografted and 335 patients allografted with a 10/10 compatible unrelated donor in first molecular remission.Patients were stratified using the ELN European Leukemia Net classification.ELN favorable group: (234 auto and 70 unrelated transplants). By univariate analysis, in the auto group, the Non Relapse Mortality (NRM) was lower (3.7% versus 19%; p< 10−4), Relapse Incidence (RI) higher (29% versus 17%, p< 10−4), Leukemia Free Survival (LFS) identical (67% versus 64%) and Overall Survival (OS) better than in the allogeneic group (83% versus 62%; p=0.008). By multivariate analysis, autologous transplantation was associated with a lower NRM (HR: 4, p =0.01) and a better OS (HR: 2.08, p= 0.04).ELN intermediate group 1: (87 autologous and 172 unrelated transplants). By univariate analysis, in the auto group, NRM was lower (2.5% versus 11.8%; p= 0.03), RI higher (59% versus 18%, p< 10−6), LFS lower (39% versus 70%; p< 10−6) and OS lower than in the unrelated donor group (61% versus 74%; p=0.005). By multivariate analysis, unrelated donor was superior to autologous transplantation for LFS (HR: 0.36, p 
      PubDate: 2017-09-11T03:40:22.171323-05:
      DOI: 10.1002/ajh.24904
       
  • Clinical management of peripherally-inserted central catheters (PICCs)
           compared to conventional central venous catheters (cCVCs) in patients with
           hematological malignancies: a large multicenter study of the REL GROUP
           (Rete Ematologica Lombarda - Lombardy Hematologic Network, Italy)
    • Authors: Nicola Stefano Fracchiolla; Elisabetta Todisco, Andrea Bilancia, Sara Gandolfi, Nicola Orofino, Francesca Guidotti, Valentina Mancini, Laura Marbello, Andrea Assanelli, Massimo Bernardi, Armando Santoro, Roberto Cairoli, Dario Consonni, Agostino Cortelezzi
      PubDate: 2017-09-10T20:35:52.357951-05:
      DOI: 10.1002/ajh.24903
       
  • Identification of novel mutations in the HbF repressor gene BCL11A in
           patients with autism and intelligence disabilities
    • Authors: Tao Cai; Xiang Chen, Jinchen Li, Bingwu Xiang, Liu Yang, Yidian Liu, Qiuli Chen, Zhouwen He, Kevin Sun, P. Paul Liu
      PubDate: 2017-09-10T20:20:38.793562-05:
      DOI: 10.1002/ajh.24902
       
  • Targeted next-generation sequencing in myelodysplastic syndromes and
           prognostic interaction between mutations and IPSS-R
    • Authors: Ayalew Tefferi; Terra L Lasho, Mrinal M Patnaik, Lyla Saeed, Mythri Mudireddy, Dame Idossa, Christy Finke, Rhett P Ketterling, Animesh Pardanani, Naseema Gangat
      Abstract: A 27-gene panel was used for next-generation sequencing (NGS) in 179 patients (median age 73 years) with primary myelodysplastic syndromes (MDS); risk distribution according to the revised International Prognostic Scoring System (IPSS-R) was 11% very high, 18% high, 17% intermediate, 38% low and 16% very low. At least one mutation/variant was detected in 147 (82%) patients; 23% harbored three or more mutations/variants. The most frequent mutations/variants included ASXL1 (30%), TET2 (25%), SF3B1 (20%), U2AF1 (16%), SRSF2 (16%), TP53 (13%), RUNX1 (11%) and DNMT3A (10%). At a median follow up of 30 months, 148 (83%) deaths and 26 (15%) leukemic transformations were recorded. Multivariable analysis of mutations/variants identified ASXL1 (HR 1.7, 95% CI 1.2-2.5), SETBP1 (HR 4.1, 95% CI 1.6-10.2) and TP53 (HR 2.2, 95% CI 1.3-3.4) as risk factors for overall and SRSF2 (HR 3.9, 95% CI 1.5-10.2), IDH2 (HR 3.7, 95% CI 1.2-11.4) and CSF3R (HR 6.0, 95% CI 1.6-22.6) for leukemia-free survival. Addition of age to the multivariable model did not affect these results while accounting for IPSS-R weakened the significance of TP53 mutations/variants (p=0.1). An apparently favorable survival impact of SF3B1 mutations was no longer evident after adjustment for IPSS-R. Approximately 41% and 20% of patients harbored at least one adverse mutation/variant for overall and leukemia-free survival, respectively. Number of mutations/variants did not provide additional prognostic value. The survival impact of adverse mutations was most evident in IPSS-R very low/low risk patients. These observations suggest that targeted NGS might assist in treatment decision-making in lower risk MDS. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-05T20:10:50.903276-05:
      DOI: 10.1002/ajh.24901
       
  • Causes of Hospital Admission in β-Thalassemia (CHAT) in Lebanon from 1995
           to 2015: A pilot retrospective study from a tertiary care center
    • Authors: Antoine N. Saliba; Hassan M. Moukhadder, Afif Harb, Hassan Beydoun, Rayan Bou-Fakhredin, Ali T. Taher
      PubDate: 2017-08-31T03:55:25.18808-05:0
      DOI: 10.1002/ajh.24900
       
  • Enhancing diversity in the hematology biomedical research workforce: A
           mentoring program to improve the odds of career success for early stage
           investigators
    • Authors: Betty S. Pace; Levi H. Makala, Rita Sarkar, Li Liu, Mayuko Takezaki, Narla Mohandas, Glorias Dixon, Ellen M. Werner, Donna B. Jeffe, Treva K. Rice, Nita J. Maihle, Juan González
      PubDate: 2017-08-31T03:36:11.886381-05:
      DOI: 10.1002/ajh.24899
       
  • Long-term survival of beta thalassemia major patients treated with
           hematopoietic stem cell transplantation compared with survival with
           conventional treatment
    • Authors: Giovanni Caocci; Maria Grazia Orofino, Adriana Vacca, Antonio Piroddi, Eugenia Piras, Maria Carmen Addari, Rossella Caria, Maria Paola Pilia, Raffaella Origa, Paolo Moi, Giorgio La Nasa
      Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia remains a challenge. We reported a single-centre case-control study of a large cohort of 516 children and adult patients treated with HSCT or blood transfusion support and iron chelation therapy; 258 patients (median age 12, range 1-45) underwent sibling (67%) or unrelated (33%) HSCT; 97 patients were adults (age ≥ 16 years). The median follow-up after HSCT was 11 years (range 1-30). The conditioning regimen was busulfan (80.6%) or treosulfan-based (19.4%). A cohort of 258 age-sex matched conventionally treated (CT) patients was randomly selected. In transplanted patients the 30-year overall survival (OS) and thalassemia-free survival (TFS) were 82.6±2.7% and 77.8±2.9%, compared to the OS of 85.3±2.7% in CT patients (p=NS); The incidence of grade II-IV acute and chronic graft versus host disease (GvHD) was 23.6% and 12.9% respectively. The probability of rejection was 6.9%. Transplant-related mortality (TRM) (13.8%) was similar to the probability of dying of cardiovascular events in CT patients (12.2%). High-risk Pesaro score (class 3) was associated with lower OS (OR=1.99, 95% C.I.=1.31-3.03) and TFS (OR=1.54, 95% C.I.=1.12-2.12). In adult patients, the 23-years OS and TFS after HSCT were 70±5% and 67.3±5%, compared to 71.2±5% of OS in CT (p=NS). Finally, treosulfan was associated with lower risk of acute GvHD (p=0.004; OR=0.28, 95% C.I.=0.12-0.67). In conclusion, the 30-year survival rate of ex-thalassemia patients after HSCT was similar to that expected in CT thalassemia patients, with the vast majority of HSCT survivors cured from thalassemia. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-29T02:31:28.405494-05:
      DOI: 10.1002/ajh.24898
       
  • Clinical Outcomes in Adult Patients with Aplastic Anemia- a single
           institution experience
    • Authors: Prajwal Boddu; Guillermo Garcia-Manero, Farhad Ravandi, Gautam Borthakur, Elias Jabbour, Courtney DiNardo, Nitin Jain, Naval Daver, Naveen Pemmaraju, Paolo Anderlini, Simrit Parmar, Devendra KC, Mary Akosile, Sherry A. Pierce, Richard Champlin, Jorge Cortes, Hagop Kantarjian, Tapan Kadia
      Abstract: Newer treatment modalities are being investigated to improve upon historical outcomes with standard immunosuppressive therapy (IST) in aplastic anemia (AA). We analyzed outcomes of adult patients with AA sequentially treated with various combinatorial anti-thymoglobulin-based IST regimens in frontline and relapsed/refractory (R/R) settings. Pretreatment and on-treatment clinical characteristics were analyzed for relationships to response and outcome. Among 126 patients reviewed, 95 were treatment-naïve (TN) and 63, R/R (including 32 from the TN cohort); median ages were 49 and 50 years, respectively. Overall survival (OS) was superior in IST responders (p
      PubDate: 2017-08-29T02:31:26.168622-05:
      DOI: 10.1002/ajh.24897
       
  • Changes in intestinal microbiota and their effects on allogeneic stem cell
           transplantation
    • Authors: Rory M Shallis; Christopher M Terry, Seah H Lim
      Abstract: The human intestinal microbiota is essential for microbial homeostasis, regulation of metabolism, and intestinal immune tolerance. Rapidly evolving understanding of the importance of the microbiota implicates changes in the composition and function of intestinal microbial communities in an assortment of systemic conditions. Complications following allogeneic stem cell transplant now join the ever-expanding list of pathologic states regulated by intestinal microbiota. Dysbiosis, or disruption of the normal ecology of this microbiome, has been directly implicated in the pathogenesis of entities such as Clostridium difficile infections, graft-versus-host disease, and most recently disease relapse, all of which are major causes of morbidity and mortality in patients undergoing allogeneic stem cell transplant. In this review, we elucidate the key origins of microbiotic alterations and discuss how dysbiosis influences complications following allogeneic stem cell transplant. Our emerging understanding of the importance of a balanced and diverse intestinal microbiota is prompting investigation into the appropriate treatment of dysbiosis, reliable and early detection of such, and ultimately its prevention in patients to improve the outcome following allogeneic hematopoietic stem cell transplant. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-26T03:30:43.446923-05:
      DOI: 10.1002/ajh.24896
       
  • A Single Center Phase II Study of Ixazomib in Patients with Relapsed or
           Refractory Cutaneous or Peripheral T-cell Lymphomas
    • Authors: Philip S. Boonstra; Avery Polk, Noah Brown, Alexandra C. Hristov, Nathanael G. Bailey, Mark S. Kaminski, Tycel Phillips, Sumana Devata, Tera Mayer, Ryan A. Wilcox
      Abstract: The transcription factor GATA-3, highly expressed in many cutaneous and peripheral T-cell lymphomas, confers resistance to chemotherapy in a cell-autonomous manner. As GATA-3 is transcriptionally regulated by NF-κB, we sought to determine the extent to which proteasomal inhibition impairs NF-κB activation and GATA-3 expression and cell viability in malignant T cells. Proteasome inhibition, NF-κB activity, GATA-3 expression, and cell viability were examined in patient-derived cell lines and primary T-cell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib. Significant reductions in cell viability, NF-κB activation, and GATA-3 expression were observed pre-clinically in ixazomib-treated cells. Therefore, an investigator-initiated, single-center, phase II study with this agent in patients with relapsed/refractory CTCL/PTCL was conducted. Concordant with our pre-clinical observations, a significant reduction in NF-κB activation and GATA-3 expression was observed in an exceptional responder following one month of treatment with ixazomib. While ixazomib had limited activity in this small and heterogeneous cohort of patients, inhibition of the NF-κB/GATA-3 axis in a single exceptional responder suggests that ixazomib may have utility in appropriately selected patients or in combination with other agents. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-26T03:30:22.320945-05:
      DOI: 10.1002/ajh.24895
       
  • Imatinib-induced psoriasiform eruption in a patient with chronic myeloid
           leukemia
    • Authors: Connie R. Shi; Vinod E. Nambudiri
      PubDate: 2017-08-24T01:25:22.857562-05:
      DOI: 10.1002/ajh.24894
       
  • Considerations on POEMS associated optic neuropathy
    • Authors: Julio González Martín-Moro; Inés Contreras Martín, María Castro-Rebollo, Belén Pilo de la Fuente
      PubDate: 2017-08-22T22:35:27.152845-05:
      DOI: 10.1002/ajh.24893
       
  • Clinical and Laboratory Findings Associated with Sleep Disordered
           Breathing in Sickle Cell Disease
    • Authors: Christopher M. Worsham; Stephon T. Martin, Mehdi Nouraie, Robyn T. Cohen, Elizabeth S. Klings
      PubDate: 2017-08-22T22:30:24.538162-05:
      DOI: 10.1002/ajh.24892
       
  • Comprehensive Evaluation of the Revised International Staging System in
           Multiple Myeloma Patients Treated with Novel Agents as a Primary Therapy
    • Authors: Hyungwoo Cho; Dok Hyun Yoon, Jung Bok Lee, Sung-Yong Kim, Joon Ho Moon, Young Rok Do, Jae Hoon Lee, Yong Park, Ho Sup Lee, Hyeon Seok Eom, Ho-Jin Shin, Chang-Ki Min, Jin Seok Kim, Jae-Cheol Jo, Hye Jin Kang, Yeung-Chul Mun, Won Sik Lee, Je-Jung Lee, Cheolwon Suh, Kihyun Kim,
      Abstract: The revised International Staging System (R-ISS) has recently been developed to improve the risk stratification of multiple myeloma (MM) patients over the ISS. We assessed the R-ISS in MM patients who were treated with novel agents as a primary therapy and evaluated its discriminative power and ability to reclassify patients from the ISS. A total of 514 newly diagnosed MM patients treated with novel agents including thalidomide, bortezomib, and lenalidomide as a primary therapy were included in this retrospective analysis. With a median follow-up duration of 42.3 months (range, 40.5–44.1), the median overall survival (OS) was 61.0 months. There was a significant difference in median OS (not reached, 60.9, and 50.1 months for stages 1, 2, and 3, respectively, P 
      PubDate: 2017-08-22T09:22:17.006814-05:
      DOI: 10.1002/ajh.24891
       
  • First-line treatment selection and early monitoring patterns in chronic
           phase-chronic myeloid leukemia in routine clinical practice: SIMPLICITY
    • Authors: Stuart L. Goldberg; Jorge Cortes, Carlo Gambacorti-Passerini, Rüdiger Hehlmann, H. Jean Khoury, Mauricette Michallet, Ron Paquette, Bengt Simonsson, Teresa Zyczynski, Aimee Foreman, Elisabetta Abruzzese, David Andorsky, Aart Beeker, Pascale Cony-Makhoul, Richard Hansen, Elza Lomaia, Eduardo Olavarria, Michael Mauro
      Abstract: Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n=416), dasatinib (n=418) or nilotinib (n=408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1,242 prospective patients (enrolled October 01 2010–September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift towards dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82% and 95% of patients by 3, 6 and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P
      PubDate: 2017-08-17T03:15:31.26589-05:0
      DOI: 10.1002/ajh.24887
       
  • Treatment of Individuals Who Cannot Receive Blood Products for Religious
           or Other Reasons
    • Authors: Carlton D. Scharman; Joseph J. Shatzel, Edward Kim, Thomas G. DeLoughery
      Abstract: By virtue of their religious principles, Jehovah's Witnesses (JWs) generally object to receiving blood products, raising numerous ethical, legal, and medical challenges for providers who care for these patients, especially in the emergent setting. In this review, we discuss several areas relevant to the care of JWs, including the current literature on “bloodless” medical care in the setting of peri- and intra-operative management, acute blood loss, trauma, pregnancy, and malignancy. We have found that medical and administrative efforts in the form of bloodless medicine and surgery programs can be instrumental in helping to reduce risks of morbidity and mortality in these patients. Planning prior to an anticipated event associated with blood loss or anemia (such as elective surgery, pregnancy, and chemotherapy) is critical. Specifically, bloodless medicine programs should prioritize vigilant early screening and management of anemias, early establishment of patient wishes regarding transfusion, and the incorporation of those wishes into multidisciplinary medical and surgical care. Although there are now a variety of human- and non-human-based products available as transfusion alternatives, the degree and quality of evidence to support their use varies significantly between products and is also largely dependent on the clinical setting. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-17T03:15:28.62568-05:0
      DOI: 10.1002/ajh.24889
       
  • Bmp2 controls iron homeostasis in mice independent of Bmp6
    • Authors: Susanna Canali; Chia-Yu Wang, Kimberly B. Zumbrennen-Bullough, Abraham Bayer, Jodie L. Babitt
      Abstract: Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody. Moreover, BMP2/4 antibody inhibits hepcidin expression and induces iron loading in wildtype mice, whereas a BMP4 antibody has no effect. Compared with other liver cell populations, Bmp2 mRNA is predominantly expressed in endothelial cells, where it's baseline expression is higher, but it's induction by iron is less robust than Bmp6. Mice with a conditional ablation of Bmp2 in endothelial cells exhibit hepcidin deficiency, serum iron overload, and tissue iron loading in liver, pancreas and heart, with reduced spleen iron. Together, these data demonstrate that in addition to BMP6, endothelial cell BMP2 has a non-redundant role in hepcidin regulation by iron This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-17T03:15:24.842408-05:
      DOI: 10.1002/ajh.24888
       
  • Ibrutinib-associated Pneumocystis jirovecii pneumonia
    • Authors: Regina Lee; Afrouz Nayernama, S. Christopher Jones, Tanya Wroblewski, Peter E. Waldron
      PubDate: 2017-08-17T03:15:20.358366-05:
      DOI: 10.1002/ajh.24890
       
  • Diagnosis of thrombotic thrombocytopenic purpura among patients with
           adamts13 activity 10-20%
    • Authors: Adanma Ayanambakkam; Johanna A. Kremer Hovinga, Sara K. Vesely, James N. George
      PubDate: 2017-08-17T03:10:34.798271-05:
      DOI: 10.1002/ajh.24885
       
  • A distinctive histidine residue is essential for in vivo
           glycation-inactivation of human CD59 transgenically expressed in mice
           erythrocytes: Implications for human diabetes complications
    • Authors: Rupam Sahoo; Pamela Ghosh, Michael Chorev, Jose A Halperin
      Abstract: Clinical and experimental evidences support a link between the complement system and the pathogenesis of diabetes complications. CD59, an extracellular cell membrane-anchored protein, inhibits formation of the membrane attack complex (MAC), the main effector of complement-mediated tissue damage. This complement regulatory activity of human CD59 (hCD59) is inhibited by hyperglycemia-induced ε-amino glycation of Lys41. Biochemical and structural analyses of glycated proteins with known three-dimensional structure revealed that glycation of ε-amino lysyl residues occurs predominantly at “glycation motives” that include lysyl/lysyl pairs or proximity of a histidyl residue, in which the imidazolyl moiety is ≈ 5Å from the ε-amino group. hCD59 contains a distinctive Lys41/His44 putative glycation motif within its active site. In a model of transgenic diabetic mice expressing in erythrocytes either the wild type or a H44Q mutant form of hCD59, we demonstrate in vivo that the His44 is required for Lys41 glycation and consequent functional inactivation of hCD59, as evidenced using a mouse erythrocytes hemolytic assay. Since 1) the His44 residue is not present in CD59 form other animal species and 2) humans are particularly prone to develop complications of diabetes, our results indicate that the Lys41/His44 glycation motif in human CD59 may confer humans a higher risk of developing vascular disease in response to hyperglycemia. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-17T03:10:33.180364-05:
      DOI: 10.1002/ajh.24886
       
  • Rare complication of treated immune thrombocytopenia
    • Authors: Radhika Gangaraju; Anton Rets, Kristi J Smock, Nahla M Heikal
      PubDate: 2017-08-12T00:45:24.985537-05:
      DOI: 10.1002/ajh.24884
       
  • Efficacy of daratumumab-based therapies in patients with relapsed,
           refractory multiple myeloma treated outside of clinical trials
    • Authors: Arjun Lakshman; Jithma P. Abeykoon, Shaji K. Kumar, S. Vincent Rajkumar, David Dingli, Francis K. Buadi, Wilson I. Gonsalves, Nelson Leung, Angela Dispenzieri, Taxiarchis V. Kourelis, Ronald S. Go, Martha Q. Lacy, Miriam A. Hobbs, Yi Lin, Rahma Warsame, John Lust, Amie L. Fonder, Yi L. Hwa, Suzanne R. Hayman, Stephen J. Russell, Robert A. Kyle, Morie A. Gertz, Prashant Kapoor
      Abstract: Outside of clinical trials, experience with daratumumab-based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43-93) years. High-risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1-14) and time to first DCT from diagnosis was 4.3 years (range, 0.4-13.0). Seventeen (13%) patients were refractory to single agent daratumumab. Fifty-two (41%), 34 (27%), 23 (18%) and 17 (14%) received DPd, DRd, DVd and ‘other' DCTs, respectively. Overall response rate was 47%. Median follow-up was 5.5 months (95%CI, 4.2-6.1). Median progression free survival (PFS) was 5.5 months (95%CI, 4.2-7.8). Median overall survival was not reached (NR) with any regimen. Median PFS (months) was worst for penta-refractory MM (n=8) vs quadruple refractory MM (n=18) and others (n=100) (2.2 [95%CI, 1-2.4] vs 3.1 [95%CI, 2.1-NR] vs 5.9 [95%CI, 5.0-NR]; p2 prior therapies vs others (5.0 months [95%CI, 3.7-5.9] vs NR [95%CI, NR-NR]; p=0.002). Non-hematologic toxicities included infections (38%), fatigue (32%), and infusion reactions (18%). Grade 3 or higher hematological toxicities were seen in 41% of patients. DCTs are effective in RRMM. ORR and PFS in heavily pre-treated patients are lower than those reported in clinical trials. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-11T03:35:38.533119-05:
      DOI: 10.1002/ajh.24883
       
  • Gender and survival in essential thrombocythemia: A two-center study of
           1,494 patients
    • Authors: Ayalew Tefferi; Silvia Betti, Daniela Barraco, Mythri Mudireddy, Sahrish Shah, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, Giacomo Coltro, Paola Guglielmelli, Alessandro M. Vannucchi
      Abstract: Based on suggestive information from recent epidemiologic data and earlier retrospective studies, we revisited the effect of gender on survival in 1,494 patients with essential thrombocythemia (ET). The primary study population included 904 patients from the Mayo Clinic (median age 58 years; 65% females); risk distribution, according to the international prognostic score for ET (IPSET), was 23% high, 42% intermediate and 35% low. Multivariable analysis that included IPSET-relevant risk factors identified male sex (HR 1.6, 95% CI 1.3-2.0), age ≥60 years (HR 4.3, 95% CI 3.4-5.4) and leukocyte count ≥11 x 10(9)/L (HR 1.5, 95% CI 1.3-1.9) as independent predictors of shortened survival. These findings were confirmed by analysis of a separate cohort of 590 ET patients (65% females) from the University of Florence, Italy, with corresponding HRs (95% CI) of 1.6 (1.1-2.5), 4.6 (2.2-9.5) and 1.8 (1.1-2.8). The independent prognostic effect of gender was further corroborated by a separate multivariable analysis against IPSET risk categories; HR (95% CI) for the Mayo Clinic/Florence cohorts were 1.5/1.6 (1.2/1.1-1.8/2.5) for male sex, 6.8/7.5 (5.0/3.1-9.3/18.3) for IPSET high risk and 2.8/4.1 (2.1/1.8-3.8/9.5) for IPSET intermediate risk. Furthermore, the survival disadvantage in men was most apparent in IPSET high risk category and in patients older than 60 years. In both patient cohorts, thrombosis history garnered significance in univariate, but not in multivariable analysis. The observations from the current study suggest that women with ET live longer than their male counterparts and that gender might supersede thrombosis history as a risk variable for overall survival. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-10T03:35:23.769412-05:
      DOI: 10.1002/ajh.24882
       
  • Risk factors and a prognostic model for post-splenectomy survival in
           myelofibrosis
    • Authors: Ayalew Tefferi; Mythri Mudireddy, Naseema Gangat, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, David M. Nagorney
      Abstract: Palliative treatment in myelofibrosis (MF) includes transfusion support, JAK2 inhibitors, involved field radiotherapy and splenectomy. In order to assist in selecting patients who are likely to benefit from splenectomy, we looked into risk factors for post-splenectomy survival, in 120 consecutive cases (median age 66 years); at the time of splenectomy, 61% displayed red cell transfusion need, 49% platelet count 25 x 10(9)/L, 60% constitutional symptoms and 13% circulating blasts ≥5%; dynamic international prognostic scoring system risk categories were 21% high, 55% intermediate-2, 21% intermediate-1 and 3% low. Among informative cases, karyotype was abnormal in 60% and driver mutational status was JAK2 75%, CALR 15%, MPL 4% and triple-negative 6%. At median follow-up of 1.3 years, from time of splenectomy, 95 (79%) deaths and 30 (25%) leukemic transformations were recorded. Median post-splenectomy survival was 1.5 years; in multivariable analysis, survival was adversely affected by age>65 years, transfusion need, leukocyte count>25 x 10(9)/L and circulating blasts ≥5%; these variables were subsequently used to devise an HR-weighted scoring system with high (3-4 risk factors), intermediate (2 risk factors) and low (0-1 risk factors) risk categories; the corresponding post-splenectomy median survivals were 0.3 (HR 5.9, 95% CI 3.2-11.0), 1.3 (HR 2.9, 95% CI 1.8-4.6) and 2.9 years. Post-splenectomy survival was not affected by driver mutational status or occurrence of leukemic transformation. Leukemia-free survival was predicted by very high risk karyotype. The observations from the current study might help identify appropriate candidates for splenectomy in MF. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-07T03:01:31.113641-05:
      DOI: 10.1002/ajh.24881
       
  • Emerging role of bevacizumab in management of patients with symptomatic
           hepatic involvement in Hereditary Hemorrhagic Telangiectasia
    • Authors: Ajay Chavan; Silke Schumann-Binarsch, Bernhard Schmuck, Franziska Oltmer, Urban Geisthoff, Florian Hoppe, Kornelia Wirsching, Juergen Klempnauer, Michael Manns, Rohit Philip Thomas, Claus-Henning Köhne
      PubDate: 2017-08-04T01:26:11.974784-05:
      DOI: 10.1002/ajh.24878
       
  • SIRT1 Activates the Expression of Fetal Hemoglobin Genes
    • Authors: Yan Dai; Tyngwei Chen, Heba Ijaz, Elizabeth H Cho, Martin H Steinberg
      Abstract: High fetal hemoglobin (HbF, α2γ2) levels ameliorate the clinical manifestations of sickle cell disease and β thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells. The small molecule SIRT1 activators SRT2104 and SRT1720 enhanced HBG expression in cord blood human erythroblasts and reactivated silenced HBG in adult human erythroblasts. Furthermore, SIRT1 binds in the β-globin gene cluster locus control region (LCR) and HBG promoters, promotes the looping of the LCR to HBG promoter, and increases the binding of RNA polymerase II and H4K16Ac in the HBG promoter. SIRT1 suppressed the expression of the HBG suppressors BCL11A, KLF1, HDAC1 and HDAC2. Lastly, SIRT1 did not change the proliferation of human erythroid progenitor cells or the expression of differentiation marker CD235a. These data suggest that SIRT1 activates HBG expression through facilitating LCR looping to the HBG promoter, inhibiting the expression of transcriptional suppressors of HBG, and indirectly increasing histone acetylation in HBG promoter. SIRT1 is a potential therapeutic target for γ-globin gene induction, and small molecule SIRT1 activators might serve as a lead compound for the development of new HbF inducers. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-04T01:25:52.783371-05:
      DOI: 10.1002/ajh.24879
       
  • Thrombotic and hemorrhagic complications in idiopathic erythrocytosis
    • Authors: Irene Bertozzi; Marco Ruggeri, Ilaria Nichele, Giacomo Biagetti, Elisabetta Cosi, Maria Luigia Randi
      PubDate: 2017-08-01T03:05:28.892193-05:
      DOI: 10.1002/ajh.24873
       
  • The impact of antibody profile in thrombosis associated with primary
           antiphospholipid syndrome
    • Authors: Sabrina da Silva Saraiva; Bruna de Moraes Mazetto, Lais Quinteiro Tobaldine, Marina Pereira Colella, Erich Vinícius De Paula, Joyce Annichinno-Bizzachi, Fernanda Andrade Orsi
      Abstract: Triple positivity (TP) for antiphospholipid antibodies(aPL) may identify aPL carriers with poorer prognosis. The clinical impact of TP in primary antiphospholipid syndrome(PAPS) remains unclear and further clinical evidences are needed to validate TP as a marker of severity. The aim of this study was to evaluate the impact of TP on the clinical course of PAPS with thrombosis(t-PAPS). We performed a retrospective analysis of a cohort of t-PAPS patients, comparing groups of patients with TP and non-TP profiles according to their demographic, clinical and laboratory features. We included 105 patients with t-PAPS, the median follow-up time of 3.7 years. Twenty-two patients(21%) had TP; the demographic distribution, the presence of cardiovascular risk factors and the site of thrombosis were similar between TP and non-TP patients. The frequency of thrombotic events did not differ between TP and non-TP patients during the study period. Pregnancy morbidities were more frequent in women with t-PAPS and TP than in those with non-TP profile (80% vs. 52.8%,P=0.05). Patients with t-PAPS and TP presented, at diagnosis, higher dRVVT ratio (median R=2.44 vs. 1.57,P
      PubDate: 2017-08-01T02:55:36.231821-05:
      DOI: 10.1002/ajh.24875
       
  • Outcomes after 18 Months of Eliglustat Therapy in Treatment-Naïve Adults
           with Gaucher Disease Type 1: The Phase 3 ENGAGE Trial
    • Authors: Pramod K. Mistry; Elena Lukina, Hadhami Ben Turkia, Suma P. Shankar, Hagit Baris, Marwan Ghosn, Atul Mehta, Seymour Packman, Gregory Pastores, Milan Petakov, Sarit Assouline, Manisha Balwani, Sumita Danda, Evgueniy Hadjiev, Andres Ortega, Sebastiaan J.M. Gaemers, Regina Tayag, M. Judith Peterschmitt
      Abstract: Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double-blind period, eliglustat treatment during the 9-month, open-label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double-blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment-naive patients. Eliglustat was well-tolerated, and there were no new safety concerns with longer-term exposure. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-01T02:55:30.296125-05:
      DOI: 10.1002/ajh.24877
       
  • Kidney Function of Transfused Children with Sickle Cell Anemia: Baseline
           Data from the TWiTCH Study with Comparison to Non-Transfused Cohorts
    • Authors: Ofelia Alvarez; Kerri Nottage, Lara M. Simpson, John Wood, Barry R. Davis, Beng Fuh, Sharada Sarnaik, Banu Aygun, Kathleen Helton, Russell E. Ware
      PubDate: 2017-07-25T03:20:50.090718-05:
      DOI: 10.1002/ajh.24871
       
  • Inflammatory and endothelial markers during vaso-occlusive crisis and
           acute chest syndrome in sickle cell disease
    • Authors: M. Schimmel; B.M. Luken, E. Nur, C.F.J. van Tuijn, J.W. Sins, D.P.M. Brandjes, S.S. Zeerleder, B.J. Biemond
      PubDate: 2017-07-25T03:16:22.4124-05:00
      DOI: 10.1002/ajh.24868
       
  • Validation of and proposals for refinements of the WHO 2016 classification
           for myelodysplastic syndromes
    • Authors: M. F. van Spronsen; T. M. Westers, H. Rozema, G. J. Ossenkoppele, R. E. Kibbelaar, M. Hoogendoorn, A. A. van de Loosdrecht
      PubDate: 2017-07-25T03:16:20.630123-05:
      DOI: 10.1002/ajh.24867
       
  • Plasmapheresis may improve clinical condition in sickle cell disease
           through its effects on red blood cell rheology
    • Authors: Elie Nader; Philippe Connes, Yann Lamarre, Céline Renoux, Philippe Joly, Marie-Dominique Hardy-Dessources, Giovanna Cannas, Nathalie Lemonne, Samir K. Ballas
      PubDate: 2017-07-25T03:15:31.254432-05:
      DOI: 10.1002/ajh.24870
       
  • Earlier initiation of transfusional and iron chelation therapies in
           recently born children with transfusion-dependent thalassemia
    • Authors: Raffaella Origa; Federica Tatti, Antonietta Zappu, GiovanBattista Leoni, Carlo Dessì, Paolo Moi, Maddalena Morittu, Valeria Orecchia, AnnaRita Denotti, Maria Paola Pilia, Franco Anni, Maria Perra, Maria Rosaria Casini, Susanna Barella
      PubDate: 2017-07-25T03:15:29.328517-05:
      DOI: 10.1002/ajh.24869
       
  • Fetal Hemoglobin in Sickle Cell Anemia: The Arab-Indian Haplotype and New
           Therapeutic Agents
    • Authors: Alawi H. Habara; Elmutaz M. Shaikho, Martin H. Steinberg
      Abstract: Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly two-fold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-24T03:36:03.514684-05:
      DOI: 10.1002/ajh.24872
       
  • Current treatment preferences in chronic myeloid leukemia: The Mayo Clinic
           Physicians' survey
    • Authors: Kebede Begna; Aref Al-Kali, Michelle Elliott, James Foran, Naseema Gangat, William Hogan, Christopher Hook, Jose Leis, Mark Litzow, Ruben Mesa, Jeanne Palmer, Animesh Pardanani, Mrinal Patnaik, Candido Rivera, Lisa Sproat, Raoul Tibes, Alexandra Wolanskyj-Spinner, Ayalew Tefferi
      PubDate: 2017-07-21T03:17:21.269012-05:
      DOI: 10.1002/ajh.24866
       
  • Frequency, Risk Factors, and Outcomes of Central Nervous System Relapse in
           Lymphoma Patients Treated with Dose-Adjusted EPOCH plus Rituximab
    • Authors: M.K. Malecek; A.M. Petrich, S. Rozell, B. Chu, S. Trifilio, N. Galanina, M. Maurer, U. Farooq, B. Link, G.S. Nowakowski, C. Nabhan, A.O. Ayed
      Abstract: BackgroundCentral nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) is a rare but serious complication that carries a poor prognosis. The use of infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) for frontline treatment of diffuse large B cell lymphoma (DLBCL) is increasing, though little is known about incidence of and risk factors for CNS relapse with this regimenPatients and methodsWe completed a chart review of patients with NHL who received EPOCH-R as front line therapy. Data obtained included baseline and treatment characteristics including if patients received CNS directed therapy. We measured overall survival (OS), progression free survival (PFS), and progression to CNS involvement.ResultsWe identified 223 patients who met the inclusion criteria, 72% had DLBCL. Of all the patients, 5.8% experienced CNS relapse, and 38.6% were treated with CNS prophylaxis. There was no difference in rate of CNS relapse, overall survival (OS), or progression free survival (PFS) between patients who had and had not received CNS prophylaxis. Patients whose serum lactate dehydrogenase (LDH) was greater than twice the upper limit of normal at diagnosis and those with extranodal disease were significantly more likely to have CNS relapse (p=0.0247 and 0.022 respectively) than their counterparts.ConclusionsThe rate of CNS relapse in this patient population approaches 6%, not significantly different from reports on those receiving R-CHOP. The results of this study suggest that CNS prophylaxis might be more selectively used among patients treated with EPOCH-R with certain high-risk features. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T03:25:20.384696-05:
      DOI: 10.1002/ajh.24864
       
  • Individuals with sickle cell disease have a significantly greater
           vasoconstriction response to thermal pain than controls and have
           significant vasoconstriction in response to anticipation of pain
    • Authors: Maha Khaleel; Mammen Puliyel, Payal Shah, John Sunwoo, Roberta M. Kato, Patjanaporn Chalacheva, Wanwara Thuptimdang, Jon Detterich, John C Wood, Jennie Tsao, Lonnie Zeltzer, Richard Sposto, Michael C.K. Khoo, Thomas D. Coates
      Abstract: The painful vaso-occlusive crises (VOC) that characterize sickle cell disease (SCD) progress over hours from the asymptomatic steady-state. SCD patients report that VOC can be triggered by stress, cold exposure and pain itself. We anticipated that pain could cause neural-mediated vasoconstriction, decreasing regional blood flow and promoting entrapment of sickle cells in the microvasculature. Therefore, we measured microvascular blood flow in the fingers of both hands using plethysmography and laser-Doppler flowmetry while applying a series of painful thermal stimuli on the right forearm in 23 SCD patients and 25 controls. Heat pain applied to one arm caused bilateral decrease in microvascular perfusion. The vasoconstriction response started before administration of the thermal pain stimulus in all subjects, suggesting that pain anticipation also causes significant vasoconstriction. The time delay between thermal pain application and global vasoconstriction ranged from 5 to 15.5 seconds and increased with age (p 
      PubDate: 2017-07-13T19:20:56.179117-05:
      DOI: 10.1002/ajh.24858
       
  • Not Bitten by the Bug: A CD30+ lymphoproliferative disorder masquerading
           as arthropod bites
    • Authors: Jacqueline McKesey; Travis Vandergriff, Heather Wickless
      PubDate: 2017-07-11T21:21:15.803414-05:
      DOI: 10.1002/ajh.24846
       
  • A re-appraisal of the benefit-risk profile of Hydroxyurea in polycythemia
           vera: A propensity-matched study
    • Authors: Tiziano Barbui; Alessandro M Vannucchi, Guido Finazzi, Maria Chiara Finazzi, Arianna Masciulli, Alessandra Carobbio, Arianna Ghirardi, Gianni Tognoni
      Abstract: The use of Hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has been criticized because no solid demonstration that this drug prevents thrombosis or prolongs survival has been so far produced. Here we present the outcomes of a large cohort of patients with PV included in the European Collaborative Low-dose Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow-up, had received only phlebotomy (PHL) or HU to maintain the hematocrit level
      PubDate: 2017-07-11T21:21:11.908736-05:
      DOI: 10.1002/ajh.24851
       
  • Marked leukemoid reaction in a patient with metastatic breast carcinoma
    • Authors: Yasmin Harvey; Shane Bleakley, Piers Blombery, Barbara J. Bain
      PubDate: 2017-07-11T21:21:10.188469-05:
      DOI: 10.1002/ajh.24849
       
  • A monocyte-TNF-endothelial activation axis in sickle transgenic mice:
           Therapeutic benefit from TNF blockade
    • Authors: Anna Solovey; Arif Somani, John D Belcher, Liming Milbauer, Lucile Vincent, Rafal Pawlinski, Karl A Nath, Robert J Kelm Jr, Nigel Mackman, M Gerard O'Sullivan, Kalpna Gupta, Gregory M Vercellotti, Robert P Hebbel
      Abstract: Elaboration of tumor necrosis factor (TNF) is a very early event in development of ischemia/reperfusion injury pathophysiology. Therefore, TNF may be a prominent mediator of endothelial cell and vascular wall dysfunction in sickle cell anemia, a hypothesis we addressed using NY1DD, S+SAntilles, and SS-BERK sickle transgenic mice. Transfusion experiments revealed participation of abnormally activated blood monocytes exerting an endothelial activating effect, dependent upon Egr-1 in both vessel wall and blood cells, and upon NFκB(p50) in a blood cell only. Involvement of TNF was identified by beneficial impact from TNF blockers, etanercept and infliximab, with less benefit from an IL-1 blocker, anakinra. In therapeutic studies, etanercept ameliorated multiple disturbances of the murine sickle condition: monocyte activation, blood biomarkers of inflammation, low platelet count and Hb, vascular stasis triggered by hypoxia/reoxygenation (but not if triggered by hemin infusion), tissue production of neuro-inflammatory mediators, endothelial activation (monitored by tissue factor and VCAM-1 expression), histopathologic liver injury, and three surrogate markers of pulmonary hypertension (perivascular inflammatory aggregates, arteriolar muscularization, and right ventricular mean systolic pressure). In aggregate, these studies identify a prominent – and possibly dominant – role for an abnormal monocyte-TNF-endothelial activation axis in the sickle context. Its presence, plus the many benefits of etanercept observed here, argue that pilot testing of TNF blockade should be considered for human sickle cell anemia, a challenging but achievable translational research goal. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-11T21:21:04.569305-05:
      DOI: 10.1002/ajh.24856
       
  • POEMS Syndrome: An Elusive Diagnosis
    • Authors: Jithma P Abeykoon; Wilson I. Gonsalves, Jennifer Oliveira, Prashant Kapoor
      PubDate: 2017-07-11T21:20:49.428344-05:
      DOI: 10.1002/ajh.24845
       
  • 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
       
  • 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
       
  • Juvenile myelomonocytic leukemia in an infant with congenital HIV and CMV
           infection
    • 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
       
  • 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
       
  • Secondary CNS involvement of ALK-negative anaplastic large cell lymphoma
    • Authors: Ajay Major; Zenggang Pan, Manali Kamdar
      PubDate: 2017-06-05T04:35:39.129866-05:
      DOI: 10.1002/ajh.24733
       
  • Botryoid nuclei resulting from cocaine abuse
    • Authors: Maurizio Fumi; Ylenia Pancione, Silvia Sale, Vincenzo Rocco, Barbara J. Bain
      PubDate: 2017-05-30T06:05:45.191589-05:
      DOI: 10.1002/ajh.24769
       
  • 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
       
  • Issue Information – Table of Contents
    • Pages: 1115 - 1117
      PubDate: 2017-10-17T06:57:51.085218-05:
      DOI: 10.1002/ajh.24522
       
  • World Health Organization-defined eosinophilic disorders: 2017 update on
           diagnosis, risk stratification, and management
    • Authors: Jason Gotlib
      Pages: 1243 - 1259
      Abstract: Disease overviewThe eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage.DiagnosisHypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm3 and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder.Risk stratificationDisease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes which includes the major category “myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2,” and the “MPN subtype, chronic eosinophilic leukemia, not otherwise specified” (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.Risk-adapted therapyThe goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g., 
      PubDate: 2017-10-17T06:57:52.786869-05:
      DOI: 10.1002/ajh.24880
       
 
 
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