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Publisher: John Wiley and Sons   (Total: 1592 journals)

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Showing 1 - 200 of 1592 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 13, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 66, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 54, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 175, 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: 14, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 6, 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: 37, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 5)
Addiction     Hybrid Journal   (Followers: 36, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 15, 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: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 283, 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: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 18, 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: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 11)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 16, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 155, 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: 93, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 35, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 13, 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: 17, 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: 38, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 300, 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: 4, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 18, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 10, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 143, 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: 20)
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: 236, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, 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: 49, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 26, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 18, 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: 93, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 52, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, 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: 73, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 183, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 51, 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: 32, 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: 30, 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: 27, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 13, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 270, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 55, 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: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 330, 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   (Followers: 1, SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, 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: 3, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, 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: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, 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: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 13, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 6, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, 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: 15, 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: 433, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 6, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 74, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 23, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 37, 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: 11, 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: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, 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: 18, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 5, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, 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: 37, 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: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 160, 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: 38, 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: 7, 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: 250, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Hematology
  [SJR: 1.761]   [H-I: 77]   [35 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  [1592 journals]
  • Prognosis in Myelodysplastic Syndromes: The Attractions and Limitations of
           Simplicity
    • Authors: David P. Steensma
      PubDate: 2018-02-16T05:05:27.395565-05:
      DOI: 10.1002/ajh.25068
       
  • EDTA-related degranulation mimicking storage pool disease
    • Authors: Marco Amoruso; Lorenzo Alberio, Monika Nagy
      PubDate: 2018-02-12T03:01:16.320427-05:
      DOI: 10.1002/ajh.25067
       
  • Predictive value of the new renal response criteria in AL amyloidosis
           treated with high dose melphalan and stem cell transplantation
    • Authors: Andrea Havasi; Gheorghe Doros, Vaishali Sanchorawala
      PubDate: 2018-02-12T03:01:15.253942-05:
      DOI: 10.1002/ajh.25066
       
  • Mayo CALR mutation type classification guide using alpha helix propensity
    • Authors: Terra L. Lasho; Christy M. Finke, Alexander Tischer, Animesh Pardanani, Ayalew Tefferi
      PubDate: 2018-02-09T08:00:26.027372-05:
      DOI: 10.1002/ajh.25065
       
  • Decitabine improves response rate and prolongs progression-free survival
           in older patients with newly diagnosed acute myeloid leukemia and with
           monosomal karyotype: A subgroup analysis of the DACO-016 trial
    • Authors: Agnieszka Wierzbowska; Ewa Wawrzyniak, Agnieszka Pluta, Tadeusz Robak, Grzegorz J. Mazur, Anna Dmoszynska, Jaroslav Cermak, Albert Oriol, Daniel Lysak, Chris Arthur, Margaret Doyle, Liang Xiu, Farhad Ravandi, Hagop M. Kantarjian
      PubDate: 2018-02-08T03:52:38.932817-05:
      DOI: 10.1002/ajh.25062
       
  • Ruxolitinib as First-Line Treatment in Secondary Hemophagocytic
           Lymphohistiocytosis: A Second Experience
    • Authors: Inuk Zandvakili; Caitlin B. Conboy, Ayed O. Ayed, Elizabeth J. Cathcart-Rake, Ayalew Tefferi
      PubDate: 2018-02-08T03:50:32.787357-05:
      DOI: 10.1002/ajh.25063
       
  • Mutations and prognosis in myelodysplastic syndromes: Karyotype-adjusted
           analysis of targeted sequencing in 300 consecutive cases and development
           of a genetic risk model
    • Authors: Naseema Gangat; Mythri Mudireddy, Terra L. Lasho, Christy M. Finke, Maura Nicolosi, Natasha Szuber, Mrinal M. Patnaik, Animesh Pardanani, Curtis A. Hanson, Rhett P. Ketterling, Ayalew Tefferi
      Abstract: In order to develop a genetic risk model for primary myelodysplastic syndromes (MDS), we queried the prognostic significance of next-generation sequencing (NGS)-derived mutations, in the context of the Mayo cytogenetic risk stratification, which includes high-risk (monosomal karyotype; MK), intermediate-risk (non-MK, classified as intermediate/poor/very poor, per the revised international prognostic scoring system; IPSS-R), and low-risk (classified as good/very good, per IPSS-R). Univariate analysis in 300 consecutive patients with primary MDS identified TP53, RUNX1, U2AF1, ASXL1, EZH2 and SRSF2 mutations as “unfavorable” and SF3B1 as “favorable” risk factors for survival; for the purposes of the current study, the absence of SF3B1 mutation was accordingly dubbed as an “adverse” mutation. Analysis adjusted for age and MK, based on our previous observation of significant clustering between MK and TP53 mutations, confirmed independent prognostic contribution from RUNX1, ASXL1 and SF3B1 mutations. Multivariable analysis that included age, the Mayo cytogenetics risk model and the number of adverse mutations resulted in HRs (95% CI) of 5.3 (2.5-10.3) for presence of three adverse mutations, 2.4 (1.6-3.7) for presence of two adverse mutations, 1.5 (1.02-2.2) for presence of one adverse mutation, 5.6 (3.4-9.1) for high-risk karyotype, 1.5 (1.1-2.2) for intermediate-risk karyotype and 2.4 (1.8-3.3) for age>70 years; HR-weighted risk point assignment generated a three-tiered genetic risk model: high (N=65; 5-year survival 2%), intermediate (N=100; 5-year survival 18%) and low (N=135; 5-year survival 56%). The current study provides a practically simple risk model in MDS that is based on age, karyotype and mutations only. This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T03:50:30.305992-05:
      DOI: 10.1002/ajh.25064
       
  • Longitudinal detection of DNMT3AR882H transcripts in patients with acute
           myeloid leukemia
    • Authors: Tiziana Ottone; Valentina Alfonso, Licia Iaccarino, Syed Khizer Hasan, Melissa Mancini, Mariadomenica Divona, Serena Lavorgna, Laura Cicconi, Paola Panetta, Luca Maurillo, Maria Ilaria Del Principe, Maria Irno Consalvo, Luca Franceschini, Daniela Francesca Angelini, Luca Battistini, Gisella Guerrera, Marco De Bardi, Emiliano Fabiani, Giulia Falconi, William Arcese, Sergio Amadori, Francesco Buccisano, Adriano Venditti, Maria Teresa Voso, Francesco Lo-Coco
      PubDate: 2018-02-08T03:50:21.562212-05:
      DOI: 10.1002/ajh.25061
       
  • Comparative safety of intravenous ferumoxytol vs ferric carboxymaltose in
           iron deficiency anemia: A randomized trial
    • Authors: N. Franklin Adkinson; William E. Strauss, Iain C. Macdougall, Kristine E. Bernard, Michael Auerbach, Robert F. Kaper, Glenn M. Chertow, Julie S. Krop
      Abstract: Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia. This randomized, multicenter, double-blind clinical trial compared the safety and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with iron deficiency anemia of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate-to-severe HSRs, including anaphylaxis, or moderate-to-severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate-to-severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P 
      PubDate: 2018-02-08T03:46:10.285098-05:
      DOI: 10.1002/ajh.25060
       
  • Multi-gene panel testing improves diagnosis and management of patients
           with hereditary anemias
    • Authors: Roberta Russo; Immacolata Andolfo, Francesco Manna, Antonella Gambale, Roberta Marra, Barbara Eleni Rosato, Paola Caforio, Valeria Pinto, Piero Pignataro, Kottayam Radhakrishnan, Sule Unal, Giovanna Tomaiuolo, Gian Luca Forni, Achille Iolascon
      Abstract: Mutations in more than 70 genes cause hereditary anemias (HA), a highly heterogeneous group of rare/low frequency disorders in which we included: hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA) and Diamond-Blackfan anemia; hemolytic anemias due to erythrocyte membrane defects, as hereditary spherocytosis and stomatocytosis; hemolytic anemias due to enzymatic defects.The study describes the diagnostic workflow for HA, based on the development of two consecutive versions of a targeted-NGS panel, including 34 and 71 genes, respectively. Seventy-four probands from 62 unrelated families were investigated. Our study includes the most comprehensive gene set for these anemias and the largest cohort of patients described so far. We obtained an overall diagnostic yield of 64.9%. Despite 54.2% of cases showed conclusive diagnosis fitting well to the clinical suspicion, the multi-gene analysis modified the original clinical diagnosis in 45.8% of patients (non-matched phenotype-genotype). Of note, 81.8% of non-matched patients were clinically suspected to suffer from CDA. Particularly, 45.5% of the probands originally classified as CDA exhibited a conclusive diagnosis of chronic anemia due to enzymatic defects, mainly due to mutations in PKLR gene. Interestingly, we also identified a syndromic CDA patient with mild anemia and epilepsy, showing a homozygous mutation in CAD gene, recently associated to early infantile epileptic encephalopathy-50 and CDA-like anemia.Finally, we described a patient showing marked iron overload due to the co-inheritance of PIEZO1 and SEC23B mutations, demonstrating that the multi-gene approach is valuable not only for achieving a correct and definitive diagnosis, but also for guiding treatment. This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-03T03:10:30.903435-05:
      DOI: 10.1002/ajh.25058
       
  • Effectiveness and Safety of Anticoagulants for the Treatment of Venous
           Thromboembolism in Patients With Cancer
    • Authors: Michael Blake Streiff; Dejan Milentijevic, Keith McCrae, Daniel Yannicelli, Jonathan Fortier, Winnie W. Nelson, François Laliberté, Concetta Crivera, Patrick Lefebvre, Jeff Schein, Alok A. Khorana
      Abstract: Anticoagulation is used to treat venous thromboembolism (VTE) in cancer patients, but may be associated with an increased risk of bleeding. VTE recurrence and major bleeding were assessed in cancer patients treated for VTE with the most currently prescribed anticoagulants in clinical practice. Newly diagnosed cancer patients (first VTE 1/1/2013-05/31/2015) who initiated rivaroxaban, low-molecular-weight heparin (LMWH), or warfarin were identified from Humana claims data and observed until end of eligibility or end of data availability. VTE recurrence was a hospitalization with a primary diagnosis of VTE ≥7 days after first VTE. Major bleeding events on treatment were identified using validated criteria. Cohorts were compared using Kaplan-Meier rates at 6 and 12 months and Cox proportional hazards models. Cohorts were adjusted for their differences at baseline. A total of 2,428 patients (rivaroxaban: 707; LMWH: 660; warfarin: 1,061) met inclusion criteria. Patient characteristics were well balanced after weighting. There was a trend for lower VTE recurrence rates in rivaroxaban users compared to LMWH users at 6 months (13.2% vs. 17.1%; p=0.060) and significantly lower at 12 months (16.5% vs. 22.2%; p=0.030) [HR:0.72, 95% CI:(0.52-0.95); p=0.024]. VTE recurrence rates were also lower for rivaroxaban than warfarin users at 6 months (13.2% vs. 17.5%; p=0.014) and 12 months (15.7% vs. 19.9%; p=0.017) [HR:0.74, 95% CI:(0.56-0.96); p=0.028]. Major bleeding rates were similar across cohorts. This real-world analysis suggests cancer patients with VTE treated with rivaroxaban had significantly lower risk of recurrent VTE and similar risk of bleeding compared to those treated with LMWH or warfarin. This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-03T03:05:32.129664-05:
      DOI: 10.1002/ajh.25059
       
  • Current and potential use of pathological targets in the treatment of
           Hodgkin lymphoma
    • Authors: Antonino Carbone; Annunziata Gloghini
      PubDate: 2018-02-02T20:45:30.63041-05:0
      DOI: 10.1002/ajh.25054
       
  • Phenotypes and survival in Erdheim-Chester disease: Results from a
           165-patient cohort
    • Authors: Fleur Cohen-Aubart; Jean-François Emile, Fabrice Carrat, Zofia Helias-Rodzewicz, Valérie Taly, Frédéric Charlotte, Philippe Cluzel, Jean Donadieu, Ahmed Idbaih, Stéphane Barete, Zahir Amoura, Julien Haroche
      PubDate: 2018-02-02T20:45:29.330065-05:
      DOI: 10.1002/ajh.25055
       
  • N-acetyl-L-cysteine Improves Bone Marrow Endothelial Progenitor Cells in
           Prolonged Isolated Thrombocytopenia Patients post Allogeneic Hematopoietic
           Stem Cell Transplantation
    • Authors: Yuan Kong; Min-Min Shi, Yuan-Yuan Zhang, Xie-Na Cao, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
      Abstract: Prolonged isolated thrombocytopenia (PT) is a serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to murine studies, endothelial progenitor cells (EPCs) play a crucial role in the regulation of hematopoiesis and thrombopoiesis in the bone marrow (BM) microenvironment. We previously showed that the reduced frequency of BM EPCs was an independent risk factor for the occurrence of PT following allo-HSCT. However, the functional role of BM EPCs and methods to improve the impaired BM EPCs in PT patients are unknown. In the current case-control study, we investigated whether the BM EPCs in PT patients differed from those in good graft function patients. Moreover, we evaluated whether N-acetyl-L-cysteine (NAC, a reactive oxygen species (ROS) scavenger) could enhance BM EPCs from PT patients in vitro and in vivo. The PT patients exhibited dysfunctional BM EPCs characterized by high levels of ROS and apoptosis and decreased migration and angiogenesis capabilities. In vitro treatment with NAC improved the quantity and function of the BM EPCs cultivated from the PT patients by down-regulating the p38 MAPK pathway and rescued the impaired BM EPCs to support megakaryocytopoiesis. Furthermore, according to the results of a preliminary clinical study, NAC is safe and effective in PT patients. In summary, these results suggested that the reduced and dysfunctional BM EPCs are involved in the occurrence of PT. The defective BM EPCs in the PT patients can be quantitatively and functionally improved by NAC, indicating that NAC is a promising therapeutic approach for PT patients following allo-HSCT. This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-02T20:45:28.114482-05:
      DOI: 10.1002/ajh.25056
       
  • Flai (fludarabine, cytarabine, idarubicin) plus low-dose gemtuzumab
           ozogamicin as induction therapy in cd33-positive aml: Final results and
           long term outcome of a phase ii multicenter clinical trial
    • Authors: Anna Candoni; Cristina Papayannidis, Giovanni Martinelli, Erica Simeone, Michele Gottardi, Ilaria Iacobucci, Filippo Gherlinzoni, Giuseppe Visani, Michele Baccarani, Renato Fanin
      Abstract: The aim of this prospective clinical trial was to evaluate the efficacy and safety of a combination of Gemtuzumab-Ozogamicin (GO) and FLAI scheme (fludarabine, cytarabine, idarubicin) as a first-line therapy in CD33 positive acute myeloid leukemia (AML). We treated 130 consecutive patients, aged
      PubDate: 2018-02-02T20:45:25.176036-05:
      DOI: 10.1002/ajh.25057
       
  • Feasibility trial for primary stroke prevention in children with sickle
           cell anemia in Nigeria (SPIN trial)
    • Authors: Najibah A. Galadanci; Shehu Umar Abdullahi, Leah D. Vance, Abdulkadir Musa Tabari, Shehi Ali, Raymond Belonwu, Auwal Salihu, Aisha Amal Galadanci, Binta Wudil Jibir, Halima Bello-Manga, Kathleen Neville, Fenella J. Kirkham, Yu Shyr, Sharon Phillips, Brittany V. Covert, Adetola A. Kassim, Lori C. Jordan, Muktar H. Aliyu, Michael R. DeBaun
      PubDate: 2018-02-02T09:05:25.797344-05:
      DOI: 10.1002/ajh.25012
       
  • Allogeneic hematopoietic stem cell transplant overcomes the adverse
           survival effect of very high risk and unfavorable karyotype in
           myelofibrosis
    • Authors: Ayalew Tefferi; Daniel K. Partain, Jeanne M. Palmer, James L. Slack, Vivek Roy, William J. Hogan, Mark L. Litzow, Rhett P. Ketterling, Mrinal M. Patnaik
      Abstract: The prognostic importance of genetic information in primary myelofibrosis (PMF) was recently highlighted in a study of over 1,000 cytogenetically-annotated patients; 5-year survival rates were 8% for very high risk (VHR), 27% “unfavorable” and 45% “favorable” karyotype. The current study addresses the practice-relevant question of whether or not allogeneic hematopoietic stem cell transplant (HCT) can overcome the detrimental survival effect of VHR or unfavorable karyotype. The study included 67 patients with PMF or secondary MF who received HCT at the Mayo Clinic and in whom pre-transplant cytogenetic information was available. Dynamic international prognostic scoring system (DIPSS) risk distribution was 13% high, 66% intermediate-2 and 21% intermediate-1. Cytogenetic risk distribution was 11% VHR, 34% unfavorable and 55% favorable. At median post-HCT follow-up of 60 months for living patients (range 34-170), 28 (42%) deaths were recorded. Five-year survival was 62% and was not affected by VHR or unfavorable karyotype (p=0.68). The salutary effect of HCT in patients with VHR or unfavorable karyotype was also apparent during analysis of a combined dataset that included a non-transplant cohort of 383 patients with PMF; multivariable analysis of the combined dataset (n=450) resulted in HRs (95% CI) of 2.4 (1.6-3.6) for absence of transplant, 3.3 (2.2-4.8) for VHR karyotype, 1.6 (1.2-2.1) for unfavorable karyotype, 2.9 (2.0-4.2) for DIPSS high and 1.7 (1.4-2.2) for DIPSS intermediate-2. These observations were further confirmed by analysis of more stringently matched case-control subset cohorts and provide the evidence for the therapeutic preference of HCT in cytogenetically high risk patients with MF. This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-01T04:20:29.982124-05:
      DOI: 10.1002/ajh.25053
       
  • Lymphoproliferative disorders in patients with chronic myeloproliferative
           neoplasms: A systematic review
    • Authors: Monia Marchetti; Alessandra Carobbio, Enrica Capitoni, Tiziano Barbui
      Abstract: Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or develop lymphoproliferative disorders (LPD), however, the clinical and molecular determinants of MPN and LPD co-occurrence are still uncertain. In order to systematically pool the available knowledge, we conducted a scoping review of literature published since January 2005 and analyzed single-patient clinical data from 50 papers reporting 214 individuals harboring both MPN and LPD. Patients had been diagnosed essential thrombocythemia (44%), polycythemia vera (29%) or myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD diagnosis was antecedent or synchronous. Patients mainly incurred indolent LPD, particularly chronic lymphocytic leukemia, while aggressive lymphomas and multiple myeloma were a relevant portion of the LPDs occurring in the follow-up of MPN. Chronic lymphocytic leukemia was preferentially diagnosed in PV patients and was associated with a very high male-to-female ratio, as well as an older age at MPN diagnosis. On converse, multiple myeloma was rarely reported in PV patients and was preferentially diagnosed in female patients not harboring the JAK2 V617F mutation. Based on the 46 cases reporting follow-up data, median survival after MPN diagnosis was 96 months. This thorough review of published evidence confirms that LPD are relevant clinical events in the history of MPN patients. Controlled studies are needed to better refine individuals at higher risk of developing LPD, in order to support surveillance programs and to avoid therapies possibly favoring LPD. This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-27T15:52:32.586571-05:
      DOI: 10.1002/ajh.25049
       
  • Nationwide Survey on the Use of Horse Antithymocyte Globulins (ATGAM) in
           Patients with Acquired Aplastic Anemia: A Report on Behalf of the French
           Reference Center for Aplastic Anemia
    • Authors: Régis Peffault de Latour; Reza Tabrizi, Ambroise Marcais, Thierry Leblanc, Thierry Lamy, Mohamad Mohty, Suzanne Tavitian, Charlotte Jubert, Marlène Pasquet, Claire Galambrun, Stéphanie Nguyen, Jean Yves Cahn, Thorsten Braun, Eric Deconinck, Jacques Olivier Bay, Flore Sicre de Fontbrune, Fiorenza Barraco, Gérard Socié
      Abstract: Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard immunosuppressive treatment (IST) for patients with aplastic anemia. A prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG for first-line treatment of severe AA. The French Health Agency (ANSM) permitted a patient-named Authorization for Temporary Use (ATU) program of hATG (ATGAM, Pfizer) in patients with AA in 2011 since commercial access to hATG is not approved. We took advantage of this program to analyze the outcomes of 465 patients who received ATGAM plus CSA as first line treatment (n=379; 81.5%), or for refractory (n=26) or relapsed disease (n=33), from September 2011 to March 2017. In the entire cohort one year, 72% of the patients had partial and 13% had complete response, with worse response for patients with severe AA and a longer interval between diagnosis and IST (more than 6 months). Severe adverse events were mainly linked to infections (24%), hemorrhages (6%) and elevated liver function tests (5%). Overall at 12 months, 9.7% of patients required second line IST and 15.6% received transplantation. Fifty-five patients died during the study mainly because of infections (53%).Factors predicting independently worse survival were age over 40 years, neutrophils less than 0.5x109/L, male gender and longer delay between diagnosis and hATG (>6 months period). This study does illustrate the results of ATGAM with CSA in a true-life perspective and confirms ATGAM as standard of care IST to treat patients with AA not eligible for HSCT. This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-27T10:50:20.28764-05:0
      DOI: 10.1002/ajh.25050
       
  • Glucose-6-Phosphate-Dehydrogenase Deficient Red Blood Cell Units are
           Associated with Decreased Post-Transfusion Red Blood Cell Survival in
           Children with Sickle Cell Disease
    • Authors: Eyal Sagiv; Ross M. Fasano, Naomi L.C. Luban, Cassandra D. Josephson, Sean R. Stowell, John D. Roback, Richard O. Francis, Marianne E.M. Yee
      Abstract: Chronic transfusion therapy (CTT) for sickle cell disease (SCD) reduces disease morbidity by suppressing the amount of circulating hemoglobin S (HbS)-containing red blood cells (RBC). The effectiveness of CTT depends on the rate of RBC clearance. Glucose-6-phosphate dehydrogenase (G6PD) deficient donor RBC may exhibit increased hemolysis, but it is unknown if transfusion of these units results in less effective transfusion outcomes in SCD.Children with SCD on CTT were followed prospectively for multiple transfusions. G6PD activity of transfused units was measured prior to expiration date. HbA clearance (ΔHbA) was calculated as the difference of estimated post-transfusion HbA to the pre-transfusion HbA of the subsequent transfusion episode. Sixty-two patients received 388 transfusions. Of 755 RBC units, 687 (91%) had normal G6PD (>60% activity), 38 (5%) had moderately low G6PD (10 – 60% activity), and 30 (4%) had severely low G6PD (
      PubDate: 2018-01-27T10:45:35.884585-05:
      DOI: 10.1002/ajh.25051
       
  • You don't always get what you want: Does hypoxia cause sickle cell
           crisis'
    • Authors: Thomas D Coates
      PubDate: 2018-01-27T10:45:19.722406-05:
      DOI: 10.1002/ajh.25048
       
  • A prospective analysis for prevalence of complications in Thai
           non-transfusion-dependent Hb E/β-thalassemia and α-thalassemia (Hb H
           disease)
    • Authors: Supachai Ekwattanakit; Noppadol Siritanaratkul, Vip Viprakasit
      Abstract: Background: Recently, complications in patients with non-transfusion-dependent thalassemia (NTDT), in particular those with β-thalassemia intermedia (β-TI), were found to be significantly different from those in patients with transfusion dependent thalassemia (TDT), mainly β-thalassemia major (β–TM). However, this information is rather limited in other forms of NTDT.Methods: In this prospective study, adult Thai NTDT patients were interviewed and clinically evaluated for thalassemia related complications.Results: Fifty-seven NTDT patients (age 18-74 years), 59.6% Hb E/β-thalassemia and 40.4% Hb H disease, were recruited; 26.4% were splenectomized. The most common complications were gallstones (68.4%), osteoporosis (26.3%), and pulmonary hypertension (15.8%). Splenectomy was associated with higher rate of gallstones and serious infection (p=0.001 and 0.052, respectively), consistent with a multivariate analysis (RR=9.5, p=0.044 and RR=15.1, p=0.043, respectively). In addition, a higher hemoglobin level was inversely associated with gallstones in both univariate and multivariate analyses (p=0.01 and 0.022, respectively). Serum ferritin was associated with abnormal liver function (p=0.002). In contrast to the previous study, the prevalence of thrombosis was less common in our population (1.7%), probably due to differences in transfusion therapy, ethnicity, and underlying genotypes.Conclusions: For the first time, this prospective study provided the current prevalence of NTDT related complications in a Southeast Asian population with a different underlying genetic basis compared with previous studies. Although individual prevalence of each complication might differ from other studies, several important clinical factors such as splenectomy, degree of anemia, and iron overload seem to be determining risks of developing these complications consistently across different ethnicities. This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-23T02:35:50.61388-05:0
      DOI: 10.1002/ajh.25046
       
  • The spleen of patients with myelofibrosis harbors defective mesenchymal
           stromal cells
    • Authors: Maria Antonietta Avanzini; Vittorio Abbonante, Paolo Catarsi, Irene Dambruoso, Melissa Mantelli, Valentina Poletto, Elisa Lenta, Paola Guglielmelli, Stefania Croce, Lorenzo Cobianchi, Basilio Jemos, Rita Campanelli, Elisa Bonetti, Christian Andrea Di Buduo, Silvia Salmoiraghi, Laura Villani, Margherita Massa, Marina Boni, Rita Zappatore, Alessandra Iurlo, Alessandro Rambaldi, Alessandro Maria Vannucchi, Paolo Bernasconi, Alessandra Balduini, Giovanni Barosi, Vittorio Rosti,
      Abstract: Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant up-regulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point towards the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage. This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-23T02:35:23.831546-05:
      DOI: 10.1002/ajh.25047
       
  • Safety of anticoagulation in patients with atrial fibrillation and MDS/AML
           complicated by thrombocytopenia
    • Authors: Jessica Caro; Shyamala Navada
      PubDate: 2018-01-20T05:09:05.211925-05:
      DOI: 10.1002/ajh.25045
       
  • Band 3 phosphorylation induces irreversible alterations of stored red
           blood cells
    • Authors: Slim Azouzi; Marc Romana, Nobuto Arashiki, Yuichi Takakuwa, Wassim El Nemer, Thierry Peyrard, Yves Colin, Pascal Amireault, Caroline Le Van Kim
      PubDate: 2018-01-20T05:08:26.093661-05:
      DOI: 10.1002/ajh.25044
       
  • Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC):
           A phase 1b open-label study
    • Authors: Carlo Gambacorti-Passerini; Sergey Orlov, Li Zhang, Fadi Braiteh, Huiqiang Huang, Taito Esaki, Keizo Horibe, Jin-Seok Ahn, Joseph T. Beck, William Jeffrey Edenfield, Yuankai Shi, Matthew Taylor, Kenji Tamura, Brian A. Van Tine, Shang-Ju Wu, Jolanda Paolini, Paulina Selaru, Tae Min Kim
      Abstract: Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single-arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty-four patients were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective response rate was 53% (95% confidence interval [CI], 28–77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30–93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2–36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2-year progression-free survival of 63% and 67%, respectively. The most common treatment-related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK-positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long-term treatment. This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-20T05:08:06.456828-05:
      DOI: 10.1002/ajh.25043
       
  • Voxelotor (GBT440), a first-in-class hemoglobin oxygen-affinity modulator,
           has promising and reassuring preclinical and clinical data
    • Authors: Jeremie H. Estepp
      PubDate: 2018-01-20T05:07:59.933503-05:
      DOI: 10.1002/ajh.25042
       
  • Pan-Pseudothrombocytopenia: An Unusual Case of Platelet Clumping
    • Authors: Hany Elmariah; Satish Shanbhag
      PubDate: 2018-01-17T04:33:04.854767-05:
      DOI: 10.1002/ajh.25040
       
  • Concomitant cutaneous squamous cell carcinoma and CLL in a patient: The
           utility of 18F- FDG PET/CT in differentiation of nodal metastasis
    • Authors: Kerem Ozturk; Celalettin Ustun, Sobia Khaja, Faqian Li, Matthew Rischall, Zuzan Cayci
      Abstract: Introduction: Head and neck cutaneous squamous cell carcinoma (cSCC) often presents with cervical lymph node metastases. Lymphoma is the second most common malignancy in the cervical region, however, it is rarely synchronous with head and neck cSCC.Methods: We describe the unusual presentation of a patient with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and metastatic head and neck cSCC on 18-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT).Results: In our case, 18F-FDG PET/CT was able to detect single sub-centimeter SCC metastatic node among numerous other enlarged CLL infiltrated lymph nodes since SCC was markedly more FDG avid comparison with CLL lymph nodes. This single highly FDG avid node was otherwise occult by clinical examination and indifferent from the rest of the lymph nodes on routine cross-sectional imaging.Conclusion: This report describes the role of 18F-FDG PET/CT in differentiation of the single sub-centimeter metastatic nodal disease from cSCC from the remainder innumerable leukemia infiltrated nodes. This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-17T04:33:03.56762-05:0
      DOI: 10.1002/ajh.25041
       
  • Microangiopathy and acute kidney injury in paroxysmal cold haemoglobinuria
           – a challenge for management
    • Authors: Neill Storrar; Eve Miller-Hodges, John Neary, Jeremy Hughes, Nicole Priddee
      PubDate: 2018-01-17T04:32:59.101188-05:
      DOI: 10.1002/ajh.25038
       
  • Evans syndrome secondary to undiagnosed chronic lymphocytic leukemia in a
           patient with unexplained bleeding
    • Authors: Christopher B. Hergott; Olga Pozdnyakova
      PubDate: 2018-01-17T04:25:22.012212-05:
      DOI: 10.1002/ajh.25039
       
  • Urinary Orosomucoid is Associated with Progressive Chronic Kidney Disease
           Stage in Patients with Sickle Cell Anemia
    • Authors: Marina Jerebtsova; Santosh L. Saraf, Simran Soni, Nowah Afangbedji, Xionghao Lin, Rasha Raslan, Victor R. Gordeuk, Sergei Nekhai
      PubDate: 2018-01-12T02:26:08.162547-05:
      DOI: 10.1002/ajh.25036
       
  • A retrospective survey of exposure history to chemotherapy or radiotherapy
           in 940 consecutive patients with primary myelofibrosis
    • Authors: Maura Nicolosi; Mythri Mudireddy, Mrinal M. Patnaik, Naseema Gangat, Animesh Pardanani, Ayalew Tefferi
      PubDate: 2018-01-12T02:20:24.593579-05:
      DOI: 10.1002/ajh.25037
       
  • Inhaled Corticosteroid Use to Prevent Severe Vaso-occlusive Episode
           Recurrence in Children Between 1 and 4 With Sickle Cell Disease: A
           Multicenter Feasibility Trial
    • Authors: Leah Vance Utset; Zalaya Ivy, Shaina M. Willen, Mark Rodeghier, Amanda Watt, Leann Schilling, Chantel L. Jenkins, Stefanie Pepper, Barbara Speller-Brown, Deepika S. Darbari, Suvankar Majumdar, Olufolake Adisa, Michael R. DeBaun
      PubDate: 2018-01-11T03:46:24.220803-05:
      DOI: 10.1002/ajh.25033
       
  • Effect of Eptifibatide on Inflammation During Acute Pain Episodes in
           Sickle Cell Disease
    • Authors: Julia E. Brittain; Ciprian Anea, Payal Desai, Jack Delaney, Adam McDonald, Stephen W. Looney, Nigel S. Key, Leslie V. Parise, Kenneth I. Ataga
      PubDate: 2018-01-11T03:46:22.784862-05:
      DOI: 10.1002/ajh.25032
       
  • A Phase II study of Tacrolimus and Thymoglobulin as
           Graft-Versus-Host-Disease Prophylaxis in Related Donor Allogeneic
           Hematopoietic Cell Transplantation
    • Authors: Dipenkumar Modi; Zaid Al-Kadhimi, Wei Chen, Hyejeong Jang, Abhinav Deol, Lois Ayash, Divaya Bhutani, Asif Alavi, Voravit Ratanatharathorn, Joseph P. Uberti
      PubDate: 2018-01-10T03:31:18.907988-05:
      DOI: 10.1002/ajh.25035
       
  • Description and Prognostic Significance of the Kinetics of Minimal
           Residual Disease Status in Adults with Acute Lymphoblastic Leukemia
           Treated with HyperCVAD
    • Authors: Ryan D. Cassaday; Philip A. Stevenson, Brent L. Wood, Pamela S. Becker, Paul C. Hendrie, Brenda M. Sandmaier, Jerald L. Radich, Andrei R. Shustov
      Abstract: HyperCVAD is a commonly-used regimen for adults with newly-diagnosed acute lymphoblastic leukemia (ALL). However, relatively little is known about the application of minimal residual disease (MRD) detection with this treatment. To address this, we studied 142 adults with ALL treated with hyperCVAD over a 10-year period who had MRD assessed by either multi-parameter flow cytometry or (for patients with Philadelphia chromosome positive ALL) reverse transcriptase polymerase chain reaction for the BCR-ABL1 translocation. In a multivariate analysis, patients who achieved MRD negativity (MRDNeg) at any point had significantly better overall survival (OS; hazard ratio [HR] 0.43; P = 0.01) and event-free survival (EFS; HR 0.27; P 
      PubDate: 2018-01-10T03:31:00.96286-05:0
      DOI: 10.1002/ajh.25030
       
  • Realizing Effectiveness Across Continents with Hydroxyurea: Enrollment and
           Baseline Characteristics of the Multicenter REACH Study in sub-Saharan
           Africa
    • Authors: Patrick T. McGann; Thomas N. Williams, Peter Olupot-Olupot, George A. Tomlinson, Adam Lane, José Luís Reis da Fonseca, Robert Kitenge, George Mochamah, Ham Wabwire, Susan Stuber, Thad A. Howard, Kathryn McElhinney, Banu Aygun, Teresa Latham, Brígida Santos, Léon Tshilolo, Russell E. Ware,
      Abstract: Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries. Following comprehensive training of local research teams, REACH was approved by local Ethics Committees and achieved full enrollment ahead of projections with 635 participants enrolled over a 30-month period, despite half of families living>12km from their clinical site. At enrollment, study participants (age 5.4±2.4 years) had substantial morbidity, including a history of vaso-occlusive pain (98%), transfusion (68%), malaria (85%), and stroke (6%). Significant differences in laboratory characteristics were noted across sites, with lower hemoglobin concentrations (p
      PubDate: 2018-01-10T03:30:32.012556-05:
      DOI: 10.1002/ajh.25034
       
  • Factor VII deficiency in major artery occlusion stroke
    • Authors: Slaven Pikija; Simon Peter Gampenrieder, Katharina Millesi, Georg Pilz, Serge Weis, Johannes Sebastian Mutzenbach
      PubDate: 2018-01-10T03:25:34.184371-05:
      DOI: 10.1002/ajh.25031
       
  • Methylene blue-induced Heinz body hemolytic anemia in a premature neonate
    • Authors: Lewis Vanhinsbergh; Sabita Uthaya, Barbara J. Bain
      PubDate: 2018-01-05T03:31:13.11737-05:0
      DOI: 10.1002/ajh.25028
       
  • Reply to Castillo et al.
    • Authors: Jithma P. Abeykoon; Rebecca King, Stephen M. Ansell, S. Vincent Rajkumar, Jonas Paludo, Robert A. Kyle, Shaji Kumar, Morie A. Gertz, Prashant Kapoor
      PubDate: 2018-01-05T03:30:50.975547-05:
      DOI: 10.1002/ajh.25029
       
  • Toward complement inhibition 2.0: Next generation anti-complement agents
           for paroxysmal nocturnal hemoglobinuria
    • Authors: Antonio M Risitano; Serena Marotta
      Abstract: Therapeutic complement inhibition by eculizumab has revolutionized the treatment of paroxysmal nocturnal hemoglobinuria (PNH) with a major impact on its natural history. Nevertheless, emerging unmet clinical needs may benefit from the development of novel complement inhibitors. Novel strategies of complement inhibition exploit different agents targeting C5, as well as compound intercepting the complement cascade at the level of its key component C3, or even upstream at the level of components involved in complement alternative pathway initiation. Many of these agents are already in their clinical development; preliminary data together with a deep understanding of PNH biology may help to anticipate their possible clinical effect. Novel anti-C5 agents include monoclonal antibodies (even long-lasting) as well as other small molecules bioavailable by subcutaneous administration; an anti-C5 small interfering RNA has been developed too. All these anti-C5 agents seem to recapitulate safety and efficacy of current eculizumab treatment; their main improvement pertains to better patient's convenience due to longer dosing interval and/or possible subcutaneous self-administration. The possibility of achieving a deeper C5 inhibition has been shown as well, but its actual clinical meaning remains to be elucidated. Upstream complement inhibitors include the anti-C3 small peptide compstatin (and its derivatives), and small inhibitors of complement factor D or complement factor B. This class of compound anticipates a possible efficacy in prevention of C3-mediated extravascular hemolysis, in addition to inhibition of intravascular hemolysis, possibly leading to improved hematological responses. The availability of all these compounds will result soon in a substantial improvement of PNH management. This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-04T02:45:40.793501-05:
      DOI: 10.1002/ajh.25016
       
  • ISSUE INFORMATION – TABLE OF CONTENTS
    • Pages: 317 - 319
      PubDate: 2018-02-07T00:22:04.029869-05:
      DOI: 10.1002/ajh.25052
       
  • Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring
    • Authors: Elias Jabbour; Hagop Kantarjian
      Pages: 442 - 459
      Abstract: Disease overviewChronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.DiagnosisCML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR-ABL1 fusion oncogene, which in turn translates into a BCR-ABL1 oncoprotein.Frontline therapy: Four tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, dasatinib, and bosutinib are approved by the United States Food and Drug Administration for first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; this has not translated into improved long-term survival, because of the availability of effective salvage therapies.Salvage therapy: For patients who fail frontline therapy, second-line options include second and third generation TKIs. Second and third generation TKIs, although potent and selective, exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients’ comorbidities, disease stage, and BCR-ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP who have failed at least 2 TKIs, and for all patients in CML advanced phases.
      PubDate: 2018-02-07T00:22:09.748797-05:
      DOI: 10.1002/ajh.25011
       
  • FLT3 Inhibitors in Acute Myeloid Leukemia: Choosing the Best when the
           Optimal Does Not Exist
    • Authors: Rita Assi; Farhad Ravandi
      Abstract: Despite significant advances in deciphering the molecular and cytogenetic pathways governing acute myeloid leukemia, improvements in treatment strategies and clinical outcomes have been limited. The discovery of FLT3 pathway and its potential role in leukemogenesis has generated excitement in the field and has provided a potential target for drug development. Despite setbacks encountered with first-generation inhibitors, we are witnessing an outbreak of novel agents with potent activity and improved pharmacodynamics which continue to generate promising results. The disease, however, remains a challenge to both patients and physicians with rapid emergence of resistance and subsequent treatment failure. Multiple unanswered questions remain as to which are the optimal FLT3-inhibitors and which strategies and combinations are likely to overcome resistance. This review revisits the development of FLT3-inhibitors, the pathways incriminated in their failure and summarizes available molecularly-designed strategies to design better clinical trials. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T01:10:38.184259-05:
      DOI: 10.1002/ajh.25027
       
  • Ataluren-driven Restoration of Shwachman-Bodian-Diamond Syndrome Protein
           Function in Shwachman-Diamond Syndrome Bone Marrow Cells
    • Authors: Valentino Bezzerri; Donatella Bardelli, Jacopo Morini, Antonio Vella, Simone Cesaro, Claudio Sorio, Andrea Biondi, Cesare Danesino, Piero Farruggia, Baroukh Maurice Assael, Giovanna D'Amico, Marco Cipolli
      Abstract: Shwachman-Diamond syndrome (SDS) is a rare inherited recessive disease mainly caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, which encodes for the homonymous protein SBDS, whose function still remains to be fully established. SDS affects several organs causing bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, and cognitive disorders. About 15% of SDS patients develop myelodysplastic syndromes (MDS) and are at higher risk of developing acute myeloid leukemia (AML). Deficiency in SBDS expression has been associated with increased apoptosis and lack of myeloid differentiation in bone marrow hematopoietic progenitors. Importantly, most SDS patients carry nonsense mutations in SBDS. Since ataluren is a well-characterized small molecule inhibitor that can suppress nonsense mutations, here we have assessed the efficacy of this drug in restoring SBDS expression in hematopoietic cells obtained from a cohort of SDS patients. Remarkably, we show that ataluren treatment readily restores SBDS protein expression in different cell types, particularly bone marrow stem cells. Furthermore, ataluren promotes myeloid differentiation in hematopoietic progenitors, reduces apoptotic rate in primary PBMCs, and brings mTOR phosphorylation levels back to normal in both lymphoblasts and bone marrow mesenchymal stromal cells (BM-MSCs). Since a specific therapy against SDS is currently lacking, these results provide the rationale for ataluren repurposing clinical trials. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T01:10:29.383955-05:
      DOI: 10.1002/ajh.25025
       
  • Centrifugation-free washing: A novel approach for removing IgA from stored
           red blood cells
    • Authors: Eszter Vörös; Nathaniel Z. Piety, Briony C. Strachan, Madeleine Lu, Sergey S. Shevkoplyas
      Abstract: Washed red blood cells (RBCs) are indicated for immunoglobulin A (IgA) deficient recipients. Centrifugation-based cell processors commonly used by hospital blood banks cannot consistently reduce IgA below the recommended levels, hence double washing is frequently required. Here we describe a prototype of a simple, portable, disposable system capable of washing stored RBCs without centrifugation, while reducing IgA below 0.05 mg/dL in a single run. Samples from RBC units (n = 8, leukoreduced, 4-6 weeks storage duration) were diluted with normal saline to a hematocrit of 10%, and then washed using either the prototype washing system, or via conventional centrifugation. The efficiency of the two washing methods was quantified and compared by measuring several key in vitro quality metrics. The prototype of the washing system was able to process stored RBCs at a rate of 300 mL/hr, producing a suspension of washed RBCs with 43 ± 3% hematocrit and 86 ± 7% cell recovery. Overall, the two washing methods performed similarly for most measured parameters, lowering the concentration of free hemoglobin by>4-fold and total free protein by>10-fold. Importantly, the new washing system reduced the IgA level to 0.02 ± 0.01 mg/mL, a concentration 5-fold lower than that produced by conventional centrifugation. This proof-of-concept study showed that centrifugation may be unnecessary for washing stored RBCs. A simple, disposable, centrifugation-free washing system could be particularly useful in smaller medical facilities and resource limited settings that may lack access to centrifugation-based cell processors. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T01:10:26.944763-05:
      DOI: 10.1002/ajh.25026
       
  • Fatal Cache Valley virus meningoencephalitis associated with rituximab
           maintenance therapy
    • Authors: Yuanquan Yang; Jingxin Qiu, Abigail Snyder-Keller, Yongping Wu, Shufeng Sun, Haixin Sui, Amy B. Dean, Laura Kramer, Francisco Hernandez-Ilizaliturri
      PubDate: 2017-12-28T03:35:36.915393-05:
      DOI: 10.1002/ajh.25024
       
  • Ibrutinib discontinuation in Waldenström macroglobulinemia: etiologies,
           outcomes, and IgM rebound
    • Authors: Joshua N. Gustine; Kirsten Meid, Toni Dubeau, Patricia Severns, Zachary R. Hunter, Guang Yang, Lian Xu, Steven P. Treon, Jorge J. Castillo
      Abstract: Ibrutinib is the first approved therapy for symptomatic patients with Waldenström macroglobulinemia (WM). The reasons for discontinuing ibrutinib and subsequent outcomes have not been previously evaluated in WM patients. We therefore conducted a retrospective review of 189 WM patients seen at our institution who received treatment with ibrutinib, of whom 51 (27%) have discontinued therapy. Reasons for discontinuation include: disease progression (n=27; 14%), toxicity (n=15; 8%), non-response (n=5; 3%), and other unrelated reasons (n=4; 2%). The cumulative incidence of ibrutinib discontinuation at 12, 24, 36, and 48 months from treatment initiation was 22%, 26%, 35%, and 43%, respectively. A baseline platelet count ≤100 K/µL and presence of tumor CXCR4 mutations were independently associated with 4-fold increased odds of ibrutinib discontinuation. An IgM rebound (≥25% increase in serum IgM) was observed in 37 patients (73%) following ibrutinib discontinuation and occurred within 4 weeks for nearly half of patients. The response rate to salvage therapy was 71%; responses were higher in patients without an IgM rebound and when salvage therapy was initiated within 2 weeks of stopping ibrutinib. Patients who discontinued ibrutinib due to disease progression versus non-progression events had significantly shorter overall survival (21 versus 32 months; p=0.046). Response to salvage therapy was associated with an 82% reduction in the risk of death following ibrutinib discontinuation. WM patients who discontinue ibrutinib require close monitoring, and continuation of ibrutinib until the next therapy should be considered to maintain disease control. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-27T00:40:31.418152-05:
      DOI: 10.1002/ajh.25023
       
  • JAK2 exon 12 mutated polycythemia vera: Mayo-Careggi MPN Alliance study of
           33 consecutive cases and comparison with JAK2V617F mutated disease
    • Authors: Ayalew Tefferi; Sravanthi Lavu, Mythri Mudireddy, Terra L. Lasho, Christy M. Finke, Naseema Gangat, Animesh Pardanani, Curtis A. Hanson, Carmela Mannarelli, Paola Guglielmelli, Alessandro M. Vannucchi
      PubDate: 2017-12-23T03:15:58.523773-05:
      DOI: 10.1002/ajh.25017
       
  • A Distinct Immunophenotype Identifies a Subset of NPM1-mutated AML With
           TET2 or IDH1/2 Mutations and Improved Outcome
    • Authors: Emily F. Mason; Frank C. Kuo, Robert P. Hasserjian, Adam C. Seegmiller, Olga Pozdnyakova
      Abstract: Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. NPM1 is one of the most common recurrently mutated genes in acute myeloid leukemia (AML). NPM1 mutations often co-occur with FLT3-ITDs and mutations in genes regulating DNA methylation, such as DNMT3A, TET2, and IDH1/2. It remains unclear whether these genetic alterations are associated with distinct immunophenotypic findings or affect prognosis. We identified 133 cases of NPM1-mutated AML and correlated sequencing data with immunophenotypic and clinical findings. Of 84 cases (63%) that lacked monocytic differentiation (“myeloid AML”), 40 (48%) demonstrated an acute promyelocytic leukemia-like (APL-like) immunophenotype by flow cytometry, with absence of CD34 and HLA-DR and strong myeloperoxidase expression, in the absence of a PML-RARA translocation. Pathologic variants in TET2, IDH1 or IDH2 were identified in 39/40 APL-like cases. This subset of NPM1-mutated AML was associated with longer relapse-free and overall survival, as compared to cases that were positive for CD34 and/or HLA-DR. The combination of NPM1 and TET2 or IDH1/2 mutations along with an APL-like immunophenotype identifies a distinct subtype of AML. Further studies addressing its biology and clinical significance may be especially relevant in the era of IDH inhibitors and recent work showing efficacy of ATRA therapy in NPM1 and IDH1-mutated AML. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-23T03:15:57.103632-05:
      DOI: 10.1002/ajh.25018
       
  • Intestinal microbiome analysis revealed dysbiosis in sickle cell disease
    • Authors: Seah H Lim; Alison Morris, Kelvin Li, Adam C Fitch, Loren Fast, Laura Goldberg, Matthew Quesenberry, Philippa Sprinz, Barbara Methé
      PubDate: 2017-12-23T03:15:51.529332-05:
      DOI: 10.1002/ajh.25019
       
  • Prognostic impact of bone marrow fibrosis and dyserythropoiesis in
           autoimmune hemolytic anemia
    • Authors: B Fattizzo; A Zaninoni, U Gianelli, A Zanella, A Cortelezzi, AG Kulasekararaj, W Barcellini
      PubDate: 2017-12-23T03:15:41.463613-05:
      DOI: 10.1002/ajh.25020
       
  • A Single Center Experience with Romiplostim for the Management of
           Chemotherapy-Induced Thrombocytopenia
    • Authors: Jennifer Miao; Houry Leblebjian, Bridget Scullion, Aric Parnes
      PubDate: 2017-12-23T03:15:37.324969-05:
      DOI: 10.1002/ajh.25022
       
  • Sarcoid-like granulomatosis in a patient receiving anti-TNFα for
           psoriasis
    • Authors: Vasiliki Leventaki; Jamie Flerlage
      PubDate: 2017-12-23T03:15:32.371186-05:
      DOI: 10.1002/ajh.25021
       
  • Developmental Differences Between Neonatal and Adult Human Erythropoiesis
    • Authors: Hongxia Yan; John Hale, Julie Jaffray, Jie Li, Yaomei Wang, Yumin Huang, Xiuli An, Christopher Hillyer, Nan Wang, Sandrina Kinet, Naomi Taylor, Narla Mohandas, Anupama Narla, Lionel Blanc
      Abstract: Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood (CB)- and peripheral blood (PB)-HSPC induced towards erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC. Upon in vitro erythroid differentiation, CB-derived cells proliferated 4-fold more than PB-derived cells. However, CB-derived cells exhibited a delayed kinetics of differentiation, resulting in an increased number of progenitors, notably CFU-E. The phenotypes of early erythroid differentiation stages also differed between the two sources with a significantly higher percentage of IL3R-GPA-CD34+CD36+ cells generated from PB- than CB-HSPCs. This subset was found to generate both BFU-E and CFU-E colonies in colony-forming assays. To further understand the differences between CB- and PB-HSPC, cells at eight stages of erythroid differentiation were sorted from each of the two sources and their transcriptional profiles were compared. We document differences at the CD34, BFU-E, poly- and orthochromatic stages. Genes exhibiting the most significant differences in expression between HSPC sources clustered into cell cycle- and autophagy-related pathways. Altogether, our studies provide a qualitative and quantitative comparative analysis of human erythropoiesis, highlighting the impact of the developmental origin of HSPCs on erythroid differentiation. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-23T03:15:29.00313-05:0
      DOI: 10.1002/ajh.25015
       
  • Clinical and biological characterization of MPN patients harboring two
           driver mutations, a French Intergroup of Myeloproliferative neoplasms
           (FIM) study
    • Authors: Olivier Mansier; Damien Luque Paz, Jean-Christophe Ianotto, Yannick Le Bris, Aurélie Chauveau, Françoise Boyer, Carole Conejero, Olivier Fitoussi, Jérémie Riou, Didier Adiko, Mohamed Touati, Jasmine Chauzeix, Jean-François Viallard, Marie C Béné, Stéphane Giraudier, Valérie Ugo, Eric Lippert
      PubDate: 2017-12-21T02:18:21.212444-05:
      DOI: 10.1002/ajh.25014
       
  • Sleep disordered breathing does not predict acute severe pain episodes in
           children with sickle cell anemia
    • Authors: Shaina M. Willen; Mark Rodeghier, Carol L. Rosen, Michael R. DeBaun
      Abstract: Conflicting evidence has suggested that low mean nocturnal hemoglobin oxygen saturation (SpO2) predicts future hospital days for acute severe pain in children with sickle cell anemia (SCA). In an unselected multi-center prospective cohort study, we tested the hypothesis that either low mean nocturnal SpO2 or high obstructive apnea-hypopnea index (OAHI; the number of obstructive apneas and hypopneas with ≥ 3% desaturation or arousal per hour of sleep) or high oxygen desaturation index (ODI; number of ≥ 3% desaturation from baseline saturation per hour of sleep) is associated with increased incidence rates of pain. A total of 140 children with SCA with a median age of 10.8 years (interquartile range 7.2) were followed for a median 4.9 years (interquartile range 1.8). Overnight polysomnography evaluations at baseline health were measured and adjudicated centrally. Multivariable models created in two steps were included. First all plausible covariates were included in a screening model. Subsequently, covariates meeting significance criteria of p 
      PubDate: 2017-12-20T03:20:25.992873-05:
      DOI: 10.1002/ajh.25013
       
  • A Phase I/II Trial of Vorinostat (SAHA) in Combination with Rituximab-CHOP
           in Patients with Newly Diagnosed Advanced Stage Diffuse Large B-Cell
           Lymphoma (DLBCL): SWOG S0806
    • Authors: Daniel O. Persky; Hongli Li, Lisa M. Rimsza, Paul M. Barr, Leslie L. Popplewell, Charles L. Bane, Ann Von Gehr, Michael LeBlanc, Richard I. Fisher, Sonali M. Smith, Jonathan W. Friedberg
      Abstract: Loss of major histocompatibility Class II expression (MHCII) in diffuse large B-cell lymphoma (DLBCL) correlates with decreased survival. MHCII transcription is in part regulated by histone acetylation. We tested the hypothesis that combination of histone deacetylase inhibitor (HDACI) with standard chemotherapy would improve outcomes in DLBCL in part through increased MHCII expression. S0806 was a single arm phase I/II trial of vorinostat given at 400 mg po daily on days 1-9 (subsequently amended to days 1-5 due to toxicity), combined with R-CHOP given on day 3 of a 21-day cycle for 8 cycles, with primary phase II endpoint of 2-year progression free survival (PFS). With 72 evaluable patients, at median follow up of 3 years, 2-year PFS estimate was 73%, and OS estimate was 86%. Considering that the regimen fell short of pre-defined efficacy improvement and was associated with high rates of febrile neutropenia (38%) and sepsis (19%), it cannot be recommended for general use. Consistent with our hypothesis, patients with low MCHII expression on S0806 had numerically superior outcomes compared to those from trial S0433 which did not use an HDACI, but the difference was not statistically significant. Current studies are focused on finding biomarkers of response to HDACI. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-20T02:40:28.2731-05:00
      DOI: 10.1002/ajh.25010
       
  • Lack of correlation between heart, liver and pancreas MRI-R2*: Results
           from long term follow-up in a cohort of adult β-thalassemia major
           patients
    • Authors: Valeria Maria Pinto; Lorenzo Bacigalupo, Barbara Gianesin, Manuela Balocco, Lucia De Franceschi, Roberto Malagò, John Wood, Gian Luca Forni
      PubDate: 2017-12-18T22:23:11.29716-05:0
      DOI: 10.1002/ajh.25009
       
  • Efficacy and safety of rituximab for systemic lupus
           erythematosus-associated immune cytopenias. A multicenter retrospective
           cohort study of 71 adults
    • Authors: Alexandra Serris; Zahir Amoura, Florence Canouï-Poitrine, Benjamin Terrier, Eric Hachulla, Nathalie Costedoat-Chalumeau, Thomas Papo, Olivier Lambotte, David Saadoun, Miguel Hié, Philippe Blanche, Bertrand Lioger, Jacques-Eric Gottenberg, Bertrand Godeau, Marc Michel
      Abstract: The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)-associated immune cytopenias.This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE-associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions.In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31-48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6-11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%) and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow-up after the first injection of RTX was 26.4 months [14.3-71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX re-treatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX-induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE-associated immune cytopenias. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-16T16:51:21.861879-05:
      DOI: 10.1002/ajh.24999
       
  • Intravenous Immunoglobulin as Salvage Therapy for Refractory Thrombotic
           Thrombocytopenic Purpura
    • Authors: Jennifer Ding; Maria R. Baer, John R. Hess, Ann B. Zimrin
      PubDate: 2017-12-16T16:51:17.920292-05:
      DOI: 10.1002/ajh.25007
       
  • The Role of Extracellular Matrix Stiffness in Megakaryocyte Development
           and Function
    • Authors: Orly Leiva; Catherine Leon, Seng Kah Ng, Pierre Mangin, Christian Gachet, Katya Ravid
      Abstract: The extracellular matrix (ECM) is a key acellular structure in constant remodeling to provide tissue cohesion and rigidity. Deregulation of the balance between matrix deposition, degradation and crosslinking results in fibrosis. Bone marrow fibrosis (BMF) is associated with several malignant and nonmalignant pathologies severely affecting blood cell production. BMF results from abnormal deposition of collagen fibers and enhanced lysyl oxidase-mediated ECM crosslinking within the marrow, thereby increasing marrow stiffness. Bone marrow stiffness has been recently recognized as an important regulator of blood cell development, notably by modifying the fate and differentiation process of hematopoietic or mesenchymal stem cells. This review surveys the different components of the ECM and their influence on stem cell development, with a focus on the impact of the ECM composition and stiffness on the megakaryocytic lineage in health and disease. Megakaryocyte maturation and the biogenesis of their progeny, the platelets, are thought to respond to environmental mechanical forces through a number of mechanosensors, including integrins and mechanosensitive ion channels, reviewed here. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-16T16:51:16.205361-05:
      DOI: 10.1002/ajh.25008
       
  • Design and Implementation of a Novel Advanced Training Curriculum in
           Hemoglobinopathies
    • Authors: Richard Ward
      PubDate: 2017-12-11T03:12:01.613942-05:
      DOI: 10.1002/ajh.25001
       
  • Similar outcome of allogeneic stem cell transplantation after
           myeloablative and sequential conditioning regimen in patients with
           refractory or relapsed acute myeloid leukemia: A study from the Société
           Francophone de Greffe de Moelle et de Thérapie Cellulaire
    • Authors: Justine Decroocq; Raphaël Itzykson, Stéphane Vigouroux, Mauricette Michallet, Ibrahim Yakoub-Agha, Anne Huynh, Florence Beckerich, Felipe Suarez, Patrice Chevallier, Stéphanie Nguyen-Quoc, Marie-Pierre Ledoux, Laurence Clement, Yosr Hicheri, Gaëlle Guillerm, Jérôme Cornillon, Nathalie Contentin, Martin Carre, Natacha Maillard, Mélanie Mercier, Mohamad Mohty, Yves Beguin, Jean-Henri Bourhis, Amandine Charbonnier, Charles Dauriac, Jacques-Olivier Bay, Didier Blaise, Eric Deconinck, Charlotte Jubert, Nicole Raus, Regis Peffault de Latour, Nathalie Dhedin
      Abstract: Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions.We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions.With a median follow–up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (p=0.39), and 2-year cumulative incidence of relapse was 57% versus 50% respectively (p=0.99). Non-relapse mortality was not higher in the myeloablative group (17% versus 15%, p=0.44). In multivariate analysis, overall survival, cumulative incidence of relapse and non-relapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; p
      PubDate: 2017-12-11T03:06:22.326797-05:
      DOI: 10.1002/ajh.25004
       
  • Pure erythroid leukemia
    • Authors: Barbara J. Bain
      PubDate: 2017-12-11T03:06:06.026574-05:
      DOI: 10.1002/ajh.25005
       
  • Age is the only predictor of small decrease in lung function in children
           with sickle cell anemia
    • Authors: Shaina M. Willen; Robyn Cohen, Mark Rodeghier, Fenella Kirkham, Susan S. Redline, Carol Rosen, Jane Kirkby, Michael R. DeBaun
      Abstract: The longitudinal pattern of lung function in children with sickle cell anemia (SCA) has shown a decrease in FEV1% predicted, a risk factor for death in adults with SCA, but predictors for this decline are poorly characterized. In a prospective longitudinal multi-center cohort of children with SCA, we tested the hypotheses that: 1) FEV1% predicted declines over time; and 2) SCA-specific characteristics and therapy predict this decline. At three clinical centers, children with SCA (HbSS or HbSβ0 thalassemia), unselected for respiratory disease, were enrolled in the Sleep and Asthma Cohort (SAC) study. Study-certified pulmonary function technicians performed spirometry and lung volumes. Each assessment was reviewed centrally. Predicted values were determined for TLC, FEV1, FVC, and FEV1/FVC ratio. A total of 197 participants, mean age 11.0 years at first testing (range 4-19.3 years), had a minimum of three spirometry measurements an average of 4.4 years (range 1.08-6.5 years) from baseline to endpoint. In a multivariable model, FEV1% predicted declines by 0.3% for every additional year of age (95% CI -0.56 - -0.05, p=0.020). Sex, asthma history, hemoglobin, reticulocyte count, white blood cell count, incidence rate of severe acute pain and acute chest syndrome episodes, and hydroxyurea therapy were not associated with a decline in FEV1% predicted. In a large rigorously evaluated, prospective cohort of an unselected group of children with SCA, FEV1% predicted declines minimally over an average of 4 years, and none of the examined disease features predict the decline. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-11T03:05:37.00445-05:0
      DOI: 10.1002/ajh.25003
       
  • No Major Differences in Outcomes Between the Initial and Relapse Episodes
           in Patients with Thrombotic Thrombocytopenic Purpura: The Experience from
           the Ohio State University Registry
    • Authors: Camila Masias; Haiwa Wu, Michael McGookey, Lauren Jay, Spero Cataland, Shangbin Yang
      PubDate: 2017-12-11T03:05:21.475994-05:
      DOI: 10.1002/ajh.25002
       
  • Comparing Apples to Oranges: A commentary on the Mayo study of MYD88
           significance in Waldenstrom's Macroglobulinemia
    • Authors: Jorge J. Castillo; Joshua N. Gustine, Kirsten Meid, Lian Xu, Zachary R. Hunter, Steven P. Treon
      PubDate: 2017-12-08T03:11:22.775788-05:
      DOI: 10.1002/ajh.24997
       
  • Clinical Experience with the BCL2-inhibitor Venetoclax in Combination
           Therapy for Relapsed and Refractory Acute Myeloid Leukemia and Related
           Myeloid Malignancies
    • Authors: Courtney D DiNardo; Caitlin R Rausch, Christopher Benton, Tapan Kadia, Nitin Jain, Naveen Pemmaraju, Naval Daver, Wendy Covert, Kayleigh R Marx, Morgan Mace, Elias Jabbour, Jorge Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Kapil N Bhalla, Hagop Kantarjian, Marina Konopleva
      Abstract: Introduction: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML) and efficacy in lower-intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported.Methods: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed.Results: 43 patients with median age 68 (range, 25-83) were treated for AML (91%), MDS (5%) or BPDCN (5%). Most (n=36, 84%) were ≥salvage-2 treatment status, including prior hypomethylating agent (HMA) in 77%. In combination with VEN, most patients received HMA therapy (n=31, 72%); eight (19%) received low-dose cytarabine (LDAC). Patients received a median of 2 treatment cycles (range, 1-4). Objective response was observed in 9 (21%) patients, including 2 complete responses (CR), 3 CRi, and 4 morphologic leukemia-free state (MLFS). Median survival was 3.0 months (range, 0.5-8.0), and estimated 6-month survival was 24%.Responses were observed in five (24%) of 21 patients with intermediate-risk cytogenetics, 3 (27%) of 11 IDH1/2-mutant, and 4 (50%) of 8 RUNX1-mutated patients. Two (20%) of 10 TP53-mutated patients responded; both had concurrent RUNX1 mutations. Of the 3 (15%) responding patients with adverse cytogenetics, all had concurrent RUNX1 mutations.Conclusion: Low-intensity chemotherapy, i.e. HMAs or LDAC, in combination with VEN is a viable salvage option, even in multiply relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were identified in patients with diploid/intermediate cytogenetics, RUNX1 and/or IDH1/2 mutations. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-08T03:11:04.352333-05:
      DOI: 10.1002/ajh.25000
       
  • Successful liver transplantation for homozygous protein C deficiency with
           a Type II mutation using a heterozygous living related donor
    • Authors: Alexander A. Boucher; Lori Luchtman-Jones, Jaimie D. Nathan, Joseph S. Palumbo
      PubDate: 2017-12-08T03:11:02.593653-05:
      DOI: 10.1002/ajh.24998
       
  • Hereditary xerocytosis: Diagnostic considerations
    • Authors: Mary Risinger; Edyta Glogowska, Satheesh Chonat, Kejian Zhang, Neha Dagaonkar, Clinton H. Joiner, Charles T. Quinn, Theodosia A. Kalfa, Patrick G. Gallagher
      PubDate: 2017-12-06T03:15:28.186614-05:
      DOI: 10.1002/ajh.24996
       
  • Comprehensive Management Reduces Incidence and Mortality of Acute Chest
           Syndrome in Patients with Sickle Cell Disease
    • Authors: Givi Basishvili; Joseph Gotesman, Kathy Vandervoort, Charleen Jacobs, Leena Vattappally, Caterina P. Minniti
      PubDate: 2017-12-05T03:35:50.07404-05:0
      DOI: 10.1002/ajh.24994
       
  • Macrophage activation syndrome and post-transplant microangiopathy
           following haploidentical bone marrow transplantation for sickle cell
           anemia
    • Authors: James O. J. Davies; Alice C. Hart, Josu De La Fuente, Barbara J. Bain
      PubDate: 2017-12-02T03:25:23.59615-05:0
      DOI: 10.1002/ajh.24995
       
  • Anthracycline-induced acute myocarditis and ventricular fibrillation
           arrest
    • Authors: Vincent A. Pallazola; Joseph C. Murray, Munjid Al Harthy, Stefan L. Zimmerman, Jonathan Webster, Lukasz P. Gondek
      PubDate: 2017-12-01T04:56:21.814456-05:
      DOI: 10.1002/ajh.24989
       
  • Splanchnic vein thrombosis in patients with myeloproliferative neoplasms:
           The Mayo Clinic experience with 84 consecutive cases
    • Authors: Sravanthi Lavu; Natasha Szuber, Mythri Mudireddy, Meera Yogarajah, Naseema Gangat, Animesh Pardanani, Curtis A. Hanson, Rhett P. Ketterling, Aneel A. Ashrani, Patrick S. Kamath, Ayalew Tefferi
      PubDate: 2017-12-01T04:50:20.799557-05:
      DOI: 10.1002/ajh.24993
       
  • Survival Following Salvage Therapy for Primary Refractory Peripheral
           T-Cell Lymphomas (PTCL)
    • Authors: Janie Y. Zhang; Robert Briski, Sumana Devata, Mark S. Kaminski, Tycel J. Phillips, Tera L. Mayer, Nathanael G. Bailey, Ryan A. Wilcox
      Abstract: Optimal salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL) and the role of hematopoietic stem cell transplant remain poorly defined. We conducted a retrospective review of clinical outcomes and prognostic factors in a single-center cohort of 93 patients with primary refractory PTCL, defined as progression during first-line therapy or relapse within 6 months of its completion. Clinical outcomes were poor in this population, with median event-free survival (EFS) of 3.5 months, median overall survival (OS) of 9.1 months, and 34% 3-year survival. Outcomes were comparable in patients who progressed through first-line therapy and patients who achieved CR/PR and subsequently relapsed within 6 months. A majority exhibited high-risk features and had intermediate to high risk IPI, which correlated with inferior outcomes. There was no difference in outcomes between patients who received single-agent salvage regimens and patients who underwent traditional, multi-agent salvage regimens. Thus, participation in well-designed clinical trials should be encouraged in this population. Additionally, there may be a trend toward improved EFS and OS in patients who underwent autologous or allogeneic SCT compared to patients who achieved CR or PR but were not transplanted. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T04:13:21.15448-05:0
      DOI: 10.1002/ajh.24992
       
  • The role of tmprss6 and hfe variants in iron deficiency anemia in celiac
           disease
    • Authors: Luigia De Falco; Raffaella Tortora, Nicola Imperatore, Mariasole Bruno, Mario Capasso, Domenico Girelli, Annalisa Castagna, Nicola Caporaso, Achille Iolascon, Antonio Rispo
      Abstract: We investigated the role of HFE C282Y, H63D and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1-year of gluten free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P=0.001), whereas H63D and A736V allele frequencies were similar among patients and controls (P=0.92 and 0.84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to non-anemic group (2% and 0.5%, P=0.04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P
      PubDate: 2017-12-01T04:10:41.955086-05:
      DOI: 10.1002/ajh.24991
       
  • “Double-hit” chronic lymphocytic leukemia: An aggressive subgroup with
           17p deletion and 8q24 gain
    • Authors: Elise Chapiro; Claude Lesty, Clémentine Gabillaud, Eric Durot, Simon Bouzy, Marine Armand, Magali Le Garff-Tavernier, Nadia Bougacha, Stéphanie Struski, Audrey Bidet, Elodie Laharanne, Carole Barin, Lauren Veronese, Nolwen Prié, Virginie Eclache, Baptiste Gaillard, Lucienne Michaux, Christine Lefebvre, Jean-Baptiste Gaillard, Christine Terré, Dominique Penther, Christian Bastard, Nathalie Nadal, Sandra Fert-Ferrer, Nathalie Auger, Catherine Godon, Laurent Sutton, Olivier Tournilhac, Santos A. Susin, Florence Nguyen-Khac,
      Abstract: Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (p=0.04), unbalanced translocations (p=0.03) and 8q24 gain (p=0.001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this “double-hit” CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T03:31:17.51531-05:0
      DOI: 10.1002/ajh.24990
       
  • Outcome of Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia
           after Blinatumomab Failure: No Change in the Level of CD19 Expression
    • Authors: Elias Jabbour; Johannes Düll, Musa Yilmaz, Joseph D. Khoury, Farhad Ravandi, Nitin Jain, Hermann Einsele, Guillermo Garcia-Manero, Marina Konopleva, Nicholas J. Short, Philip A. Thompson, William Wierda, Naval Daver, Jorge Cortes, Susan O'Brien, Hagop Kantarjian, Max S. Topp
      Abstract: Blinatumomab, a bi-specific T-cell engaging CD3-CD19 antibody construct, has shown significant activity in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). Despite this improvement, most patients relapse. Here, we describe the outcome of 68 patients with R/R ALL after failure of blinatumomab therapy: 38 (56%) blinatumomab refractory; 30 (44%) relapsing after initial response. After a median follow-up of 49 months, 9 (13%) patients remained alive. The median overall survival after blinatumomab failure was 5.2 months. At the time of failure, among 61 patients evaluated for immunophenotype, 56 (92%) had CD19-positive blasts; only five (8%) had ALL recurrence with CD19-negative disease. Two patients progressed with lower CD19 expression. In summary, the outcome of patients with R/R ALL after blinatumomab failure is poor and treatment of these patients remains an unmet medical need. Our findings indicate that blinatumomab therapy would not exclude a significant number of patients from the potential benefit of subsequent CD19-directed therapies such as chimeric antigen receptor T-cell therapy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-27T03:28:59.641458-05:
      DOI: 10.1002/ajh.24987
       
  • Hereditary hypochromic microcytic anemia associated with loss-of-function
           DMT1 gene mutations and absence of liver iron overload
    • Authors: Maddalena Casale; Adriana Borriello, Saverio Scianguetta, Domenico Roberti, Martina Caiazza, Debora Bencivenga, Immacolata Tartaglione, Saverio Ladogana, Matteo Maruzzi, Fulvio Della Ragione, Silverio Perrotta
      PubDate: 2017-11-27T03:28:37.628045-05:
      DOI: 10.1002/ajh.24988
       
  • Visualization of the bone marrow biopsy needle track
    • Authors: Shirin Attarian; Louis Reed, Shashi Singh, Alexander Shestopalov, Aditi P Singh, Anjali Budhathoki, Simon Abi-Aad, Urvi Shah, Salem Kim, Kimo Bachiashvili, Tarek Elrafei, Weijuan Li, Conway Yee, Ellen Friedman
      PubDate: 2017-11-23T03:47:07.360368-05:
      DOI: 10.1002/ajh.24985
       
  • The clinical epidemiology of sickle cell anemia in Africa
    • Authors: Alex W Macharia; George Mochamah, Sophie Uyoga, Carolyne M Ndila, Gideon Nyutu, Johnstone Makale, Metrine Tendwa, Emily Nyatichi, John Ojal, Mohammed Shebe, Kennedy O Awuondo, Neema Mturi, Norbert Peshu, Benjamin Tsofa, J Anthony G Scott, Kathryn Maitland, Thomas N Williams
      Abstract: Sickle cell anemia (SCA) is the commonest severe monogenic disorders of humans. The disease has been highly characterized in high-income countries but not in sub-Saharan Africa where SCA is most prevalent. We conducted a retrospective cohort study of all children 0-13 years admitted from within a defined study area to Kilifi County Hospital in Kenya over a five-year period. Children were genotyped for SCA retrospectively and incidence rates calculated with reference to population data. Overall, 576 of 18,873 (3.1%) admissions had SCA of whom the majority (399; 69.3%) were previously undiagnosed. The incidence of all-cause hospital admission was 57.2/100 person years of observation (PYO; 95%CI 52.6-62.1) in children with SCA and 3.7/100 PYO (95%CI 3.7-3.8) in those without SCA (IRR 15.3; 95%CI 14.1-16.6). Rates were higher for the majority of syndromic diagnoses at all ages beyond the neonatal period, being especially high for severe anemia (hemoglobin
      PubDate: 2017-11-23T03:40:41.929303-05:
      DOI: 10.1002/ajh.24986
       
  • Bendamustine plus rituximab for indolent B-cell lymphoma of renal
           significance
    • Authors: David Ribes; Hélène El Hachem, Lucie Oberic, François Vergez, Audrey Delas, Julie Belliere, Caroline Protin, Nassim Kamar, Inès Ferrandiz, Suzanne Tavitian, Camille Laurent, Antoine Huart, Dominique Chauveau, Loïc Ysebaert, Stanislas Faguer
      Abstract: Treatment of indolent B-cell non-Hodgkin lymphomas (iNHL) of renal significance is challenging given the need for deep and prolonged hematological response to restore and control renal function overtime, yet to be balanced with the risk of adverse drug-related events. This prospective single-center study included 20 patients with iNHL of renal significance (tubulointerstitial presentation [n=8], glomerulopathy with or without monoclonal Ig deposits [n=12]) who received a steroid-sparing regimen of rituximab plus bendamustine (BR), with either no or
      PubDate: 2017-11-23T03:40:26.720773-05:
      DOI: 10.1002/ajh.24984
       
  • Driver mutations and prognosis in primary myelofibrosis: Mayo-Careggi MPN
           alliance study of 1,095 patients
    • Authors: Ayalew Tefferi; Maura Nicolosi, Mythri Mudireddy, Natasha Szuber, Christy M. Finke, Terra L. Lasho, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, Carmela Mannarelli, Tiziana Fanelli, Paola Guglielmelli, Alessandro M. Vannucchi
      Abstract: The 2013 discovery of calreticulin (CALR) mutations in myeloproliferative neoplasms was attended by their association with longer survival in primary myelofibrosis (PMF). Subsequent studies have suggested prognostic distinction between type 1/like and type 2/like CALR mutations and detrimental effect from triple-negative mutational status. Among 709 Mayo Clinic patients with PMF, 467 (66%) harbored JAK2, 112 (16%) CALR type 1/like, 24 (3.4%) CALR type 2/like, 38 (5.4%) MPL mutations and 68 (10%) were triple-negative. Survival was longer with type 1/like CALR, compared to JAK2 (HR 2.6, 95% CI 1.9-3.5), type 2/like CALR (HR 2.5, 95% CI 1.4-4.5), MPL (HR 1.8, 95% CI 1.1-2.9) and triple-negative mutational status (HR 2.4, 95% CI 1.6-3.6), but otherwise similar between the non-type 1/like CALR mutational states (p=0.41). In multivariable analysis, the absence of type 1/like CALR (p
      PubDate: 2017-11-22T03:30:58.454961-05:
      DOI: 10.1002/ajh.24978
       
  • Sickle hemoglobin oxygen affinity-shifting strategies have unequal
           cerebrovascular risks
    • Authors: Robert P. Hebbel; Bo E. Hedlund
      PubDate: 2017-11-18T02:40:29.352286-05:
      DOI: 10.1002/ajh.24975
       
  • Ruxolitinib-associated infections: a systematic review and meta-analysis
    • Authors: Federico Lussana; Marco Cattaneo, Alessandro Rambaldi, Alessandro Squizzato
      Abstract: Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib.Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI).Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N=10), hepatitis B reactivation (N=5) and pneumocystis jeroveci infection (N=2).Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-18T02:40:26.423675-05:
      DOI: 10.1002/ajh.24976
       
  • Impact of gene mutations on treatment response and prognosis of acute
           myeloid leukemia secondary to myeloproliferative neoplasms
    • Authors: G. Venton; F. Courtier, A. Charbonnier, E. D'Incan, C. Saillard, B. Mohty, MJ. Mozziconacci, D. Birnbaum, A. Murati, N. Vey, J. Rey
      Abstract: Acute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult to obtain and there is very little scientific literature or prospective trials for determining robust prognostic markers and efficient treatments.We analyzed event-free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics, the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next-generation DNA sequencing (NGS). For 24 patients, we were able to do a comparative NGS analysis at both MPN and sAML phase.After acute transformation EFS and OS were respectively of 2.9 months (range: 0-48.1) and 4.7 months (range: 0.1-58.8). No difference in EFS or OS regarding the previous MPN, the ELN2017 prognostic classification, the first-line therapy or the response was found. After univariate analysis, three genes, TP53, SRSF2 and TET2, impacted pejoratively sAML prognosis at sAML time. In multivariate analysis, TP53 (p=0.0001), TET2 (p=0.011) and SRSF2 (p=0.018) remained independent prognostic factors. Time to sAML transformation was shorter in SRSF2-mutated patients (51.2 months, range: 14.7-98) than in SRSF2-unmutated patients (133.8 months, range: 12.6-411.2) (p
      PubDate: 2017-11-17T00:55:27.898523-05:
      DOI: 10.1002/ajh.24973
       
  • Annual clinical updates in hematological malignancies: a continuing
           medical education series
    • PubDate: 2017-10-25T04:35:55.84648-05:0
      DOI: 10.1002/ajh.24907
       
  • Acute promyelocytic leukemia and chronic lymphocytic leukemia diagnosed
           concurrently
    • Authors: Catherine C. Coombs; Stephanie P. Mathews
      PubDate: 2017-10-20T02:25:45.186881-05:
      DOI: 10.1002/ajh.24950
       
  • 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
       
  • 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
       
 
 
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