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Publisher: John Wiley and Sons   (Total: 1577 journals)

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Showing 1 - 200 of 1577 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 61, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 46, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 49, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 144, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 3)
Addiction     Hybrid Journal   (Followers: 33, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 12, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 24, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 50, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 251, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 35, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 10, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 30, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 49, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 133, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 91, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 27, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 31, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 36, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 254, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 16, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 126, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 159)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 211, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 36, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 8, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 44, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 92, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 45, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 6, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 69, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 140, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 34, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 14, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 224, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 50, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 28, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 14)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 315, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 13, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 43, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 25, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 13, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 398, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 68, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 31, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 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: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 15, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 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: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 136, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 18, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 35, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 222, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Hematology
  [SJR: 1.761]   [H-I: 77]   [31 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0361-8609 - ISSN (Online) 1096-8652
   Published by John Wiley and Sons Homepage  [1577 journals]
  • First-line treatment selection and early monitoring patterns in chronic
           phase-chronic myeloid leukemia in routine clinical practice: SIMPLICITY
    • Authors: Stuart L. Goldberg; Jorge Cortes, Carlo Gambacorti-Passerini, Rüdiger Hehlmann, H. Jean Khoury, Mauricette Michallet, Ron Paquette, Bengt Simonsson, Teresa Zyczynski, Aimee Foreman, Elisabetta Abruzzese, David Andorsky, Aart Beeker, Pascale Cony-Makhoul, Richard Hansen, Elza Lomaia, Eduardo Olavarria, Michael Mauro
      Abstract: Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n=416), dasatinib (n=418) or nilotinib (n=408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1,242 prospective patients (enrolled October 01 2010–September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift towards dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82% and 95% of patients by 3, 6 and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P
      PubDate: 2017-08-17T03:15:31.26589-05:0
      DOI: 10.1002/ajh.24887
  • Treatment of Individuals Who Cannot Receive Blood Products for Religious
           or Other Reasons
    • Authors: Carlton D. Scharman; Joseph J. Shatzel, Edward Kim, Thomas G. DeLoughery
      Abstract: By virtue of their religious principles, Jehovah's Witnesses (JWs) generally object to receiving blood products, raising numerous ethical, legal, and medical challenges for providers who care for these patients, especially in the emergent setting. In this review, we discuss several areas relevant to the care of JWs, including the current literature on “bloodless” medical care in the setting of peri- and intra-operative management, acute blood loss, trauma, pregnancy, and malignancy. We have found that medical and administrative efforts in the form of bloodless medicine and surgery programs can be instrumental in helping to reduce risks of morbidity and mortality in these patients. Planning prior to an anticipated event associated with blood loss or anemia (such as elective surgery, pregnancy, and chemotherapy) is critical. Specifically, bloodless medicine programs should prioritize vigilant early screening and management of anemias, early establishment of patient wishes regarding transfusion, and the incorporation of those wishes into multidisciplinary medical and surgical care. Although there are now a variety of human- and non-human-based products available as transfusion alternatives, the degree and quality of evidence to support their use varies significantly between products and is also largely dependent on the clinical setting. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-17T03:15:28.62568-05:0
      DOI: 10.1002/ajh.24889
  • Bmp2 controls iron homeostasis in mice independent of Bmp6
    • Authors: Susanna Canali; Chia-Yu Wang, Kimberly B. Zumbrennen-Bullough, Abraham Bayer, Jodie L. Babitt
      Abstract: Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody. Moreover, BMP2/4 antibody inhibits hepcidin expression and induces iron loading in wildtype mice, whereas a BMP4 antibody has no effect. Compared with other liver cell populations, Bmp2 mRNA is predominantly expressed in endothelial cells, where it's baseline expression is higher, but it's induction by iron is less robust than Bmp6. Mice with a conditional ablation of Bmp2 in endothelial cells exhibit hepcidin deficiency, serum iron overload, and tissue iron loading in liver, pancreas and heart, with reduced spleen iron. Together, these data demonstrate that in addition to BMP6, endothelial cell BMP2 has a non-redundant role in hepcidin regulation by iron This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-17T03:15:24.842408-05:
      DOI: 10.1002/ajh.24888
  • Ibrutinib-associated Pneumocystis jirovecii pneumonia
    • Authors: Regina Lee; Afrouz Nayernama, S. Christopher Jones, Tanya Wroblewski, Peter E. Waldron
      PubDate: 2017-08-17T03:15:20.358366-05:
      DOI: 10.1002/ajh.24890
  • Diagnosis of thrombotic thrombocytopenic purpura among patients with
           adamts13 activity 10-20%
    • Authors: Adanma Ayanambakkam; Johanna A. Kremer Hovinga, Sara K. Vesely, James N. George
      PubDate: 2017-08-17T03:10:34.798271-05:
      DOI: 10.1002/ajh.24885
  • A distinctive histidine residue is essential for in vivo
           glycation-inactivation of human CD59 transgenically expressed in mice
           erythrocytes: Implications for human diabetes complications
    • Authors: Rupam Sahoo; Pamela Ghosh, Michael Chorev, Jose A Halperin
      Abstract: Clinical and experimental evidences support a link between the complement system and the pathogenesis of diabetes complications. CD59, an extracellular cell membrane-anchored protein, inhibits formation of the membrane attack complex (MAC), the main effector of complement-mediated tissue damage. This complement regulatory activity of human CD59 (hCD59) is inhibited by hyperglycemia-induced ε-amino glycation of Lys41. Biochemical and structural analyses of glycated proteins with known three-dimensional structure revealed that glycation of ε-amino lysyl residues occurs predominantly at “glycation motives” that include lysyl/lysyl pairs or proximity of a histidyl residue, in which the imidazolyl moiety is ≈ 5Å from the ε-amino group. hCD59 contains a distinctive Lys41/His44 putative glycation motif within its active site. In a model of transgenic diabetic mice expressing in erythrocytes either the wild type or a H44Q mutant form of hCD59, we demonstrate in vivo that the His44 is required for Lys41 glycation and consequent functional inactivation of hCD59, as evidenced using a mouse erythrocytes hemolytic assay. Since 1) the His44 residue is not present in CD59 form other animal species and 2) humans are particularly prone to develop complications of diabetes, our results indicate that the Lys41/His44 glycation motif in human CD59 may confer humans a higher risk of developing vascular disease in response to hyperglycemia. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-17T03:10:33.180364-05:
      DOI: 10.1002/ajh.24886
  • Rare complication of treated immune thrombocytopenia
    • Authors: Radhika Gangaraju; Anton Rets, Kristi J Smock, Nahla M Heikal
      PubDate: 2017-08-12T00:45:24.985537-05:
      DOI: 10.1002/ajh.24884
  • Efficacy of daratumumab-based therapies in patients with relapsed,
           refractory multiple myeloma treated outside of clinical trials
    • Authors: Arjun Lakshman; Jithma P. Abeykoon, Shaji K. Kumar, S. Vincent Rajkumar, David Dingli, Francis K. Buadi, Wilson I. Gonsalves, Nelson Leung, Angela Dispenzieri, Taxiarchis V. Kourelis, Ronald S. Go, Martha Q. Lacy, Miriam A. Hobbs, Yi Lin, Rahma Warsame, John Lust, Amie L. Fonder, Yi L. Hwa, Suzanne R. Hayman, Stephen J. Russell, Robert A. Kyle, Morie A. Gertz, Prashant Kapoor
      Abstract: Outside of clinical trials, experience with daratumumab-based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43-93) years. High-risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1-14) and time to first DCT from diagnosis was 4.3 years (range, 0.4-13.0). Seventeen (13%) patients were refractory to single agent daratumumab. Fifty-two (41%), 34 (27%), 23 (18%) and 17 (14%) received DPd, DRd, DVd and ‘other' DCTs, respectively. Overall response rate was 47%. Median follow-up was 5.5 months (95%CI, 4.2-6.1). Median progression free survival (PFS) was 5.5 months (95%CI, 4.2-7.8). Median overall survival was not reached (NR) with any regimen. Median PFS (months) was worst for penta-refractory MM (n=8) vs quadruple refractory MM (n=18) and others (n=100) (2.2 [95%CI, 1-2.4] vs 3.1 [95%CI, 2.1-NR] vs 5.9 [95%CI, 5.0-NR]; p2 prior therapies vs others (5.0 months [95%CI, 3.7-5.9] vs NR [95%CI, NR-NR]; p=0.002). Non-hematologic toxicities included infections (38%), fatigue (32%), and infusion reactions (18%). Grade 3 or higher hematological toxicities were seen in 41% of patients. DCTs are effective in RRMM. ORR and PFS in heavily pre-treated patients are lower than those reported in clinical trials. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-11T03:35:38.533119-05:
      DOI: 10.1002/ajh.24883
  • Gender and survival in essential thrombocythemia: A two-center study of
           1,494 patients
    • Authors: Ayalew Tefferi; Silvia Betti, Daniela Barraco, Mythri Mudireddy, Sahrish Shah, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, Giacomo Coltro, Paola Guglielmelli, Alessandro M. Vannucchi
      Abstract: Based on suggestive information from recent epidemiologic data and earlier retrospective studies, we revisited the effect of gender on survival in 1,494 patients with essential thrombocythemia (ET). The primary study population included 904 patients from the Mayo Clinic (median age 58 years; 65% females); risk distribution, according to the international prognostic score for ET (IPSET), was 23% high, 42% intermediate and 35% low. Multivariable analysis that included IPSET-relevant risk factors identified male sex (HR 1.6, 95% CI 1.3-2.0), age ≥60 years (HR 4.3, 95% CI 3.4-5.4) and leukocyte count ≥11 x 10(9)/L (HR 1.5, 95% CI 1.3-1.9) as independent predictors of shortened survival. These findings were confirmed by analysis of a separate cohort of 590 ET patients (65% females) from the University of Florence, Italy, with corresponding HRs (95% CI) of 1.6 (1.1-2.5), 4.6 (2.2-9.5) and 1.8 (1.1-2.8). The independent prognostic effect of gender was further corroborated by a separate multivariable analysis against IPSET risk categories; HR (95% CI) for the Mayo Clinic/Florence cohorts were 1.5/1.6 (1.2/1.1-1.8/2.5) for male sex, 6.8/7.5 (5.0/3.1-9.3/18.3) for IPSET high risk and 2.8/4.1 (2.1/1.8-3.8/9.5) for IPSET intermediate risk. Furthermore, the survival disadvantage in men was most apparent in IPSET high risk category and in patients older than 60 years. In both patient cohorts, thrombosis history garnered significance in univariate, but not in multivariable analysis. The observations from the current study suggest that women with ET live longer than their male counterparts and that gender might supersede thrombosis history as a risk variable for overall survival. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-10T03:35:23.769412-05:
      DOI: 10.1002/ajh.24882
  • Risk factors and a prognostic model for post-splenectomy survival in
    • Authors: Ayalew Tefferi; Mythri Mudireddy, Naseema Gangat, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, David M. Nagorney
      Abstract: Palliative treatment in myelofibrosis (MF) includes transfusion support, JAK2 inhibitors, involved field radiotherapy and splenectomy. In order to assist in selecting patients who are likely to benefit from splenectomy, we looked into risk factors for post-splenectomy survival, in 120 consecutive cases (median age 66 years); at the time of splenectomy, 61% displayed red cell transfusion need, 49% platelet count 25 x 10(9)/L, 60% constitutional symptoms and 13% circulating blasts ≥5%; dynamic international prognostic scoring system risk categories were 21% high, 55% intermediate-2, 21% intermediate-1 and 3% low. Among informative cases, karyotype was abnormal in 60% and driver mutational status was JAK2 75%, CALR 15%, MPL 4% and triple-negative 6%. At median follow-up of 1.3 years, from time of splenectomy, 95 (79%) deaths and 30 (25%) leukemic transformations were recorded. Median post-splenectomy survival was 1.5 years; in multivariable analysis, survival was adversely affected by age>65 years, transfusion need, leukocyte count>25 x 10(9)/L and circulating blasts ≥5%; these variables were subsequently used to devise an HR-weighted scoring system with high (3-4 risk factors), intermediate (2 risk factors) and low (0-1 risk factors) risk categories; the corresponding post-splenectomy median survivals were 0.3 (HR 5.9, 95% CI 3.2-11.0), 1.3 (HR 2.9, 95% CI 1.8-4.6) and 2.9 years. Post-splenectomy survival was not affected by driver mutational status or occurrence of leukemic transformation. Leukemia-free survival was predicted by very high risk karyotype. The observations from the current study might help identify appropriate candidates for splenectomy in MF. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-07T03:01:31.113641-05:
      DOI: 10.1002/ajh.24881
  • Emerging role of bevacizumab in management of patients with symptomatic
           hepatic involvement in Hereditary Hemorrhagic Telangiectasia
    • Authors: Ajay Chavan; Silke Schumann-Binarsch, Bernhard Schmuck, Franziska Oltmer, Urban Geisthoff, Florian Hoppe, Kornelia Wirsching, Juergen Klempnauer, Michael Manns, Rohit Philip Thomas, Claus-Henning Köhne
      PubDate: 2017-08-04T01:26:11.974784-05:
      DOI: 10.1002/ajh.24878
  • SIRT1 Activates the Expression of Fetal Hemoglobin Genes
    • Authors: Yan Dai; Tyngwei Chen, Heba Ijaz, Elizabeth H Cho, Martin H Steinberg
      Abstract: High fetal hemoglobin (HbF, α2γ2) levels ameliorate the clinical manifestations of sickle cell disease and β thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells. The small molecule SIRT1 activators SRT2104 and SRT1720 enhanced HBG expression in cord blood human erythroblasts and reactivated silenced HBG in adult human erythroblasts. Furthermore, SIRT1 binds in the β-globin gene cluster locus control region (LCR) and HBG promoters, promotes the looping of the LCR to HBG promoter, and increases the binding of RNA polymerase II and H4K16Ac in the HBG promoter. SIRT1 suppressed the expression of the HBG suppressors BCL11A, KLF1, HDAC1 and HDAC2. Lastly, SIRT1 did not change the proliferation of human erythroid progenitor cells or the expression of differentiation marker CD235a. These data suggest that SIRT1 activates HBG expression through facilitating LCR looping to the HBG promoter, inhibiting the expression of transcriptional suppressors of HBG, and indirectly increasing histone acetylation in HBG promoter. SIRT1 is a potential therapeutic target for γ-globin gene induction, and small molecule SIRT1 activators might serve as a lead compound for the development of new HbF inducers. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-04T01:25:52.783371-05:
      DOI: 10.1002/ajh.24879
  • Thrombotic and hemorrhagic complications in idiopathic erythrocytosis
    • Authors: Irene Bertozzi; Marco Ruggeri, Ilaria Nichele, Giacomo Biagetti, Elisabetta Cosi, Maria Luigia Randi
      PubDate: 2017-08-01T03:05:28.892193-05:
      DOI: 10.1002/ajh.24873
  • Engineered red blood cells as therapeutic agents
    • Authors: Mauro Magnani
      PubDate: 2017-08-01T02:56:01.581399-05:
      DOI: 10.1002/ajh.24874
  • The impact of antibody profile in thrombosis associated with primary
           antiphospholipid syndrome
    • Authors: Sabrina da Silva Saraiva; Bruna de Moraes Mazetto, Lais Quinteiro Tobaldine, Marina Pereira Colella, Erich Vinícius De Paula, Joyce Annichinno-Bizzachi, Fernanda Andrade Orsi
      Abstract: Triple positivity (TP) for antiphospholipid antibodies(aPL) may identify aPL carriers with poorer prognosis. The clinical impact of TP in primary antiphospholipid syndrome(PAPS) remains unclear and further clinical evidences are needed to validate TP as a marker of severity. The aim of this study was to evaluate the impact of TP on the clinical course of PAPS with thrombosis(t-PAPS). We performed a retrospective analysis of a cohort of t-PAPS patients, comparing groups of patients with TP and non-TP profiles according to their demographic, clinical and laboratory features. We included 105 patients with t-PAPS, the median follow-up time of 3.7 years. Twenty-two patients(21%) had TP; the demographic distribution, the presence of cardiovascular risk factors and the site of thrombosis were similar between TP and non-TP patients. The frequency of thrombotic events did not differ between TP and non-TP patients during the study period. Pregnancy morbidities were more frequent in women with t-PAPS and TP than in those with non-TP profile (80% vs. 52.8%,P=0.05). Patients with t-PAPS and TP presented, at diagnosis, higher dRVVT ratio (median R=2.44 vs. 1.57,P
      PubDate: 2017-08-01T02:55:36.231821-05:
      DOI: 10.1002/ajh.24875
  • Outcomes after 18 Months of Eliglustat Therapy in Treatment-Naïve Adults
           with Gaucher Disease Type 1: The Phase 3 ENGAGE Trial
    • Authors: Pramod K. Mistry; Elena Lukina, Hadhami Ben Turkia, Suma P. Shankar, Hagit Baris, Marwan Ghosn, Atul Mehta, Seymour Packman, Gregory Pastores, Milan Petakov, Sarit Assouline, Manisha Balwani, Sumita Danda, Evgueniy Hadjiev, Andres Ortega, Sebastiaan J.M. Gaemers, Regina Tayag, M. Judith Peterschmitt
      Abstract: Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double-blind period, eliglustat treatment during the 9-month, open-label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double-blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment-naive patients. Eliglustat was well-tolerated, and there were no new safety concerns with longer-term exposure. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-01T02:55:30.296125-05:
      DOI: 10.1002/ajh.24877
  • Kidney Function of Transfused Children with Sickle Cell Anemia: Baseline
           Data from the TWiTCH Study with Comparison to Non-Transfused Cohorts
    • Authors: Ofelia Alvarez; Kerri Nottage, Lara M. Simpson, John Wood, Barry R. Davis, Beng Fuh, Sharada Sarnaik, Banu Aygun, Kathleen Helton, Russell E. Ware
      PubDate: 2017-07-25T03:20:50.090718-05:
      DOI: 10.1002/ajh.24871
  • Inflammatory and endothelial markers during vaso-occlusive crisis and
           acute chest syndrome in sickle cell disease
    • Authors: M. Schimmel; B.M. Luken, E. Nur, C.F.J. van Tuijn, J.W. Sins, D.P.M. Brandjes, S.S. Zeerleder, B.J. Biemond
      PubDate: 2017-07-25T03:16:22.4124-05:00
      DOI: 10.1002/ajh.24868
  • Validation of and proposals for refinements of the WHO 2016 classification
           for myelodysplastic syndromes
    • Authors: M. F. van Spronsen; T. M. Westers, H. Rozema, G. J. Ossenkoppele, R. E. Kibbelaar, M. Hoogendoorn, A. A. van de Loosdrecht
      PubDate: 2017-07-25T03:16:20.630123-05:
      DOI: 10.1002/ajh.24867
  • Plasmapheresis may improve clinical condition in sickle cell disease
           through its effects on red blood cell rheology
    • Authors: Elie Nader; Philippe Connes, Yann Lamarre, Céline Renoux, Philippe Joly, Marie-Dominique Hardy-Dessources, Giovanna Cannas, Nathalie Lemonne, Samir K. Ballas
      PubDate: 2017-07-25T03:15:31.254432-05:
      DOI: 10.1002/ajh.24870
  • Earlier initiation of transfusional and iron chelation therapies in
           recently born children with transfusion-dependent thalassemia
    • Authors: Raffaella Origa; Federica Tatti, Antonietta Zappu, GiovanBattista Leoni, Carlo Dessì, Paolo Moi, Maddalena Morittu, Valeria Orecchia, AnnaRita Denotti, Maria Paola Pilia, Franco Anni, Maria Perra, Maria Rosaria Casini, Susanna Barella
      PubDate: 2017-07-25T03:15:29.328517-05:
      DOI: 10.1002/ajh.24869
  • Fetal Hemoglobin in Sickle Cell Anemia: The Arab-Indian Haplotype and New
           Therapeutic Agents
    • Authors: Alawi H. Habara; Elmutaz M. Shaikho, Martin H. Steinberg
      Abstract: Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly two-fold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-24T03:36:03.514684-05:
      DOI: 10.1002/ajh.24872
  • Current treatment preferences in chronic myeloid leukemia: The Mayo Clinic
           Physicians' survey
    • Authors: Kebede Begna; Aref Al-Kali, Michelle Elliott, James Foran, Naseema Gangat, William Hogan, Christopher Hook, Jose Leis, Mark Litzow, Ruben Mesa, Jeanne Palmer, Animesh Pardanani, Mrinal Patnaik, Candido Rivera, Lisa Sproat, Raoul Tibes, Alexandra Wolanskyj-Spinner, Ayalew Tefferi
      PubDate: 2017-07-21T03:17:21.269012-05:
      DOI: 10.1002/ajh.24866
  • Recognition of early mortality in multiple myeloma by a prediction matrix
    • Authors: Howard Terebelo; Shankar Srinivasan, Mohit Narang, Rafat Abonour, Cristina Gasparetto, Kathleen Toomey, James W. Hardin, Gail Larkins, Amani Kitali, Robert M. Rifkin, Jatin J. Shah
      Abstract: Early mortality (EM; death ≤ 6 months from diagnosis) has been reported in several newly diagnosed multiple myeloma (NDMM) trials. Before the era of novel agents, the incidence was 10%-14%. Causes of death included infections/pneumonia, renal failure, refractory disease, and cardiac events. Staging systems, such as the revised International Staging System (r-ISS), and prognostic factors including cytogenetics, lactate dehydrogenase levels, and myeloma-specific factors, are useful to assess overall prognosis; however, they cannot predict EM. We evaluated patients treated with novel agents in the Connect MM® Registry and identified risk factors of the EM cohort. Eligible patients were enrolled in the registry within 60 days of diagnosis. Univariate and multivariate analyses were conducted to evaluate associations between baseline characteristics and EM. Prediction matrices for EM were constructed from a logistic model. Between September 2009 and December 2011, 1493 patients were enrolled in the registry and had adequate follow-up. Of these patients, 102 (6.8%) had EM and 1391 (93.2%) survived for > 180 days. Baseline factors significantly associated with increased EM risk included age > 75 years, higher Eastern Cooperative Oncology Group performance status, lower EQ-5D mobility score, higher ISS stage, lower platelet count, and prior hypertension. Renal insufficiency trended toward increased EM risk. These risk factors were incorporated into a prediction matrix for EM. The EM prediction matrix uses differential weighting of risk factors to calculate EM risk in patients with NDMM. Identifying patients at risk for EM may provide new opportunities to implement patient-specific treatment strategies to improve outcomes.
      PubDate: 2017-07-19T01:25:58.410404-05:
      DOI: 10.1002/ajh.24796
  • Frequency, Risk Factors, and Outcomes of Central Nervous System Relapse in
           Lymphoma Patients Treated with Dose-Adjusted EPOCH plus Rituximab
    • Authors: M.K. Malecek; A.M. Petrich, S. Rozell, B. Chu, S. Trifilio, N. Galanina, M. Maurer, U. Farooq, B. Link, G.S. Nowakowski, C. Nabhan, A.O. Ayed
      Abstract: BackgroundCentral nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) is a rare but serious complication that carries a poor prognosis. The use of infusional etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) for frontline treatment of diffuse large B cell lymphoma (DLBCL) is increasing, though little is known about incidence of and risk factors for CNS relapse with this regimenPatients and methodsWe completed a chart review of patients with NHL who received EPOCH-R as front line therapy. Data obtained included baseline and treatment characteristics including if patients received CNS directed therapy. We measured overall survival (OS), progression free survival (PFS), and progression to CNS involvement.ResultsWe identified 223 patients who met the inclusion criteria, 72% had DLBCL. Of all the patients, 5.8% experienced CNS relapse, and 38.6% were treated with CNS prophylaxis. There was no difference in rate of CNS relapse, overall survival (OS), or progression free survival (PFS) between patients who had and had not received CNS prophylaxis. Patients whose serum lactate dehydrogenase (LDH) was greater than twice the upper limit of normal at diagnosis and those with extranodal disease were significantly more likely to have CNS relapse (p=0.0247 and 0.022 respectively) than their counterparts.ConclusionsThe rate of CNS relapse in this patient population approaches 6%, not significantly different from reports on those receiving R-CHOP. The results of this study suggest that CNS prophylaxis might be more selectively used among patients treated with EPOCH-R with certain high-risk features. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T03:25:20.384696-05:
      DOI: 10.1002/ajh.24864
  • Somatic mutations identified at diagnosis by exome sequencing can predict
           response to imatinib in chronic phase CML patients
    • Authors: Luca Mologni; Rocco Piazza, Praveen Khandelwal, Alessandra Pirola, Carlo Gambacorti-Passerini
      PubDate: 2017-07-18T03:21:05.979395-05:
      DOI: 10.1002/ajh.24865
  • Pure erythroid leukemia: the need gather data on this condition as defined
           in the World Health Organisation classification
    • Authors: Barbara J. Bain
      PubDate: 2017-07-13T19:23:20.150118-05:
      DOI: 10.1002/ajh.24863
  • Response to Dr. Bain's comment on our review article: Pure Erythroid
    • Authors: Wei Wang; Sa Wang, L. Jeffrey Medeiros, Joseph D. Khoury
      PubDate: 2017-07-13T19:22:58.385617-05:
      DOI: 10.1002/ajh.24862
  • Individuals with sickle cell disease have a significantly greater
           vasoconstriction response to thermal pain than controls and have
           significant vasoconstriction in response to anticipation of pain
    • Authors: Maha Khaleel; Mammen Puliyel, Payal Shah, John Sunwoo, Roberta M. Kato, Patjanaporn Chalacheva, Wanwara Thuptimdang, Jon Detterich, John C Wood, Jennie Tsao, Lonnie Zeltzer, Richard Sposto, Michael C.K. Khoo, Thomas D. Coates
      Abstract: The painful vaso-occlusive crises (VOC) that characterize sickle cell disease (SCD) progress over hours from the asymptomatic steady-state. SCD patients report that VOC can be triggered by stress, cold exposure and pain itself. We anticipated that pain could cause neural-mediated vasoconstriction, decreasing regional blood flow and promoting entrapment of sickle cells in the microvasculature. Therefore, we measured microvascular blood flow in the fingers of both hands using plethysmography and laser-Doppler flowmetry while applying a series of painful thermal stimuli on the right forearm in 23 SCD patients and 25 controls. Heat pain applied to one arm caused bilateral decrease in microvascular perfusion. The vasoconstriction response started before administration of the thermal pain stimulus in all subjects, suggesting that pain anticipation also causes significant vasoconstriction. The time delay between thermal pain application and global vasoconstriction ranged from 5 to 15.5 seconds and increased with age (p 
      PubDate: 2017-07-13T19:20:56.179117-05:
      DOI: 10.1002/ajh.24858
  • Association of pancreatic MRI R2* with blood glucose and cardiac MRI R2*
           among thalassemia major patients in Indonesia
    • Authors: Pustika Amalia Wahidiyat; Damayanti Sekarsari, Nitish Basant Adnani, Siti Ayu Putriasih, Vasili Berdoukas
      PubDate: 2017-07-13T19:20:49.766348-05:
      DOI: 10.1002/ajh.24860
  • Clinical Significance of Prothrombin G20210A Mutation in Homozygous
    • Authors: Amit Shemesh; Ron Hoffman, Yona Nadir, Anat Keren-Politansky, Manuel Monreal, Benjamin Brenner, Inna Tzoran
      PubDate: 2017-07-13T19:20:43.364841-05:
      DOI: 10.1002/ajh.24859
  • Nucleophosmin 1 (NPM1) Mutations in Chronic Myelomonocytic Leukemia and
           Their Prognostic Relevance
    • Authors: Rangit Vallapureddy; Terra L. Lasho, Katherine Hoversten, Christy M. Finke, Rhett Ketterling, Curtis Hanson, Naseema Gangat, Ayalew Tefferi, Mrinal M. Patnaik
      PubDate: 2017-07-13T19:20:40.62291-05:0
      DOI: 10.1002/ajh.24861
  • Causes of early death in multiple myeloma patients treated with high-dose
           therapy followed by autologous stem cell transplantation: A study based on
           the nationwide Danish Multiple Myeloma Registry
    • Authors: Kristian Thidemann Andersen; Tobias Klausen, Niels Abildgaard, Mette Klarskov Andersen, Niels Frost Andersen, Ulf Christian Frølund, Carsten Helleberg, Eigil Kjeldsen, Per Pedersen, Sissel Helm-Petersen, Asta Svirskaite, Birgitte Preiss, Peter Gimsing, Annette Juul Vangsted
      PubDate: 2017-07-13T19:20:36.98391-05:0
      DOI: 10.1002/ajh.24857
  • A Postpartum perfect storm
    • Authors: Adanma Ayanambakkam; Kerry C. Owens, Jennifer J. McIntosh, Carla M. Nester, James N. George
      PubDate: 2017-07-12T03:52:15.553941-05:
      DOI: 10.1002/ajh.24848
  • Not Bitten by the Bug: A CD30+ lymphoproliferative disorder masquerading
           as arthropod bites
    • Authors: Jacqueline McKesey; Travis Vandergriff, Heather Wickless
      PubDate: 2017-07-11T21:21:15.803414-05:
      DOI: 10.1002/ajh.24846
  • Alpha-1-antitrypsin for the treatment of steroid-refractory acute
           gastrointestinal graft-versus-host disease
    • Authors: James H. Jerkins; Mehdi Hamadani, Felicia Zook, Narendranath Epperla, Bronwen E. Shaw, Wael Saber, J. Douglas Rizzo, Marcelo Pasquini, Saurabh Chhabra, William R. Drobyski, Parameswaran N. Hari, Nirav N. Shah
      PubDate: 2017-07-11T21:21:13.418587-05:
      DOI: 10.1002/ajh.24850
  • A re-appraisal of the benefit-risk profile of Hydroxyurea in polycythemia
           vera: A propensity-matched study
    • Authors: Tiziano Barbui; Alessandro M Vannucchi, Guido Finazzi, Maria Chiara Finazzi, Arianna Masciulli, Alessandra Carobbio, Arianna Ghirardi, Gianni Tognoni
      Abstract: The use of Hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has been criticized because no solid demonstration that this drug prevents thrombosis or prolongs survival has been so far produced. Here we present the outcomes of a large cohort of patients with PV included in the European Collaborative Low-dose Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow-up, had received only phlebotomy (PHL) or HU to maintain the hematocrit level
      PubDate: 2017-07-11T21:21:11.908736-05:
      DOI: 10.1002/ajh.24851
  • Marked leukemoid reaction in a patient with metastatic breast carcinoma
    • Authors: Yasmin Harvey; Shane Bleakley, Piers Blombery, Barbara J. Bain
      PubDate: 2017-07-11T21:21:10.188469-05:
      DOI: 10.1002/ajh.24849
  • A monocyte-TNF-endothelial activation axis in sickle transgenic mice:
           Therapeutic benefit from TNF blockade
    • Authors: Anna Solovey; Arif Somani, John D Belcher, Liming Milbauer, Lucile Vincent, Rafal Pawlinski, Karl A Nath, Robert J Kelm Jr, Nigel Mackman, M Gerard O'Sullivan, Kalpna Gupta, Gregory M Vercellotti, Robert P Hebbel
      Abstract: Elaboration of tumor necrosis factor (TNF) is a very early event in development of ischemia/reperfusion injury pathophysiology. Therefore, TNF may be a prominent mediator of endothelial cell and vascular wall dysfunction in sickle cell anemia, a hypothesis we addressed using NY1DD, S+SAntilles, and SS-BERK sickle transgenic mice. Transfusion experiments revealed participation of abnormally activated blood monocytes exerting an endothelial activating effect, dependent upon Egr-1 in both vessel wall and blood cells, and upon NFκB(p50) in a blood cell only. Involvement of TNF was identified by beneficial impact from TNF blockers, etanercept and infliximab, with less benefit from an IL-1 blocker, anakinra. In therapeutic studies, etanercept ameliorated multiple disturbances of the murine sickle condition: monocyte activation, blood biomarkers of inflammation, low platelet count and Hb, vascular stasis triggered by hypoxia/reoxygenation (but not if triggered by hemin infusion), tissue production of neuro-inflammatory mediators, endothelial activation (monitored by tissue factor and VCAM-1 expression), histopathologic liver injury, and three surrogate markers of pulmonary hypertension (perivascular inflammatory aggregates, arteriolar muscularization, and right ventricular mean systolic pressure). In aggregate, these studies identify a prominent – and possibly dominant – role for an abnormal monocyte-TNF-endothelial activation axis in the sickle context. Its presence, plus the many benefits of etanercept observed here, argue that pilot testing of TNF blockade should be considered for human sickle cell anemia, a challenging but achievable translational research goal. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-11T21:21:04.569305-05:
      DOI: 10.1002/ajh.24856
  • POEMS Syndrome: An Elusive Diagnosis
    • Authors: Jithma P Abeykoon; Wilson I. Gonsalves, Jennifer Oliveira, Prashant Kapoor
      PubDate: 2017-07-11T21:20:49.428344-05:
      DOI: 10.1002/ajh.24845
  • Targeted Next Generation Sequencing Identifies a Novel ß-spectrin gene
           mutation A2059P in two Omani children with Hereditary Pyropoikilocytosis
    • Authors: Arwa Z. Al-Riyami; Achille Iolascon, Shoaib Al-Zadjali, Immacolata Andolfo, Sahima Al-Mammari, Francesco Manna, AbdulHakim Al Rawas, May-Jean King, Roberta Russo
      PubDate: 2017-07-11T21:15:41.603106-05:
      DOI: 10.1002/ajh.24853
  • Prospective Evaluation Of Chronic Organ Damage In Adult Sickle Cell
           Patients. A Seven-Year Follow-Up Study
    • Authors: Charlotte F.J. van Tuijn; Marein Schimmel, Eduard J. van Beers, Erfan Nur, Bart J. Biemond
      Abstract: AbstractOrgan damage in sickle cell disease (SCD) is a crucial determinant for disease severity and prognosis. In a previous study, we analyzed the prevalence of SCD-related organ damage and complications in adult sickle cell patients. We now describe a seven-year follow-up of this cohort.All patients from the primary analysis in 2006 (n=104), were included for follow-up. Patients were screened for SCD-related organ damage and complications (microalbuminuria, renal failure, elevated tricuspid regurgitation flow velocity (TRV) (≥2.5 m/sec), retinopathy, iron overload, cholelithiasis, avascular osteonecrosis, leg ulcers, acute chest syndrome (ACS), stroke, priapism and admissions for vaso-occlusive crises (VOC) biannually.Upon 7 years of follow-up, progression in the prevalence of avascular osteonecrosis (from 12,5 to 20,4%), renal failure (from 6,7 to 23,4%), retinopathy (from 39,7 to 53,8%) was observed in the whole group. In HbSS/HbSβ0-thal patients also progression in microalbuminuria (from 34 to 45%) and elevated TRV (from 40 to 48%) was observed while hardly any progression in the prevalence of cholelithiasis, priapism, stroke or chronic ulcers was seen. The proportion of patients with at least one episode of ACS increased in the group of HbSS/HbSβ0-thal patients from 32 to 49,1%.In conclusion, 62% of the sickle cell patients in this prospective cohort study developed a new SCD-related complication in a comprehensive care setting within 7 years of follow-up. Although the hospital admission rate for VOC remained stable, multiple forms of organ damage increased substantially. These observations underline the need for continued screening for organ damage in all adult patients with SCD. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-11T21:15:36.582641-05:
      DOI: 10.1002/ajh.24855
  • Long-Term Analysis of Phase II Studies of Single-Agent Lenalidomide in
           Relapsed/Refractory Mantle Cell Lymphoma
    • Authors: Thomas E. Witzig; Pier Luigi Zinzani, Thomas M. Habermann, Joseph M. Tuscano, Johannes Drach, Radhakrishnan Ramchandren, Sevgi Kalayoglu Besisik, Kenichi Takeshita, Marie-Laure Casadebaig Bravo, Lei Zhang, Tommy Fu, Andre Goy
      Abstract: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) with aggressive disease characteristics resulting in multiple relapses after initial treatment. Lenalidomide is an immunomodulatory agent approved in the US for patients with relapsed/refractory MCL following bortezomib based on results from 3 multicenter phase II studies (2 including relapsed/refractory aggressive NHL and 1 focusing on MCL post-bortezomib). The purpose of this report is to provide longer follow-up on the MCL-001 study (follow-ups were 6.8 [NHL-002], 7.6 [NHL-003], and 52.2 [MCL-001] months). The 206 relapsed MCL patients treated with single-agent lenalidomide (25 mg/day PO, days 1-21 every 28 days) had a median age of 67 years (63% ≥65 years), 91% with stage III/IV disease, and 50% with ≥4 previous treatment regimens. With a median follow-up of X, the combined best overall response rate was 33% (including 11% with complete remission [CR]/unconfirmed CR). Lenalidomide produced rapid and durable responses with a median time to response of 2.2 months and median duration of response of 16.6 months (95% CI: 11.1%-29.8%). The safety profile was consistent and manageable; myelosuppression was the most common adverse event. Overall, single-agent lenalidomide showed consistent efficacy and safety in multiple phase II studies of heavily pretreated patients with relapsed/refractory MCL, including those previously treated with bortezomib. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-11T20:46:16.461448-05:
      DOI: 10.1002/ajh.24854
  • Intensive Consolidation with G-CSF Support: Tolerability, Safety, Reduced
           Hospitalization, and Efficacy in AML Patients ≥60 Years
    • Authors: Wolfgang R. Sperr; Susanne Herndlhofer, Karoline Gleixner, Michael Girschikofsky, Ansgar Weltermann, Sigrid Machherndl-Spandl, Thamer Sliwa, Rainer Poehnl, Veronika Buxhofer-Ausch, Karin Strecker, Gregor Hoermann, Paul Knoebl, Ulrich Jaeger, Klaus Geissler, Michael Kundi, Peter Valent
      Abstract: The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA-C in cycle 1 and intermediate-dose ARA-C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalisation-time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction-chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC-P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All 4 planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation-cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P) (p
      PubDate: 2017-07-11T20:46:02.498937-05:
      DOI: 10.1002/ajh.24847
  • Chromosome 6q deletion correlates with poor prognosis and low relative
           expression of FOXO3 in chronic lymphocytic leukemia patients
    • Authors: Marie Jarosova; Martina Hruba, Alexandra Oltova, Karla Plevova, Lenka Kruzova, Eva Kriegova, Regina Fillerova, Eva Koritakova, Michael Doubek, Daniel Lysak, Vit Prochazka, Marek Mraz, Karel Indrak, Tomas Papajik
      PubDate: 2017-07-11T20:45:50.647627-05:
      DOI: 10.1002/ajh.24852
  • European LeukemiaNet study on the reproducibility of bone marrow features
           in masked polycythemia vera and differentiation from essential
    • Authors: Hans Michael Kvasnicka; Attilio Orazi, Juergen Thiele, Giovanni Barosi, Carlos E. Bueso-Ramos, Alessandro M. Vannucchi, Robert P. Hasserjian, Jean-Jacques Kiladjian, Umberto Gianelli, Richard Silver, Tariq I. Mughal, Tiziano Barbui
      Abstract: The purpose of the study was to assess consensus and interobserver agreement among an international panel of six hematopathologists regarding characterization and reproducibility of bone marrow (BM) histologic features used to diagnose early stage myeloproliferative neoplasms, in particular differentiation of so-called masked/prodromal polycythemia vera (mPV) from JAK2-mutated essential thrombocythemia (ET). The six members of the hematopathology panel evaluated 98 BM specimens independently and in a blinded fashion without knowledge of clinical data. The specimens included 48 cases of mPV according to the originally published hemoglobin threshold values for this entity (male: 16.0 – 18.4 g/dL, female: 15.0 – 16.4 g/dL), 31 cases with overt PV according to the updated 2016 WHO criteria, and 19 control cases. The latter group included cases of JAK2-mutated ET, primary myelofibrosis, myelodysplastic syndrome, and various reactive conditions. Inter-rater agreement between the panelists was very high (overall agreement 92.6%, kappa 0.812), particularly with respect to separating mPV from ET. Virtually all cases of mPV were correctly classified as PV according to their BM morphology. In conclusion, a central blinded review of histology slides by six hematopathologists demonstrated that highly reproducible specific histological pattern characterize PV and confirmed the notion that there are no significant differences between mPV and overt PV in relation to BM morphology. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-07T03:21:21.424531-05:
      DOI: 10.1002/ajh.24837
  • The dynamics of hepcidin-ferroportin internalization and consequences of a
           novel ferroportin disease mutation
    • Authors: Daniel F. Wallace; Cameron J. McDonald, Lesa Ostini, David Iser, Annabel Tuckfield, V. Nathan Subramaniam
      Abstract: The hepcidin-ferroportin axis underlies the pathophysiology of many iron-associated disorders and is a key target for the development of therapeutics for treating iron-associated disorders. The aims of this study were to investigate the dynamics of hepcidin-mediated ferroportin internalization and the consequences of a novel disease-causing mutation on ferroportin function. Specific reagents for ferroportin are limited; we developed and characterized antibodies against the largest extracellular loop of ferroportin and developed a novel cell-based assay for studying hepcidin-ferroportin function. We show that hepcidin-mediated ferroportin internalization is a rapid process and could be induced using low concentrations of hepcidin. Targeted next-generation sequencing utilizing an iron metabolism gene panel developed in our group identified a novel ferroportin p.D84E variant in a patient with iron overload. Wild-type and mutant ferroportin constructs were generated, transfected into HEK293 cells and analysed using an all-in-one flow-cytometry-based assay to study the effects on hepcidin-mediated internalization and iron transport. Consistent with the classical phenotype of ferroportin disease, the p.D84E mutation results in an inability to transport iron and hepcidin insensitivity. These results validate a recently proposed 3D-structural model of ferroportin and highlight the significance of this variant in the structure and function of ferroportin. Our novel ferroportin antibody and assay will be valuable tools for investigating the regulation of hepcidin/ferroportin function and the development of novel approaches for the therapeutic modulation of iron homeostasis. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-06T03:35:22.392023-05:
      DOI: 10.1002/ajh.24844
  • Stimulation of Adrenergic Activity by Desipramine Enhances Hematopoietic
           Stem and Progenitor Cell Mobilization along with G-CSF in Multiple Myeloma
           - A Pilot Study
    • Authors: Aditi Shastri; Anjali Budhathoki, Stefan K Barta, Noah Kornblum, Olga Derman, Ramakrishna Battini, Radha Ragupathy, Amit Verma, Paul S. Frenette, Ira Braunschweig, Murali Janakiram
      Abstract: Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G-CSF resulted in improved HSC mobilization. Here we present the results of an open-label single-arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G-SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 106 CD34+ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G-CSF. All study patients received desipramine 100mg daily for 7 days, starting 4 days prior to G-CSF administration (D-3) and continued taking it along with G-CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5x106 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5x106 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G-CSF is safe and signals improved mobilization over G-CSF alone, providing a possible alternative means of mobilization that needs further investigation. This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-04T00:25:19.633295-05:
      DOI: 10.1002/ajh.24843
  • ITACA: A New Validated International Erythropoietic Stimulating
           Agent-Response Score that Further Refines the Predictive Power of Previous
           Scoring Systems
    • Authors: Rena Buckstein; Enrico Balleari, Richard Wells, Valeria Santini, Alessandro Sanna, Chiara Salvetti, Elena Crisà, Bernardino Allione, Paolo Danise, Carlo Finelli, Marino Clavio, Antonella Poloni, Flavia Salvi, Daniela Cilloni, Esther Natalie Oliva, Pellegrino Musto, Brett Houston, Nancy Zhu, Michelle Geddes, Heather Leitch, Brian Leber, Mitchell Sabloff, Thomas J. Nevill, Karen Yee, John M. Storring, Janika Francis, Luca Maurillo, Roberto Latagliata, Maria Antonietta Aloe Spiriti, Alessandro Andriani, Anna Lina Piccioni, Luana Fianchi, Susanna Fenu, Svitlana Gumenyuk, Francesco Buccisano
      Abstract: Background: In ‘real-life', the Nordic score guides ESA use in lower-risk MDS with predicted response rates of 25% or 74%. As new treatments emerge, a more discriminating score is needed.Objectives: To validate existing ESA predictive scores and develop a new score that identifies non-responders.Methods: ESA-treated patients were identified in 3 MDS registries in Italy and Canada (FISM 555, GROM 233, MDS-CAN 208). Clinical and disease-related variables were captured. Nordic, MDS-CAN and IPSS-R-based ESA scores were calculated and documented ESA responses compared.Results: 996 ESA-treated patients were identified. Overall response rate(ORR) was 59%. The database was randomly divided into balanced derivation (n=463) and validation (n=462) cohorts. By multivariate analysis, transfusion independence, erythropoietin level
      PubDate: 2017-07-04T00:20:29.123064-05:
      DOI: 10.1002/ajh.24842
  • Early switch to second-line tyrosine kinase inhibitor in chronic myeloid
           leukemia patients failing to achieve early molecular response
    • Authors: Adi J. Klil-Drori; Hui Yin, Laurent Azoulay, Michaël Harnois, Michel-Olivier Gratton, Alexa Del Corpo, Harold J. Olney, Robert Delage, Pierre Laneuville, Luigina Mollica, Lambert Busque, Sarit E. Assouline,
      PubDate: 2017-07-03T03:41:00.052937-05:
      DOI: 10.1002/ajh.24838
  • “Limitations of poor Bone Marrow Aspirations (for an accurate diagnosis)
           despite the multi-modal analytical era: A longitudinal retrospective
    • Authors: John M. Astle; Mina L. Xu, Tamir Friedman, Elliott Brown
      PubDate: 2017-07-03T03:40:38.684143-05:
      DOI: 10.1002/ajh.24839
  • Estimation of Glomerular Filtration Rate Using Serum Cystatin C and
           Creatinine in Adults with Sickle Cell Anemia
    • Authors: Marianne E.M. Yee; Peter A. Lane, David R. Archer, Clinton H. Joiner, James R. Eckman, Antonio Guasch
      PubDate: 2017-07-03T03:40:37.006283-05:
      DOI: 10.1002/ajh.24840
  • "CLL progression after one cycle of FCR: Richter's transformation versus
           EBV-associated lympho-proliferation"
    • Authors: Preetesh Jain; Jan Burger, Joseph D. Khoury
      PubDate: 2017-07-03T03:40:34.369553-05:
      DOI: 10.1002/ajh.24841
  • Sickle Cells Produce Functional Immune Modulators and Cytotoxics
    • Authors: Chiao-Wang Sun; Li-Chen Wu, Peter L. Knopick, David S. Bradley, Tim Townes, David S. Terman
      Abstract: Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers. We partially replaced the β-globin coding region of this vector with genes from the T cell cytolytics, perforin and granzyme or immune modulating superantigens SEG and SEI. These modified vectors efficiently transduced Sca+ckit-Lin- HSCs from humanized sickle cell knockin mice. Irradiated mice reconstituted with these HSCs displayed robust expression of transgenic RNAs and proteins in host sickle cells that was sustained for more than 10 months. SSRBCs from reconstituted mice harboring SEG/SEI transgenes induced robust proliferation and prototypical superantigen-induced cytokine reaction when exposed to human CD4+/CD8+ cells. The β-globin lentiviral vector therefore produces a high level of functional, erythroid-specific immune modulators and cytotoxics that circulate without toxicityCoupled with their unique ability to target and occlude hypoxic tumor vessels these armed SSRBCs constitute a potentially useful tool for treatment of solid tumors. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-24T03:37:42.17274-05:0
      DOI: 10.1002/ajh.24836
  • History of consolidation is prognostic in AML patients undergoing
           allogeneic hematopoietic cell transplantation in minimal residual
           disease-negative first complete remission
    • Authors: Armin Rashidi; Michael A. Linden, Todd E. DeFor, Erica Warlick, Nelli Bejanyan, Sophia Yohe, Daniel J. Weisdorf, Celalettin Ustun
      Abstract: Background: Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in minimal residual disease (MRD)-negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo-HCT in MRD-negative CR1, does a history of prior consolidation provide additional prognostic information' Methods: The inclusion criteria were: (i) Age > 18 years, (ii) AML in CR1 after 1-2 cycles of intensive induction chemotherapy, with or without consolidation, (iii) Allo-HCT between 1/2003 and 4/2016 at our institution, (iv) Available standard-sensitivity 4-color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, (v) Flow cytometry-based MRD-negative status at the time of HCT. Results: A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35-0.99], P = 0.046), relapse-free survival (0.60 [0.37-0.96], P = 0.036), and relapse (0.50 [0.27-0.92], P = 0.025). Analysis of potential sources of bias was unrevealing. Conclusions: In AML patients undergoing allo-HCT in MRD-negative CR1 state, a history of prior consolidation was associated with favorable outcomes. If the path to pre-HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD-negative state. These results warrant validation in larger cohorts. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-24T03:37:38.153039-05:
      DOI: 10.1002/ajh.24834
  • Clinical characteristics and outcomes of previously untreated patients
           with adult onset T-ALL and T-lymphoblastic lymphoma (T-LL) with Hyper-CVAD
           based regimens
    • Authors: Preetesh Jain; Hagop Kantarjian, Nitin Jain, Nicholas J. Short, Cameron C. Yin, Rashmi Kanagal-Shamanna, Joseph Khoury, Marina Konopleva, Koji Sasaki, Tapan M. Kadia, Rebecca Garris, Sherry Pierce, Zeev Estrov, William Wierda, Jorge Cortes, Susan O'Brien, Farhad Ravandi, Elias Jabbour
      PubDate: 2017-06-24T03:37:29.192396-05:
      DOI: 10.1002/ajh.24833
  • Elevated soluble α-hemoglobin pool in Sickle Cell Anemia
    • Authors: Corinne Vasseur; Elisa Domingues-Hamdi, Sadaf Pakdaman, Caroline Barau, Serge Pissard, Philippe Le Corvoisier, France Pirenne, Frédéric Galactéros, Véronique Baudin-Creuza
      PubDate: 2017-06-24T03:37:27.203081-05:
      DOI: 10.1002/ajh.24835
  • Prevalence and Predictors of Anemia in Hereditary Hemorrhagic
    • Authors: Raj S. Kasthuri; Megan Montifar, Jeffrey Nelson, Helen Kim, Michael T. Lawton, Marie E. Faughnan,
      PubDate: 2017-06-22T02:20:55.898227-05:
      DOI: 10.1002/ajh.24832
  • Bone Marrow Hematons: An Access Point to the Human Hematopoietic Niche
    • Authors: Alexandre Janel; Juliette Berger, Céline Bourgne, Richard Lemal, Nathalie Boiret-Dupré, Frédérique Dubois-Galopin, Pierre Déchelotte, Charlotte Bothorel, Eric Hermet, Sara Chabi, Jacques-Olivier Bay, Céline Lambert, Bruno Pereira, Françoise Pflumio, Rima Haddad, Marc G. Berger
      Abstract: To understand the complex interactions between hematopoietic stem cells and the bone marrow niche, a human experimental model is needed. Our hypothesis is that hematons are an appropriate ex vivo model of human bone marrow.We analyzed the hierarchical hematopoietic cell content and the tissue organization of single hematons from healthy donors.Most (>90%) hematons contained precursors of all cell lineages, myeloid progenitors, and LTC-ICs without preferential commitment. Approximately half of the hematons could generate significant levels of lympho-myeloid hematopoiesis after transplantation in an NSG mouse model, despite the low absolute numbers of transplanted CD34+ cells. Mesenchymal STRO-1+ and/or CD271+ cells formed a critical network that preserved hematon cohesion, and STRO-1+ cells co-localized with most hematopoietic CD34+ cells (68%). We observed an influence of age and gender.These structures represent a particularly attractive model for studying the homeostasis of the bone marrow niche and pathological changes that occur during diseases. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-22T02:20:52.458237-05:
      DOI: 10.1002/ajh.24830
  • Acute leukemic transformation of myelodysplastic syndrome – is
           cytochemistry still relevant'
    • Authors: Imogen Caldwell; Anna Ruskova, Nicola Eaddy, Barbara J. Bain
      PubDate: 2017-06-22T02:15:48.738401-05:
      DOI: 10.1002/ajh.24831
  • Early Mortality in Patients with Acute Myelogenous Leukemia Treated in
           Teaching versus Non-teaching Hospitals: A Large Database Analysis
    • Authors: Adam Levin; Ariel Kleman, Lisa Rein, Sergey Tarima, Laura C. Michaelis, Karen Sue Carlson, Mehdi Hamadani, Timothy S. Fenske, Parameswaran Hari, Ehab Atallah, Binod Dhakal
      PubDate: 2017-06-20T01:10:25.439226-05:
      DOI: 10.1002/ajh.24825
  • Missing HLA C group 1 ligand in patients with AML and MDS is associated
           with reduced risk of relapse and better survival after allogeneic stem
           cell transplantation with fludarabine and treosulfan reduced toxicity
    • Authors: Avichai Shimoni; Luca Vago, Massimo Bernardi, Ronit Yerushalmi, Jacopo Peccatori, Raffaella Greco, Noga Shem-Tov, Alessandro Lo Russo, Ivetta Danylesko, Arie Apel, Chiara Bonini, Maria Teresa Lupo Stanghellini, Arnon Nagler, Fabio Ciceri
      Abstract: Reduced-toxicity conditioning with fludarabine and treosulfan is a dose-intensive regimen with enhanced anti-leukemia effect and acceptable toxicity in AML/MDS. HLA-C regulates natural-killer (NK) cell function by inhibiting Killer immunoglobulin-like receptors (KIR) and is divided into C1 and C2 epitopes. The missing-ligand theory suggests that missing recipient KIR ligands drives NK-alloreactivity after SCT, in the absence of HLA-mismatch by activating unlicensed donor NK cells. We analyzed SCT outcomes in 203 patients with AML/MDS, median age 58 years, given SCT from matched-siblings (n=97) or matched-unrelated donors (n=106), using two treosulfan doses (total 36 or 42 gr/m2). 34% expressed one HLA-C group 1 allele (C1C1), 19% one HLA-C group 2 allele (C2C2) and 48% both KIR ligands (C1C2). Median follow-up was 48 months. 5-year relapse, non-relapse mortality (NRM) and leukemia-free survival (LFS) rates were 38%, 27% and 36%, respectively. Relapse rates were 43%, 45% and 26% in patients expressing C1C1, C1C2 and C2C2 ligands, respectively (P=0.03). Multivariate-analysis identified chemo-refractory disease (HR 3.1, P=0.003), poor cytogenetics (HR 1.7, P=0.08), female donor to male recipient (HR 0.4, P=0.01) and C2C2 ligands (HR 0.4, P=0.04) as independent factors predicting relapse. HLA-C ligands were not associated with GVHD or NRM. LFS was 33%, 30% and 46%, respectively (P=0.07). Chemo-refractory disease (HR 3.1, P=0.0004) and C2C2 group ligand (HR 0.6, P=0.06) independently predicted LFS. Treosulfan dose did not predict any SCT outcome. In conclusion, missing HLA-C group 1 ligand is associated with reduced relapse risk, similar NRM and improved LFS, after HLA-matched SCT with treosulfan conditioning in AML/MDS. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-19T22:35:27.243302-05:
      DOI: 10.1002/ajh.24827
  • High prevalence of osteonecrosis among the HLH population: Single
           institution 10 year retrospective data review
    • Authors: Paul Craig; Shelly Marette, Jutta Ellermann, Surbhi Shah, Takashi Takahashi
      PubDate: 2017-06-19T22:20:28.32516-05:0
      DOI: 10.1002/ajh.24828
  • Platelet counts in women with normal pregnancies: A systematic review
    • Authors: Jessica A. Reese; Jennifer D. Peck, Jennifer J. McIntosh, Sara K. Vesely, James N. George
      Abstract: The occurrence of thrombocytopenia in 5% of pregnant women at delivery, described as gestational thrombocytopenia, is well documented. A commonly believed concept is that gestational thrombocytopenia is the result of gradually decreasing platelet counts in all women during pregnancy. The goal of our study was to evaluate the data supporting this concept. To learn what is known about platelet counts throughout normal pregnancies, we systematically reviewed all publications describing platelet counts during pregnancy. We identified 3039 studies; 46 reporting ≥30 women with normal pregnancies were included in our analyses. The combined mean platelet counts from all studies supported the concept that platelet counts decrease during pregnancy and increase postpartum: first trimester, 251,000/µL (95% CI, 238,000-264,000/µL); second trimester, 238,000/µL (95% CI, 222,000-253,000/µL); third trimester, 224,000/µL (95% CI, 213,000-235,000/µL); delivery, 237,000/µL (95% CI, 209,000-264,000/µL); 4-8 weeks postpartum, 247,000/µL (95% CI, 207,000-287,000/µL). However, individual studies were inconsistent. Eleven longitudinal studies compared platelet counts on the same women at different times during gestation: seven reported a decrease; four reported no change. Ten cross-sectional studies compared platelet counts of different women at different times during gestation: five reported a decrease; five reported no change. Five studies compared platelet counts of pregnant to nonpregnant women: three reported that platelet counts were lower in pregnant women; one reported no difference; one reported that platelet counts were higher in pregnant women. These inconsistent data emphasize the need to accurately describe platelet counts throughout normal pregnancies. Accurate data are essential for evaluating the clinical importance of thrombocytopenia during pregnancy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-19T22:20:24.723942-05:
      DOI: 10.1002/ajh.24829
  • Effect of velaglucerase alfa enzyme replacement therapy on red blood cell
           properties in Gaucher disease
    • Authors: Melanie Franco; Nelly Reihani, Mickael Marin, Marine De Person, Thierry Billette de Villemeur, Christian Rose, Yves Colin, Fathi Moussa, Nadia Belmatoug, Caroline Le Van Kim
      PubDate: 2017-06-16T09:50:37.919709-05:
      DOI: 10.1002/ajh.24816
  • Long-term Follow-up of Chemoimmunotherapy with Rituximab, Oxaliplatin,
           Cytosine Arabinoside, Dexamethasone (ROAD) in Patients With Relapsed CD20+
           B–Cell Non-Hodgkin Lymphoma: Results of a study of the Mayo Clinic
           Cancer Research Consortium (MCCRC) MC0485 now known as Academic and
           Community Cancer Research United (ACCRU)
    • Authors: Thomas E. Witzig; Patrick B. Johnston, Betsy R. LaPlant, Paul J. Kurtin, Levi D. Pederson, Dennis F. Moore, Nassim H. Nabbout, Daniel A. Nikcevich, Kendrith M. Rowland, Axel Grothey
      Abstract: Patients with relapsed aggressive non-Hodgkin lymphoma (NHL) are often treated with platinum-based chemoimmunotherapy regimens in preparation for autologous stem cell transplant. We sought to reduce toxicity and maintain efficacy by using oxaliplatin with rituximab, cytarabine and dexamethasone (ROAD) in a phase II clinical trial in patients who had relapsed after one prior regimen. ROAD was delivered q21 days and consisted of rituximab 375 mg/m2 IV weekly x 4 doses (cycle 1 only); dexamethasone 40 mg PO/IV d2 – 5; oxaliplatin 130 mg/m2 IV d2; cytarabine 2000 mg/m2 IV x two doses on days 2 – 3; and pegfilgrastim 6 mg SC on d4. Forty-five eligible patients were accrued between 2006- 2008. Patient characteristics were a median age of 69 years; 96% had received prior rituximab; 53% were within one year of diagnosis. The median number of cycles received was 2 (range, 1-6). Forty-four % received ROAD as an outpatient. The overall response rate was 71% with 27% (12/45) CR and 44% (20/45) PR. Forty-four % (20/45) of all patients and 69% (18/26) of patients whom responded after 2 cycles proceeded to transplant. Median overall survival was 26 mos (95% CI: 7.3 mos – not reached) and median progression-free survival was 11 mos (95% CI: 6 – 104 mos). There was no grade 3/4 nephrotoxicity; the rate of grade 3/4 neuropathy was 4%. Forty-two percent of all patients and 69% of patients transplanted remain alive at 5 years. ROAD represents an acceptable salvage therapeutic option for patients with relapsed aggressive NHL. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-14T17:57:15.426988-05:
      DOI: 10.1002/ajh.24824
  • Deformability of Transfused Red Blood Cells is a Potent Effector of
           Transfusion-Induced Hemoglobin Increment: A Study with β-Thalassemia
           Major Patients
    • Authors: Gregory Barshtein; Neta Goldschmidt, Axel R Pries, Orly Zelig, Dan Arbell, Saul Yedgar
      PubDate: 2017-06-14T17:57:14.124802-05:
      DOI: 10.1002/ajh.24821
  • Thiotepa-based conditioning versus total body irradiation as myeloablative
           conditioning prior to allogeneic stem cell transplantation for acute
           lymphoblastic leukemia: A matched-pair analysis from the Acute Leukemia
           Working Party of the European Society for Blood and Marrow Transplantation
    • Authors: Sandra Eder; Jonathan Canaani, Eric Beohou, Myriam Labopin, Miguel A. Sanz, William Arcese, Reuven Or, Juergen Finke, Agostino Cortelezzi, Dietrich Beelen, Jakob Passweg, Gerard Socié, Gunhan Gurman, Mahmoud Aljurf, Matthias Stelljes, Sebastian Giebel, Mohamad Mohty, Arnon Nagler,
      Abstract: The optimal conditioning regimen to employ before hematopoieitic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while Cy/TBI is the most commonly used myeloablative regimen, there are concerns regarding long term toxicity for patients conditioned with this regimen. Thiotepa based conditioning is an emerging radiation free regimen with recent publications indicative of comparable clinical outcomes to TBI based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched-pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa-based conditioning (n=180) with those receiving Cy/TBI conditioning (n=540). The 2 year leukemia-free survival and overall survival rates of both conditioning regimens were comparable, 33% for thiotepa [95% confidence interval (CI): 26.4 - 42.8] versus 39% for Cy/TBI (95% CI: 34.8 - 44.5] (P=0.33) and 46.5% [95% CI: 38.6 - 56.1] versus 48.8% [95% CI: 44.2 - 54] (P=0.9), respectively. There was no significant difference between the two regimens in the incidence of either acute graft versus host disease (GVHD) or chronic GVHD.Multivariate analysis demonstrated increased relapse incidence for thiotepa conditioning compared to Cy/TBI (HR=1.78, 95% CI, 1.07-2.95; P=0.03) which did not affect overall survival. Our results indicate that thiotepa based conditioning may not be inferior to Cy/TBI for adult ALL patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-14T17:57:11.32836-05:0
      DOI: 10.1002/ajh.24823
  • A comparative analysis of biosimilar vs originator filgrastim in
           combination with plerixafor for stem cell mobilization in lymphoma and
           multiple myeloma; a propensity-score weighted multicenter approach
    • Authors: F Lanza; F Saraceni, A Pezzi, M Martino, A Bosi, N Cascavilla, P Musto, E Zuffa, M Tani, C Cellini, D Laszlo, F Bonifazi,
      PubDate: 2017-06-13T19:20:26.779766-05:
      DOI: 10.1002/ajh.24817
  • Day 14 bone marrow examination in the management of acute myeloid leukemia
    • Authors: Christopher M Terry; Rory M Shallis, Elihu Estey, Seah H Lim
      Abstract: The National Comprehensive Cancer Network (NCCN) recommends that a repeat bone marrow evaluation is carried out seven to ten days following completion of induction therapy so that if a patient's day 14 bone marrow shows residual blast cell counts of>10%, the patient would proceed early to a second cycle of induction therapy. Although blast cell counts of 5% on day 14 bone marrow would still attain a complete remission of the disease without any further chemotherapy. Clinical decision based on day 14 bone marrow will result in some of these patients being given a second induction therapy unnecessarily. A second cycle of chemotherapy is associated with not only higher risk for treatment-related mortality but also increased use of hospital resources such as increased intravenous antimicrobials use, longer hospital stay, and higher demand for blood products. In this paper, we examined the utility, discussed the shortfalls, and re-appraised the values of day 14 bone marrow in the management of patients with AML. Based on our review, we suggest that the practice of day 14 bone marrow examination should be re-evaluated and should probably only be carried out in the setting of clinical trials with clear questions to address its role in predicting outcome of the therapeutic intervention. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:20:24.832926-05:
      DOI: 10.1002/ajh.24818
  • Impact of Comorbidities on Outcomes of Elderly Patients with Diffuse Large
           B-cell Lymphoma
    • Authors: Caner Saygin; Xuefei Jia, Brian Hill, Robert Dean, Brad Pohlman, Mitchell R. Smith, Deepa Jagadeesh
      Abstract: International prognostic index (IPI) has remained the primary prognostic tool in diffuse large B cell lymphoma (DLBCL) for more than 20 years. Even though the disease is more common in older population, the impact of comorbidities, dose reductions, and treatment-related adverse events (TAEs) on the outcome in elderly DLBCL patients has not been well established. We studied 413 consecutive patients aged ≥ 60 years who were treated at the Cleveland Clinic. The median age at diagnosis was 69 years, 58% of patients had high IPI score, and 85% had low Charlson comorbidity index (CCI). Forty percent of patients required dose reductions during treatment, 78% achieved CR, and 70% experienced at least one grade II-IV TAE. High IPI score, high CCI, reduced dose chemotherapy, TAE, and hospitalization were significant predictors of death and relapse. In multivariable analysis, high IPI and CCI were independent predictors of overall and progression free survival. A simple model combining IPI and CCI could reliably distinguish three prognostically separate risk groups. Our results suggest that incorporation of CCI in current prognostic models can improve prognostication of older DLBCL patients and CCI might be a valuable tool in evaluating the eligibility of older patients for clinical trial enrollment. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:20:22.784329-05:
      DOI: 10.1002/ajh.24819
  • Genetic Determinants of HbF in Saudi Arabian and African Benin Haplotype
           Sickle Cell Anemia
    • Authors: Elmutaz M. Shaikho; John J. Farrell, Abdulrahman Alsultan, Paola Sebastiani, Martin H. Steinberg
      PubDate: 2017-06-13T19:20:20.655602-05:
      DOI: 10.1002/ajh.24822
  • Juvenile myelomonocytic leukemia in an infant with congenital HIV and CMV
    • Authors: Jessica Bazin; Leena Karnik, Gareth Tudor-Williams, Anne M. Kelly, Barbara J. Bain
      PubDate: 2017-06-13T19:20:18.751115-05:
      DOI: 10.1002/ajh.24815
  • Iron deficiency across chronic inflammatory conditions: International
           expert opinion on definition, diagnosis and management
    • Authors: Maria Domenica Cappellini; Josep Comin-Colet, Angel de Francisco, Axel Dignass, Wolfram Doehner, Carolyn SP Lam, Iain C Macdougall, Gerhard Rogler, Clara Camaschella, Rezan Kadir, Nicholas J Kassebaum, Donat R Spahn, Ali T Taher, Khaled M Musallam,
      Abstract: Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines.In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease-specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:15:24.454116-05:
      DOI: 10.1002/ajh.24820
  • Multidimensional assessment of patient condition and mutational analysis
           in peripheral blood, as tools to improve outcome prediction in
           myelodysplastic syndromes: A prospective study of the Spanish MDS Group
    • Authors: Fernando Ramos; Cristina Robledo, Arturo Pereira, Carmen Pedro, Rocío Benito, Raquel de Paz, Mónica del Rey, Andrés Insunza, Mar Tormo, María Díez-Campelo, Blanca Xicoy, Eduardo Salido, Javier Sánchez-del-Real, Leonor Arenillas, Lourdes Florensa, Elisa Luño, Consuelo del Cañizo, Guillermo F. Sanz, Jesús María Hernández-Rivas,
      Abstract: The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS-R, for estimating overall survival and the risk of leukemic transformation in patients with MDS.A prospective cohort (2006-2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS-R. Patients were further stratified according to patient condition (assessed using the multidimensional Lee index for older adults) and genetic mutations (peripheral blood samples screened using next-generation sequencing). The change in likelihood-ratio was tested in Cox models after adding individual covariates.The addition of the Lee index to the IPSS-R significantly improved prediction of overall survival [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.96–4.66, p
      PubDate: 2017-06-13T19:15:22.462678-05:
      DOI: 10.1002/ajh.24813
  • Transplantation Related Toxicity and Mortality in Older Autologous
           Hematopoietic Cell Transplantation Recipients
    • Authors: Hewan Belete; Linda J Burns, Ryan Shanley, Manju Nayar, Brian McClune, Aleksandr Lazaryan, Veronika Bachanova, Nelli Bejanyan, Celalettin Ustun, Claudio Brunstein, Daniel J Weisdorf, Mukta Arora
      Abstract: With advances in supportive care, autologous hematopoietic cell transplant (AHCT) is increasingly being performed for patients older than 60 years. We analyzed patients receiving an AHCT for multiple myeloma or lymphoma in a contemporary cohort (2010-2012), with consistent treatment and supportive care and compared outcomes [CTCAE grade 3-5 toxicities, non-relapse mortality (NRM) and overall-survival (OS)] of younger (40-59 years, n=77) versus older (≥ 60 years, n=67) recipients. The proportion of patients with neutropenic infections was higher in the older group (64% vs. 44%; p=0.02). The proportion of patients with any grade 3-5 toxicity was also higher in the older group (84% vs. 67%, p=0.03). In multivariate analysis, older age was significantly associated with higher odds (OR: 2.57, 95% CI:1.09-6.05) of grade 3-5 toxicity. The NRM was 3% (older) vs. 0% (younger) at one-year. The probability of OS at 2-years was lower in the older group (76% vs. 90%, p=0.04). Though AHCT can be performed safely in older recipients, the higher toxicity and slightly higher NRM in this population needs attention. Studies focusing on risk-stratification in older patients would further help predict toxicity. Further studies addressing enhanced supportive care needs for older patients who are most likely to benefit are indicated. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T19:15:20.309524-05:
      DOI: 10.1002/ajh.24814
  • Cross-altitude analysis suggests a turning point at the elevation of
           4,500m for polycythemia prevalence in Tibetans
    • Authors: Hui Zhang; Yaoxi He, Chaoying Cui, Ouzhuluobu, Baimakangzhuo, Duojizhuoma, Dejiquzong, Bianba, Gonggalanzi, Yongyue Pan, Qula, Kangmin, Cirenyangji, Baimayangji, Caijuan Bai, Wei Guo, Yangla, Yi Peng, Xiaoming Zhang, Kun Xiang, Zhaohui Yang, Shiming Liu, Xiang Tao, Gengdeng, Wangshan Zheng, Yongbo Guo, Tianyi Wu, Xuebin Qi, Bing Su
      PubDate: 2017-06-07T03:50:23.669209-05:
      DOI: 10.1002/ajh.24809
  • Losartan for the Nephropathy of Sickle Cell Anemia: A Phase-2,
           Multi-Center Trial
    • Authors: Charles T. Quinn; Santosh L. Saraf, Victor R. Gordeuk, Courtney D. Fitzhugh, Susan E. Creary, Prasad Bodas, Alex George, Ashok B. Raj, Alecia C. Nero, Catherine E. Terrell, Lisa McCord, Adam Lane, Hans C. Ackerman, Yu Yang, Omar Niss, Michael D. Taylor, Prasad Devarajan, Punam Malik
      Abstract: Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase-2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA=14, MicroA=12, MacroA=6). The primary endpoint was met in 83% of the MacroA group (P50% (0.2➝0.3 mg/dL), N=1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase-3, randomized, placebo-controlled trial of losartan for the nephropathy of SCA. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-07T03:30:30.099014-05:
      DOI: 10.1002/ajh.24810
  • Safety and Efficacy of Recombinant Activated Coagulation Factor VII in
           Congenital Hemophilia with Inhibitors in the Home Treatment Setting: A
           Review of Clinical Studies and Registries
    • Authors: Guy Young; Miguel A. Escobar, Steven W. Pipe, David L. Cooper
      Abstract: Self-administration of factor and bypassing agents by persons with hemophilia in the home setting is recommended to facilitate earlier intervention after bleeding episodes. The objective of this review was to summarize recombinant activated coagulation factor VII (rFVIIa) safety and efficacy data from clinical trials and patient registries documenting use in the home treatment setting in people with congenital hemophilia with inhibitors (CHwI). A total of 16 studies and registries were identified for inclusion; 14 evaluated on-demand treatment of acute bleeding episodes (865 patients, 9024 bleeding episodes) and 2 evaluated use for secondary prophylaxis (108 patients, 42,861 prophylaxis days). In the on-demand studies, efficacy was consistently high (81%-96%), and thrombotic events were uncommon (n=3). In the secondary prophylaxis studies, rFVIIa was associated with a 45% to 59% reduction in bleeding episodes and no thrombotic events. These data support the clinical practice of administering rFVIIa in patients in the home treatment setting after initiation under a physician's care. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-07T03:30:22.938194-05:
      DOI: 10.1002/ajh.24811
  • IGHV Mutational Status Testing in Chronic Lymphocytic Leukemia
    • Authors: Jennifer Crombie; Matthew S. Davids
      Abstract: As the therapeutic landscape for chronic lymphocytic leukemia (CLL) continues to expand, biological predictors of response to therapy are becoming increasingly important. One such predictive biomarker is the mutational status of the variable region of the immunoglobulin heavy chain (IGHV) gene, which is a powerful predictor of duration of response and overall survival with chemoimmunotherapy (CIT). As this test may influence choice of therapy between CIT and novel agents, it is critical that providers understand how mutational status is determined and the limitations of testing. Here, we describe the details of IGHV mutational status testing, highlighting the appropriate way to interpret this information and best apply it to the care of patients with CLL. This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-07T03:30:21.785173-05:
      DOI: 10.1002/ajh.24808
  • Secondary CNS involvement of ALK-negative anaplastic large cell lymphoma
    • Authors: Ajay Major; Zenggang Pan, Manali Kamdar
      PubDate: 2017-06-05T04:35:39.129866-05:
      DOI: 10.1002/ajh.24733
  • Developmentally-Faithful and Effective Human Erythropoiesis in
           Immunodeficient and Kit Mutant Mice
    • Authors: Claudia Fiorini; Nour J. Abdulhay, Sean K. McFarland, Mathias Munschauer, Jacob C. Ulirsch, Roberto Chiarle, Vijay G. Sankaran
      Abstract: Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis from various human developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-31T20:00:28.196168-05:
      DOI: 10.1002/ajh.24805
  • Allogeneic hematopoietic cell transplantation in morphologic leukemia-free
           aplastic state
    • Authors: Armin Rashidi; Alaa M. Ali, Kiran R. Vij, Ryan Shanley, Rizwan Romee, Sarah A Cooley, Peter Westervelt, John F. DiPersio, Jeffrey S. Miller, Daniel J. Weisdorf, Celalettin Ustun
      PubDate: 2017-05-31T19:55:26.432032-05:
      DOI: 10.1002/ajh.24804
  • Transformation in Pre-treatment Manifestations of Gaucher Disease Type 1
           during Two Decades of Alglucerase/Imiglucerase Enzyme Replacement Therapy
           in the International Collaborative Gaucher Group (ICGG) Registry
    • Authors: Pramod K. Mistry; Julie L. Batista, Hans C. Andersson, Manisha Balwani, Thomas Andrew Burrow, Joel Charrow, Paige Kaplan, Aneal Khan, Priya S. Kishnani, Edwin H. Kolodny, Barry Rosenbloom, C. Ronald Scott, Neal Weinreb
      Abstract: This study tests the hypothesis that the prevalence of severe clinical manifestations in Gaucher disease type 1 (GD1) patients at the time of treatment initiation has changed since alglucerase/imiglucerase enzyme replacement therapy (ERT) was approved in the United States (US) in 1991. US alglucerase/imiglucerase-treated GD1 patients from the International Collaborative Gaucher Group Gaucher Registry were stratified by age at ERT initiation (
      PubDate: 2017-05-31T19:55:25.595721-05:
      DOI: 10.1002/ajh.24801
  • The Prognostic Significance of Polyclonal Bone Marrow Plasma Cells in
           Patients with Relapsing Multiple Myeloma
    • Authors: Toshi Ghosh; Wilson I. Gonsalves, Dragan Jevremovic, Angela Dispenzieri, David Dingli, Michael M. Timm, William G. Morice, Prashant Kapoor, Taxiarchis V. Kourelis, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, Nelson Leung, Ronald S. Go, Yi Lin, Stephen J. Russell, John A. Lust, Steven R. Zeldenrust, Rahma Warsame, Yi L. Hwa, Robert A. Kyle, Morie A. Gertz, S. Vincent Rajkumar, Shaji K. Kumar
      Abstract: Prior studies have revealed that the presence of increasing number of polyclonal plasma cells (pPCs) in the bone marrow (BM) are associated with better outcomes in newly diagnosed multiple myeloma (MM) patients. This effect has not been studied in patients with MM at the time of disease relapse. We determined the prognostic value of depletion of pPCs in the BM by 7-color multiparameter flow cytometry in a series of 174 relapsing MM patients. The time to next therapy (TTNT) in those with
      PubDate: 2017-05-31T19:55:24.188635-05:
      DOI: 10.1002/ajh.24807
  • Autoimmune neutropenia of childhood secondary to other autoimmune
           disorders: data from the Italian Neutropenia Registry
    • Authors: Piero Farruggia; Giuseppe Puccio, Francesca Fioredda, Tiziana Lanza, Laura Porretti, Ugo Ramenghi, Angelica Barone, Sonia Bonanomi, Andrea Finocchi, Roberta Ghilardi, Saverio Ladogana, Nicoletta Marra, Baldassare Martire, Lucia Dora Notarangelo, Daniela Onofrillo, Marta Pillon, Giovanna Russo, Laura Lo Valvo, Jessica Serafinelli, Fabio Tucci, Fiammetta Zunica, Federico Verzegnassi, Carlo Dufour
      PubDate: 2017-05-31T19:55:23.056964-05:
      DOI: 10.1002/ajh.24803
  • A follow-up on Desiderosmia (olfactory craving), a novel symptom
           associated with iron deficiency anemia
    • Authors: Bryar R. Hansen; Wayne A. Bottner, Aishwarya Ravindran, Ramona DeJesus, Ronald S. Go
      PubDate: 2017-05-31T19:55:21.926608-05:
      DOI: 10.1002/ajh.24806
  • Cardiac Tamponade in Myelofibrosis: A Mayo Clinic Series of 9 Consecutive
    • Authors: Sravanthi Lavu; Ayalew Tefferi
      PubDate: 2017-05-31T19:50:23.527121-05:
      DOI: 10.1002/ajh.24800
  • Botryoid nuclei resulting from cocaine abuse
    • Authors: Maurizio Fumi; Ylenia Pancione, Silvia Sale, Vincenzo Rocco, Barbara J. Bain
      PubDate: 2017-05-30T06:05:45.191589-05:
      DOI: 10.1002/ajh.24769
  • Factors associated with risk of central nervous system relapse in patients
           with non-core binding factor acute myeloid leukemia
    • Authors: Elias Jabbour; Naval Guastad Daver, Nicholas James Short, Xuelin Huang, Hsiang-Chun Chen, Abhishek Maiti, Farhad Ravandi, Jorge Cortes, Simon Abi Aad, Guillermo Garcia-Manero, Zeev Estrov, Tapan Kadia, Susan O'Brien, Bouthaina Dabaja, Carlos Bueso-Ramos, Paolo Strati, Carol Bivins, Sherry Pierce, Hagop Kantarjian
      Abstract: Central nervous system (CNS) relapse is uncommon in patients with acute myeloid leukemia (AML) with the use of high-dose cytarabine containing chemotherapy regimens. The clinical and molecular features associated with a higher risk of CNS relapse are not well defined. We assessed the incidence and outcome of CNS relapses among 1245 patients with relapsed/refractory AML referred to our institution between 2000 and 2014. CNS leukemia relapse was observed in 51 patients (4.1%). Using a multivariate regression model and after adjusting for age, FLT3-ITD mutation (OR=2.33; p=0.02) and elevated LDH (>1000 IU/L, OR=1.99; p=0.04) were independent predictive factors for CNS relapse. Patients under 64 years of age with 0, 1, or 2 baseline adverse features had a probability of 3.8%, 7.0-8.0%, and 13.9% for developing CNS disease, respectively. Our study identifies patients with AML at higher risk for CNS relapse in whom prophylactic CNS therapy may be warranted. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-27T02:55:23.5782-05:00
      DOI: 10.1002/ajh.24799
  • A puzzling case of methemoglobinemia
    • Authors: Audrey Morris; Barbara J. Bain, Maria Atta, D. Mark Layton
      PubDate: 2017-05-26T04:10:58.205913-05:
      DOI: 10.1002/ajh.24747
  • Multicenter analysis of the use of transjugular intrahepatic portosystemic
           shunt (TIPS) for management of MPN-associated portal hypertension
    • Authors: Christopher R. Reilly; Daria V. Babushok, Karlyn Martin, Jerry L. Spivak, Michael Streiff, Ranjeeta Bahirwani, Jeffrey Mondschein, Brady Stein, Alison Moliterno, Elizabeth O. Hexner
      Abstract: BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders defined by proliferation of one or more myeloid lineages, and carry an increased risk of vascular events and progression to myelofibrosis and leukemia. Portal hypertension (pHTN) occurs in 7-18% of MPN patients via both thrombotic and nonthrombotic mechanisms and portends a poor prognosis. Transjugular intrahepatic portosystemic shunt (TIPS) has been used in the management of MPN-associated pHTN; however, data on long-term outcomes of TIPS in this setting is limited and the optimal management of medically refractory MPN-associated pHTN is not known. In order to assess the efficacy and long-term outcomes of TIPS in MPN-associated pHTN, we performed a retrospective analysis of 29 MPN patients who underwent TIPS at three academic medical centers between 1997 and 2016. The majority of patients experienced complete clinical resolution of pHTN and its clinical sequelae following TIPS. One, two, three, and four-year overall survival post-TIPS was 96.4%, 92.3%, 84.6%, and 71.4%, respectively. However, despite therapeutic anticoagulation, in-stent thrombosis occurred in 31.0% of patients after TIPS, necessitating additional interventions. In conclusion, TIPS can be an effective intervention for MPN-associated pHTN regardless of etiology. However, TIPS thrombosis is a frequent complication in the MPN population and indefinite anticoagulation post-TIPS should be considered. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-24T18:00:28.229997-05:
      DOI: 10.1002/ajh.24798
  • Ibrutinib Therapy for Lymphoplasmacytic Lymphoma
    • Authors: Margaret J. Helber; Jeremiah E. Moore, AnnaLynn M. Williams, Philip J. Meacham, Paul G. Rothberg, Clive S. Zent
      PubDate: 2017-05-24T18:00:25.166102-05:
      DOI: 10.1002/ajh.24795
  • Clinical impact of pre-transplant use of multiple tyrosine kinase
           inhibitors on the outcome of allo-HSCT for CML
    • Authors: Takeshi Kondo; Tokiko Nagamura-Inoue, Arinobu Tojo, Fumitaka Nagamura, Naoyuki Uchida, Hirohisa Nakamae, Takahiro Fukuda, Takehiko Mori, Shingo Yano, Mineo Kurokawa, Hironori Ueno, Heiwa Kanamori, Hisako Hashimoto, Makoto Onizuka, Minoko Takanashi, Tatsuo Ichinohe, Yoshiko Atsuta, Kazuteru Ohashi,
      Abstract: Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with chronic myelogenous leukemia in the chronic phase (CML-CP), and outcomes of TKI treatment for patients with CML-CP have been excellent. Since multiple TKIs are currently available, second-line or third-line TKI therapy is considered for patients who are intolerant of or resistant to the previous TKI treatment. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered only for patients with disease progression or for patients after treatment failure with multiple TKIs. To reflect the current clinical situation of patients with CML-CP, we tried to clarify whether prior TKI treatment affects the outcome of allo-HSCT. Data from 237 patients for whom the number of pre-transplant TKIs varied from one to three were used for analysis. Before allo-HSCT, 153 patients were treated with one TKI, 49 patients were treated with two TKIs and 35 patients were treated with three TKIs. In addition to conventional risk factors, i.e., disease status at transplantation and patient's age, the use of three TKIs before transplantation was identified as a significant adverse factor for prognosis. Non-relapse mortality rate was higher in patients treated with three TKIs than in patients treated with one or two TKIs. Our results suggest that allo-HSCT could be considered for young patients with CML-CP who manifest resistance to second-line TKI therapy and who have an appropriate donor. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-20T03:30:30.848038-05:
      DOI: 10.1002/ajh.24793
  • Pre-fibrotic/early primary myelofibrosis vs. WHO-defined essential
           thrombocythemia: The impact of minor clinical diagnostic criteria on the
           outcome of the disease
    • Authors: Georg Jeryczynski; Juergen Thiele, Bettina Gisslinger, Albert Wölfler, Martin Schalling, Andreas Gleiß, Sonja Burgstaller, Veronika Buxhofer-Ausch, Thamer Sliwa, Ernst Schlögl, Klaus Geissler, Maria-Theresa Krauth, Alexander Nader, Michael Vesely, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Christine Beham-Schmid, Heinz Gisslinger
      Abstract: The 2016 revised WHO criteria for the diagnosis of pre-fibrotic/early primary myelofibrosis (pre-PMF) require at least one of the following four borderline expressed minor clinical criteria: anemia, leukocytosis, elevated lactate dehydrogenase and splenomegaly. In this study, we evaluated the relative frequency of these four criteria in a group of 170 pre-PMF patients and compared them to 225 ET cases. More than 91% of pre-PMF cases showed one or more of these features required for diagnosis, by contrast with only 48.0% of ET patients. According to clinical data the cumulative risk of progression to advanced/overt PMF in pre-PMF was 36.9% after 15 years. After fitting cox regression models to analyze the impact of the minor criteria on overall survival, only leukocytosis remained as a significant predictor of survival in both pre-PMF and ET.Molecular characterization showed differences in survival in pre-PMF but not ET, with CALR being a more favorable mutation than JAK2. The different outcome of pre-PMF versus ET and associated molecular genetic data supports the concept of two different entities, rather than a continuum of the same disease.Although slightly less than 50% of ET patients also show one or more minor clinical criteria, accurate distinction between ET and pre-PMF is possible by following an integrated approach including histomorphological diagnosis and presence of minor clinical criteria. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-20T02:45:24.354158-05:
      DOI: 10.1002/ajh.24788
  • Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing
           after autologous stem cell transplant in the current era of novel
           therapeutics: A retrospective analysis
    • Authors: SM Bair; L Strelec, SJ Nagle, SD Nasta, DJ Landsburg, AR Mato, AW Loren, SJ Schuster, EA Stadtmauer, J Svoboda
      Abstract: Patients with relapsed/refractory Hodgkin lymphoma (RR-HL) who progress or relapse following autologous stem cell transplantation (ASCT) have historically had a poor prognosis. Several novel agents, particularly brentuximab vedotin, have shown efficacy in this setting. However, there remains a paucity of data characterizing outcomes outside of clinical trials and how these novel agents impacted prognosis in general population of patients with RR-HL. Here, we conducted a retrospective analysis to evaluate outcomes in 87 patients with RR-HL with relapse post-ASCT. Treatment with novel agents (including brentuximab vedotin) was associated with significant improvement in median overall survival (OS) compared to patients who did not receive novel agents (85.6 vs 17.1 months; p
      PubDate: 2017-05-16T21:00:30.546864-05:
      DOI: 10.1002/ajh.24792
  • Implementation of Multi-Disciplinary Care Reduces Maternal Mortality in
           Women with Sickle Cell Disease Living in Low-resource Setting
    • Authors: Eugenia Vicky Asare; Edeghonghon Olayemi, Theodore Boafor, Yvonne Dei-Adomakoh, Enoch Mensah, Harriet Ghansah, Yvonne Osei-Bonsu, Selina Crabbe, Latif Musah, Charles Hayfron-Benjamin, Brittany Covert, Adetola A. Kassim, Andra James, Mark Rodeghier, Michael R. DeBaun, Samuel A. Oppong
      Abstract: Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Intervention consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10,791 per 100,000 live births at pre-intervention to 1,176 per 100,000 at post-intervention, representing a risk reduction of 89.1% (p = 0.007). Perinatal mortality decreased from 60.8 per 1,000 total births at pre-intervention to 23.0 per 1,000 at post-intervention, representing a risk reduction of 62.2% (p = 0.20).A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-16T20:45:56.902867-05:
      DOI: 10.1002/ajh.24790
  • Look Into My Eyes: An Unusual First Presentation of Sickle Cell Disease
    • Authors: Rupali Sood; Kim Jiramongkolchai, Michael Streiff, Christopher Gonzalez, Satish Shanbhag, Sophie Lanzkron, J. Fernando Arevalo, Rakhi Naik
      PubDate: 2017-05-11T18:55:24.824436-05:
      DOI: 10.1002/ajh.24787
  • Minimal Residual Disease Eradication with Epigenetic Therapy in Core
           Binding Factor Acute Myeloid Leukemia
    • Authors: Brittany Knick Ragon; Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
      Abstract: Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival. Real-time quantitative (RTPCR) trends were reviewed in 23 patients (median age 53 years) with CBF-AML that received HMA therapy following induction/consolidation with fludarabine, cytarabine and G-CSF (FLAG) with low dose gemtuzumab or idarubicin (NCT00801489). Of the 23 patients evaluated, 17 had a detectable RTPCR at HMA initiation. Five patients had progressive disease and a notable increase in RTPCR values over 1 to 2 cycles of HMA therapy. Twelve patients did not fail HMA and had a median RTPCR at HMA initiation of 0.06 (range, 0.01-0.91). Unlike the HMA failure subset, 11 of these patients had a reduction in RTPCR after the first or second cycle of HMA. Our data suggests that CBF-AML patients with low levels of RTPCR (between 0.01 and 0.05) at the conclusion of induction/consolidation chemotherapy benefit most from maintenance HMA, particularly those that have a reduction in the RTPCR within the first 2 cycles of HMA therapy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T18:45:45.280492-05:
      DOI: 10.1002/ajh.24782
  • Estimates of total body iron indicate 19 mg and 38 mg oral iron are
           equivalent for the mitigation of iron deficiency in individuals
           experiencing repeated phlebotomy
    • Authors: Walter Bialkowski; Joseph E. Kiss, David J. Wright, Ritchard Cable, Rebecca Birch, Pam D'Andrea, Barbara J. Bryant, Bryan R. Spencer, Alan E. Mast
      Abstract: Iron deficiency anemia is a common clinical condition often treated with tablets containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side effects lowering patient compliance. Oral iron supplements also increase hepcidin production causing decreased fractional absorption of subsequent doses. Frequent blood donors often become iron deficient. Therefore, they were enrolled in a two-year study involving continued blood donations and randomization to receive no pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI) did not change for the subset of donors in the no pill and placebo groups who completed both enrollment and final visits (p=0.21 and p=0.28, respectively). However, repeated measures regression analysis on the complete dataset estimated a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (p=0.001). The effects of 19 and 38 mg iron supplementation on TBI were indistinguishable (p=0.54). TBI increased by 229 mg after the initial 60 days of iron supplementation (p
      PubDate: 2017-05-11T18:45:37.334668-05:
      DOI: 10.1002/ajh.24784
  • Cutaneous septic emboli from Candida glabrata in a haematological patient
    • Authors: Andrea Lombardi; Giorgio Alberto Croci, Valeria Brazzelli, Marco Vecchia, Valentina Zuccaro, Marco Sciarra, Raffaele Bruno
      PubDate: 2017-05-09T03:51:05.118357-05:
      DOI: 10.1002/ajh.24729
  • Mitotic figure in the peripheral blood smear
    • Authors: Sebastian Hörber; Ingo Rettig, Andreas Peter
      Abstract: A previously healthy 19-year-old man presented with fever, sore throat and strong feeling of illness. Physical examination showed strong swelling of throat tonsils and moderate hepatosplenomegaly. The laboratory values were as following: a total white blood count of 10.9 x 109/L, hemoglobin 14.1 g/dL and a platelet count of 109 x 109/L. Total bilirubin was 1.4 mg/dL and CRP was 1.32 mg/dL. The serological analyses revealed IgG and IgM antibodies against EBV-VCA consistent with an acute Epstein-Barr virus infection. The peripheral blood smear revealed 80.0% lymphocytes, 12.4% neutrophils, 6.9% monocytes, 0.4% eosinophils and 0.3% basophils. In it a mitotic figure was found (see illustration). Mitotic figures are an extremely uncommon finding as they are usually seen in patients with acute leukemia or rarer in EBV infections. Symptomatic therapy led to complete resolution of the symptoms. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-12T12:15:38.164844-05:
      DOI: 10.1002/ajh.24761
  • Issue Information – Table of Contents
    • Pages: 841 - 843
      PubDate: 2017-08-07T06:42:26.296299-05:
      DOI: 10.1002/ajh.24518
  • Correlates of resistance and relapse during blinatumomab therapy for
           relapsed/refractory acute lymphoblastic leukemia
    • Authors: Ibrahim Aldoss; Joo Song, Tracey Stiller, Tina Nguyen, Joycelynne Palmer, Margaret O'Donnell, Anthony S. Stein, Guido Marcucci, Stephen Forman, Vinod Pullarkat
      Pages: 858 - 865
      Abstract: We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM-ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts>50%) (P = .02), history of prior EM-ALL (P = .005), and active EM-ALL at the time of initiating blinatumomab (P = .05) predicted lower CR rate. Among refractory cases, 13 (41%) had evidence of EM-ALL progression, and CD19 expression was negative or dim in 18% and 23%, respectively. Among responders, 20 (61%) subsequently relapsed among whom EM-ALL relapse occurred in 8 (40%) patients, and CD19 expression was negative or dim in 35 and 6% of evaluable cases, respectively. Pretreatment moderate/strong CD19 expression (P = .01) and history of prior EM-ALL during ALL course (P = .04) were risk factors for developing EM-ALL at progression/relapse. However, no pretreatment factors predicted progression/relapse with CD19-negative ALL. Overall-survival (OS) and even-free survival were improved for patients underwent allogeneic HCT compared to responders who did not. Furthermore, OS was superior for patients responded to blinatumomab compared to those who did not. Extramedullary and CD19-negative disease are common during blinatumomab failure in r/r ALL. In addition to high leukemia burden, concurrent or prior history EM-ALL were associated with lower response to blinatumomab. Higher CD19 expression as well as prior history of EM-ALL were associated with EM-ALL at the time of blinatumomab failure.
      PubDate: 2017-06-05T04:35:34.397506-05:
      DOI: 10.1002/ajh.24783
  • Outcome of elderly patients after failure to hypomethylating agents given
           as frontline therapy for acute myeloid leukemia: Single institution
    • Authors: Rama Nanah; Kristen McCullough, William Hogan, Kebede Begna, Mrinal Patnaik, Michelle Elliott, Mark Litzow, Aref Al-Kali
      Pages: 866 - 871
      Abstract: Outcomes of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy is challenging. Hypomethylating agents (HMAs) can be effective in these patients but responses are usually short-lived. The majority of patients will either have stable disease or progress through therapy. We hereby describe the outcome of these patients at our institution after they fail HMAs. The data on 56 AML patients at Mayo Clinic, Rochester were reviewed. Patients were considered for our study if they received HMA as frontline therapy for their AML. Out of 56 patients, 15 (27%) patients received azacitidine (AZA) and 41 (73%) received decitabine. Complete remission was found in 10 (18%), with overall response of 28% and median response duration of 10 months. Thirteen (81%) out of 16 responders relapsed. Therefore 53 patients were included in the primary or secondary failure analysis with a median overall survival (OS) of 2 months after the date of failure. Out of 53 patients, 12 (23%) received subsequent treatments. None of the 12 patients who got first salvage therapy achieved remission. Five out of the 12 patients received second salvage therapy, 2 (40%) of which achieved CR. Median OS for patients who received subsequent salvage therapies was better than those who did not receive any subsequent therapy after failing HMA (9.5 vs. 2 months, P = .0009). Outcome for patients who have primary or secondary failure is very poor. Our study provides important historical data for future novel therapies, which are sorely needed for these patients.
      PubDate: 2017-06-05T04:35:29.969815-05:
      DOI: 10.1002/ajh.24780
  • Chimeric antigen receptor modified T cells that target chemokine receptor
           CCR4 as a therapeutic modality for T-cell malignancies
    • Authors: Liyanage P. Perera; Meili Zhang, Masao Nakagawa, Michael N. Petrus, Michiyuki Maeda, Marshall E. Kadin, Thomas A. Waldmann, Pin-Yu Perera
      Pages: 892 - 901
      Abstract: With the emerging success of treating CD19 expressing B cell malignancies with ex vivo modified, autologous T cells that express CD19-directed chimeric antigen receptors (CAR), there is intense interest in expanding this evolving technology to develop effective modalities to treat other malignancies including solid tumors. Exploiting this approach to develop a therapeutic modality for T cell malignancies for which the available regimens are neither curative, nor confer long term survival we generated a lentivirus-based CAR gene transfer system to target the chemokine receptor CCR4 that is over-expressed in a spectrum of T cell malignancies as well as in CD4+CD25+Foxp3+T regulatory cells that accumulate in the tumor microenvironment constituting a barrier against anti-tumor immunity. Ex vivo modified, donor-derived T cells that expressed CCR4 directed CAR displayed antigen-dependent potent cytotoxicity against patient-derived cell lines representing ATL, CTCL, ALCL and a subset of HDL. Furthermore, these CAR T cells also eradicated leukemia in a mouse xenograft model of ATL illustrating the potential utility of this modality in the treatment of a wide spectrum of T cell malignancies.
      PubDate: 2017-06-05T04:35:44.857015-05:
      DOI: 10.1002/ajh.24794
  • Chronic lymphocytic leukemia: 2017 update on diagnosis, risk
           stratification, and treatment
    • Authors: Michael Hallek
      Pages: 946 - 965
      Abstract: Disease OverviewChronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells.DiagnosisThe diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers.PrognosisTwo prognostic staging systems exist, the Rai and Binet staging systems, which are established by physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene predict resistance to available chemotherapies. A comprehensive prognostic score (CLL-IPI) using genetic, biological, and clinical variables has recently been developed allowing to classify CLL into very distinct risk groups.TherapyPatients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For physically fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab remains the current standard therapy. For unfit patients, currently available evidence supports two options for a first-line therapy: chlorambucil combined with an anti-CD20 antibody (obinutuzumab or rituximab or ofatumumab) or a continuous therapy with ibrutinib. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds 3 years. If the disease relapses earlier, therapy should be changed using alternative agents such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, idelalisib, or venetoclax. Patients with a del(17p) or TP53 mutation can be treated with ibrutinib, venetoclax, or a combination of idelalisib and rituximab. An allogeneic SCT may be considered in relapsing patients with TP53 mutations or del(17p) or patients that are refractory to chemoimmunotherapy and the novel inhibitors.Future ChallengesThe new agents (ibrutinib, idelalisib, venetoclax, and obinutuzumab) hold the potential to significantly improve the outcome of CLL patients. However, their optimal use (in terms of combination, sequence, and duration) remains unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.
      PubDate: 2017-08-07T06:42:20.403553-05:
      DOI: 10.1002/ajh.24826
  • The significance of irregularly contracted cells and hemighosts in sickle
           cell disease
    • Authors: Wenchee Siow; Francis Matthey, Barbara J. Bain
      Pages: 966 - 967
      PubDate: 2017-02-21T00:26:07.934864-05:
      DOI: 10.1002/ajh.24658
  • A centrocyte blood count of a quarter million
    • Authors: Matthew Behrens; Rajasree P. Chowdry, Saliba Saba, Nakhle S. Saba
      Pages: 972 - 973
      PubDate: 2017-04-06T05:40:41.678301-05:
      DOI: 10.1002/ajh.24708
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