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Publisher: John Wiley and Sons   (Total: 1582 journals)

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Showing 1 - 200 of 1583 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 11, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 53, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 43, SJR: 0.547, h-index: 30)
ACEP NOW     Free  
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 50, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 134, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 54, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 7, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 5, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 2)
Addiction     Hybrid Journal   (Followers: 32, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 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: 24, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 47, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 247, 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: 4, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 4)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 14, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 9, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 28, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 49, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 130, 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: 89, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 28, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 30, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Orthopsychiatry     Hybrid Journal   (Followers: 4, SJR: 0.756, h-index: 69)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 35, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 237, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 15, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 118, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 11, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 15)
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: 154)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 204, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 34, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 5, 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: 42, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 16, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 14)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 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: 66, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 6, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 130, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 47, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 13, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 34, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 14, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 24, 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: 205, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 48, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 13)
Asia & the Pacific Policy Studies     Open Access   (Followers: 15)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 318, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 3, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 13, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 12, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 7, 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: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 42, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 21, 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: 16, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 384, 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: 64, 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: 9, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 3, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 7, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 21, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 14, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 2, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 44, 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: 137, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 17, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 10, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 33, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)

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Journal Cover American Journal of Hematology
  [SJR: 1.761]   [H-I: 77]   [30 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  [1582 journals]
  • Clinical impact of pre-transplant use of multiple tyrosine kinase
           inhibitors on the outcome of allo-HSCT for CML
    • Authors: Takeshi Kondo; Tokiko Nagamura-Inoue, Arinobu Tojo, Fumitaka Nagamura, Naoyuki Uchida, Hirohisa Nakamae, Takahiro Fukuda, Takehiko Mori, Shingo Yano, Mineo Kurokawa, Hironori Ueno, Heiwa Kanamori, Hisako Hashimoto, Makoto Onizuka, Minoko Takanashi, Tatsuo Ichinohe, Yoshiko Atsuta, Kazuteru Ohashi,
      Abstract: Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with chronic myelogenous leukemia in the chronic phase (CML-CP), and outcomes of TKI treatment for patients with CML-CP have been excellent. Since multiple TKIs are currently available, second-line or third-line TKI therapy is considered for patients who are intolerant of or resistant to the previous TKI treatment. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered only for patients with disease progression or for patients after treatment failure with multiple TKIs. To reflect the current clinical situation of patients with CML-CP, we tried to clarify whether prior TKI treatment affects the outcome of allo-HSCT. Data from 237 patients for whom the number of pre-transplant TKIs varied from one to three were used for analysis. Before allo-HSCT, 153 patients were treated with one TKI, 49 patients were treated with two TKIs and 35 patients were treated with three TKIs. In addition to conventional risk factors, i.e., disease status at transplantation and patient's age, the use of three TKIs before transplantation was identified as a significant adverse factor for prognosis. Non-relapse mortality rate was higher in patients treated with three TKIs than in patients treated with one or two TKIs. Our results suggest that allo-HSCT could be considered for young patients with CML-CP who manifest resistance to second-line TKI therapy and who have an appropriate donor. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-20T03:30:30.848038-05:
      DOI: 10.1002/ajh.24793
       
  • Chimeric Antigen Receptor Modified T cells That Target Chemokine Receptor
           CCR4 as a Therapeutic Modality for T-cell Malignancies
    • Authors: Liyanage P. Perera; Meili Zhang, Masao Nakagawa, Michael N. Petrus, Michiyuki Maeda, Marshall E. Kadin, Thomas A. Waldmann, Pin-Yu Perera
      PubDate: 2017-05-20T03:30:26.803875-05:
      DOI: 10.1002/ajh.24794
       
  • Pre-fibrotic/early primary myelofibrosis vs. WHO-defined essential
           thrombocythemia: The impact of minor clinical diagnostic criteria on the
           outcome of the disease
    • Authors: Georg Jeryczynski; Juergen Thiele, Bettina Gisslinger, Albert Wölfler, Martin Schalling, Andreas Gleiß, Sonja Burgstaller, Veronika Buxhofer-Ausch, Thamer Sliwa, Ernst Schlögl, Klaus Geissler, Maria-Theresa Krauth, Alexander Nader, Michael Vesely, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Christine Beham-Schmid, Heinz Gisslinger
      Abstract: The 2016 revised WHO criteria for the diagnosis of pre-fibrotic/early primary myelofibrosis (pre-PMF) require at least one of the following four borderline expressed minor clinical criteria: anemia, leukocytosis, elevated lactate dehydrogenase and splenomegaly. In this study, we evaluated the relative frequency of these four criteria in a group of 170 pre-PMF patients and compared them to 225 ET cases. More than 91% of pre-PMF cases showed one or more of these features required for diagnosis, by contrast with only 48.0% of ET patients. According to clinical data the cumulative risk of progression to advanced/overt PMF in pre-PMF was 36.9% after 15 years. After fitting cox regression models to analyze the impact of the minor criteria on overall survival, only leukocytosis remained as a significant predictor of survival in both pre-PMF and ET.Molecular characterization showed differences in survival in pre-PMF but not ET, with CALR being a more favorable mutation than JAK2. The different outcome of pre-PMF versus ET and associated molecular genetic data supports the concept of two different entities, rather than a continuum of the same disease.Although slightly less than 50% of ET patients also show one or more minor clinical criteria, accurate distinction between ET and pre-PMF is possible by following an integrated approach including histomorphological diagnosis and presence of minor clinical criteria. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-20T02:45:24.354158-05:
      DOI: 10.1002/ajh.24788
       
  • The aggressive peripheral T-cell lymphomas: 2017
    • Authors: James O. Armitage
      PubDate: 2017-05-18T00:35:39.687236-05:
      DOI: 10.1002/ajh.24791
       
  • Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing
           after autologous stem cell transplant in the current era of novel
           therapeutics: A retrospective analysis
    • Authors: SM Bair; L Strelec, SJ Nagle, SD Nasta, DJ Landsburg, AR Mato, AW Loren, SJ Schuster, EA Stadtmauer, J Svoboda
      Abstract: Patients with relapsed/refractory Hodgkin lymphoma (RR-HL) who progress or relapse following autologous stem cell transplantation (ASCT) have historically had a poor prognosis. Several novel agents, particularly brentuximab vedotin, have shown efficacy in this setting. However, there remains a paucity of data characterizing outcomes outside of clinical trials and how these novel agents impacted prognosis in general population of patients with RR-HL. Here, we conducted a retrospective analysis to evaluate outcomes in 87 patients with RR-HL with relapse post-ASCT. Treatment with novel agents (including brentuximab vedotin) was associated with significant improvement in median overall survival (OS) compared to patients who did not receive novel agents (85.6 vs 17.1 months; p
      PubDate: 2017-05-16T21:00:30.546864-05:
      DOI: 10.1002/ajh.24792
       
  • A hit to current ‘HIT' wisdom: A century later, it's time for a
           change
    • Authors: Francesco Rodeghiero
      PubDate: 2017-05-16T20:46:00.904929-05:
      DOI: 10.1002/ajh.24789
       
  • Implementation of Multi-Disciplinary Care Reduces Maternal Mortality in
           Women with Sickle Cell Disease Living in Low-resource Setting
    • Authors: Eugenia Vicky Asare; Edeghonghon Olayemi, Theodore Boafor, Yvonne Dei-Adomakoh, Enoch Mensah, Harriet Ghansah, Yvonne Osei-Bonsu, Selina Crabbe, Latif Musah, Charles Hayfron-Benjamin, Brittany Covert, Adetola A. Kassim, Andra James, Mark Rodeghier, Michael R. DeBaun, Samuel A. Oppong
      Abstract: Sickle cell disease (SCD) is associated with adverse pregnancy outcome. In women with SCD living in low-resource settings, pregnancy is associated with significantly increased maternal and perinatal mortality rates. We tested the hypothesis that implementing a multidisciplinary obstetric and hematology care team in a low-resource setting would significantly reduce maternal and perinatal mortality rates. We conducted a before-and-after study, at the Korle-Bu Teaching Hospital in Accra, Ghana, to evaluate the effect of a multidisciplinary obstetric-hematology care team for women with SCD in a combined SCD-Obstetric Clinic. The pre-intervention period was assessed through a retrospective chart review to identify every death and the post-intervention period was assessed prospectively. Intervention consisted of joint obstetrician and hematologist outpatient and acute inpatient reviews, close maternal and fetal surveillance, and simple protocols for management of acute chest syndrome and acute pain episodes. Primary outcomes included maternal and perinatal mortality rates before and after the study period. A total of 158 and 90 pregnant women with SCD were evaluated in the pre- and post- intervention periods, respectively. The maternal mortality rate decreased from 10,791 per 100,000 live births at pre-intervention to 1,176 per 100,000 at post-intervention, representing a risk reduction of 89.1% (p = 0.007). Perinatal mortality decreased from 60.8 per 1,000 total births at pre-intervention to 23.0 per 1,000 at post-intervention, representing a risk reduction of 62.2% (p = 0.20).A multidisciplinary obstetric and hematology team approach can dramatically reduce maternal and perinatal mortality in a low-resource setting. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-16T20:45:56.902867-05:
      DOI: 10.1002/ajh.24790
       
  • Look Into My Eyes: An Unusual First Presentation of Sickle Cell Disease
    • Authors: Rupali Sood; Kim Jiramongkolchai, Michael Streiff, Christopher Gonzalez, Satish Shanbhag, Sophie Lanzkron, J. Fernando Arevalo, Rakhi Naik
      PubDate: 2017-05-11T18:55:24.824436-05:
      DOI: 10.1002/ajh.24787
       
  • Urinary Prednisolone Excretion is a Determinant of Serum Hepcidin Levels
           in Renal Transplant Recipients
    • Authors: Michele F. Eisenga; Robin P. F. Dullaart, Stefan P. Berger, Daan J. Touw, Stephan J.L. Bakker, Carlo A.J.M. Gaillard
      PubDate: 2017-05-11T18:45:51.138627-05:
      DOI: 10.1002/ajh.24785
       
  • Characterization of TP53 mutations in clonal cytopenia of undetermined
           significance
    • Authors: Wei Wang; Mark J. Routbort, Chi Young OK, Keyur P. Patel, Yi Sun, Rashmi Kanagal-Shamanna, L. Jeffrey Medeiros, Sa A. Wang
      PubDate: 2017-05-11T18:45:48.338495-05:
      DOI: 10.1002/ajh.24786
       
  • Minimal Residual Disease Eradication with Epigenetic Therapy in Core
           Binding Factor Acute Myeloid Leukemia
    • Authors: Brittany Knick Ragon; Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
      Abstract: Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival. Real-time quantitative (RTPCR) trends were reviewed in 23 patients (median age 53 years) with CBF-AML that received HMA therapy following induction/consolidation with fludarabine, cytarabine and G-CSF (FLAG) with low dose gemtuzumab or idarubicin (NCT00801489). Of the 23 patients evaluated, 17 had a detectable RTPCR at HMA initiation. Five patients had progressive disease and a notable increase in RTPCR values over 1 to 2 cycles of HMA therapy. Twelve patients did not fail HMA and had a median RTPCR at HMA initiation of 0.06 (range, 0.01-0.91). Unlike the HMA failure subset, 11 of these patients had a reduction in RTPCR after the first or second cycle of HMA. Our data suggests that CBF-AML patients with low levels of RTPCR (between 0.01 and 0.05) at the conclusion of induction/consolidation chemotherapy benefit most from maintenance HMA, particularly those that have a reduction in the RTPCR within the first 2 cycles of HMA therapy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T18:45:45.280492-05:
      DOI: 10.1002/ajh.24782
       
  • Estimates of total body iron indicate 19 mg and 38 mg oral iron are
           equivalent for the mitigation of iron deficiency in individuals
           experiencing repeated phlebotomy
    • Authors: Walter Bialkowski; Joseph E. Kiss, David J. Wright, Ritchard Cable, Rebecca Birch, Pam D'Andrea, Barbara J. Bryant, Bryan R. Spencer, Alan E. Mast
      Abstract: Iron deficiency anemia is a common clinical condition often treated with tablets containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side effects lowering patient compliance. Oral iron supplements also increase hepcidin production causing decreased fractional absorption of subsequent doses. Frequent blood donors often become iron deficient. Therefore, they were enrolled in a two-year study involving continued blood donations and randomization to receive no pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI) did not change for the subset of donors in the no pill and placebo groups who completed both enrollment and final visits (p=0.21 and p=0.28, respectively). However, repeated measures regression analysis on the complete dataset estimated a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (p=0.001). The effects of 19 and 38 mg iron supplementation on TBI were indistinguishable (p=0.54). TBI increased by 229 mg after the initial 60 days of iron supplementation (p
      PubDate: 2017-05-11T18:45:37.334668-05:
      DOI: 10.1002/ajh.24784
       
  • Correlates of resistance and relapse during blinatumomab therapy for
           relapsed/refractory acute lymphoblastic leukemia
    • Authors: Ibrahim Aldoss; Joo Song, Tracey Stiller, Tina Nguyen, Joycelynne Palmer, Margaret O'Donnell, Anthony S Stein, Guido Marcucci, Stephen Forman, Vinod Pullarkat
      Abstract: We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM-ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts>50%) (P=0.02), history of prior EM-ALL (P=0.005), and active EM-ALL at the time of initiating blinatumomab (P=0.05) predicted lower CR rate. Among refractory cases, 13 (41%) had evidence of EM-ALL progression, and CD19 expression was negative or dim in 18% and 23%, respectively. Among responders, 20 (61%) subsequently relapsed among whom EM-ALL relapse occurred in 8 (40%) patients, and CD19 expression was negative or dim in 35% and 6% of evaluable cases, respectively. Pre-treatment moderate/strong CD19 expression (P=0.01) and history of prior EM-ALL during ALL course (P=0.04) were risk factors for developing EM-ALL at progression/relapse. However, no pretreatment factors predicted progression/relapse with CD19-negative ALL. Overall-survival (OS) and even-free survival were improved for patients underwent allogeneic HCT compared to responders who did not. Furthermore, OS was superior for patients responded to blinatumomab compared to those who did not. Extramedullary and CD19-negative disease are common during blinatumomab failure in r/r ALL. In addition to high leukemia burden, concurrent or prior history EM-ALL were associated with lower response to blinatumomab. Higher CD19 expression as well as prior history of EM-ALL were associated with EM-ALL at the time of blinatumomab failure. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T18:45:30.512175-05:
      DOI: 10.1002/ajh.24783
       
  • Outcome of Elderly Patients after Failure to Hypomethylating Agents Given
           as Frontline Therapy for Acute Myeloid Leukemia (AML): Single Institution
           Experience
    • Authors: Rama Nanah; Kristen McCullough, William Hogan, Kebede Begna, Mrinal Patnaik, Michelle Elliott, Mark Litzow, Aref Al-Kali
      Abstract: Outcomes of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy is challenging. Hypomethylating agents (HMAs) can be effective in these patients but responses are usually short-lived. The majority of patients will either have stable disease or progress through therapy. We hereby describe the outcome of these patients at our institution after they fail HMAs. The data on 56 AML patients at Mayo Clinic, Rochester were reviewed. Patients were considered for our study if they received HMA as frontline therapy for their AML. Out of 56 patients, 15 (27%) patients received azacitidine (AZA) and 41 (73%) received decitabine. Complete remission was found in 10 (18%), with overall response of 28% and median response duration of 10 months. Thirteen (81%) out of 16 responders relapsed. Therefore 53 patients were included in the primary or secondary failure analysis with a median overall survival (OS) of two months after the date of failure. Out of 53 patients, 12 (23%) received subsequent treatments. None of the 12 patients who got first salvage therapy achieved remission. Five out of the 12 patients received second salvage therapy, 2 (40%) of which achieved CR. Median OS for patients who received subsequent salvage therapies was better than those who did not receive any subsequent therapy after failing HMA (9.5 vs 2 months, p = 0.0009). Outcome for patients who have primary or secondary failure is very poor. Our study provides important historical data for future novel therapies, which are sorely needed for these patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:18:46.445914-05:
      DOI: 10.1002/ajh.24780
       
  • Chronic lymphocytic leukemia in Brazil: A retrospective analysis of 1903
           cases
    • Authors: Matheus Vescovi Gonçalves; Celso Arrais Rodrigues, Irene Gyongyver Heidemarie Lorand Metze, Marcelo Pitombeira Lacerda, Alita Azevedo, Cintia Machado, Carlos Sérgio Chiattone, Sérgio Fortier, Leila Perobelli, Maura Rosane Valerio Ikoma, Nelma Clementino, Nelson Hamerschlak, Inara Lucia Arce, Vivia Machado Stehl, Larissa Veloso Mendes Ommati, Danielle Leão Cordeiro Farias, Fernando Barroso Duarte, Valeria Buccheri, Ana Paula Azambuja, Denise Ramos Almeida, Vera Lucia Piratininga Figueiredo, Mihoko Yamamoto,
      PubDate: 2017-05-05T06:14:05.836186-05:
      DOI: 10.1002/ajh.24779
       
  • Daratumumab Monotherapy Compared With Historical Control Data in Heavily
           Pretreated and Highly Refractory Patients With Multiple Myeloma: An
           Adjusted Treatment Comparison
    • Authors: Saad Z Usmani; Joris Diels, Tetsuro Ito, Maneesha Mehra, Imran Khan, Annette Lam
      Abstract: Daratumumab is a human CD38-directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison. Patient-level data were pooled from 2 daratumumab monotherapy studies (16 mg/kg; GEN501 and SIRIUS) and 2 independent US databases (IMS LifeLink and OPTUM), which reflect treatments used in real-world patients with MM who received ≥3 prior LOTs or were double refractory to a PI and an IMiD. Using a multivariate proportional hazards regression model, the relative treatment effect of daratumumab versus historical controls was estimated, adjusting for imbalances in characteristics between cohorts. Baseline characteristics that differed between patients treated with daratumumab (N=148) and historical control (N=658) were prior treatment with pomalidomide (55% vs 15%) or carfilzomib (41% vs 28%) and triple/quadruple refractory status (64% vs 14%). The adjusted overall survival–hazard ratio (OS-HR) for daratumumab versus historical control was 0.33 (95% confidence interval, 0.24-0.46) compared with 0.46 (0.35-0.59) for unadjusted HR. Impact of adjustment was mainly driven by refractory status and prior pomalidomide/carfilzomib exposure. This adjusted treatment comparison suggests that daratumumab demonstrates improved OS compared with historical control data in heavily pretreated and highly refractory MM patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:13:57.327007-05:
      DOI: 10.1002/ajh.24781
       
  • A novel in vivo model for studying conditional dual loss of BLIMP-1 and
           p53 in B-cells, leading to tumor transformation
    • Authors: Antonio Sacco; Yawara Kawano, Michele Moschetta, Oksana Zavidij, Daisy Huynh, Michaela Reagan, Yuji Mishima, Salomon Manier, Jihye Park, Elizabeth Morgan, Satoshi Takagi, Kwok K Wong, Ruben Carrasco, Irene M. Ghobrial, Aldo M. Roccaro
      Abstract: The tumor suppressors B-Lymphocyte-Induced Maturation Protein-1 (BLIMP-1) and p53 play a crucial role in B-cell lymphomas, and their inactivation contributes to the pathogenesis of a wide spectrum of lymphoid malignancies, including diffuse large B-cell lymphomas (DLBCLs). Patients with activated B-cell-like (ABC) DLBCL may present with loss of BLIMP-1, c-Myc over-expression, decreased p53, and poor prognosis. Nevertheless, there is a lack of in vivo models recapitulating the biology of high-grade ABC DLBCL. We therefore aimed to develop an in vivo model aiming to recapitulate the phenotype observed in this cohort of patients.A Cre-Lox approach was used to achieve inactivation of both p53 and BLIMP-1 in murine B-cells. Contextual ablation of BLIMP-1 and p53 led to development of IgM-positive B-cell lymphoma with an aggressive phenotype, supported by c-Myc up-regulation, and accumulation of somatic mutations, as demonstrated by whole exome sequencing. Sensitivity of B-tumor cells to BTK inhibition was demonstrated. This model mirrors what reported in patients with ABC DLBLC, and therefore represents a novel model for studying the biology of ABC-DLBCL harboring the dual loss of BLIMP-1/p53 and c-Myc over-expression. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:07:33.690921-05:
      DOI: 10.1002/ajh.24778
       
  • Acquired hemophilia A: Updated review of evidence and treatment guidance
    • Authors: Rebecca Kruse-Jarres; Christine L. Kempton, Francesco Baudo, Peter W. Collins, Paul Knoebl, Cindy A. Leissinger, Andreas Tiede, Craig M. Kessler
      Abstract: Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies (inhibitors) against endogenous factor VIII (FVIII) that leads to bleeding, which is often spontaneous and severe. AHA tends to occur in elderly patients with comorbidities and is associated with high mortality risk from underlying comorbidities, bleeding, or treatment complications. Treatment, which consists of hemostatic management and eradication of the inhibitors, can be challenging to manage.Few data are available to guide the management of AHA-related bleeding and eradication of the disease-causing antibodies. An extensive literature review was conducted with the aim to build on and complement already existing guidelines since the emergence of a newly approved hemostatic agent for this condition.An international panel of 8 experts in AHA was convened in 2015. A comprehensive literature search of PubMed and Embase was conducted; duplicate records and single-patient case studies were removed; and outputs were evaluated by at least 2 reviewers. Key questions were identified and analyzed; evidence was weighted; and consensus was formed. The resulting guidance for the management of AHA, presented here, was endorsed by the Hemostasis and Thrombosis Research Society of North America.AHA is rarely encountered by most physicians, and is likely to be underdiagnosed and misdiagnosed in real-world clinical practice. Data for AHA are limited and mainly restricted to registries, case reports, and clinical expertise. Recommendations for the management of AHA are summarized here based on the available data, integrated with the clinical experience of panel participants. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-03T18:20:57.713249-05:
      DOI: 10.1002/ajh.24777
       
  • Global hypomethylation is an independent prognostic factor in diffuse
           large B cell lymphoma
    • Authors: Eileen Wedge; Jakob Werner Hansen, Christian Garde, Fazila Asmar, Dorte Tholstrup, Søren Sommer Kristensen, Helga D. Munch-Petersen, Elisabeth Ralfkiaer, Peter Brown, Kirsten Grønbæk, Lasse Sommer Kristensen
      Abstract: Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure for global methylation, was measured in DNA from 67 tumor biopsies. Additionally, cell-free circulating DNA (cfDNA) in plasma samples from 74 patients was tested to assess the feasibility of global hypomethylation as a biomarker in liquid biopsies. LINE1 methylation was assessed using a commercially available kit, based on pyrosequencing of PCR amplified bisulfite-treated DNA. Global hypomethylation was detected in a subset of cases and was associated with poor overall survival in both tumor biopsies (P=0.001) and cfDNA (P=0.009). It was the strongest risk factor in multivariate analysis in both biopsies (HR: 10.65, CI: 2.03-55.81, P=0.005) and cfDNA (HR: 11.87, CI: 2.80-50.20, P=0.001), outperforming conventional clinical risk factors. Finally, hierarchical cluster analyses were performed for the cfDNA samples using previously published gene-specific methylation data. This analysis shows that global hypomethylation co-occurs with other epigenetic abnormalities, including DAPK1 promoter hypermethylation. In conclusion, we have shown that global hypomethylation is strongly associated with poor survival in DLBCL both when present in tumor biopsy DNA and when detected in plasma cfDNA, and has potential for clinical application as a prognostic biomarker. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-03T08:55:25.703539-05:
      DOI: 10.1002/ajh.24751
       
  • The BCR-ABL1 transcript type influences response and outcome in
           Philadelphia chromosome-positive chronic myeloid leukemia patients treated
           frontline with imatinib
    • Authors: Fausto Castagnetti; Gabriele Gugliotta, Massimo Breccia, Alessandra Iurlo, Luciano Levato, Francesco Albano, Paolo Vigneri, Elisabetta Abruzzese, Giuseppe Rossi, Serena Rupoli, Francesco Cavazzini, Bruno Martino, Ester Orlandi, Patrizia Pregno, Mario Annunziata, Emilio Usala, Mario Tiribelli, Simona Sica, Massimiliano Bonifacio, Carmen Fava, Filippo Gherlinzoni, Monica Bocchia, Simona Soverini, Maria Teresa Bochicchio, Michele Cavo, Giovanni Martinelli, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Gianantonio Rosti,
      Abstract: The most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed. A qualitative PCR was performed at baseline: 52% patients had a e14a2 transcript, 37% a e13a2 transcript, 11% co-expressed both transcripts and 1% had other rare transcripts. The median follow-up was 76 months (95% of the patients had at least a 5-year observation). The complete cytogenetic response rates were comparable in e14a2 and e13a2 patients. The median time to MR3.0 (6 and 12 months) and MR4.0 (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR3.0 (88% and 83%, p
      PubDate: 2017-05-02T19:15:34.068537-05:
      DOI: 10.1002/ajh.24774
       
  • Adrenal insufficiency: An emerging challenge in thalassemia'
    • Authors: Marina Baldini; Marta Mancarella, Elena Cassinerio, Alessia Marcon, Alberto Giacinto Ambrogio, Irene Motta
      PubDate: 2017-05-02T09:00:37.60848-05:0
      DOI: 10.1002/ajh.24726
       
  • Validation of the 2016 Revisions to the WHO Classification in Lower-Risk
           Myelodysplastic Syndrome
    • Authors: Rashmi Kanagal-Shamanna; Juliana E. Hidalgo Lopez, Denái R. Milton, Hye Ryoun Kim, Chong Zhao, Zhuang Zuo, Michelle Janania Martinez, Francesco Stingo, John Lee, Rajyalakshmi Luthra, Elias J. Jabbour, Guillermo Garcia-Manero, L. Jeffrey Medeiros, Carlos E. Bueso-Ramos
      PubDate: 2017-04-29T10:24:27.890231-05:
      DOI: 10.1002/ajh.24776
       
  • A life-threatening ruxolitinib discontinuation syndrome
    • Authors: Giacomo Coltro; Francesco Mannelli, Paola Guglielmelli, Annalisa Pacilli, Alberto Bosi, Alessandro Maria Vannucchi
      PubDate: 2017-04-29T10:24:23.269551-05:
      DOI: 10.1002/ajh.24775
       
  • Haploidentical bone marrow transplantation in patients with advanced
           myelodysplastic syndrome
    • Authors: Varaldo Riccardo; Raiola Anna Maria, Di Grazia Carmen, Aquino Sara, Beltrami Germana, Bregante Stefania, Cruciani Fabio, Dominietto Alida, Ghiso Anna, Giannoni Livia, Gualandi Francesca, Ibatici Adalberto, Lamparelli Teresa, Marani Carlo, Van Lint Maria Teresa, Valeria Santini, Bacigalupo Andrea, Angelucci Emanuele
      PubDate: 2017-04-29T03:30:20.049524-05:
      DOI: 10.1002/ajh.24725
       
  • A comment on improving transcranial Doppler ultrasonography screening in
           children with sickle cell anemia
    • Authors: Margaret O. Lewen; Patricia L. Kavanagh, Amy E. Sobota
      PubDate: 2017-04-29T03:30:18.409467-05:
      DOI: 10.1002/ajh.24727
       
  • Clinical Outcomes in a Cohort of Patients with Heparin-induced
           Thrombocytopenia
    • Authors: David J. Kuter; Barbara A. Konkle, Taye H. Hamza, Lynne Uhl, Susan F. Assmann, Joseph E. Kiss, Richard M. Kaufman, Nigel S. Key, Bruce S. Sachais, John R. Hess, Paul Ness, Keith R. McCrae, Cindy Leissinger, Ronald G. Strauss, Janice G. McFarland, Ellis Neufeld, James B. Bussel, Thomas L. Ortel
      Abstract: BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder usually prompting treatment with non-heparin anticoagulants. The benefits and risks of such treatments have not been fully assessed.METHODS: We analyzed data for 442 patients having a positive heparin-platelet factor 4 antibody test and recent heparin exposure. The primary outcome was a composite endpoint (death, limb amputation/gangrene, or new thrombosis). Secondary outcomes included bleeding and the effect of anticoagulation.FINDINGS: Seventy-one patients (16%) had HIT with thrombosis (HIT-T); 284 (64%) had HIT without thrombosis (isolated HIT); 87 (20%) did not have HIT. An intermediate or high “4T” score was found in 85%, 58%, and 8% of the three respective groups. Non-heparin anticoagulation was begun in 80%, 56% and 45%. The composite endpoint occurred in 48%, 36% and 17% (P=0.01) of which 61%, 38% and 40% were receiving non-heparin anticoagulation. Compared with the no HIT group, the composite endpoint was significantly more likely in HIT-T [HR 2.48 (1.35-4.55), P=0.003)] and marginally more likely in isolated HIT [HR 1.66 (0.96-2.85), P=0.071]. Importantly, risk increased (HR 1.77, P=0.02) after platelet transfusion. Major bleeding occurred in 48%, 36%, and 16% of the three groups (P=0.005). Non-heparin anticoagulation was not associated with a reduction in composite endpoint events in either HIT group.INTERPRETATION: HIT patients have high risks of death, limb amputation/gangrene, thrombosis, and bleeding. Non-heparin anticoagulant treatment may not benefit all patients and should be considered only after careful assessment of the relative risks of thrombosis and bleeding in individual patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-26T01:11:02.38029-05:0
      DOI: 10.1002/ajh.24759
       
  • Real-world results of ibrutinib in relapsed/refractory CLL in France:
           Early results on a large series of 428 patients
    • Authors: Loic Ysebaert; Thérèse Aurran-Schleinitz, Caroline Dartigeas, Marie-Sarah Dilhuydy, Pierre Feugier, Anne-Sophie Michallet, Olivier Tournilhac, Jehan Dupuis, Pierre Sinet, Claire Albrecht, Florence Cymbalista
      PubDate: 2017-04-25T03:51:30.806815-05:
      DOI: 10.1002/ajh.24773
       
  • ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic
           cell transplantation for acute myeloid leukemia - a report from the acute
           leukemia working party of the EBMT
    • Authors: Jonathan Canaani; Bipin N Savani, Myriam Labopin, Mauricette Michallet, Charles Craddock, Gerard Socié, Lisa Volin, Johan A Maertens, Charles Crawley, Didier Blaise, Per T Ljungman, Jan Cornelissen, Nigel Russell, Frédéric Baron, Norbert Gorin, Jordi Esteve, Fabio Ciceri, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
      Abstract: ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P=0.32], and non-relapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P=0.2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P=0.35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P=0.87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching [Hazard ratio (HR) of 0.7, 95% CI, 0.5-1; P = 0.049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T03:51:08.59011-05:0
      DOI: 10.1002/ajh.24771
       
  • Botryoid nuclei resulting from cocaine abuse
    • Authors: Maurizio Fumi; Ylenia Pancione, Silvia Sale, Vincenzo Rocco, Barbara J. Bain
      PubDate: 2017-04-25T03:50:53.475352-05:
      DOI: 10.1002/ajh.24769
       
  • Feasibility Trial for Primary Stroke Prevention in Children with Sickle
           Cell Anemia in Nigeria (SPIN Trial)
    • Authors: Najibah Galadanci; Shehu Umar Abdullahi, Leah D. Vance, Abdulkadir Musa Tabari, Shehi Ali, Raymond Belonwu, Auwal Salihu, Aisha Amal Galadanci, Binta Wudil Jibir, Halima Bello-Manga, Kathleen Neville, Fenella J. Kirkham, Yu Shyr, Sharon Phillips, Brittany V. Covert, Adetola A. Kassim, Lori C. Jordan, Muktar H. Aliyu, Michael R. DeBaun
      Abstract: The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥ 200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements 
      PubDate: 2017-04-25T03:50:29.092133-05:
      DOI: 10.1002/ajh.24770
       
  • The utility of MASS-FIX to detect and monitor monoclonal proteins in the
           clinic
    • Authors: Paolo Milani; David L. Murray, David R. Barnidge, Mindy C. Kohlhagen, John R. Mills, Giampaolo Merlini, Surendra Dasari, Angela Dispenzieri
      Abstract: The detection and quantification of monoclonal-proteins (M-proteins) are necessary for the diagnosis and evaluation of response in plasma cell dyscrasias. Immunoglobulin enrichment-coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MASS-FIX) is a simple and inexpensive method to identify M-proteins, but its clinical generalizability has not yet been elucidated. We compared MASS-FIX to protein electrophoresis (PEL), serum/urine immunofixation-electrophoresis (IFE) and quantitative serum free-light chain (FLC) for the identification of M-proteins in different clinical diagnoses. Paired serum and urine samples from 257 patients were tested. There were six patients for whom s-IFE and FLC ratio were positive and serum MASS-FIX was negative, but when serum and urine MASS-FIX results were combined, only one patient with light chain-MGUS was missed. Serum/urine-MASS-FIX detected M-proteins in 18 patients with negative serum/urine-PEL/IFE and serum-FLC, 10 of whom had multiple myeloma or AL amyloidosis, who were mistakenly thought to have complete hematologic response by serum/urine-PEL/IFE and serum-FLC. Nearly half of the AL amyloidosis patients had atypical spectra, which may prove to be a clue to the diagnosis and pathogenesis of the disease. In conclusion, MASS-FIX has a comparable sensitivity with PEL/IFE/FLC methods and can help inform the clinical diagnosis. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T03:50:13.45982-05:0
      DOI: 10.1002/ajh.24772
       
  • High prevalence of monoclonal gammopathy among patients with warm
           autoimmune hemolytic anemia
    • Authors: Aishwarya Ravindran; Janani Sankaran, Eapen K. Jacob, Justin D. Kreuter, C. Christopher Hook, Morie A. Gertz, Timothy G. Call, Rajiv K. Pruthi, Mark R. Litzow, Alexandra P. Wolanskyj, William J. Hogan, Aneel A. Ashrani, Kebede H. Begna, Ariela L. Marshall, Robert A. Kyle, Neil E. Kay, Ronald S. Go
      PubDate: 2017-04-24T18:15:57.947054-05:
      DOI: 10.1002/ajh.24765
       
  • Clinical Significance of IgE in a Large Cohort of Patients with Moderate
           or Severe Chronic Graft-versus-Host Disease
    • Authors: Sencer Goklemez; Filip Pirsl, Lauren M. Curtis, Seth M. Steinberg, Edward W. Cowen, Jacqueline W. Mays, Meg Kenyon, Judy Baruffaldi, Fran T. Hakim, Steven Z. Pavletic
      PubDate: 2017-04-24T18:15:56.853007-05:
      DOI: 10.1002/ajh.24768
       
  • Early Mortality and Overall Survival of Acute Myeloid Leukemia Based on
           Facility Type
    • Authors: Vijaya R. Bhatt; Valerie Shostrom, Smith Giri, Krishna Gundabolu, K.M. Monirul Islam, Frederick R. Appelbaum, Lori J. Maness
      Abstract: Cancer health disparities may exist based on the facility type. We aimed to determine the association between the academic status of centers and outcomes of patients with acute myeloid leukemia (AML). Using the National Cancer Data Base, we compared one-month mortality and longer-term overall survival (OS) of 60,738 patients with AML, who received first course treatment between 2003-2011 at academic or non-academic centers (community cancer program, comprehensive community cancer program, and others). Multivariate analysis was done using logistic regression for one-month mortality and Cox regression with backward elimination approach for OS. Patients treated at academic centers differed from those at non-academic centers in that they were younger with a median age of 62 versus 70 years (p
      PubDate: 2017-04-24T18:15:54.775481-05:
      DOI: 10.1002/ajh.24767
       
  • The impact of sample site and storage on thromboelastography values
    • Authors: Mari Tuovila; Tiina Erkinaro, Eeva-Riitta Savolainen, Paivi Laurila, Pasi Ohtonen, Tero Ala-Kokko
      PubDate: 2017-04-24T18:15:52.356242-05:
      DOI: 10.1002/ajh.24766
       
  • Heterogeneity of neutrophil spontaneous death
    • Authors: Yan Teng; Hongbo R Luo, Hiroto Kambara
      PubDate: 2017-04-24T18:15:51.635813-05:
      DOI: 10.1002/ajh.24764
       
  • Mitotic figure in the peripheral blood smear
    • Authors: Sebastian Hörber; Ingo Rettig, Andreas Peter
      Abstract: A previously healthy 19-year-old man presented with fever, sore throat and strong feeling of illness. Physical examination showed strong swelling of throat tonsils and moderate hepatosplenomegaly. The laboratory values were as following: a total white blood count of 10.9 x 109/L, hemoglobin 14.1 g/dL and a platelet count of 109 x 109/L. Total bilirubin was 1.4 mg/dL and CRP was 1.32 mg/dL. The serological analyses revealed IgG and IgM antibodies against EBV-VCA consistent with an acute Epstein-Barr virus infection. The peripheral blood smear revealed 80.0% lymphocytes, 12.4% neutrophils, 6.9% monocytes, 0.4% eosinophils and 0.3% basophils. In it a mitotic figure was found (see illustration). Mitotic figures are an extremely uncommon finding as they are usually seen in patients with acute leukemia or rarer in EBV infections. Symptomatic therapy led to complete resolution of the symptoms. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-12T12:15:38.164844-05:
      DOI: 10.1002/ajh.24761
       
  • CD105 expression in early erythroid precursors
    • Authors: José Antonio García-Vela; Isaac Martin Rubio, Juan Marquet, Miguel Angel Alvarez Juarez
      PubDate: 2017-04-12T12:15:34.44241-05:0
      DOI: 10.1002/ajh.24763
       
  • Akt inhibitor MK-2206 in combination with Bendamustine and Rituximab in
           Relapsed or Refractory Chronic Lymphocytic Leukemia: Results from the
           N1087 Alliance Study
    • Authors: Jeremy T. Larsen; Tait D. Shanafelt, Jose F. Leis, Betsy LaPlant, Tim Call, Adam Pettinger, Curtis Hanson, Charles Erlichman, Thomas Matthew Habermann, Craig Reeder, Daniel Nikcevich, Deborah Bowen, Michael Conte, Justin Boysen, Charla Secreto, Connie Lesnick, Renee Tschumper, Diane Jelinek, Neil E. Kay, Wei Ding
      Abstract: Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single-agent MK-2206 (weekly dosed) was administered one-week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2-6. Phase II employed the MTD of MK-2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6-cycle of therapy. The maximum tolerated dose of MK-2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-12T10:37:23.271765-05:
      DOI: 10.1002/ajh.24762
       
  • A Somatic Mosaicism in the G6PD Gene Inducing a Late Onset Chronic non
           Spherocytic Hemolytic Anemia
    • Authors: Lucile Couronné; Gérard Tertian, Audrey Boutron, Véronique Picard, Patricia Hughes, Olivier Hermine, Claude Préhu, Gil Tchernia, Loïc Garçon
      PubDate: 2017-04-10T11:32:23.924921-05:
      DOI: 10.1002/ajh.24760
       
  • Associations between Elevated Pre-treatment Serum Cytokines and Peripheral
           Blood Cellular Markers of Immunosuppression in Patients with Lymphoma
    • Authors: Moritz Binder; Megan M. O'Byrne, Matthew J. Maurer, Stephen Ansell, Andrew L. Feldman, James Cerhan, Anne Novak, Luis Francisco Porrata, Svetomir Markovic, Brian K. Link, Thomas E. Witzig
      Abstract: Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n=390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r=-0.36), IL-12 (r=-0.17), IP-10 (r=-0.23), and MIG (r=-0.32) concentrations (p
      PubDate: 2017-04-06T05:40:23.785406-05:
      DOI: 10.1002/ajh.24758
       
  • Chronic lymphocytic leukemia (CLL) and prognostic models: A bridge between
           clinical and biological markers
    • Authors: Gianluigi Reda; Ramona Cassin, Bruno Fattizzo, Diana Giannarelli, Veronica Mattiello, Wilma Barcellini, Agostino Cortelezzi
      PubDate: 2017-04-06T05:35:31.651583-05:
      DOI: 10.1002/ajh.24755
       
  • IgM Myeloma: A Multicenter Retrospective Study of 134 Patients
    • Authors: Jorge J. Castillo; Artur Jurczyszyn, Lucie Brozova, Edvan Crusoe, Jacek Czepiel, Julio Davila, Angela Dispenzieri, Marion Eveillard, Mark A. Fiala, Irene M. Ghobrial, Alessandro Gozzetti, Joshua N. Gustine, Roman Hajek, Vania Hungria, Jiri Jarkovsky, David Jayabalan, Jacob P. Laubach, Barbara Lewicka, Vladimir Maisnar, Elisabet E. Manasanch, Philippe Moreau, Elizabeth A. Morgan, Hareth Nahi, Ruben Niesvizky, Claudia Paba-Prada, Tomas Pika, Ludek Pour, John L. Reagan, Paul G. Richardson, Jatin Shah, Ivan Spicka, Ravi Vij, Anna Waszczuk-Gajda, Morie A. Gertz
      Abstract: IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37%, 43%, 19% and 70%, respectively. The median serum IgM level was 2,895 mg/dl with 19% of patients presenting with levels >6,000 mg/dl. International Staging System (ISS) stages 1, 2 and 3 were seen in 40 (33%), 54 (44%) and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (p=0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-06T05:35:27.756816-05:
      DOI: 10.1002/ajh.24753
       
  • Clinical characteristics and prognostic factors in multiple myeloma
           patients with light chain deposition disease
    • Authors: Meera Mohan; Amy Buros, Pankaj Mathur, Neriman Gokden, Manisha Singh, Sandra Susanibar, Jorge Jo Kamimoto, Shadiqul Hoque, Muthukumar Radhakrishnan, Aasiya Matin, Cynthia Davis, Monica Grazziutti, Sharmilan Thanendrarajan, Frits van Rhee, Maurizio Zangari, Faith Davies, Gareth Morgan, Joshua Epstein, Bart Barlogie, Carolina Schinke
      Abstract: Light chain deposition disease (LCDD) is characterized by monotypic immunoglobulin depositions which will eventually lead to loss of organ function if left untreated. While the kidney is almost always affected, the presence and degree of LCDD in other organs vary. Ten to 30% of LCDD patients have underlying Multiple Myeloma (MM), yet outcome and prognostic markers in this particular patient group are still lacking. Here, we analyzed 69 patients with MM and biopsy proven LCDD and report on renal and extra-renal involvement and its impact on prognosis as well as renal response depending on hematologic response. Coexisting light chain diseases such as AL amyloid and cast nephropathy were found in 30% of patients; those with LCDD and concurrent amyloid tended to have shorter survival. Cardiac involvement by LCDD was seen in one-third of our patients and was associated with shorter overall survival; such patients also had a significantly higher risk of treatment related mortality (TRM) after stem cell transplant (SCT) compared to LCDD patients without cardiac involvement. This study highlights that MM patients with LCDD present with different clinical features compared to previously reported LCDD cohorts. Rapid initiation of treatment is necessary to prevent progressive renal disease and worse outcome. Coexisting light chain diseases and cardiac involvement are more common than previously reported and confer worse clinical outcome, emphasizing the need for careful patient careful patient evaluation and treatment selection. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-06T05:35:13.223541-05:
      DOI: 10.1002/ajh.24756
       
  • Monosomal karyotype in chronic lymphocytic leukemia: association with
           clinical and biological features and potential prognostic significance
    • Authors: Maria Joao Baptista; Isabel Granada, Mireia Morgades, María-José Calasanz, Jordi Canals, Diego Robles De Castro, Elisa Luño, Neus Ruiz-Xivillé, Inés Rodríguez-Hernández, Teresa González, María-José Terol, Alberto Valiente, Francisco Ortuño, María-Dolores Garcia-Malo, María-Ángeles Piñan, Ana Carla Oliveira, Maria Talavera, Ismael Buño, Ana Batlle-López, Carol Moreno, Christelle Ferra, Francesc Solé
      PubDate: 2017-04-06T05:35:03.476211-05:
      DOI: 10.1002/ajh.24754
       
  • "Anemia is present years before myelodysplastic syndrome diagnosis –
           results from the pre-diagnostic period"
    • Authors: Jakob Werner Hansen; Håkon Sandholdt, Volkert Siersma, Andreas Due Ørskov, Staffan Holmberg, Ole Weis Bjerrum, Hans Carl Hasselbalch, Niels F Olivarius, Kirsten Groenbaek, Christen Andersen
      PubDate: 2017-04-06T05:34:43.05235-05:0
      DOI: 10.1002/ajh.24757
       
  • The Association of Histologic Grade with Acute Graft-versus-Host Disease
           Response and Outcomes
    • Authors: Mayur Narkhede; Lisa Rybicki, Donna Abounader CCRP, Brian Bolwell, Robert Dean, Aaron T. Gerds, Rabi Hanna, Brian Hill, Deepa Jagadeesh, Matt Kalaycio, Hien D Liu, Brad Pohlman, Ronald Sobecks, Navneet S Majhail, Betty Ky Hamilton
      Abstract: Consensus criteria are routinely used to clinically grade acute graft-versus-host disease (GVHD). A histologic grading system for acute GVHD is available, but there are limited data on its correlation with clinical grade and hematopoietic cell transplantation (HCT) outcomes. Among 503 patients who underwent allogeneic HCT from 2005-2013, we identified 300 biopsy episodes of the skin and gastrointestinal (GI) tract in 231 patients. Histologic grade was correlated with clinical grade of GVHD, day 28 treatment response, and outcome. Both skin (R=0.32) and GI (R=0.61) histologic grade correlated with clinical grade (p
      PubDate: 2017-04-04T18:05:48.240779-05:
      DOI: 10.1002/ajh.24749
       
  • The 2016 WHO diagnostic criteria for polycythemia vera renders an accurate
           diagnosis to a broader range of patients including masked polycythemia
           vera: comparison with the 2008 WHO diagnostic criteria
    • Authors: Kyohei Misawa; Hajime Yasuda, Marito Araki, Tomonori Ochiai, Soji Morishita, Mai Nudejima, Yumi Hironaka, Shuichi Shirane, Yoko Edahiro, Akihiko Gotoh, Akimichi Ohsaka, Norio Komatsu
      PubDate: 2017-04-04T18:05:43.919383-05:
      DOI: 10.1002/ajh.24752
       
  • A multicenter prospective study on efficacy and safety of imatinib
           generics; a report from Polish Adult Leukemia Group imatinib generics
           registry
    • Authors: T. Sacha; J. Góra-Tybor, M. Szarejko, G. Bober, O. Grzybowska-Izydorczyk, J. Niesiobędzka-Krężel, M. Dudziński, E. Wasilewska, K. Myśliwiec, J. Gil, M. Gniot, I. Pietkun, E. Mędraś, J. Hołojda, J. Wącław, K. Giannopoulos
      Abstract: The efficacy and safety of imatinib generics were not studied and reported on larger cohort of patients yet. We report on efficacy and safety of imatinib generics in 726 chronic myeloid leukemia patients in chronic phase who completed one-year observation, prospectively assessed within Polish Adult Leukemia Group imatinib generics registry. In 99 previously untreated patients the rate of early molecular response achieved at 3 months and major molecular response achieved at 12 months was 65.7% and 53.4% respectively. Complete cytogenetic response at 6 months was achieved in 55.4% of patients. In 627 patients switched from branded to generic imatinib the molecular response was sustained in 64.8%, worsened in 15% and improved in 19% of them. Complete cytogenetic response, major molecular response and MR4,5 were lost in 0.3%, 1.3% and 10.3%, respectively. Hematologic toxicity (grade 3 or 4) and non-hematologic toxicity (any grade) occurred in 3% and 40% of 99 previously untreated patients and in 0.2% and 14.4% of "switched" patients, respectively. In one-year observation the efficacy and safety of tested imatinib generics are not inferior to branded imatinib. No increased switching rate from first to second generation tyrosine kinase inhibitors was noticed This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-04T18:05:40.870471-05:
      DOI: 10.1002/ajh.24748
       
  • An exploratory clinical trial of bortezomib in patients with lower risk
           myelodysplastic syndromes
    • Authors: May Daher; Juliana Elisa Hidalgo Lopez, Jasleen K. Randhawa, Kausar Jabeen Jabbar, Yue Wei, Naveen Pemmaraju, Gautam Borthakur, Tapan Kadia, Marina Konopleva, Hagop M. Kantarjian, Katherine Hearn, Zeev Estrov, Steven Reyes, Carlos E. Bueso-Ramos, Guillermo Garcia-Manero
      Abstract: Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis and an increased risk of transformation. Few effective therapies are available for lower risk MDS patients, especially after the failure of hypomethylating agents. MDS progenitor cells are dependent on the nuclear factor-κB (NF-κB) for survival, which makes it an attractive therapeutic target. As a proteosomal inhibitor, bortezomib is thought to have inhibitory activity against NF-κB. We designed a proof-of-principle study of subcutaneous (SC) bortezomib in lower risk MDS patients with evidence of NF-κB activation in their bone marrow. Fifteen patients were treated, their median age was 71 (range 56-87), 33% were low and 67% int-1 by IPSS, median number of prior therapies was 2, all patients were transfusion dependent. Baseline median pp65 percentage was 31% and 11 patients had evidence of ring sideroblasts. SC bortezomib was safe, well tolerated with no excess toxicity. Three patients out of the 15 (20%) had evidence of response with hematologic improvement (HI-E). Bortezomib caused a decrease in pp65 levels in 7 out of 13 evaluable patients (54%, p=0.025). Of interest, unexpectedly, we observed a significant decrease in ring sideroblasts in 7 out of 10 (70%) evaluable patients during treatment. In conclusion, this study suggests that NF-κB activation, measured by pp65 levels, may be a useful biomarker in MDS. Bortezomib is safe in this patient population but has modest clinical activity. The role of the proteasome in the genesis of ring sideroblasts needs further study. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-31T18:20:35.062261-05:
      DOI: 10.1002/ajh.24746
       
  • A puzzling case of methemoglobinemia
    • Authors: Audrey Morris; Barbara J. Bain, Maria Atta, D. Mark Layton
      PubDate: 2017-03-31T18:10:27.877779-05:
      DOI: 10.1002/ajh.24747
       
  • Clinical Presentation and Outcomes of Patients with Type 1 Monoclonal
           Cryoglobulinemia
    • Authors: Surbhi Sidana; S. Vincent Rajkumar, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, David Dingli, Prashant Kapoor, Wilson I. Gonsalves, Ronald S. Go, Yi Lisa Hwa, Nelson Leung, Amie L. Fonder, Miriam A. Hobbs, Steven R. Zeldenrust, Stephen J. Russell, John A. Lust, Robert A. Kyle, Shaji K. Kumar
      Abstract: We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n=43, 42%) and ulcers/gangrene (n=35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n=24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS – 39, myeloma – 20, lymphoplasmacytic lymphoma – 21 and others – 14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia-related symptoms in 57. Treatment regimens consisted of: steroids +/- alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab +/- steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n=47) or stabilization (n=16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one-half. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-29T12:19:13.806616-05:
      DOI: 10.1002/ajh.24745
       
  • A Phase 1 Study of AMG 900, an Orally Administered Pan-Aurora Kinase
           Inhibitor, in Adult Patients With Acute Myeloid Leukemia
    • Authors: Hagop M. Kantarjian; Michael W. Schuster, Nitin Jain, Anjali Advani, Elias Jabbour, Erick Gamelin, Erik Rasmussen, Gloria Juan, Abraham Anderson, Vincent F. Chow, Greg Friberg, Florian D. Vogl, Mikkael A. Sekeres
      Abstract: Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small-molecule inhibitor of both Aurora kinase A and B, in patients with AML. Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every-2-week dose-escalation schedules using a modified 3 + 3+3 design were used: AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule). Thirty-five patients were enrolled at 9 different dose levels: 22 patients on the 4/10 schedule (doses from 15 to 100 mg daily), and 13 patients on the 7/7 schedule (doses from 30 to 50 mg daily). Both schedules were tolerated; nausea (31%), diarrhea (29%), febrile neutropenia (29%), and fatigue (23%) were the most common treatment-related adverse events. Three patients (9%) achieved complete response with incomplete count recovery. Patients with higher baseline expression of a set of specific pathway-related genes (BIRC5, AURKA, TTK, CDC2, and CCNB1) were more likely to respond in an exploratory biomarker analysis. AMG 900 was tolerated in a general AML population, and pathway-specific biomarkers identified a potential target population. Future research efforts will be directed toward further exploration of biomarkers of response and combination of AMG 900 with other anticancer agents. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:50:41.602061-05:
      DOI: 10.1002/ajh.24736
       
  • NPM1 mutation but not RUNX1 mutation or multilineage dysplasia defines a
           prognostic subgroup within de novo acute myeloid leukemia lacking
           recurrent cytogenetic abnormalities in the revised 2016 WHO Classification
           
    • Authors: Olga K. Weinberg; Christopher J. Gibson, Traci M. Blonquist, Donna Neuberg, Olga Pozdnyakova, Frank Kuo, Benjamin L. Ebert, Robert P. Hasserjian
      PubDate: 2017-03-28T10:50:38.067097-05:
      DOI: 10.1002/ajh.24739
       
  • Secondary CNS Involvement of ALK-Negative Anaplastic Large Cell Lymphoma
    • Authors: Ajay Major; Zenggang Pan, Manali Kamdar
      PubDate: 2017-03-28T10:50:34.806914-05:
      DOI: 10.1002/ajh.24733
       
  • Long term impact of hyperleukocytosis in newly diagnosed acute myeloid
           leukemia patients undergoing allogeneic stem cell transplantation: an
           analysis from the acute leukemia working party of the EBMT
    • Authors: Jonathan Canaani; Myriam Labopin, Gerard Socié, Anne Nihtinen, Anne Huynh, Jan Cornelissen, Eric Deconinck, Tobias Gedde-Dahl, Edouard Forcade, Patrice Chevallier, Jean Henri Bourhis, Didier Blaise, Mohamad Mohty, Arnon Nagler
      Abstract: Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the EBMT. A cohort of 357 patients with hyperleukocytosis (159 patients with WBC 50K-100K, 198 patients with WBC≥100K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14 - 2.12; p=0.004), decreased leukemia-free survival (HR of 1.38, 95% CI, 1.07 - 1.78; p=0.013), and inferior overall survival (HR of 1.4, 95% CI, 1.07 - 1.84; p=0.013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:50:33.397973-05:
      DOI: 10.1002/ajh.24737
       
  • Independent Adjudicator Assessments of Platelet Refractoriness and rFVIIa
           Efficacy in Bleeding Episodes and Surgeries from the Multinational
           Glanzmann's Thrombasthenia Registry
    • Authors: Michael Recht; Madhvi Rajpurkar, Meera Chitlur, Roseline d'Oiron, Rainer Zotz, Giovanni Di Minno, David L. Cooper, Man-Chiu Poon
      Abstract: Glanzmann's thrombasthenia (GT) is a rare congenital bleeding disorder associated with decreased platelet aggregation due to qualitative/quantitative deficiencies of the fibrinogen receptor. Severe bleeding episodes and perioperative bleeding are typically managed with platelet transfusions, although patients can develop anti-platelet antibodies or experience clinical refractoriness. The GT Registry (GTR) was established to collect efficacy/safety data on hemostatic treatments for GT, including recombinant factor VIIa (rFVIIa). At the request of the United States Food and Drug Administration, three hematology experts evaluated platelet refractoriness, antibody status, and rFVIIa efficacy data on a case-by-case basis to support a potential indication for rFVIIa in GT. Adjudication included 195 patients with 810 events (619 severe bleeding episodes, 192 surgeries), and a consensus algorithm was developed to describe adjudicators' coding of refractoriness and antibody status based on treatment patterns over time. Most rFVIIa-treated events were in patients without refractoriness or antibodies. Adjudicators rated most rFVIIa-treated bleeding episodes as successful (251/266, 94.4%; rFVIIa only, 101/109, 92.7%; rFVIIa ± platelets ± other agents, 150/157, 95.5%); efficacy was consistent in patients with platelet refractoriness ± antibodies (75/79, 94.9%), antibodies only (10/10, 100.0%), and neither/unknown (166/177, 93.8%). Adjudicators also rated most rFVIIa-treated surgeries as successful (159/160, 99.4%; rFVIIa only, 65/66, 98.5%; rFVIIa ± platelets ± other agents, 94/94, 100.0%); efficacy was consistent in patients with platelet refractoriness ± antibodies (69/70, 98.6%), antibodies only (24/24, 100.0%), and neither/unknown (66/66, 100.0%). Unblinding the adjudicators to investigator efficacy ratings changed few assessments. Doses of rFVIIa were narrowly distributed, regardless of other hemostatic agents used. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:50:30.411683-05:
      DOI: 10.1002/ajh.24741
       
  • Monocytosis in Polycythemia Vera: Clinical and Molecular Correlates
    • Authors: Daniela Barraco; Sonia Cerquozzi, Naseema Gangat, Mrinal M Patnaik, Terra Lasho, Christy Finke, Curtis A Hanson, Rhett P Ketterling, Animesh Pardanani, Ayalew Tefferi
      Abstract: Monocytosis (absolute monocyte count, AMC ≥1 x 109/L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)-defined PV, 55 (21%) patients displayed an AMC of ≥1 x 109/L and 18 (7%) an AMC of ≥1.5 x 109/L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs 50% at AMC ≥1 x 109/L) and TET2/SRSF2 mutations (57%/29% vs 19%/1% at AMC≥1.5 x 109/L). In univariate analysis, AMC ≥1.5 x 109/L adversely affected overall (OS; p=0.004; HR 2.6, 95% CI 1.4-4.8) and myelofibrosis-free (MFFS; p=0.02; HR 4.4, 95% CI 1.3-15.1) survival; during multivariable analysis, significance was borderline sustained for OS (p=0.05) and MFFS (p=0.06). Other independent risk factors for OS included unfavorable karyotype (p=0.02, HR 3.39, 95% CI 1.17-9.79), older age (p
      PubDate: 2017-03-28T10:50:28.504525-05:
      DOI: 10.1002/ajh.24740
       
  • Renal Outcomes in Patients with AL Amyloidosis: Prognostic Factors, Renal
           response and the Impact of Therapy
    • Authors: Efstathios Kastritis; Maria Gavriatopoulou, Maria Roussou, Magdalini Migkou, Despina Fotiou, Dimitrios C. Ziogas, Nikos Kanellias, Evangelos Eleutherakis-Papaiakovou, Ioannis Panagiotidis, Stavroula Giannouli, Erasmia Psimenou, Smaragdi Marinaki, Theofanis Apostolou, Hariklia Gakiopoulou, Anna Tasidou, Ioannis Papassotiriou, Evangelos Terpos, Meletios A. Dimopoulos
      Abstract: A staging system for patients with renal AL amyloidosis, based on eGFR (
      PubDate: 2017-03-28T10:50:23.837826-05:
      DOI: 10.1002/ajh.24738
       
  • Inhaled Steroids Reduce Pain and sVCAM Levels in Individuals with Sickle
           Cell Disease: A Triple-Blind, Randomized Trial
    • Authors: Jeffrey Glassberg; Caterina Minnitti, Caroline Cromwell, Lawrence Cytryn, Thomas Kraus, Gwen S. Skloot, Jason T. Connor, Adeeb H. Rahman, William J. Meurer
      Abstract: Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance and hyperreactivity) is an intrinsic component of SCD and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 non-asthmatic individuals with SCD. Participants received once daily mometasone furoate 220 mcg dry powder inhalation or placebo for 16 weeks. The primary outcome was feasibility (the number who complete the trial divided by the total number enrolled) with pre-specified efficacy outcomes including daily pain score over time (patient reported) and change in soluble vascular cell adhesion molecule (sVCAM) levels between entry and 8-weeks. For the primary outcome of feasibility, the result was 96% (52 of 54, 95% CI 87% - 99%) for the intent-to-treat analysis and 83% (45 of 54, 95% CI 71% - 91%) for the per-protocol analysis. The adjusted treatment effect of mometasone was a reduction in daily pain score of 1.42 points (95%CI 0.61 - 2.21, p = 0.001). Mometasone was associated with a reduction in sVCAM levels of 526.94 ng/mL more than placebo (95% CI 50.66 - 1,003.23, p = 0.03). These results support further study of ICS in SCD including multi-center trials and longer durations of treatment. www.clinicaltrials.gov (NCT02061202) This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-28T10:35:56.217691-05:
      DOI: 10.1002/ajh.24742
       
  • Enumerating Bone Marrow Blasts from Nonerythroid Cellularity Improves
           Outcome Prediction in Myelodysplastic Syndromes and Permits a Better
           Definition of the Intermediate Risk Category of the Revised International
           Prognostic Scoring System (IPSS-R)
    • Authors: Xavier Calvo; Leonor Arenillas, Elisa Luño, Leonor Senent, Montserrat Arnan, Fernando Ramos, Carme Pedro, Mar Tormo, Julia Montoro, María Díez-Campelo, María Laura Blanco, Beatriz Arrizabalaga, Blanca Xicoy, Santiago Bonanad, Andrés Jerez, Meritxell Nomdedeu, Ana Ferrer, Guillermo F Sanz, Lourdes Florensa,
      Abstract: The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3,924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. 24% patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS
      PubDate: 2017-03-28T10:35:52.510098-05:
      DOI: 10.1002/ajh.24732
       
  • Pediatric patients undergoing hematopoietic stem cell transplantation can
           greatly benefit from a novel once-daily intravenous busulfan dosing
           nomogram
    • Authors: Su-jin Rhee; Ji Won Lee, Kyung-Sang Yu, Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Kyung Duk Park, Hee Young Shin, Sang Hoon Song, Hyoung Jin Kang, Howard Lee
      Abstract: Busulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aims of this study were to derive a novel once-daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2,183 busulfan concentrations in 137 pediatric patients (age: 0.6 - 22.2 years), who received IV busulfan once-daily for 4 days before undergoing HSCT. Based on the final population PK model, an optimal once-daily IV busulfan dosing nomogram was derived. The percentage of simulated patients achieving the daily target area under the concentration-time curve (AUC) by the new nomogram was compared with that by other busulfan dosing regimens including the FDA regimen, the EMA regimen, and the empirical once-daily regimen without TDM. A one-compartment open linear PK model incorporating patient's body surface area, age, dosing day, and aspartate aminotransferase as a significant covariate adequately described the concentration–time profiles of busulfan. An optimal dosing nomogram based on the PK model performed significantly better than the other dosing regimens, resulting in >60% of patients achieving the target AUC while the percentage of patients exceeding the toxic AUC level was kept
      PubDate: 2017-03-28T10:35:41.097009-05:
      DOI: 10.1002/ajh.24734
       
  • Natural history of chronic myelomonocytic leukemia treated with
           hypomethylating agents
    • Authors: Ana Alfonso; Guillermo Montalban-Bravo, Koichi Takahashi, Elias J. Jabbour, Tapan Kadia, Farhad Ravandi, Jorge Cortes, Zeev Estrov, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos Bueso-Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
      Abstract: Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n=151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow-up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20-28) and event-free survival 14 months (95%CI: 11-17). By multivariate analysis, age 
      PubDate: 2017-03-28T10:35:31.932396-05:
      DOI: 10.1002/ajh.24735
       
  • Neonatal Anemia: Revisiting the Enigmatic Pyknocyte
    • Authors: Michele L. Nassin; Jo-Anne Vergilio, Matthew M. Heeney, James L. LaBelle
      PubDate: 2017-03-23T18:38:35.327392-05:
      DOI: 10.1002/ajh.24731
       
  • Cutaneous septic emboli from Candida glabrata in a haematological patient
    • Authors: Andrea Lombardi; Giorgio Alberto Croci, Valeria Brazzelli, Marco Vecchia, Valentina Zuccaro, Marco Sciarra, Raffaele Bruno
      PubDate: 2017-03-23T18:33:38.977836-05:
      DOI: 10.1002/ajh.24729
       
  • Correcting a 25-year old error: Preanalytical conditions affect
           determination of Von Willebrand factor variability as a function of
           menstrual cycle
    • Authors: Margareta Blombäck
      PubDate: 2017-03-15T10:30:36.638615-05:
      DOI: 10.1002/ajh.24719
       
  • Outcomes of adults with relapsed or refractory Burkitt and high-grade
           B-cell leukemia/lymphoma
    • Authors: Nicholas J. Short; Hagop M. Kantarjian, Heidi Ko, Joseph D. Khoury, Farhad Ravandi, Deborah A. Thomas, Guillermo Garcia-Manero, Maria Khouri, Jorge E. Cortes, William G. Wierda, Srdan Verstovsek, Zeev Estrov, Alessandra Ferrajoli, Philip A. Thompson, Sherry Pierce, Susan M. O'Brien, Elias Jabbour
      PubDate: 2017-03-15T10:30:26.996112-05:
      DOI: 10.1002/ajh.24720
       
  • Telomere attrition in sickle cell anemia
    • Authors: Armand Mekontso Dessap; Jérôme Cecchini, Vicky Chaar, Elisabeth Marcos, Anoosha Habibi, Pablo Bartolucci, Bijan Ghaleh, Frederic Galacteros, Serge Adnot
      PubDate: 2017-03-15T10:30:25.993009-05:
      DOI: 10.1002/ajh.24721
       
  • Assessment of renal response with urinary exosomes in patients with AL
           amyloidosis: A proof of concept
    • Authors: Marina Ramirez-Alvarado; David R. Barnidge, David L. Murray, Angela Dispenzieri, Marta Marin-Argany, Christopher J. Dick, Shawna A. Cooper, Samih H Nasr, Christopher J. Ward, Surendra Dasari, Víctor H. Jiménez-Zepeda, Nelson Leung
      Abstract: Immunoglobulin light chain (AL) amyloidosis is a fatal complication of B-cell proliferation secondary to deposition of amyloid fibrils in various organs. Urinary exosomes (UEX) are the smallest of the microvesicles excreted in the urine. Previously, we found UEX of patients with AL amyloidosis contained immunoglobulin light chain (LC) oligomers that patients with multiple myeloma did not have. To further explore the role of the LC oligomers, UEX was isolated from an AL amyloidosis patient with progressive renal disease despite achieving a complete response. LC oligomers were identified. Mass spectrometry (MS) of the UEX and serum identified two monoclonal lambda LCs. Proteomics of the trypsin digested amyloid fragments in the kidney by laser microdissection and MS analysis identified a λ6 LC. The cDNA from plasma cell clone was from the IGLV- 6-57 family and it matched the amino acid sequences of the amyloid peptides. The predicted mass of the peptide product of the cDNA matched the mass of one of the two LCs identified in the UEX and serum. UEX combined with MS were able to identify 2 monoclonal lambda LCs that current clinical methods could not. It also identified the amyloidogenic LC which holds potential for response assessment in the future. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-10T17:50:29.079941-05:
      DOI: 10.1002/ajh.24717
       
  • Beyond the transition of adolescents and young adults with sickle cell
           disease to adult care: Role of geography
    • Authors: Nina Anderson; James R. Eckman, Samir K. Ballas
      PubDate: 2017-03-10T17:50:26.697332-05:
      DOI: 10.1002/ajh.24718
       
  • Erythrocytes from Hereditary Xerocytosis patients heterozygous for KCNN4
           V282M exhibit increased spontaneous Gardos channel-like activity inhibited
           by Senicapoc
    • Authors: Alicia Rivera; David H. Vandorpe, Boris E. Shmukler, Denis R. Gallagher, Christopher C. Fikry, Frans A. Kuypers, Carlo Brugnara, L. Michael Snyder, Seth L. Alper
      PubDate: 2017-03-10T17:50:24.583616-05:
      DOI: 10.1002/ajh.24716
       
  • Factors predicting survival in chronic lymphocytic leukemia patients
           developing Richter syndrome transformation into Hodgkin lymphoma
    • Authors: Francesca Romana Mauro; Piero Galieni, Alessandra Tedeschi, Luca Laurenti, Giovanni Del Poeta, Gianluigi Reda, Marina Motta, Alessandro Gozzetti, Roberta Murru, Maria Denise Caputo, Melissa Campanelli, Anna Maria Frustaci, Idanna Innocenti, Sara Raponi, Anna Guarini, Fortunato Morabito, Robin Foà, Massimo Gentile
      Abstract: We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%. Prior treatment for CLL had been received by 82% of patients and included fludarabine in 67%. Coexistence of CLL and HL was detected in the same bioptic tissue in 87% of cases. The most common administered treatment was the ABVD regimen given to 22 patients (66.6%). The complete response (CR) rate after ABVD was 68%, and was influenced by the IPS (p=.03) and interval from the last CLL treatment (p=.057). Survival from HL was also influenced by the IPS (p=.006) and time from the last CLL treatment (p=.047). The achievement of CR with ABVD was the only significant and independent factor predicting survival (p=.037). Taken together, our results show that the IPS and the interval from the prior CLL treatment influence the likelihood of achieving CR after ABVD, which is the most important factor predicting survival of patients with CLL developing HL. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-10T17:45:27.406446-05:
      DOI: 10.1002/ajh.24714
       
  • Ibrutinib in very elderly patients with relapsed/refractory chronic
           lymphocytic leukemia: A real-world experience of 71 patients treated in
           France A study from the French Innovative Leukemia Organization (FILO)
           group
    • Authors: Anne-Sophie Michallet; Arnaud Campidelli, Helene Lequeu, Marie-Sarah Dilhuydy, Olivier Tournilhac, Luc-Matthieu Fornecker, Jehan Dupuis, Florence Cymbalista, Sophie De Guibert, Alain Delmer, Jean-Pierre Vilque, David Ghez, Veronique Leblond, Fabien. Subtil, Pierre Feugier, Loic Ysebaert
      PubDate: 2017-03-10T17:45:24.667176-05:
      DOI: 10.1002/ajh.24715
       
  • Recombinant erythropoietin vs. blood transfusion care in infants with
           hereditary spherocytosis: A retrospective cohort study of A.I.E.O.P.
           patients (Associazione Italiana Emato-Oncologia Pediatrica)
    • Authors: Piero Farruggia; Giuseppe Puccio, Ugo Ramenghi, Raffaella Colombatti, Paola Corti, Angela Trizzino, Angelica Barone, Gianluca Boscarol, Fabrizia Ferraro, Paolo Grotto, Laura Lo Valvo, Laura Luti, Sofia Maria Rosaria Matarese, Clara Mosa, Maria Caterina Putti, Laura Rubert, Giovan Battista Ruffo, Laura Sainati, Immacolata Tartaglione, Giovanna Russo, Silverio Perrotta
      PubDate: 2017-03-06T11:15:35.625927-05:
      DOI: 10.1002/ajh.24713
       
  • The association between race and venous thromboembolism risk after
           initiation of chemotherapy: An analysis of the SAVE-ONCO Trial control arm
           
    • Authors: Yu-Wei Chen; Alok Khorana
      PubDate: 2017-03-06T11:15:33.089093-05:
      DOI: 10.1002/ajh.24712
       
  • Incidence, clinical findings, and survival of hepatosplenic T-cell
           lymphoma in the United States
    • Authors: Urshila Durani; Ronald S. Go
      PubDate: 2017-03-06T11:15:32.015654-05:
      DOI: 10.1002/ajh.24711
       
  • Pregnancy in β-thalassemia intermedia at two tertiary care centers in
           Lebanon and Italy: A follow-up report on fetal and maternal outcomes
    • Authors: Joseph E. Roumi; Hassan M. Moukhadder, Giovanna Graziadei, Martina Pennisi, Maria Domenica Cappellini, Ali T. Taher
      PubDate: 2017-03-04T08:55:27.565604-05:
      DOI: 10.1002/ajh.24690
       
  • Orbital cellulitis as the initial presentation of Langerhans cell
           histiocytosis in an adult patient
    • Authors: Avash Das; Arjun Gupta, Harris V. K. Naina
      PubDate: 2017-03-04T00:55:26.938036-05:
      DOI: 10.1002/ajh.24670
       
  • Myeloid Neoplasms with Concurrent BCR-ABL1 and CBFB Rearrangements: A
           Series of 10 Cases of a Clinically Aggressive Neoplasm
    • Authors: Alireza Salem; Sanam Loghavi, Guilin Tang, Yang O. Huh, Elias J. Jabbour, Hagop Kantarjian, Wei Wang, Shimin Hu, Rajyalakshmi Luthra, L. Jeffrey Medeiros, Joseph D. Khoury
      Abstract: Chronic myeloid leukemia (CML) is defined by the presence of t(9;22)(q34;q11.2)/BCR-ABL1. Additional chromosomal abnormalities confer an adverse prognosis and are particularly common in the blast phase of CML (CML-BP). CBFB rearrangement, particularly CBFB-MYH11 fusion resulting from inv(16)(p13.1q22) or t(16;16)(p13.1;q22), is an acute myeloid leukemia (AML)-defining alteration that is associated with a favorable outcome. The co-occurrence of BCR-ABL1 and CBFB rearrangement is extremely rare, and the significance of this finding remains unclear. We identified 10 patients with myeloid neoplasms harboring BCR-ABL1 and CBFB rearrangement. The study group included 6 men and 4 women with a median age of 51 years (range, 20-71 years). The sequence of molecular alterations could be determined in 9 cases: BCR-ABL1 preceded CBFB rearrangement in 7, CBFB rearrangement preceded BCR-ABL1 in 2, and both alterations were discovered simultaneously in 1 patient. BCR-ABL1 encoded for p210 kD in all cases in which BCR-ABL1 preceded CBFB rearrangement; a p190 kD was identified in the other 3 cases. Two patients were treated with the FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) and tyrosine kinase inhibitors (TKI); 7 with other cytarabine-based regimens and TKIs, and one with ponatinib alone. At last follow up (median, 16 months; range 2-85), 7 of 10 patients had died. The co-existence of BCR-ABL1 and CBFB rearrangement is associated with poor outcome and a clinical course similar to that of CML-BP, and unlike de novo AML with CBFB rearrangement, suggesting that high-intensity chemotherapy with TKI should be considered in these patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-02T18:15:39.403146-05:
      DOI: 10.1002/ajh.24710
       
  • Utility of factor VIII and factor VIII to von Willebrand factor ratio in
           identifying 277 unselected carriers of hemophilia A
    • Authors: Veerle Labarque; Vanitha Perinparajah, Vanessa Bouskill, Ann Marie Stain, Cindy Wakefield, Cecilia Manuel, Victor S. Blanchette, Paula D. James, David Lillicrap, Manuel D. Carcao
      PubDate: 2017-03-01T18:26:01.188868-05:
      DOI: 10.1002/ajh.24709
       
  • BCL2 mutations do not confer adverse prognosis in follicular lymphoma
           patients treated with rituximab
    • Authors: Sarah Huet; Edith Szafer-Glusman, Bruno Tesson, Luc Xerri, Wayne J. Fairbrother, Kiran Mukhyala, Chris Bolen, Elizabeth Punnoose, Laurie Tonon, Catherine Chassagne-Clément, Pierre Feugier, Alain Viari, Fabrice Jardin, Gilles Salles, Pierre Sujobert
      Abstract: BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab-containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 FL patients treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA-targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over-activation of AICDA (Activation-induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2 and BH3 functional motifs at a lower frequency than the N-terminus and flexible loop domain (FLD), with mostly conservative aminoacid changes. With a median follow-up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression-free survival. This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-01T06:11:58.696199-05:
      DOI: 10.1002/ajh.24701
       
  • A Centrocyte Blood Count of a Quarter Million
    • Authors: Matthew Behrens; Rajasree P. Chowdry, Saliba Saba, Nakhle S. Saba
      PubDate: 2017-03-01T00:51:01.588441-05:
      DOI: 10.1002/ajh.24708
       
  • Dynamic assessment of RBC-Transfusion Dependency Improves the Prognostic
           Value of the Revised-IPSS in MDS Patients
    • Authors: Devendra K. Hiwase; Deepak Singhal, Corinna Strupp, Rakchha Chhetri, Monika M. Kutyna, L. Amilia Wee, Peter B. Harrison, Shriram V. Nath, Nicholas Wickham, Chi-Hung Hui, James X. Gray, Peter Bardy, David M. Ross, Ian D. Lewis, John Reynolds, L. Bik To, Ulrich Germing
      Abstract: RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R.We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n=295) and Dusseldorf registry (Germany; validation cohort; n=113) using time-dependent Cox proportional regression and serial landmark analyses.In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P
      PubDate: 2017-03-01T00:50:56.911636-05:
      DOI: 10.1002/ajh.24704
       
  • 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: 2017-02-27T10:25:23.664052-05:
      DOI: 10.1002/ajh.24706
       
  • The Reliability of Six Prognostic Models to Predict Time-to-First-
           Treatment in Patients with Chronic Lymphocytic Leukaemia in Early Phase
    • Authors: Stefano Molica; Diana Giannarelli, Rosanna Mirabelli, Luciano Levato, Massimo Gentile, Fortunato Morabito, Emili Montserrat
      PubDate: 2017-02-27T10:25:21.655166-05:
      DOI: 10.1002/ajh.24707
       
  • Predicting Risk Of Venous Thromboembolism In Hospitalized Cancer Patients:
           Utility of A Risk Assessment Tool
    • Authors: Rushad Patell; Lisa Rybicki, Keith R. McCrae, Alok A. Khorana
      Abstract: Inpatient venous thromboembolism (VTE) is a priority preventable illness; risk in cancer varies and prophylaxis is inconsistently used. A previously validated tool [Khorana Score, KS] identifies VTE risk in cancer outpatients with 5 easily available variables but has not been studied in the inpatient setting. We evaluated the validity of KS in predicting VTE risk in hospitalized cancer patients. We conducted a retrospective cohort study of consecutive oncology inpatients at the Cleveland Clinic from 11/2012-12/2014 (n= 3531). Patients were excluded for VTE on admission (n=304), incomplete KS data (n=439) or other reasons (n=8). Data collected included demographics, cancer type, length of stay (LOS), anticoagulant use and laboratory values. Multivariate risk factors were identified with stepwise logistic regression, confirmed with bootstrap analysis. Of 2,780 patients included, 106 (3.8%) developed VTE during hospitalization. Median age was 62 (range, 19-98) years and 56% were male. Median LOS was 5 (range, 0-152) days. High risk KS (≥ 3) was significantly associated with VTE in uni- and multivariate analyses (adjusted OR 2.5, 95% CI 1.3-4.9). Other significant variables included male gender (OR 1.67, 1.1-2.53), older age (OR 0.86, 0.75-0.99) and use of anticoagulants (OR 0.57, 0.39-0.85). Recursive partitioning analysis suggested optimal cut point for KS is 2 (OR 1.82, 1.23-2.69). This is the first report validating KS as a risk tool to predict VTE in hospitalized cancer patients. Using this tool could lead to more consistent and successful application of inpatient thromboprophylaxis. This article is protected by copyright. All rights reserved.
      PubDate: 2017-02-27T10:20:33.965839-05:
      DOI: 10.1002/ajh.24700
       
  • Therapy Induced Iron Deficiency in Children Treated with Eltrombopag for
           Immune Thrombocytopenia
    • Authors: Michele P. Lambert; Char M. Witmer, Janet L. Kwiatkowski
      PubDate: 2017-02-27T10:20:32.077481-05:
      DOI: 10.1002/ajh.24705
       
  • Newly diagnosed immune thrombocytopenia adults: clinical epidemiology,
           exposure to treatments and evolution. Results of the CARMEN multicenter
           prospective cohort
    • Authors: Guillaume Moulis; Johanne Germain, Thibault Comont, Natacha Brun, Claire Dingremont, Brice Castel, Sophie Arista, Laurent Sailler, Maryse Lapeyre-Mestre, Odile Beyne-Rauzy, Bertrand Godeau, Daniel Adoue,
      Abstract: The clinical epidemiology of immune thrombocytopenia (ITP) is not well known in adults. This study was aimed at assessing the clinical epidemiology of incident ITP adults, the factors associated with chronicity and exposure to treatments. This study was conducted in the CARMEN registry, a multicentric prospective cohort aimed at including all newly diagnosed ITP adults in the French Midi-Pyrénées region, South of France (3 million inhabitants) from June 2013. Descriptive analyses and multivariate logistic regression models were conducted. Out of 121 newly diagnosed ITP until December 2014, 113 patients were followed in the region and gave informed consent. Median age was 65 years. Half of the patients were female, 20.3% had a secondary ITP, 50.4% had a Charlson's score ≥1, median platelet count was 17 x109/L; 50.9% had bleeding symptoms, including 2 severe gastro-intestinal tract and 1 intracranial bleedings; 21.4% had another autoimmune disease and 20.3% experienced an infection within the six weeks before ITP onset. Persistency and chronicity rates were 68.2% and 58.7%, respectively. Antinuclear antibodies were associated with chronicity (OR: 2.89, 95% CI: 1.08-7.74). Sixty-eight (60.2%) patients were treated during the week following the diagnosis. Factors associated with the use of intravenous corticosteroids were secondary ITP and high bleeding score. Those associated with the use of IVIg were a high bleeding score and low platelet count. In conclusion, severe bleeding is rare at ITP onset. Associated autoimmune diseases and recent infections were frequent. Antinuclear antibodies seem predictors of chronicity. Intravenous corticosteroids and IVIg were frequently used. This article is protected by copyright. All rights reserved.
      PubDate: 2017-02-27T10:20:25.957453-05:
      DOI: 10.1002/ajh.24702
       
  • Mutations of RUNX1 in families with inherited thrombocytopenia
    • Authors: Daniela De Rocco; Federica Melazzini, Caterina Marconi, Alessandro Pecci, Roberta Bottega, Chiara Gnan, Flavia Palombo, Paola Giordano, Maria Susanna Coccioli, Ana C. Glembotsky, Paula G. Heller, Marco Seri, Anna Savoia, Patrizia Noris
      PubDate: 2017-02-27T10:20:23.742926-05:
      DOI: 10.1002/ajh.24703
       
  • Plasmodium knowlesi
    • Authors: Peter Chiodini; Barbara J. Bain
      PubDate: 2017-02-23T07:25:54.80021-05:0
      DOI: 10.1002/ajh.24697
       
  • Identification of renal infiltration based on urinary findings in a child
           with burkitt leukemia/lymphoma
    • Authors: Zühre Kaya; Nurettin Alıcı, Özlem Ezgi Özmen, Meltem Akgül, Büşra Topuz, Emine Akkuzu
      PubDate: 2017-02-22T03:45:26.542078-05:
      DOI: 10.1002/ajh.24694
       
  • In vivo confocal microscopy of multiple myeloma associated crystalline
           keratopathy
    • Authors: Caleb Busch; Shizuka Koh, Yoshinori Oie, Michiko Ichii, Yuzuru Kanakura, Kohji Nishida
      PubDate: 2017-02-21T03:35:24.667705-05:
      DOI: 10.1002/ajh.24692
       
  • The distinctive cytological features of T-cell prolymphocytic leukemia
    • Authors: Vishal Jayakar; Kan Cheung, Eva Yebra-Fernandez, Barbara J. Bain
      PubDate: 2017-02-21T00:26:12.320801-05:
      DOI: 10.1002/ajh.24659
       
  • The significance of irregularly contracted cells and hemighosts in sickle
           cell disease
    • Authors: Wenchee Siow; Francis Matthey, Barbara J. Bain
      PubDate: 2017-02-21T00:26:07.934864-05:
      DOI: 10.1002/ajh.24658
       
  • Lifespan care in SCD: Whom to transition, the patients or the health care
           system'
    • Authors: Caterina P. Minniti; Elliott Vichinsky
      PubDate: 2017-02-17T03:25:26.902429-05:
      DOI: 10.1002/ajh.24685
       
  • DAT-positive Plasmodium ovale malaria presenting in a child with sickle
           cell anemia
    • Authors: Nicholas S. Whipple; Jason R. Schwartz, Kerri A. Nottage
      PubDate: 2017-02-17T03:25:24.73837-05:0
      DOI: 10.1002/ajh.24691
       
  • Can we have some platelets please' A reason not to put your microscope
           on eBay
    • Authors: Wenchee Siow; Barbara J. Bain
      PubDate: 2017-01-23T08:25:32.919164-05:
      DOI: 10.1002/ajh.24630
       
  • Issue Information – Table of Contents
    • Pages: 483 - 485
      PubDate: 2017-05-08T07:27:03.528238-05:
      DOI: 10.1002/ajh.24512
       
  • Thalassemia: Yesterday, Today, Tomorrow
    • Authors: Maria Hadjidemetriou
      First page: 490
      PubDate: 2017-04-26T01:11:06.045028-05:
      DOI: 10.1002/ajh.24744
       
  • Targeted next generation sequencing and identification of risk factors in
           World Health Organization defined atypical chronic myeloid leukemia
    • Authors: Mrinal M. Patnaik; Daniela Barraco, Terra L. Lasho, Christy M. Finke, Kaaren Reichard, Katherine P. Hoversten, Rhett P. Ketterling, Naseema Gangat, Ayalew Tefferi
      First page: 542
      Abstract: Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly-annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8% and PTPN11 4%. Fifteen patients (60%) had >1 mutation, while 9 (36%) had ≥3. The median overall survival (OS) was 10.8 months and at last follow up (median 11 months), 17 (68%) deaths and 2 (8%) leukemic transformations were documented. On univariate analysis, survival was adversely impacted by advanced age (p=0.02), low hemoglobin (p=0.01), red blood cell transfusion dependence (p=0.03), high white blood cell count (p=0.02), TET2 (p=0.03), NRAS (p=0.04), PTPN11 (p=0.02) mutations and the presence of ≥3 gene mutations (p=0.006); ASXL1, SETBP1, and ETNK1 mutations did not impact OS. In multivariable analysis, advanced age (p=0.003) [age >67: HR 10.1, 95% CI 1.3-119], low hemoglobin (p=0.008) [HB< 10gm/dl: HR 8.2, 95% CI 1.6-23.2] and TET2 mutations (p=0.01) [HR 8.8, 95% CI 1.6-47.7] retained prognostic significance. We then used age >67 years, hemoglobin
      PubDate: 2017-04-29T03:30:22.484238-05:
      DOI: 10.1002/ajh.24722
       
  • Treatment Patterns and Outcome Following Initial Relapse or Refractory
           Disease in Patients with Systemic Light Chain Amyloidosis
    • Authors: Nidhi Tandon; Surbhi Sidana, Morie A. Gertz, Angela Dispenzieri, Martha Q. Lacy, Francis K. Buadi, David Dingli, Amie L. Fonder, Miriam A. Hobbs, Suzanne R. Hayman, Wilson I. Gonsalves, Yi Lisa Hwa, Prashant Kapoor, Robert A. Kyle, Nelson Leung, Ronald S. Go, John A. Lust, Stephen J. Russell, Steven R. Zeldenrust, S. Vincent Rajkumar, Shaji K. Kumar
      First page: 549
      Abstract: We analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1-93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22m vs 32.3m; p= 0.01) as compared to different therapy; but did not have any impact OS (30.8m vs 51.1m; p = 0.5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-26T01:10:55.2993-05:00
      DOI: 10.1002/ajh.24723
       
  • Clinical Characteristics and Whole Exome/Transcriptome Sequencing of
           Coexisting Chronic Myeloid Leukemia and Myelofibrosis
    • Authors: Malathi Kandarpa; Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M. Chinnaiyan, Moshe Talpaz
      First page: 555
      Abstract: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent. In an effort to characterize the underlying genetic events that might contribute to the appearance of more than one MPN in a patient, we studied neoplastic cells from patients with dual MPNs by next-generation sequencing. We observed that most patients with two MPNs harbored mutations in genes known to contribute to clonal hematopoiesis through altered epigenetic regulation such as TET2, ASXL1/2, SRSF2, and IDH2 at varying frequencies (1-47%). In addition, we found that some patients also harbored oncogenic mutations in N/KRAS, TP53, BRAF, EZH2, GNAS at low frequencies, which probably represent clonal evolution. These findings support the hypothesis that hematopoietic cells from MPN patients harbor multiple genetic aberrations, some of which can contribute to clonal dominance. Acquiring mutations in JAK2/CALR/MPL or the BCR-ABL translocation probably drive the oncogenic phenotype towards a specific MPN. Further, we propose that the acquisition of BCR-ABL in these patients is frequently a secondary event resulting from an unstable genome. This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-02T09:00:36.241178-05:
      DOI: 10.1002/ajh.24728
       
  • Identification of New BMP6 Pro-Peptide Mutations in Patients with Iron
           Overload
    • Authors: Chiara Piubelli; Annalisa Castagna, Giacomo Marchi, Monica Rizzi, Fabiana Busti, Sadaf Badar, Monia Marchetti, Marco De Gobbi, Antonella Roetto, Luciano Xumerle, Eda Suku, Alejandro Giorgetti, Massimo Delledonne, Oliviero Olivieri, Domenico Girelli
      First page: 562
      Abstract: Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least 5 different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription. A recent seminal study by French authors has described three heterozygous missense mutations in BMP6 associated with mild to moderate late-onset iron overload (IO). Using an updated next-generation sequencing (NGS)-based genetic test in IO patients negative for the classical HFE p.Cys282Tyr mutation, we found three BMP6 heterozygous missense mutations in 4 patients from 3 different families. One mutation (p.Leu96Pro) has already been described and proven to be functional. The other two (p.Glu112Gln, p.Arg257His) were novel, and both were located in the pro-peptide domain known to be crucial for appropriate BMP6 processing and secretion. In silico modeling also showed results consistent with their pathogenetic role. The patients' clinical phenotypes were similar to that of other patients with BMP6-related IO recently described. Our results independently add further evidence to the role of BMP6 mutations as likely contributing factors to late-onset moderate IO unrelated to mutations in the established 5 HH genes. This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-29T03:30:28.097929-05:
      DOI: 10.1002/ajh.24730
       
  • The Role of Carbon Monoxide and Heme Oxygenase in the Prevention of Sickle
           Cell Disease Vaso-Occlusive Crises
    • Authors: Edward Gomperts; John D. Belcher, Leo E. Otterbein, Thomas D. Coates, John Wood, Brett E. Skolnick, Howard Levy, Gregory M. Vercellotti
      First page: 569
      PubDate: 2017-04-29T03:29:45.833516-05:
      DOI: 10.1002/ajh.24750
       
  • 2B or not 2B' A prothrombotic tendency masquerading as a bleeding
           disorder
    • Authors: Yvonne Brennan; Jennifer Curnow, Emmanuel J. Favaloro
      First page: 584
      PubDate: 2017-03-17T19:15:46.523373-05:
      DOI: 10.1002/ajh.24724
       
  • Refractory hairy cell leukemia-variant
    • Authors: Zhihong Hu; Yi Sun, Wei Wang, L. Jeffrey Medeiros, Rashmi Kanagal-Shamanna
      PubDate: 2016-11-12T01:55:33.06988-05:0
      DOI: 10.1002/ajh.24580
       
 
 
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