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Publisher: John Wiley and Sons   (Total: 1589 journals)

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Showing 1 - 200 of 1589 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 165, 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: 6, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 268, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 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: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 10)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 148, 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: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 33, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 276, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 137, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
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: 225)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 222, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 47, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 89, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 207, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
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: 245, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 52, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 319, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 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: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 5, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 406, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 21, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 4, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 142, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 6, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 243, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Hematology
  [SJR: 1.761]   [H-I: 77]   [33 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0361-8609 - ISSN (Online) 1096-8652
   Published by John Wiley and Sons Homepage  [1589 journals]
  • Design and Implementation of a Novel Advanced Training Curriculum in
    • Authors: Richard Ward
      PubDate: 2017-12-11T03:12:01.613942-05:
      DOI: 10.1002/ajh.25001
  • Similar outcome of allogeneic stem cell transplantation after
           myeloablative and sequential conditioning regimen in patients with
           refractory or relapsed acute myeloid leukemia: A study from the Société
           Francophone de Greffe de Moelle et de Thérapie Cellulaire
    • Authors: Justine Decroocq; Raphaël Itzykson, Stéphane Vigouroux, Mauricette Michallet, Ibrahim Yakoub-Agha, Anne Huynh, Florence Beckerich, Felipe Suarez, Patrice Chevallier, Stéphanie Nguyen-Quoc, Marie-Pierre Ledoux, Laurence Clement, Yosr Hicheri, Gaëlle Guillerm, Jérôme Cornillon, Nathalie Contentin, Martin Carre, Natacha Maillard, Mélanie Mercier, Mohamad Mohty, Yves Beguin, Jean-Henri Bourhis, Amandine Charbonnier, Charles Dauriac, Jacques-Olivier Bay, Didier Blaise, Eric Deconinck, Charlotte Jubert, Nicole Raus, Regis Peffault de Latour, Nathalie Dhedin
      Abstract: Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions.We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions.With a median follow–up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (p=0.39), and 2-year cumulative incidence of relapse was 57% versus 50% respectively (p=0.99). Non-relapse mortality was not higher in the myeloablative group (17% versus 15%, p=0.44). In multivariate analysis, overall survival, cumulative incidence of relapse and non-relapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; p
      PubDate: 2017-12-11T03:06:22.326797-05:
      DOI: 10.1002/ajh.25004
  • Pure erythroid leukemia
    • Authors: Barbara J. Bain
      PubDate: 2017-12-11T03:06:06.026574-05:
      DOI: 10.1002/ajh.25005
  • Age is the only predictor of small decrease in lung function in children
           with sickle cell anemia
    • Authors: Shaina M. Willen; Robyn Cohen, Mark Rodeghier, Fenella Kirkham, Susan S. Redline, Carol Rosen, Jane Kirkby, Michael R. DeBaun
      Abstract: The longitudinal pattern of lung function in children with sickle cell anemia (SCA) has shown a decrease in FEV1% predicted, a risk factor for death in adults with SCA, but predictors for this decline are poorly characterized. In a prospective longitudinal multi-center cohort of children with SCA, we tested the hypotheses that: 1) FEV1% predicted declines over time; and 2) SCA-specific characteristics and therapy predict this decline. At three clinical centers, children with SCA (HbSS or HbSβ0 thalassemia), unselected for respiratory disease, were enrolled in the Sleep and Asthma Cohort (SAC) study. Study-certified pulmonary function technicians performed spirometry and lung volumes. Each assessment was reviewed centrally. Predicted values were determined for TLC, FEV1, FVC, and FEV1/FVC ratio. A total of 197 participants, mean age 11.0 years at first testing (range 4-19.3 years), had a minimum of three spirometry measurements an average of 4.4 years (range 1.08-6.5 years) from baseline to endpoint. In a multivariable model, FEV1% predicted declines by 0.3% for every additional year of age (95% CI -0.56 - -0.05, p=0.020). Sex, asthma history, hemoglobin, reticulocyte count, white blood cell count, incidence rate of severe acute pain and acute chest syndrome episodes, and hydroxyurea therapy were not associated with a decline in FEV1% predicted. In a large rigorously evaluated, prospective cohort of an unselected group of children with SCA, FEV1% predicted declines minimally over an average of 4 years, and none of the examined disease features predict the decline. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-11T03:05:37.00445-05:0
      DOI: 10.1002/ajh.25003
  • No Major Differences in Outcomes Between the Initial and Relapse Episodes
           in Patients with Thrombotic Thrombocytopenic Purpura: The Experience from
           the Ohio State University Registry
    • Authors: Camila Masias; Haiwa Wu, Michael McGookey, Lauren Jay, Spero Cataland, Shangbin Yang
      PubDate: 2017-12-11T03:05:21.475994-05:
      DOI: 10.1002/ajh.25002
  • Comparing Apples to Oranges: A commentary on the Mayo study of MYD88
           significance in Waldenstrom's Macroglobulinemia
    • Authors: Jorge J. Castillo; Joshua N. Gustine, Kirsten Meid, Lian Xu, Zachary R. Hunter, Steven P. Treon
      PubDate: 2017-12-08T03:11:22.775788-05:
      DOI: 10.1002/ajh.24997
  • Clinical Experience with the BCL2-inhibitor Venetoclax in Combination
           Therapy for Relapsed and Refractory Acute Myeloid Leukemia and Related
           Myeloid Malignancies
    • Authors: Courtney D DiNardo; Caitlin R Rausch, Christopher Benton, Tapan Kadia, Nitin Jain, Naveen Pemmaraju, Naval Daver, Wendy Covert, Kayleigh R Marx, Morgan Mace, Elias Jabbour, Jorge Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Kapil N Bhalla, Hagop Kantarjian, Marina Konopleva
      Abstract: Introduction: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML) and efficacy in lower-intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported.Methods: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed.Results: 43 patients with median age 68 (range, 25-83) were treated for AML (91%), MDS (5%) or BPDCN (5%). Most (n=36, 84%) were ≥salvage-2 treatment status, including prior hypomethylating agent (HMA) in 77%. In combination with VEN, most patients received HMA therapy (n=31, 72%); eight (19%) received low-dose cytarabine (LDAC). Patients received a median of 2 treatment cycles (range, 1-4). Objective response was observed in 9 (21%) patients, including 2 complete responses (CR), 3 CRi, and 4 morphologic leukemia-free state (MLFS). Median survival was 3.0 months (range, 0.5-8.0), and estimated 6-month survival was 24%.Responses were observed in five (24%) of 21 patients with intermediate-risk cytogenetics, 3 (27%) of 11 IDH1/2-mutant, and 4 (50%) of 8 RUNX1-mutated patients. Two (20%) of 10 TP53-mutated patients responded; both had concurrent RUNX1 mutations. Of the 3 (15%) responding patients with adverse cytogenetics, all had concurrent RUNX1 mutations.Conclusion: Low-intensity chemotherapy, i.e. HMAs or LDAC, in combination with VEN is a viable salvage option, even in multiply relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were identified in patients with diploid/intermediate cytogenetics, RUNX1 and/or IDH1/2 mutations. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-08T03:11:04.352333-05:
      DOI: 10.1002/ajh.25000
  • Successful liver transplantation for homozygous protein C deficiency with
           a Type II mutation using a heterozygous living related donor
    • Authors: Alexander A. Boucher; Lori Luchtman-Jones, Jaimie D. Nathan, Joseph S. Palumbo
      PubDate: 2017-12-08T03:11:02.593653-05:
      DOI: 10.1002/ajh.24998
  • Hereditary xerocytosis: Diagnostic considerations
    • Authors: Mary Risinger; Edyta Glogowska, Satheesh Chonat, Kejian Zhang, Neha Dagaonkar, Clinton H. Joiner, Charles T. Quinn, Theodosia A. Kalfa, Patrick G. Gallagher
      PubDate: 2017-12-06T03:15:28.186614-05:
      DOI: 10.1002/ajh.24996
  • Comprehensive Management Reduces Incidence and Mortality of Acute Chest
           Syndrome in Patients with Sickle Cell Disease
    • Authors: Givi Basishvili; Joseph Gotesman, Kathy Vandervoort, Charleen Jacobs, Leena Vattappally, Caterina P. Minniti
      PubDate: 2017-12-05T03:35:50.07404-05:0
      DOI: 10.1002/ajh.24994
  • Macrophage activation syndrome and post-transplant microangiopathy
           following haploidentical bone marrow transplantation for sickle cell
    • Authors: James O. J. Davies; Alice C. Hart, Josu De La Fuente, Barbara J. Bain
      PubDate: 2017-12-02T03:25:23.59615-05:0
      DOI: 10.1002/ajh.24995
  • Anthracycline-induced acute myocarditis and ventricular fibrillation
    • Authors: Vincent A. Pallazola; Joseph C. Murray, Munjid Al Harthy, Stefan L. Zimmerman, Jonathan Webster, Lukasz P. Gondek
      PubDate: 2017-12-01T04:56:21.814456-05:
      DOI: 10.1002/ajh.24989
  • Splanchnic vein thrombosis in patients with myeloproliferative neoplasms:
           The Mayo Clinic experience with 84 consecutive cases
    • Authors: Sravanthi Lavu; Natasha Szuber, Mythri Mudireddy, Meera Yogarajah, Naseema Gangat, Animesh Pardanani, Curtis A. Hanson, Rhett P. Ketterling, Aneel A. Ashrani, Patrick S. Kamath, Ayalew Tefferi
      PubDate: 2017-12-01T04:50:20.799557-05:
      DOI: 10.1002/ajh.24993
  • Survival Following Salvage Therapy for Primary Refractory Peripheral
           T-Cell Lymphomas (PTCL)
    • Authors: Janie Y. Zhang; Robert Briski, Sumana Devata, Mark S. Kaminski, Tycel J. Phillips, Tera L. Mayer, Nathanael G. Bailey, Ryan A. Wilcox
      Abstract: Optimal salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL) and the role of hematopoietic stem cell transplant remain poorly defined. We conducted a retrospective review of clinical outcomes and prognostic factors in a single-center cohort of 93 patients with primary refractory PTCL, defined as progression during first-line therapy or relapse within 6 months of its completion. Clinical outcomes were poor in this population, with median event-free survival (EFS) of 3.5 months, median overall survival (OS) of 9.1 months, and 34% 3-year survival. Outcomes were comparable in patients who progressed through first-line therapy and patients who achieved CR/PR and subsequently relapsed within 6 months. A majority exhibited high-risk features and had intermediate to high risk IPI, which correlated with inferior outcomes. There was no difference in outcomes between patients who received single-agent salvage regimens and patients who underwent traditional, multi-agent salvage regimens. Thus, participation in well-designed clinical trials should be encouraged in this population. Additionally, there may be a trend toward improved EFS and OS in patients who underwent autologous or allogeneic SCT compared to patients who achieved CR or PR but were not transplanted. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T04:13:21.15448-05:0
      DOI: 10.1002/ajh.24992
  • The role of tmprss6 and hfe variants in iron deficiency anemia in celiac
    • Authors: Luigia De Falco; Raffaella Tortora, Nicola Imperatore, Mariasole Bruno, Mario Capasso, Domenico Girelli, Annalisa Castagna, Nicola Caporaso, Achille Iolascon, Antonio Rispo
      Abstract: We investigated the role of HFE C282Y, H63D and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1-year of gluten free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P=0.001), whereas H63D and A736V allele frequencies were similar among patients and controls (P=0.92 and 0.84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to non-anemic group (2% and 0.5%, P=0.04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P
      PubDate: 2017-12-01T04:10:41.955086-05:
      DOI: 10.1002/ajh.24991
  • “Double-hit” chronic lymphocytic leukemia: An aggressive subgroup with
           17p deletion and 8q24 gain
    • Authors: Elise Chapiro; Claude Lesty, Clémentine Gabillaud, Eric Durot, Simon Bouzy, Marine Armand, Magali Le Garff-Tavernier, Nadia Bougacha, Stéphanie Struski, Audrey Bidet, Elodie Laharanne, Carole Barin, Lauren Veronese, Nolwen Prié, Virginie Eclache, Baptiste Gaillard, Lucienne Michaux, Christine Lefebvre, Jean-Baptiste Gaillard, Christine Terré, Dominique Penther, Christian Bastard, Nathalie Nadal, Sandra Fert-Ferrer, Nathalie Auger, Catherine Godon, Laurent Sutton, Olivier Tournilhac, Santos A. Susin, Florence Nguyen-Khac,
      Abstract: Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (p=0.04), unbalanced translocations (p=0.03) and 8q24 gain (p=0.001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this “double-hit” CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL. This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T03:31:17.51531-05:0
      DOI: 10.1002/ajh.24990
  • Outcome of Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia
           after Blinatumomab Failure: No Change in the Level of CD19 Expression
    • Authors: Elias Jabbour; Johannes Düll, Musa Yilmaz, Joseph D. Khoury, Farhad Ravandi, Nitin Jain, Hermann Einsele, Guillermo Garcia-Manero, Marina Konopleva, Nicholas J. Short, Philip A. Thompson, William Wierda, Naval Daver, Jorge Cortes, Susan O'Brien, Hagop Kantarjian, Max S. Topp
      Abstract: Blinatumomab, a bi-specific T-cell engaging CD3-CD19 antibody construct, has shown significant activity in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). Despite this improvement, most patients relapse. Here, we describe the outcome of 68 patients with R/R ALL after failure of blinatumomab therapy: 38 (56%) blinatumomab refractory; 30 (44%) relapsing after initial response. After a median follow-up of 49 months, 9 (13%) patients remained alive. The median overall survival after blinatumomab failure was 5.2 months. At the time of failure, among 61 patients evaluated for immunophenotype, 56 (92%) had CD19-positive blasts; only five (8%) had ALL recurrence with CD19-negative disease. Two patients progressed with lower CD19 expression. In summary, the outcome of patients with R/R ALL after blinatumomab failure is poor and treatment of these patients remains an unmet medical need. Our findings indicate that blinatumomab therapy would not exclude a significant number of patients from the potential benefit of subsequent CD19-directed therapies such as chimeric antigen receptor T-cell therapy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-27T03:28:59.641458-05:
      DOI: 10.1002/ajh.24987
  • Hereditary hypochromic microcytic anemia associated with loss-of-function
           DMT1 gene mutations and absence of liver iron overload
    • Authors: Maddalena Casale; Adriana Borriello, Saverio Scianguetta, Domenico Roberti, Martina Caiazza, Debora Bencivenga, Immacolata Tartaglione, Saverio Ladogana, Matteo Maruzzi, Fulvio Della Ragione, Silverio Perrotta
      PubDate: 2017-11-27T03:28:37.628045-05:
      DOI: 10.1002/ajh.24988
  • Visualization of the bone marrow biopsy needle track
    • Authors: Shirin Attarian; Louis Reed, Shashi Singh, Alexander Shestopalov, Aditi P Singh, Anjali Budhathoki, Simon Abi-Aad, Urvi Shah, Salem Kim, Kimo Bachiashvili, Tarek Elrafei, Weijuan Li, Conway Yee, Ellen Friedman
      PubDate: 2017-11-23T03:47:07.360368-05:
      DOI: 10.1002/ajh.24985
  • The clinical epidemiology of sickle cell anemia in Africa
    • Authors: Alex W Macharia; George Mochamah, Sophie Uyoga, Carolyne M Ndila, Gideon Nyutu, Johnstone Makale, Metrine Tendwa, Emily Nyatichi, John Ojal, Mohammed Shebe, Kennedy O Awuondo, Neema Mturi, Norbert Peshu, Benjamin Tsofa, J Anthony G Scott, Kathryn Maitland, Thomas N Williams
      Abstract: Sickle cell anemia (SCA) is the commonest severe monogenic disorders of humans. The disease has been highly characterized in high-income countries but not in sub-Saharan Africa where SCA is most prevalent. We conducted a retrospective cohort study of all children 0-13 years admitted from within a defined study area to Kilifi County Hospital in Kenya over a five-year period. Children were genotyped for SCA retrospectively and incidence rates calculated with reference to population data. Overall, 576 of 18,873 (3.1%) admissions had SCA of whom the majority (399; 69.3%) were previously undiagnosed. The incidence of all-cause hospital admission was 57.2/100 person years of observation (PYO; 95%CI 52.6-62.1) in children with SCA and 3.7/100 PYO (95%CI 3.7-3.8) in those without SCA (IRR 15.3; 95%CI 14.1-16.6). Rates were higher for the majority of syndromic diagnoses at all ages beyond the neonatal period, being especially high for severe anemia (hemoglobin
      PubDate: 2017-11-23T03:40:41.929303-05:
      DOI: 10.1002/ajh.24986
  • Bendamustine plus rituximab for indolent B-cell lymphoma of renal
    • Authors: David Ribes; Hélène El Hachem, Lucie Oberic, François Vergez, Audrey Delas, Julie Belliere, Caroline Protin, Nassim Kamar, Inès Ferrandiz, Suzanne Tavitian, Camille Laurent, Antoine Huart, Dominique Chauveau, Loïc Ysebaert, Stanislas Faguer
      Abstract: Treatment of indolent B-cell non-Hodgkin lymphomas (iNHL) of renal significance is challenging given the need for deep and prolonged hematological response to restore and control renal function overtime, yet to be balanced with the risk of adverse drug-related events. This prospective single-center study included 20 patients with iNHL of renal significance (tubulointerstitial presentation [n=8], glomerulopathy with or without monoclonal Ig deposits [n=12]) who received a steroid-sparing regimen of rituximab plus bendamustine (BR), with either no or
      PubDate: 2017-11-23T03:40:26.720773-05:
      DOI: 10.1002/ajh.24984
  • Secondary Acute Myeloid Leukaemia In Elderly patients: Patient's Fitness
           Criteria and ELN Prognostic Stratification Can Be Applied to Guide
           Treatment Decisions. An analysis of 280 Patients by the Network Rete
           Ematologica Lombarda (REL)
    • Authors: Erika Borlenghi; Chiara Pagani, Patrizia Zappasodi, Massimo Bernardi, Claudia Basilico, Elisabetta Todisco, Nicola Fracchiolla, Valentina Mancini, Mauro Turrini, Matteo Da Vià, Elisa Sala, Chiara Cattaneo, Marta Petullà, Federico Serana, Andrea Ferrario, Roberto Cairoli, Agostino Cortelezzi, Armando Santoro, Carlo Castagnola, Giuseppe Rossi
      PubDate: 2017-11-22T03:35:32.81478-05:0
      DOI: 10.1002/ajh.24977
  • Outcome of chronic lymphocytic leukemia patients who switched from either
           ibrutinib or idelalisib to alternate kinase inhibitor: A retrospective
           study of the French Innovative Leukemia Organization (FILO)
    • Authors: Sophie Godet; Caroline Protin, Jehan Dupuis, Caroline Dartigeas, Jean-Noël Bastie, Charles Herbaux, Véronique Leblond, Sophie de Guibert, David Ghez, Annie Brion, Loïc Ysebaert, Alain Delmer, Anne Quinquenel
      PubDate: 2017-11-22T03:35:23.363467-05:
      DOI: 10.1002/ajh.24981
  • Intergroup LEAP Trial (S1612): A Randomized Phase 2/3 Platform Trial to
           Test Novel Therapeutics in Medically Less Fit Older Adults with Acute
           Myeloid Leukemia
    • Authors: Roland B. Walter; Laura C. Michaelis, Megan Othus, Geoffrey L. Uy, Jerald P. Radich, Richard F. Little, Sandi Hita, Lalit Saini, James M. Foran, Aaron T. Gerds, Heidi D. Klepin, Annette E. Hay, Sarit Assouline, Jeffrey E. Lancet, Stephen Couban, Mark R. Litzow, Richard M. Stone, Harry P. Erba
      PubDate: 2017-11-22T03:31:15.101988-05:
      DOI: 10.1002/ajh.24980
  • Laboratory tests for identification or exclusion of heparin induced
           thrombocytopenia - HIT or miss'
    • Authors: Emmanuel J Favaloro
      Abstract: Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin (‘anti-PF4-heparin'). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay (‘screening'), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed. The most common contemporary immunological assays comprise enzyme-linked immunosorbent assay [ELISA], chemiluminescence, lateral flow and particle gel techniques. The most common functional assays measure platelet aggregation or platelet activation events (e.g., serotonin release assay; heparin-induced platelet activation (HIPA); flow cytometry). All assays have some sensitivity and specificity to HIT antibodies, but differ in terms of relative sensitivity and specificity for pathological HIT, as well as false negative and false positive error rate. This brief paper overviews the different available laboratory methods, as well as providing a suggested approach to diagnosis or exclusion of HIT. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-22T03:31:07.469505-05:
      DOI: 10.1002/ajh.24979
  • Driver mutations and prognosis in primary myelofibrosis: Mayo-Careggi MPN
           alliance study of 1,095 patients
    • Authors: Ayalew Tefferi; Maura Nicolosi, Mythri Mudireddy, Natasha Szuber, Christy M. Finke, Terra L. Lasho, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, Carmela Mannarelli, Tiziana Fanelli, Paola Guglielmelli, Alessandro M. Vannucchi
      Abstract: The 2013 discovery of calreticulin (CALR) mutations in myeloproliferative neoplasms was attended by their association with longer survival in primary myelofibrosis (PMF). Subsequent studies have suggested prognostic distinction between type 1/like and type 2/like CALR mutations and detrimental effect from triple-negative mutational status. Among 709 Mayo Clinic patients with PMF, 467 (66%) harbored JAK2, 112 (16%) CALR type 1/like, 24 (3.4%) CALR type 2/like, 38 (5.4%) MPL mutations and 68 (10%) were triple-negative. Survival was longer with type 1/like CALR, compared to JAK2 (HR 2.6, 95% CI 1.9-3.5), type 2/like CALR (HR 2.5, 95% CI 1.4-4.5), MPL (HR 1.8, 95% CI 1.1-2.9) and triple-negative mutational status (HR 2.4, 95% CI 1.6-3.6), but otherwise similar between the non-type 1/like CALR mutational states (p=0.41). In multivariable analysis, the absence of type 1/like CALR (p
      PubDate: 2017-11-22T03:30:58.454961-05:
      DOI: 10.1002/ajh.24978
  • Sickle hemoglobin oxygen affinity-shifting strategies have unequal
           cerebrovascular risks
    • Authors: Robert P. Hebbel; Bo E. Hedlund
      PubDate: 2017-11-18T02:40:29.352286-05:
      DOI: 10.1002/ajh.24975
  • Ruxolitinib-associated infections: a systematic review and meta-analysis
    • Authors: Federico Lussana; Marco Cattaneo, Alessandro Rambaldi, Alessandro Squizzato
      Abstract: Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib.Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI).Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N=10), hepatitis B reactivation (N=5) and pneumocystis jeroveci infection (N=2).Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-18T02:40:26.423675-05:
      DOI: 10.1002/ajh.24976
  • Impact of gene mutations on treatment response and prognosis of acute
           myeloid leukemia secondary to myeloproliferative neoplasms
    • Authors: G. Venton; F. Courtier, A. Charbonnier, E. D'Incan, C. Saillard, B. Mohty, MJ. Mozziconacci, D. Birnbaum, A. Murati, N. Vey, J. Rey
      Abstract: Acute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult to obtain and there is very little scientific literature or prospective trials for determining robust prognostic markers and efficient treatments.We analyzed event-free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics, the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next-generation DNA sequencing (NGS). For 24 patients, we were able to do a comparative NGS analysis at both MPN and sAML phase.After acute transformation EFS and OS were respectively of 2.9 months (range: 0-48.1) and 4.7 months (range: 0.1-58.8). No difference in EFS or OS regarding the previous MPN, the ELN2017 prognostic classification, the first-line therapy or the response was found. After univariate analysis, three genes, TP53, SRSF2 and TET2, impacted pejoratively sAML prognosis at sAML time. In multivariate analysis, TP53 (p=0.0001), TET2 (p=0.011) and SRSF2 (p=0.018) remained independent prognostic factors. Time to sAML transformation was shorter in SRSF2-mutated patients (51.2 months, range: 14.7-98) than in SRSF2-unmutated patients (133.8 months, range: 12.6-411.2) (p
      PubDate: 2017-11-17T00:55:27.898523-05:
      DOI: 10.1002/ajh.24973
  • Phase 1 Study of Quizartinib in Combination With Induction and
           Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid
    • Authors: Jessica K. Altman; James M. Foran, Keith W. Pratz, Denise Trone, Jorge E. Cortes, Martin S. Tallman
      Abstract: Novel therapies have potential to improve outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-ITD mutations that have high risk of relapse and poor survival following standard of care (SOC) cytarabine/anthracycline-based induction/consolidation chemotherapy. Quizartinib is a selective and highly potent FLT3 inhibitor that has shown strong single-agent activity in relapsed or refractory (R/R) AML. This phase 1, open-label, sequential group dose-escalation trial (NCT 01390337) is the first evaluating safety and tolerability of quizartinib in combination with SOC chemotherapy in newly diagnosed AML (ndAML). Nineteen patients unselected for FLT3 mutational status received one of three quizartinib dihydrochloride dose levels (DL): 60 mg/d for 7 days (DL1; n=6), 60 mg/d for 14 days (DL2; n=7), and 40 mg/d for 14 days (DL-1; n=6); administered orally starting on day 4 of chemotherapy. Median age was 43.8 years. Ten patients completed induction and consolidation. Three patients experienced dose-limiting toxicities (DLTs): 2 at DL2 (1 pericardial effusion; 1 febrile neutropenia, decreased platelet count, and QT prolongation); 1 at DL-1 (pericarditis). Maximum tolerated dose (MTD) was identified as DL-1. Most common grade 3/4 adverse events were febrile neutropenia (47%), neutropenia (42%), thrombocytopenia (32%), and anemia (26%). There were no apparent additional toxicities with addition of quizartinib to chemotherapy although grade ≤1 QT prolongation was observed at MTD. Sixteen patients (84%) achieved a response; 14 (74%) composite complete response; 2 (11%) morphologic leukemia-free state. The phase 3 QuANTUM-First trial (NCT02668653) is further evaluating the effect of quizartinib plus SOC chemotherapy in ndAML FLT3-ITD mutated patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-15T03:25:21.424515-05:
      DOI: 10.1002/ajh.24974
  • Ruxolitinib as First-Line Treatment in Secondary Hemophagocytic
           Lymphohistiocytosis: A Single Patient Experience
    • Authors: J. Slostad; P. Hoversten, C.L. Haddox, K. Cisak, J. Paludo, A. Tefferi
      PubDate: 2017-11-14T03:30:24.923549-05:
      DOI: 10.1002/ajh.24971
  • Identification of ceruloplasmin as a biomarker of chronic kidney disease
           in urine of sickle cell disease patients by proteomic analysis
    • Authors: Marina Jerebtsova; Santosh L. Saraf, Xionghao Lin, Gillian Lee, Elena Afia Adjei, Namita Kumari, Nowah Afangbedji, Rasha Raslan, Charlee McLean, Victor R. Gordeuk, Sergei Nekhai
      PubDate: 2017-11-10T21:50:31.337317-05:
      DOI: 10.1002/ajh.24965
  • A key role for Rac and Pak signaling in Neutrophil Extracellular Traps
           (NETs) formation defines a new potential therapeutic target
    • Authors: M Gavillet; K Martinod, R Renella, DD Wagner, DA Williams
      Abstract: NET formation in mice (NETosis) is supported by reactive oxygen species (ROS) production by NADPH oxidase and histone hypercitrullination by peptidylarginine deiminase 4 (PAD4). Rac1 and Rac2, expressed in polymorphonuclear neutrophils (PMNs), regulate the cytoskeleton, cell shape, adhesion and migration and are also essential components of the NADPH oxidase complex. We aimed to explore the role of the Rac signaling pathway including the upstream guanosine exchange factor (GEF) activator, Vav, and a downstream effector, the p21-activated kinase, Pak, on NETosis in PMNs using a previously described flow-cytometry-based assay. Rac2-/- PMNs showed reduced levels of citrullinated histone H3 (H3Cit)-positive cells and defective NETosis. Rac1Δ/Δ; Rac2-/- PMNs demonstrated a further reduction in PMA-induced H3Cit levels and a more profound impairment of NETosis than deletion of Rac2 alone, suggesting an overlapping role of these two highly related proteins. Genetic knockouts of Vav1, or Vav2, did not impair H3Cit response to phorbol myristate ester (PMA) or NETosis. Combined, Vav1 and Vav3 deletions decreased H3Cit response and caused a modest but significant impairment of NETosis. Pharmacologic inhibition of Pak by two inhibitors with distinct mechanisms of action, led to reduced H3Cit levels after PMA stimulation, as well as significant inhibition of NETosis. We validated the importance of Pak using Pak2Δ/Δ PMNs, which demonstrated significantly impaired histone H3 citrullination and NETosis. These data confirm and more comprehensively define the key role of the Rac signaling pathway in PMN NETosis. The Rac signaling cascade may represent a valuable target for inhibition of NETosis and related pathological processes. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-10T03:25:32.108412-05:
      DOI: 10.1002/ajh.24970
  • Safety and Efficacy of Early Start of Iron Chelation Therapy with
           Deferiprone in Young Children Newly Diagnosed with Transfusion-Dependent
           Thalassemia: A Randomized Controlled Trial
    • Authors: Mohsen Saleh Elalfy; Amira Adly, Hanem Awad, Mohamed Tarif Salam, Vasilios Berdoukas, Fernando Tricta
      Abstract: Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion-dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants (N=64 their age ranged from10-18 (median 12) months, 54.7% males; receiving 400-< 1000 ng/ml were randomized to “early start deferiprone” (.ES-DFP) at a low dose (50 mg/kg/day) or to “delay chelation” (DC), and remained in the study until their serum ferritin (SF) level reached ≥1000 μg/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months post-randomization, 100% of the subjects in DC group had achieved SF > 1000 µg/L and TSAT > 70% compared with none in the ES-DFP group. LPI level>0.6 µM was observed in 97% vs. 40% of the DS and ES groups, respectively, (p1000 µg/L was delayed by 6 months in the ES-DFP group (P
      PubDate: 2017-11-09T03:40:41.124527-05:
      DOI: 10.1002/ajh.24966
  • The Risk of Venous Thromboembolism in Patients with Clinically Overt
           Gastrointestinal Bleeding
    • Authors: Mohammed Almakadi; Christopher Sheasgreen, Ahmed Barefah, Lucy Lu, Nidhi Kumar Tyagi, Gillian Mazzetti, Lindsay Crabbe, Yuhong Yuan, Mark Crowther, Grigorios Leontiadis
      PubDate: 2017-11-09T03:19:28.977208-05:
      DOI: 10.1002/ajh.24967
  • A Phase I Study of Lenalidomide plus Chemotherapy with Mitoxantrone,
           Etoposide, and Cytarabine for the Reinduction of Patients with Acute
           Myeloid Leukemia
    • Authors: Daniel J. DeAngelo; Andrew M. Brunner, Lillian Werner, David Avigan, Amir T. Fathi, Adam S. Sperling, Abigail Washington, Dina Stroopinsky, Jacalyn Rosenblatt, Malgorzata McMasters, Katarina Luptakova, Martha Wadleigh, David P. Steensma, Gabriela S. Hobbs, Eyal C. Attar, Philip C. Amrein, Benjamin L. Ebert, Richard M. Stone, Karen K. Ballen
      Abstract: Patients with relapsed AML have a poor prognosis and limited responses to standard chemotherapy. Lenalidomide is an immunomodulatory drug that may modulate anti-tumor immunity. We performed a study to evaluate the safety and tolerability of lenalidomide with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory AML. Adult patients with relapsed/refractory AML were eligible for this phase I dose-escalation study. We enrolled 35 patients using a ‘3 + 3' design, with a 10 patient expansion cohort at the maximum tolerated dose (MTD). Lenalidomide was initially given days 1-14 and MEC days 4-8; due to delayed count recovery, the protocol was amended to administer lenalidomide days 1-10. The dose of lenalidomide was then escalated starting at 5 mg/d (5-10-25-50). The primary objective was tolerability and MTD determination, with secondary outcomes including overall survival (OS). The MTD of lenalidomide combined with MEC was 50mg/d days 1-10. Among the 35 enrolled patients, 12 achieved complete remission (CR) (34%, 90%CI 21-50%); 30-day mortality was 6% and 60-day mortality 13%. The median OS for all patients was 11.5 months. Among 17 patients treated at the MTD, 7 attained CR (41%); the median OS was not reached while 12-month OS was 61%. Following therapy with MEC and lenalidomide, patient CD4+ and CD8+ T-cells demonstrated increased inflammatory responses to autologous tumor lysate. The combination of MEC and lenalidomide is tolerable with an RP2D of lenalidomide 50mg/d days 1-10, yielding encouraging response rates. Further studies are planned to explore the potential immunomodulatory effect of lenalidomide and MEC. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-09T03:05:45.225221-05:
      DOI: 10.1002/ajh.24968
  • Hispanic ethnicity as a risk factor for requiring glucarpidase rescue in
           pediatric patients receiving high-dose methotrexate
    • Authors: Eric S. Schafer; M. Brooke Bernhardt, Kate E. Reichert, Tara E. Haworth, Mona D. Shah
      PubDate: 2017-11-09T03:05:28.16025-05:0
      DOI: 10.1002/ajh.24969
  • Donor age determines outcome in acute leukemia patients over 40 undergoing
           haploidentical hematopoietic cell transplantation
    • Authors: Jonathan Canaani; Bipin N Savani, Myriam Labopin, Xiao-jun Huang, Fabio Ciceri, William Arcese, Yener Koc, Johanna Tischer, Didier Blaise, Zafer Gülbas, Maria Teresa Van Lint, Benedetto Bruno, Mohamad Mohty, Arnon Nagler
      Abstract: Haploidentical hematopoietic cell transplantation (haplo-HCT) is being increasingly used in acute leukemia patients as an alternative transplant modality when matched sibling or matched unrelated donors are unavailable. As several potential haploidentical relative donors are typically available for a given patient, optimizing donor selection to improve clinical outcome is crucial. The impact of donor age and kinship on the outcome of acute leukemia patients is not clearly established in this setting. Using the multinational registry of the acute leukemia working party of the European society for blood and marrow transplantation we retrospective analyzed the clinical outcome of 1270 acute myeloid leukemia and acute lymphoblastic leukemia patients who underwent haplo-HCT between 2005 and 2015. Patients over the age of 40 were significantly affected by increasing donor age resulting in higher non-relapse mortality (NRM) [Hazard ratio (HR)=1.86, confidence interval (CI) 95%, 1.18–2.94; P=0.007], inferior leukemia-free survival (LFS) (HR=1.59, CI 95%, 1.13–2.24; P=0.007), and overall survival (OS) (HR=1.74, CI 95%, 1.22–2.47; P=0.002) when donors were over the age of 40. Additionally, kinship was found to be prognostically significant as patients transplanted from children donors over the age of 35 experienced an increased rate of NRM (HR=1.82, CI 95%, 1.13–2.9; P=0.01), inferior LFS (HR=1.5, CI 95%, 1.05–2.13; P=0.03), and OS (HR=1.5, CI 95%, 1.04–2.15; P=0.03). For patients younger than 40 years, donor age and kinship were mostly not clinically impactful. Our data establish donor age and kinship as significant determinants of outcome following haplo-HCT for acute leukemia patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T00:15:51.422683-05:
      DOI: 10.1002/ajh.24963
  • Excess Mortality Among Ten-Year Survivors of Classical Hodgkin Lymphoma in
           Adolescents and Young Adults
    • Authors: Ana C. Xavier; Narendranath Epperla, Jeffrey W. Taub, Luciano J. Costa
      Abstract: Adolescents and young adults (AYA) surviving classical Hodgkin lymphoma (cHL) risk long term treatment-related toxicity that may be fatal. Although changes in therapy have improved short term toxicity, the subsequent impact on risk of death in survivors is less characterized. We utilized the Surveillance, Epidemiology and End Results (SEER) program to compare excess mortality rate (EMR- observed minus expected mortality) for 10-year survivors of AYA cHL diagnosed in 1973-1992 and 1993-2003 eras. The 15-year EMR reduced from 4.88% (95% C.I. 4.36%-5.48%) to 2.19% (95% C.I. 1.69%-2.86%) while the 20-year EMR reduced from 9.46% (95% C.I. 8.72%-10.26%) to 4.07% (95% C.I. 2.53%-6.52%), between eras. Survivors of stages 1-2 had lower EMR than survivors of stages 3-4 cHL in the 1993-2003 but not in the 1973-1992 era. Males had higher EMR than females in both eras. There was an overall decline in risk of death between 10 and 15 years from diagnosis, driven mostly by SMN and CVD mortality. Long term survivors of AYA HL still have a higher risk of death than the general population, in spite of reduction in late mortality and in deaths resulting from SMN and CVD with more modern therapies. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T00:15:44.521827-05:
      DOI: 10.1002/ajh.24964
  • A descriptive study of the characteristics of older adults with sickle
           cell disease
    • Authors: Anjum B. Khan; Rachel Kesse-Adu, Cormac Breen C, Patrick B. Murphy, John Chambers, Paul Holmes P, Joanna Howard
      PubDate: 2017-11-03T00:25:27.165596-05:
      DOI: 10.1002/ajh.24961
  • Comparison between the cll-ipi and the barcelona-brno prognostic model:
           Analysis of 1299 newly diagnosed cases
    • Authors: Massimo Gentile; Tait D Shanafelt, Francesca R Mauro, Luca Laurenti, Davide Rossi, Stefano Molica, Iolanda Vincelli, Giovanna Cutrona, Giuseppina Uccello, Sara Pepe, Ernesto Vigna, Giovanni Tripepi, Kari G Chaffee, Sameer A Parikh, Sabrina Bossio, Anna Grazia Recchia, Idanna Innocenti, Raffaella Pasquale, Antonino Neri, Manlio Ferrarini, Gianluca Gaidano, Robin Foà, Fortunato Morabito
      PubDate: 2017-11-03T00:25:25.748316-05:
      DOI: 10.1002/ajh.24960
  • Outgrowing the Laboratory Diagnosis of Type 1 Von Willebrand Disease: A
           Two Decade Study
    • Authors: Mouhamed Yazan Abou-Ismail; Gbolahan O. Ogunbayo, Michelle Secic, Peter A. Kouides
      Abstract: Von Willebrand Factor (VWF) levels are known to increase with age in the general population, but that effect is unclear in von Willebrand's disease (VWD) patients. Thus, it is important to assess the trends of VWF levels with age, and the extent and rate of their normalization in patients with VWD. In a retrospective cohort study, we reviewed the medical records of 126 patients between 1996 and 2016 who met the NHLBI diagnostic criteria for Type 1 VWD or “Low VWF” (LVWF). We followed all their historically documented VWF antigen (VWF:Ag), VWF activity (VWF:RCo), and Factor VIII (FVIII) levels longitudinally over time, correlating data with clinical setting at time of testing. The average duration of follow-up was 10.5 ± 3.7 years (SD). Out of the total study population, 27.8% achieved the primary outcome of complete normalization of both VWF:Ag and VWF:RCo levels, including 19.6% and 32.5% of those with VWD and LVWF respectively. Linear regression demonstrated statistically significant positive trends of VWF:Ag, VWF:RCo, FVIII with time, calculated at 2.4 U dL-1/year, 1.4 U dL-1/year and 1.4 U dL-1/year respectively (P
      PubDate: 2017-11-03T00:25:23.768237-05:
      DOI: 10.1002/ajh.24962
  • Results of a Phase 1 Study of Quizartinib as Maintenance Therapy in
           Subjects With Acute Myeloid Leukemia in Remission Following Allogeneic
           Hematopoietic Stem Cell Transplant
    • Authors: Brenda M. Sandmaier; Samer Khaled, Betül Oran, Guy Gammon, Denise Trone, Olga Frankfurt
      Abstract: FLT3-ITD–mutated acute myeloid leukemia (AML) has very high risk of relapse and is associated with poor outcome following allogeneic hematopoietic-cell transplant (allo-HCT). This two-part, phase 1, multicenter, open-label, sequential-group, dose-escalation study aimed to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and safety/tolerability of quizartinib, a selective and highly potent FLT3 inhibitor, when administered as maintenance therapy after allo-HCT. Thirteen subjects with documented FLT3-ITD–mutated AML in morphological remission following allo-HCT received one of two quizartinib dihydrochloride dose levels (DL): 40 mg/d (DL1; n=7) and 60 mg/d (DL2; n=6), administered orally in 28-day cycles for up to 24 cycles. Median age of participants was 43 years. All subjects received human leukocyte antigen (HLA)-matched allo-HCT. One subject treated at DL1 and 1 treated at DL2 had DLTs that required drug interruption (grade 3 gastric hemorrhage and grade 3 anemia, respectively). Ten subjects (77%) received quizartinib for>1 year; 5 (38%) completed 24 cycles. Four subjects (31%) discontinued quizartinib due to adverse events. One subject (8%) experienced relapse during cycle 1 and discontinued treatment. Most common (≥20%) grade 3/4 adverse events were neutropenia (23%), anemia (15%), leukopenia (15%), lymphopenia (15%), and eye disorders (15%). This study demonstrated acceptable tolerability and early evidence of reduced relapse rate following allo-HCT with quizartinib maintenance compared to historical cohorts. No MTD was identified, but 60 mg daily was selected as highest dose for continuous daily administration based on randomized comparison of daily 30 and 60 mg doses in relapsed/refractory AML. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-01T00:55:25.987036-05:
      DOI: 10.1002/ajh.24959
  • Demographics and patient characteristics of 1209 patients with Gaucher
           Disease: Descriptive analysis from the Gaucher Outcome Survey (GOS)
    • Authors: Ari Zimran; Nadia Belmatoug, Bruno Bembi, Patrick Deegan, Deborah Elstein, Diego Fernandez-Sasso, Pilar Giraldo, Ozlem Goker-Alpan, Heather Lau, Elena Lukina, Zoya Panahloo, Ida Vanessa D. Schwartz,
      Abstract: The Gaucher Outcome Survey (GOS) is an international Gaucher disease (GD) registry established in 2010 for patients with a confirmed GD diagnosis, regardless of GD type or treatment status, designed to evaluate the safety and long-term effectiveness of velaglucerase alfa and other GD-related treatments. As of February 25, 2017, 1209 patients had enrolled, the majority from Israel (44.3%) and the US (31.4%). Median age at GOS entry was 40.4 years, 44.1% were male, and 13.3% had undergone a total splenectomy. Most patients had type 1 GD (91.5%) and were of Ashkenazi Jewish ethnicity (55.8%). N370S/N370S was the most prevalent genotype, accounting for 44.2% of genotype-confirmed individuals (n=847); however, there was considerable variation between countries. A total of 887 (73.4%) patients had received ≥1 GD-specific treatment at any time, most commonly imiglucerase (n=587), velaglucerase alfa (n=507), and alglucerase (n=102). Hematological and visceral findings at the time of GOS entry were close to normal for most patients, probably a result of previous treatment; however, spleen volume of patients in Israel was almost double that of patients elsewhere (7.2 multiples of normal [MN] vs. 2.7, 2.9 and 4.9 MN in the US, UK and rest of world), which may be explained by a greater disease severity in this cohort. The aim of this analysis was to provide an overview of GOS and present baseline demographic and disease characteristics of participating patients to help improve the understanding of the natural history of GD and inform the overall management of patients with the disease. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-01T00:55:21.696434-05:
      DOI: 10.1002/ajh.24957
  • Mutations of the integrin αIIb/β3 intracytoplasmic salt bridge cause
           macrothrombocytopenia and enlarged platelet α-granules
    • Authors: Marie Favier; Jean-Claude Bordet, Remi Favier, Vasiliki Gkalea, Xavier Pillois, Philippe Rameau, Najet Debili, Marie-Christine Alessi, Paquita Nurden, Hana Raslova, Alan Nurden
      Abstract: Rare gain-of-function mutations within the ITGA2B or ITGB3 genes have been recognized to cause macrothrombocytopenia (MTP). Here we report three new families with autosomal dominant (AD) MTP, two harboring the same mutation of ITGA2B, αIIbR995W, and a third family with an ITGB3 mutation, β3D723H. In silico analysis shows how the two mutated amino acids directly modify the salt bridge linking the intra-cytoplasmic part of αIIb to β3 of the integrin αIIbβ3.For all affected patients, the bleeding syndrome and MTP was mild to moderate. Platelet aggregation tended to be reduced but not absent. Electron microscopy associated with a morphometric analysis revealed large round platelets; a feature being the presence of abnormal large α-granules with some giant forms showing signs of fusion. Analysis of the maturation and development of megakaryocytes reveal no defect in their early maturation but abnormal proplatelet formation was observed with increased size of the tips.Interestingly, this study revealed that in addition to the classical phenotype of patients with αIIbβ3 intracytoplasmic mutations there is an abnormal maturation of α-granules. It is now necessary to determine if this feature is a characteristic of all mutations disturbing the αIIb R995/β3 D723 salt bridge. This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-01T00:50:30.554924-05:
      DOI: 10.1002/ajh.24958
  • A blastic plasmacytoid dendritic cell neoplasm-like phenotype identifies a
           subgroup of NPM1-mutated AML patients with worse prognosis
    • Authors: Paola Minetto; Fabio Guolo, Marino Clavio, Annalisa Kunkl, Nicoletta Colombo, Enrico Carminati, Livia Giannoni, Filippo Ballerini, Roberto Massimo Lemoli, Marco Gobbi, Maurizio Miglino
      PubDate: 2017-10-28T03:35:49.509167-05:
      DOI: 10.1002/ajh.24956
  • Impact of MYD88 Mutation Status in Waldenström Macroglobulinemia
    • Authors: Jithma P. Abeykoon; Jonas Paludo, Rebecca L. King, Stephen M. Ansell, Morie A. Gertz, Betsy R. LaPlant, Alese E. Halvorson, Wilson I. Gonsalves, David Dingli, Hong Fang, S. Vincent Rajkumar, Martha Q. Lacy, Rong He, Taxiarchis Kourelis, Craig B. Reeder, Anne J. Novak, Ellen McPhail, David Viswanatha, Thomas E. Witzig, Ronald S. Go, Thomas Habermann, Francis K. Buadi, Angela Dispenzieri, Nelson Leung, Yi Lin, Carrie Thompson, Suzanne Hayman, Robert A. Kyle, Shaji Kumar, Prashant Kapoor
      Abstract: Waldenström macroglobulinemia (WM) is an immunoglobulin M-associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Due to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically-relevant data in this patient-population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016 to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele-specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype; 44 had active disease. The estimated median follow-up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4-16.5) for MYD88L265P vs. 13.9 years (95% CI: 6.4-29.3) for the MYD88WT (p=0.86). The time-to-next therapy from frontline treatment and the presenting features were similar in the two patient-populations. For patients with smoldering WM at diagnosis, the median time-to-progression to active disease was 2.8 years (95% CI: 2.2-3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7-3.1) in the MYD88WT cohort, (p=0.21). MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease-defining feature in WM. Our findings warrant external validation, preferably through prospective studies. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-28T03:35:38.746423-05:
      DOI: 10.1002/ajh.24955
  • Annual clinical updates in hematological malignancies: a continuing
           medical education series
    • PubDate: 2017-10-25T04:35:55.84648-05:0
      DOI: 10.1002/ajh.24907
  • Efficacy of VDT PACE-like Regimens in Treatment of Relapsed/Refractory
           Multiple Myeloma
    • Authors: Arjun Lakshman; Preet Paul Singh, S. Vincent Rajkumar, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, David Dingli, Yi Lisa Hwa, Amie L. Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven R. Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Yi Lin, Wilson I. Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, Shaji K. Kumar
      Abstract: Experience with intensive chemotherapy for relapsed/refractory multiple myeloma (RRMM) using VDT PACE regimen and its modifications (VDT PACE-like regimens-VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141 patients with RRMM who received VPLRs at our center between 2006 and 2017 in an intent-to-treat analysis. Median age was 59.7 years and 66.7% of patients were male. A median of 2.2 years (range, 0.02-11.4) separated diagnosis of myeloma and inititation of VPLR. High-risk cytogenetics were present in 52.4% patients. Patients received a median of 4 (range, 1-14) prior therapies including stem cell transplant (SCT) in 66.7% patients. Ninety five (67.4%) patients received VDT PACE, 20 (14.2%) received VD PACE and 26 (18.4) received other VPLRs. Patients received a median of 1 cycle (range, 1-9) of VPLR. We observed ≥minimal response in 68.4%, ≥partial response (PR) in 54.4% and ≥very good PR in 10.3% patients. Median progression-free survival was 3.1 months (95%CI, 1.9-3.9) and median overall survival (OS) was 8.1 months (CI, 6.2-9.9). One-hundred and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%) received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for those who received SCT after VPLR was 15.1 months (CI, 10.3-20.8). Age ≥60 years [hazard ratio (HR)- 2.3 (CI, 1.4-3.7); p
      PubDate: 2017-10-25T03:20:52.746188-05:
      DOI: 10.1002/ajh.24954
  • Pediatric to adult care Co-location transitional model for youth with
           sickle cell disease
    • Authors: Vikki G. Nolan; Sheila M. Anderson, Matthew P. Smeltzer, Jerlym S. Porter, Yvonne M. Carroll, Ian M. Brooks, Nada Elmagboul, James G. Gurney, Jane S. Hankins
      Abstract: Among youth with sickle cell disease (SCD), morbidity and mortality substantially increase following departure from pediatric care. The purpose of this study was to investigate the efficacy of co-location transitional model by comparing the rate of health care utilization pre- and post-transfer to adult care and to evaluate the relation between disease specific knowledge and the co-location model. All patients transferring from pediatric to adult care between October 2011 and December 2013, opting for the co-location model to transition from pediatric to adult care in Memphis, TN were included in the analysis. Overall utilization, comprised of both acute care visits and hospitalizations, and health-maintenance visits were compared pre- and post-transfer. Additionally, the association between patient understanding of pain and all health care utilization were assessed. There were 59 participants who established adult care using the co-location transitional model. We found an increase in acute care visits, but a decrease in hospitalizations, that resulted in no change in overall utilization (IRR: 1.11; (95%CI: 0.76, 1.63) comparing pediatric to adult care. The overall utilization rate during adult care was below those previously reported (3.61 vs. 1.65 per person-year, p
      PubDate: 2017-10-25T03:20:36.54514-05:0
      DOI: 10.1002/ajh.24953
  • Lenalidomide therapy in patients with myelodysplastic
           syndrome/myeloproliferative neoplasm with ring sideroblasts and
           thrombocytosis (MDS/MPN-RS-T)
    • Authors: Maura Nicolosi; Mythri Mudireddy, Rangit Vallapureddy, Naseema Gangat, Ayalew Tefferi, Mrinal M. Patnaik
      PubDate: 2017-10-25T03:20:19.581705-05:
      DOI: 10.1002/ajh.24952
  • Characteristics of CLL patients achieving 5+ years of remission after
           FC-based first line treatment: Retrospective observations from the FILO
    • Authors: Yann Guillermin; Charles Herbaux, Fabien Subtil, Thérèse Aurran-Schleinitz, Florence Cymbalista, Remi Letestu, Stéphane Leprêtre, Sandrine Vaudaux, Kamel Laribi, Véronique Leblond, Yasmina Defoi, Raouf Benchikh, Gilles Salles, Pascal Godmer, Henry Jardel, Fréderic Vallais, Pierre Feugier, Frédérique Orsini, Brigitte Pegourié, Vincent Lévy, Anne-Sophie Michallet
      PubDate: 2017-10-21T03:15:25.524932-05:
      DOI: 10.1002/ajh.24951
  • Acute promyelocytic leukemia and chronic lymphocytic leukemia diagnosed
    • Authors: Catherine C. Coombs; Stephanie P. Mathews
      PubDate: 2017-10-20T02:25:45.186881-05:
      DOI: 10.1002/ajh.24950
  • A Randomized Controlled Trial Comparing Two Vaso-occlusive Episode (VOE)
           Protocols in Sickle Cell Disease (SCD)
    • Authors: Paula Tanabe; Susan Silva, Hayden B. Bosworth, Regina Crawford, Judith A. Paice, Lynne D. Richardson, Christopher N. Miller, Jeffrey Glassberg
      PubDate: 2017-10-19T02:01:16.329436-05:
      DOI: 10.1002/ajh.24948
  • Donor lymphocyte infusion and methotrexate for immune recovery after
           T-cell depleted haploidentical transplantation
    • Authors: Andrew L. Gilman; Wing Leung, Morton J. Cowan, Mark Cannon, Stacy Epstein, Carrie Barnhart, Krishna Shah, Michelle Hyland, Tracy Fukes, Anastasia Ivanova
      Abstract: CD34+ cell selection minimizes graft-versus-host disease (GVHD) after haploidentical donor stem cell transplant but is associated with slow immune recovery and infections. We report a Phase I/II study of prophylactic donor lymphocyte infusion (DLI) followed by methotrexate (MTX) GVHD prophylaxis after CD34-selected haploidentical donor transplant. A prophylactic DLI was given between day +30 and +42. Rituximab was given with DLI for the last 10 patients. The goal of the study was to determine a DLI dose that would result in a CD4+ cell count > 100/µL at Day +120 in ≥ 66% of patients with ≤ 33% grade II-III, ≤ 17% grade III, and no grade IV acute GVHD by Day +180. Thirty-five patients with malignant (n=25) or non-malignant disease (n=10) were treated after CD34-selected haploidentical donor peripheral blood stem cell transplant. The DLI dose of 5 x 104/kg met the CD4/GVHD goal with 67% of patients having CD4+ cells > 100/µL and 11% grade II-IV acute GVHD. The cumulative incidence of chronic GVHD was 16%. Fatal viral and fungal infections occurred in 11%. The 2 year estimated overall survival was 69% and the relapse rate was 14% for patients in remission at transplant. There was no effect of NK alloreactivity on relapse. Nine of ten patients at the target DLI dose cohort of 5 x 104/kg are alive with median follow-up of 18 mos (range 6-29). Delayed prophylactic DLI and MTX was associated with promising outcomes at the target DLI dose. This trial was registered at, # NCT01027702. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-19T02:01:06.745372-05:
      DOI: 10.1002/ajh.24949
  • Acute immune toxicity during anti-thymocyte globulin: That's CARPA!
    • Authors: Serena Marotta; Patrizia Ricci, Luana Marano, Giuliana Beneduce, Orsola Vitagliano, Fiorenza De Gregorio, Francesco Grimaldi, Fabrizio Pane, Antonio M Risitano
      PubDate: 2017-10-19T02:01:04.459119-05:
      DOI: 10.1002/ajh.24945
  • MECOM, HBS1L-MYB, THRB-RARB, JAK2 and TERT polymorphisms defining the
           genetic predisposition to myeloproliferative neoplasms - a study on 939
    • Authors: Adrian P. Trifa; Claudia Bănescu, Anca S. Bojan, Cristian M. Voina, Ștefana Popa, Simona Vișan, Alina D. Ciubean, Florin Tripon, Delia Dima, Viola M. Popov, Ștefan C. Vesa, Mihaela Andreescu, Tünde Török-Vistai, Romeo G. Mihăilă, Nicoleta Berbec, Ioan Macarie, Andrei Coliță, Maria Iordache, Alina C. Cătană, Marius F. Farcaș, Ciprian Tomuleasa, Kinga Vasile, Cristina Truică, Adriana Todincă, Lavinia Pop-Muntean, Raluca Manolache, Horia Bumbea, Ana-Maria Vlădăreanu, Mihaela Gaman, Cristina M. Ciufu, Radu A. Popp
      Abstract: Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific somatic mutations in JAK2, CALR or MPL genes. JAK2 46/1 and TERT rs2736100 polymorphisms are known to significantly predispose to MPN. This study aimed to establish the additional contribution of the recently described MECOM rs2201862, HBS1L-MYB rs9376092 and THRB-RARB rs4858647 polymorphisms to the occurrence of MPN. These three polymorphisms, along with JAK2 46/1 and TERT rs2736100 were genotyped in 939 MPN patients (454 with ET, 337 with PV and 148 with PMF) and 483 controls. MECOM rs2201862 associated significantly with each MPN entity, except for ET, and with all major molecular sub-types, especially those CALR-mutated (OR = 1.4; 95% CI = 1.1 - 1.8; p-value = 0.005). HBS1L-MYB rs9376092 associated only with JAK2 V617F-mutated ET (OR = 1.4; 95% CI = 1.1 - 1.7; p-value = 0.003). THRB-RARB rs4858647 had a weak association with PMF only (OR = 1.5; 95% CI = 1 - 2.1; p-value = 0.04). Surprisingly, JAK2 46/1 haplotype was associated significantly not only with JAK2 V617F-mutated MPN, but also with CALR-mutated MPN (OR = 1.4; 95% CI = 1.1 - 1.8; p-value = 0.01). TERT rs2736100 was associated equally strong with all MPN, regardless of phenotype or molecular sub-type. In conclusion, JAK2 46/1, TERT rs2736100 and MECOM rs2201862 are the chief predisposing polymorphisms to MPN. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-19T02:01:02.984501-05:
      DOI: 10.1002/ajh.24946
  • Hyper-CVAD plus Nelarabine in Newly Diagnosed Adult T-Cell Acute
           Lymphoblastic Leukemia and T-Lymphoblastic Lymphoma
    • Authors: Yasmin Abaza; Hagop M. Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D. Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
      Abstract: Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-19T02:00:51.238289-05:
      DOI: 10.1002/ajh.24947
  • Severe Thrombocytopenia in a Patient Following Liver Transplantation
           Caused by HPA-1a Antibodies Produced by the Liver Donor
    • Authors: Paul F. Lindholm; Hau C. Kwaan, Glenn Ramsey, Brian R. Curtis, Jonathan Fryer
      PubDate: 2017-10-16T21:56:01.167175-05:
      DOI: 10.1002/ajh.24944
  • Prognostic significance of additional chromosomal abnormalities at the
           time of diagnosis in patients with chronic myeloid leukemia treated with
           frontline tyrosine kinase inhibitors
    • Authors: Ahmad Alhuraiji; Hagop Kantarjian, Prajwal Boddu, Farhad Ravandi, Gautam Borthakur, Courtney DiNardo, Naval Daver, Tapan Kadia, Naveen Pemmaraju, Sherry Pierce, Guillermo Garcia-Manero, William Wierda, Srdan Verstovsek, Elias Jabbour, Jorge Cortes
      Abstract: Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148 (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with ponatinib. There was a significantly higher rate of complete cytogenetic response (CCyR) at 6 months in patients without ACA (P = 0.02). However cumulative CCyR and major molecular response (MMR) rates were not different. Similarly, MR4.0 and MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5 for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact transformation-free, failure-free, event-free, or overall survival expectations. Acknowledging small sample size estimates, response rates and survival outcomes were comparable in CP with ACA irrespective of whether chromosomal abnormalities were ‘major route' or other. The presence of ACA at diagnosis does not confer worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA at diagnosis should not alter treatment strategies in these patients. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-13T01:50:24.142094-05:
      DOI: 10.1002/ajh.24943
  • Revisiting the need for bone marrow examination in chronic myeloid
    • Authors: Ayalew Tefferi; Curtis A. Hanson, Rhett P. Ketterling
      PubDate: 2017-10-13T01:50:19.417156-05:
      DOI: 10.1002/ajh.24942
  • The athlete's hematological response to hypoxia: A meta-analysis on the
           influence of altitude exposure on key biomarkers of erythropoiesis
    • Authors: Louisa M. Lobigs; Ken Sharpe, Laura A. Garvican-Lewis, Christopher J. Gore, Peter Peeling, Brian Dawson, Yorck O. Schumacher
      PubDate: 2017-10-13T01:46:28.887101-05:
      DOI: 10.1002/ajh.24941
  • Lymphoplasmacytoid cytology in plasma cell leukemia
    • Authors: Ahmad Khoder; Magda Al Obaidi, Natasha Wiles, Elisabet Nadal-Melsio, Barbara J. Bain
      PubDate: 2017-10-13T01:45:20.555896-05:
      DOI: 10.1002/ajh.24940
  • Program Expansion of a Day Hospital Dedicated to Manage Sickle Cell Pain
    • Authors: Jin Han; Santosh L. Saraf, Laura Kavoliunaite, Shivi Jain, Johara Hassan, Lewis L Hsu, Robert E. Molokie, Victor R. Gordeuk, Michel Gowhari
      PubDate: 2017-10-11T03:00:36.143758-05:
      DOI: 10.1002/ajh.24938
  • Therapy Related-Chronic Myelomonocytic Leukemia (CMML): Molecular,
           Cytogenetic and Clinical Distinctions from de novo CMML
    • Authors: Mrinal M. Patnaik; Rangit Vallapureddy, Fevzi F. Yalniz, Curtis A. Hanson, Rhett P. Ketterling, Terra L Lasho, Christy Finke, Aref Al-Kali, Naseema Gangat, Ayalew Tefferi
      Abstract: Therapy related myeloid neoplasms (t-MN) including therapy related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are associated with aggressive disease biologies and poor outcomes. In this large (n=497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t-CMML. T-CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t-CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t-MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (
      PubDate: 2017-10-11T03:00:22.154306-05:
      DOI: 10.1002/ajh.24939
  • Impact of screening and exclusion of high anti-A titer donors on the risk
           of hemolytic anemia with intravenous immunoglobulin treatment – a
           hospital-based cohort study in the US
    • Authors: Carlos Martinez; Douglas J Watson, Amgad Shebl, Christopher Wallenhorst, Alphonse Hubsch, Toby L Simon
      PubDate: 2017-10-06T03:40:34.970531-05:
      DOI: 10.1002/ajh.24931
  • Alternate use of thrombopoietin receptor agonists in adult primary immune
           thrombocytopenia patients: A retrospective collaborative survey from
           italian hematology centers
    • Authors: Silvia Cantoni; Monica Carpenedo, Maria Gabriella Mazzucconi, Valerio De Stefano, Valentina Carrai, Marco Ruggeri, Giorgina Specchia, Nicola Vianelli, Fabrizio Pane, Ugo Consoli, Andrea Artoni, Francesco Zaja, Mariella D'Adda, Andrea Visentin, Felicetto Ferrara, Wilma Barcellini, Domenica Caramazza, Erminia Baldacci, Elena Rossi, Alessandra Ricco, Angela Ciminello, Francesco Rodeghiero, Michele Nichelatti, Roberto Cairoli
      PubDate: 2017-10-06T03:40:28.026415-05:
      DOI: 10.1002/ajh.24935
  • Improved prognosis with additional medium-dose VP16 to CY/TBI in
           allogeneic transplantation for high risk ALL in adults
    • Authors: Yasuyuki Arai; Tadakazu Kondo, Akio Shigematsu, Junji Tanaka, Kazuteru Ohashi, Takahiro Fukuda, Michihiro Hidaka, Naoki Kobayashi, Koji Iwato, Toru Sakura, Makoto Onizuka, Yukiyasu Ozawa, Tetsuya Eto, Mineo Kurokawa, Kaoru Kahata, Naoyuki Uchida, Yoshiko Atsuta, Shuichi Mizuta, Shinichi Kako,
      Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium-dose etoposide (VP16, 30 – 40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30–40 mg/kg) (N=376) and CY/TBI (N=1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56–1.00; p = 0.05) with a corresponding improvement in leukemia-free survival (hazard ratio [HR], 0.76; 95%CI, 0.62–0.93; p = 0.01), particularly in patients transplanted at CR1 with advanced-risk (positive minimal residual disease, presence of poor-risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56–1.00; p = 0.05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39–0.88; p = 0.01). The addition of VP16 did not increase post-transplant complications or non-relapse mortality (HR, 0.88; 95%CI, 0.65 – 1.18; p = 0.38). This study was the first to reveal the efficacy of the addition of medium-dose VP16 to CY/TBI in high-risk ALL. To establish new myeloablative conditioning regimens including VP16, a large-scale prospective study is necessary. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-06T03:31:13.267166-05:
      DOI: 10.1002/ajh.24933
  • Transformation of MDS/MPN-RS-T to AML – Trisomy 13, Resistant
           Thrombocytosis and Transient Disease Control with Oral Busulfan Therapy
    • Authors: A. Barrett; M. Catherwood, P. Thornton, P. Murphy, J. Quinn
      PubDate: 2017-10-06T03:31:10.712926-05:
      DOI: 10.1002/ajh.24934
  • Correcting the cut-off point of hemoglobin at high altitude favors
           misclassification of anemia, erythrocytosis and excessive erythrocytosis
    • Authors: Gustavo F. Gonzales; Verónica Rubín de Celis, José Begazo, María del Rosario Hinojosa, Sandra Yucra, Alisson Zevallos, Vilma Tapia
      PubDate: 2017-10-06T03:31:09.295066-05:
      DOI: 10.1002/ajh.24932
  • Revised Prevalence Estimate of Possible Hereditary Xerocytosis as Derived
           from a Large U.S. Laboratory Database
    • Authors: Harvey W. Kaufman; Justin K. Niles, Denis R. Gallagher, Alicia Rivera, Seth L. Alper, Carlo Brugnara, L. Michael Snyder
      PubDate: 2017-10-03T03:40:42.000351-05:
      DOI: 10.1002/ajh.24923
  • Cardiovascular Evaluation and Management of Iron Overload Cardiomyopathy
           in Sickle Cell Disease
    • Authors: Mahazarin Ginwalla; Abdullah AlMasoud, David Tofovic, Tara Alin, Sadeer Al-Kindi, Guilherme Oliveira, Sanjay Rajagopalan, Robert Schilz, Jane Little
      PubDate: 2017-10-03T03:35:48.084081-05:
      DOI: 10.1002/ajh.24924
  • Current paradigms in the management of Philadelphia chromosome positive
           acute lymphoblastic leukemia in adults
    • Authors: Riad El Fakih; Elias Jabbour, Farhad Ravandi, Mona Hassanein, Farhan Anjum, Syed Ahmed, Hagop Kantarjian
      Abstract: Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) is a biologically, clinically, and genetically distinct subtype of precursor-B ALL. The Ph chromosome, results from a reciprocal translocation of the ABL1 kinase gene on chromosome 9 to the breakpoint cluster region (BCR) gene on chromosome 22. Depending on the translocation breakpoint, typically a p210 BCR-ABL1 or a p190 BCR- ABL onc protein are generated; both are constitutively active tyrosine kinases that play a central role to alter signaling pathways of cell proliferation, survival, and self-renewal, leading to leukemogenesis. In Ph-positive ALL, the p190-BCR-ABL (minor [m]-bcr) subtype is more frequent than the p210-BCR-ABL (major [M]-bcr) subtype, commonly found in chronic myeloid leukemia 1,2. The Philadelphia chromosome is the most frequent recurrent cytogenetic abnormality in elderly patients with ALL. Its incidence increases with age, reaching approximately 50% in patients with ALL aged 60 years and over 1. Patients traditionally had a very poor outcome with chemotherapy, particularly if they do not undergo allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1). With the availability of multiple tyrosine kinase inhibitors (TKI), the therapeutic armamentarium is expanding quickly. However, there is no consensus on how to best treat Ph-positive ALL. With modern therapy, improved outcomes have led to the emergence of a number of controversies, including the need for intensive chemotherapy, the ideal TKI, and whether all eligible patients should receive an allo-HSCT, and if so, what type. Here we discuss these controversies in light of the available literature. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-03T03:35:46.405937-05:
      DOI: 10.1002/ajh.24926
  • High dose chemotherapy and autologous stem cell transplantation in nodular
           lymphocyte-predominant Hodgkin lymphoma: A retrospective study by the
           European Society for Blood and Marrow Transplantation (EBMT)-Lymphoma
           Working Party
    • Authors: Saad Akhtar; Silvia Montoto, Ariane Boumendil, Herve Finel, Tamas Masszi, Pavel Jindra, Damir Nemet, Stephan Fuhrmann, Yves Beguin, Luca Castagna, Felicetto Ferrara, Saveria Capria, Ram Malladi, Jose Maria Moraleda, Adrian Bloor, Hervé Ghesquières, Julia Meissner, Anna Sureda, Peter Dreger
      Abstract: Whilst autologous stem cell transplantation (auto-SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto-SCT in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto-SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003-2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto-SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13-58), and the median number of prior treatment lines was 2 (range 1-5), including rituximab in 63% of the patients. At auto-SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. 72% of the patients received BEAM as high-dose therapy. With a median follow-up of 56 months (range 3-105), 5-year progression-free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto-SCT (vs PR, p=0.049) for OS. Auto-SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long-term survival independent of the time interval between diagnosis and transplant. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-03T03:35:41.859486-05:
      DOI: 10.1002/ajh.24927
  • Hereditary Stomatocytosis: An underdiagnosed condition
    • Authors: Immacolata Andolfo; Roberta Russo, Antonella Gambale, Achille Iolascon
      Abstract: Hereditary stomatocytoses are a wide class of hemolytic anemias characterized by alterations of ionic flux with increased cation permeability that results in inappropriate shrinkage or swelling of the erythrocytes, and water lost or gained osmotically.The last few years have been crucial for new acquisitions in this field in terms of identifying new causative genes and of studying their pathogenetic mechanisms.This review summarizes the main features of erythrocyte membrane transport diseases, dividing them into forms with either isolated erythroid phenotype (non-syndromic) or extra-hematological manifestations (syndromic), and focusing particularly on the most recent advances regarding dehydrated forms of hereditary stomatocytosis and familial pseudohyperkalemia. This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-03T03:35:39.752302-05:
      DOI: 10.1002/ajh.24929
  • Vanin 1 (VNN1) levels predict poor outcome in acute myeloid leukemia
    • Authors: Valerio Izzi; Juho Lakkala, Raman Devarajan, Eeva-Riitta Savolainen, Pirjo Koistinen, Ritva Heljasvaara, Taina Pihlajaniemi
      PubDate: 2017-10-03T03:35:33.936867-05:
      DOI: 10.1002/ajh.24925
  • Relatively favourable outcome after allogeneic stem cell transplantation
           for BCR-ABL1-positive AML: A survey from the Acute Leukemia Working Party
           of the European Society for Blood and Marrow Transplantation (EBMT)
    • Authors: Vladimir Lj Lazarevic; Myriam Labopin, Depei Wu, Ibrahim Yakoub-Agha, Anne Huynh, Per Ljungman, Nicolaas Schaap, Jan J. Cornelissen, Natacha Maillard, Pietro Pioltelli, Tobias Gedde-Dahl, Stig Lenhoff, Mohamed Houhou, Jordi Esteve, Mohamad Mohty, Arnon Nagler
      Abstract: The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR-ABL1-positive acute myeloid leukemia (AML). Fifty-seven patients (median age, 48 years, range: 19-67) with BCR-ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR-ABL1/ABL
      PubDate: 2017-10-03T03:35:22.178269-05:
      DOI: 10.1002/ajh.24928
  • Late infections and secondary malignancies after bendamustine/rituximab or
           RCHOP/RCVP chemotherapy for B-cell lymphomas
    • Authors: Adam J Olszewski; John L Reagan, Jorge J Castillo
      PubDate: 2017-09-29T10:54:03.359619-05:
      DOI: 10.1002/ajh.24921
  • Urological complications associated with adult allogeneic stem cell
    • Authors: Laila Schneidewind; Thomas Neumann, Kathrin Zimmermann, Christian Andreas Schmidt, William Krüger
      PubDate: 2017-09-29T10:51:49.196623-05:
      DOI: 10.1002/ajh.24920
  • Residual disease detection using targeted parallel sequencing predicts
           relapse in cytogenetically normal acute myeloid leukemia
    • Authors: Lukas Gaksch; Karl Kashofer, Ellen Heitzer, Franz Quehenberger, Shruti Daga, Sybille Hofer, Iris Halbwedl, Ricarda Graf, Nina Krisper, Gerald Hoefler, Armin Zebisch, Heinz Sill, Albert Wölfler
      Abstract: Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform. Furthermore, the variant allelic frequency of distinct mutations was validated by digital PCR and sequencing using a barcoding approach. Twenty-seven out of 34 patients could be analyzed for mutation clearance. We identified 68 somatic mutations at diagnosis (median, 3 mutations per patient; range 1-5) and 22 of these were still detected in 16 patients after consolidation therapy with a reliable sensitivity of 0.5% (median, 1 mutation; range 0-3). The most frequent non-cleared mutations were found in DNMT3A. However, as persistence of these mutations has recently been shown to be without any impact on relapse risk, we performed survival and relapse risk analysis excluding DNMT3A mutations. Importantly, persistence of non-DNMT3A mutations was associated with a higher risk of AML relapse (7/8 pts versus 6/19 pts; p=0.013) and with a shorter relapse-free survival (333 days vs. not reached; log-rank p=0.0219). Detection of residual disease by routine targeted parallel sequencing proved feasible and effective as persistence of somatic mutations other than DNMT3A were prognostic for relapse in CN AML. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-29T10:51:18.620427-05:
      DOI: 10.1002/ajh.24922
  • Utility and limitations of exome sequencing in the molecular diagnosis of
           pediatric inherited platelet disorders
    • Authors: Edward J. Romasko; Batsal Devkota, Sawona Biswas, Vijayakumar Jayaraman, Ramakrishnan Rajagopalan, Matthew C. Dulik, Christopher S. Thom, Jiwon Choi, Sowmya Jairam, Maria I. Scarano, Ian D. Krantz, Nancy B. Spinner, Laura K. Conlin, Michele P. Lambert
      Abstract: Inherited platelet disorders (IPD) are a heterogeneous group of rare disorders that affect platelet number and function and often predispose to other significant medical complications. In spite of the identification of over 50 IPD disease-associated genes, a molecular diagnosis is only identified in a minority (10%) of affected patients without a clinically suspected etiology. We studied a cohort of 21 pediatric patients with suspected IPDs by exome sequencing (ES) to: 1) examine the performance of the exome test for IPD genes, 2) determine if this exome-wide diagnostic test provided a higher diagnostic yield than has been previously reported, 3) to evaluate the frequency of variants of uncertain significance identified, and 4) to identify candidate variants for functional evaluation in patients with an uncertain or negative diagnosis. We established a high priority gene list of 53 genes, evaluated exome capture kit performance, and determined the coverage for these genes and disease-related variants. We identified likely disease causing variants in 5 of the 21 probands (23.8%) and variants of uncertain significance in 52% of patients studied. In conclusion, ES has the potential to molecularly diagnose causes of IPD, and to identify candidate genes for functional evaluation. Robust exome sequencing also requires that coverage of genes known to be associated with clinical findings of interest need to be carefully examined and supplemented if necessary. Clinicians who undertake ES should understand the limitations of the test and the full significance of results that may be returned. This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T03:46:57.906647-05:
      DOI: 10.1002/ajh.24917
  • Impact of involved free light chain (FLC) levels in patients achieving
           normal FLC ratio after initial therapy in light chain amyloidosis (AL)
    • Authors: Nidhi Tandon; Surbhi Sidana, Angela Dispenzieri, Morie A. Gertz, Martha Q. Lacy, David Dingli, Francis K. Buadi, Amie L. Fonder, Suzanne R. Hayman, Yi Lisa Hwa, Miriam A. Hobbs, Prashant Kapoor, Wilson I. Gonsalves, Nelson Leung, Ronald S. Go, John A. Lust, Stephen J. Russell, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
      Abstract: Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n=166; 48.1%) were compared to those who did not (n=179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; p=0.002) and patients in advanced Mayo stage (42.9 vs 32.2%; p=0.04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; p=0.0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; p
      PubDate: 2017-09-27T03:46:36.600115-05:
      DOI: 10.1002/ajh.24919
  • Changes in intestinal microbiota and their effects on allogeneic stem cell
    • Authors: Rory M Shallis; Christopher M Terry, Seah H Lim
      Abstract: The human intestinal microbiota is essential for microbial homeostasis, regulation of metabolism, and intestinal immune tolerance. Rapidly evolving understanding of the importance of the microbiota implicates changes in the composition and function of intestinal microbial communities in an assortment of systemic conditions. Complications following allogeneic stem cell transplant now join the ever-expanding list of pathologic states regulated by intestinal microbiota. Dysbiosis, or disruption of the normal ecology of this microbiome, has been directly implicated in the pathogenesis of entities such as Clostridium difficile infections, graft-versus-host disease, and most recently disease relapse, all of which are major causes of morbidity and mortality in patients undergoing allogeneic stem cell transplant. In this review, we elucidate the key origins of microbiotic alterations and discuss how dysbiosis influences complications following allogeneic stem cell transplant. Our emerging understanding of the importance of a balanced and diverse intestinal microbiota is prompting investigation into the appropriate treatment of dysbiosis, reliable and early detection of such, and ultimately its prevention in patients to improve the outcome following allogeneic hematopoietic stem cell transplant. This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-26T03:30:43.446923-05:
      DOI: 10.1002/ajh.24896
  • Imatinib-induced psoriasiform eruption in a patient with chronic myeloid
    • Authors: Connie R. Shi; Vinod E. Nambudiri
      PubDate: 2017-08-24T01:25:22.857562-05:
      DOI: 10.1002/ajh.24894
  • Not Bitten by the Bug: A CD30+ lymphoproliferative disorder masquerading
           as arthropod bites
    • Authors: Jacqueline McKesey; Travis Vandergriff, Heather Wickless
      PubDate: 2017-07-11T21:21:15.803414-05:
      DOI: 10.1002/ajh.24846
  • Marked leukemoid reaction in a patient with metastatic breast carcinoma
    • Authors: Yasmin Harvey; Shane Bleakley, Piers Blombery, Barbara J. Bain
      PubDate: 2017-07-11T21:21:10.188469-05:
      DOI: 10.1002/ajh.24849
  • Acute leukemic transformation of myelodysplastic syndrome – is
           cytochemistry still relevant'
    • Authors: Imogen Caldwell; Anna Ruskova, Nicola Eaddy, Barbara J. Bain
      PubDate: 2017-06-22T02:15:48.738401-05:
      DOI: 10.1002/ajh.24831
    • Pages: 1 - 3
      PubDate: 2017-12-07T02:33:22.096586-05:
      DOI: 10.1002/ajh.24982
  • Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification
           and management
    • Authors: Guillermo Montalban-Bravo; Guillermo Garcia-Manero
      Pages: 129 - 147
      Abstract: Disease overviewThe myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy.DiagnosisDiagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis.Risk-stratificationPrognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow and cytogenetic characteristics. The most commonly used system is probably the International Prognostic Scoring System (IPSS). IPSS is now replaced by the revised IPSS-R score. Although not systematically incorporated into new validated prognostic systems, somatic mutations can help define prognosis and should be considered as new prognostic factors.Risk-adapted therapyTherapy is selected based on risk, transfusion needs, percent of bone marrow blasts and cytogenetic and mutational profiles. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia and a chromosome 5 alteration. 5-azacitidine and decitabine have activity in both lower and higher-risk MDS. 5-azacitidine has been shown to improve survival in higher risk MDS. A number of new molecular lesions have been described in MDS that may serve as new therapeutic targets or aid in the selection of currently available agents. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation.Management of progressive or refractory diseaseAt the present time there are no approved interventions for patients with progressive or refractory disease particularly after hypomethylating based therapy. Options include participation in a clinical trial or cytarabine based therapy and stem cell transplantation.
      PubDate: 2017-12-07T02:33:20.816957-05:
      DOI: 10.1002/ajh.24930
  • Mitotic figure in the peripheral blood smear
    • Authors: Sebastian Hörber; Ingo Rettig, Andreas Peter
      Pages: 154 - 154
      PubDate: 2017-06-09T04:00:43.394513-05:
      DOI: 10.1002/ajh.24761
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