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Journal Prestige (SJR): 6.434
Citation Impact (citeScore): 7
Number of Followers: 275  
  Full-text available via subscription Subscription journal
ISSN (Print) 0006-4971 - ISSN (Online) 1528-0020
Published by American Society of Hematology Homepage  [2 journals]
  • Do you know TAFRO'
    • Authors: Lunning, M. A; Armitage, J. O.
      Pages: 2109 - 2110
      Keywords: Free Research Articles
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-09-875112
      Issue No: Vol. 132, No. 20 (2018)
  • Knick-knack PADIMAC
    • Authors: Walker B. A.
      Pages: 2110 - 2111
      Keywords: Free Research Articles
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-10-875138
      Issue No: Vol. 132, No. 20 (2018)
  • Charcot-Leyden crystals: solving an enigma
    • Authors: Klion A. D.
      Pages: 2111 - 2112
      Keywords: Free Research Articles
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-09-873653
      Issue No: Vol. 132, No. 20 (2018)
  • Int"Dll"igent control of T-cell pathology in GVHD
    • Authors: Düchler M.
      Pages: 2112 - 2114
      Keywords: Free Research Articles
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-09-875120
      Issue No: Vol. 132, No. 20 (2018)
  • International, evidence-based consensus treatment guidelines for
           idiopathic multicentric Castleman disease
    • Authors: van Rhee, F; Voorhees, P, Dispenzieri, A, Fossa, A, Srkalovic, G, Ide, M, Munshi, N, Schey, S, Streetly, M, Pierson, S. K, Partridge, H. L, Mukherjee, S, Shilling, D, Stone, K, Greenway, A, Ruth, J, Lechowicz, M. J, Chandrakasan, S, Jayanthan, R, Jaffe, E. S, Leitch, H, Pemmaraju, N, Chadburn, A, Lim, M. S, Elenitoba-Johnson, K. S, Krymskaya, V, Goodman, A, Hoffmann, C, Zinzani, P. L, Ferrero, S, Terriou, L, Sato, Y, Simpson, D, Wong, R, Rossi, J.-F, Nasta, S, Yoshizaki, K, Kurzrock, R, Uldrick, T. S, Casper, C, Oksenhendler, E, Fajgenbaum, D. C.
      Pages: 2115 - 2124
      Abstract: Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8–negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti–interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.
      Keywords: Special Reports, Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-07-862334
      Issue No: Vol. 132, No. 20 (2018)
  • Molecular monitoring in CML: how deep' How often' How should it
           influence therapy'
    • Authors: Shanmuganathan, N; Hughes, T. P.
      Pages: 2125 - 2133
      Abstract: With the advent of tyrosine kinase inhibitors (TKIs), the goals of therapy in chronic myeloid leukemia (CML) are steadily shifting. Long-term disease control on TKI therapy has been the goal and expectation for most patients. More recently, treatment-free remission (TFR) has entered mainstream practice and is increasingly being adopted as the main goal of therapy. This therapeutic shift not only influences TKI selection but also, has necessitated the refinement and dissemination of highly sensitive and accurate molecular monitoring techniques. Measurement of BCR-ABL1 messenger RNA expression through reverse transcription quantitative polymerase chain reaction, reported according to the International Scale, has become the primary tool for response assessment in CML. Achieving specific time-dependent molecular milestones, as defined by global therapeutic guidelines, has been established as critical in maximizing optimal outcomes while identifying patients at risk of therapy failure. Depth and duration of a deep molecular response have become the new therapeutic targets in patients considered for TFR. Consequently, molecular monitoring in CML has become even more critical to ongoing response assessment, identifying patients with TKI resistance and poor drug adherence, and enabling TFR to be attempted safely and effectively.
      Keywords: Myeloid Neoplasia, Review Articles
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-05-848630
      Issue No: Vol. 132, No. 20 (2018)
  • Evaluation and management of heavy menstrual bleeding in adolescents: the
           role of the hematologist
    • Authors: OBrien S. H.
      Pages: 2134 - 2142
      Abstract: Heavy menstrual bleeding (HMB) is frequently reported by adolescents. The role of the hematologist is threefold in evaluating such patients: (1) perform a clinical and laboratory evaluation for an underlying bleeding disorder on the basis of the degree of clinical suspicion, (2) identify and manage any concomitant iron deficiency, and (3) provide input to the referring provider regarding the management of HMB, particularly for patients with identified hemostatic defects. Several clues in the menstrual history should raise suspicion for an underlying bleeding disorder, such as menses lasting>7 days, menstrual flow which soaks>5 sanitary products per day or requires product change during the night, passage of large blood clots, or failure to respond to conventional therapies. A detailed personal and family history of other bleeding symptoms should also be obtained. Iron deficiency with and without anemia is commonly found in young women with HMB. Therefore, it is important to obtain measures of hemoglobin and ferritin levels when evaluating these patients. Iron supplementation is often a key component of management in the adolescent with heavy menses and is still needed in those who have received packed red cell transfusions as a result of severe anemia. Strategies for decreasing menstrual blood flow are similar for adults and adolescents with heavy menses, with combined hormonal contraceptives recommended as first-line therapy. However, there are adolescent-specific considerations for many of these agents, and they must be incorporated into shared decision-making when selecting the most appropriate treatment.
      Keywords: Thrombosis and Hemostasis, Review Articles
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-05-848739
      Issue No: Vol. 132, No. 20 (2018)
  • Preemptive rituximab prevents long-term relapses in immune-mediated
           thrombotic thrombocytopenic purpura
    • Authors: Jestin, M; Benhamou, Y, Schelpe, A.-S, Roose, E, Provot, F, Galicier, L, Hie, M, Presne, C, Poullin, P, Wynckel, A, Saheb, S, Deligny, C, Servais, A, Girault, S, Delmas, Y, Kanouni, T, Lautrette, A, Chauveau, D, Mousson, C, Perez, P, Halimi, J.-M, Charvet-Rumpler, A, Hamidou, M, Cathebras, P, Vanhoorelbeke, K, Veyradier, A, Coppo, P, on behalf of the French Thrombotic Microangiopathies Reference Center
      Pages: 2143 - 2153
      Abstract: Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity 1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; P < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.
      Keywords: Thrombocytopenia, Free Research Articles, Platelets and Thrombopoiesis, CME article, Clinical Trials and Observations
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-04-840090
      Issue No: Vol. 132, No. 20 (2018)
  • RNA-seq of newly diagnosed patients in the PADIMAC study leads to a
           bortezomib/lenalidomide decision signature
    • Authors: Chapman, M. A; Sive, J, Ambrose, J, Roddie, C, Counsell, N, Lach, A, Abbasian, M, Popat, R, Cavenagh, J. D, Oakervee, H, Streetly, M. J, Schey, S, Koh, M, Willis, F, Virchis, A. E, Crowe, J, Quinn, M. F, Cook, G, Crawley, C. R, Pratt, G, Cook, M, Braganza, N, Adedayo, T, Smith, P, Clifton-Hadley, L, Owen, R. G, Sonneveld, P, Keats, J. J, Herrero, J, Yong, K.
      Pages: 2154 - 2165
      Abstract: Improving outcomes in multiple myeloma will involve not only development of new therapies but also better use of existing treatments. We performed RNA sequencing on samples from newly diagnosed patients enrolled in the phase 2 PADIMAC (Bortezomib, Adriamycin, and Dexamethasone Therapy for Previously Untreated Patients with Multiple Myeloma: Impact of Minimal Residual Disease in Patients with Deferred ASCT) study. Using synthetic annealing and the large margin nearest neighbor algorithm, we developed and trained a 7-gene signature to predict treatment outcome. We tested the signature in independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass data set, patients who were treated correctly according to the signature had a better progression-free survival (median, 20.1 months vs not reached; hazard ratio [HR], 0.40; confidence interval [CI], 0.23-0.72; P = .0012) and overall survival (median, 30.7 months vs not reached; HR, 0.41; CI, 0.21-0.80; P = .0049) than those who were not. Indeed, the outcome for these correctly treated patients was noninferior to that for those treated with combined bortezomib, lenalidomide, and dexamethasone, arguably the standard of care in the United States but not widely available elsewhere. The small size of the signature will facilitate clinical translation, thus enabling more targeted drug regimens to be delivered in myeloma.
      Keywords: Multiple Myeloma, Lymphoid Neoplasia
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-05-849893
      Issue No: Vol. 132, No. 20 (2018)
  • IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through
           loss of Ikaros and Aiolos
    • Authors: Fedele, P. L; Willis, S. N, Liao, Y, Low, M. S, Rautela, J, Segal, D. H, Gong, J.-N, Huntington, N. D, Shi, W, Huang, D. C. S, Grigoriadis, G, Tellier, J, Nutt, S. L.
      Pages: 2166 - 2178
      Abstract: Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1/Ikaros and IKZF3/Aiolos in human MM cell lines to gain further insight into their downstream gene regulatory networks. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis. Furthermore, evaluation of the transcriptional changes resulting from their loss demonstrates striking overlap with lenalidomide treatment. This was not dependent on reduction of the IRF4-MYC "axis," as neither protein was consistently downregulated, despite cell death occurring, and overexpression of either factor failed to rescue for Ikaros loss. Importantly, Ikaros and Aiolos repress the expression of interferon-stimulated genes (ISGs), including CD38, and their loss led to the activation of an interferon-like response, contributing to MM cell death. Ikaros/Aiolos repressed CD38 expression through interaction with the nucleosome remodeling and deacetylase complex in MM. IMiD-induced loss of Ikaros or treatment with interferon resulted in an upregulation of CD38 surface expression on MM cells, priming for daratumumab-induced NK cell-mediated antibody-dependent cellular cytotoxicity. These results give further insight into the mechanism of action of the IMiDs and provide mechanistic rationale for combination with anti-CD38 monoclonal antibodies.
      Keywords: Multiple Myeloma, Lymphoid Neoplasia
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-05-850727
      Issue No: Vol. 132, No. 20 (2018)
  • miR-125a and miR-34a expression predicts Richter syndrome in chronic
           lymphocytic leukemia patients
    • Authors: Balatti, V; Tomasello, L, Rassenti, L. Z, Veneziano, D, Nigita, G, Wang, H.-Y, Thorson, J. A, Kipps, T. J, Pekarsky, Y, Croce, C. M.
      Pages: 2179 - 2182
      Abstract: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. It is characterized by the accumulation of CD19+/CD5+ lymphocytes and can have variable outcomes. Richter syndrome (RS) is a lethal complication in CLL patients that results in aggressive B-cell lymphomas, and there are no tests to predict its occurrence. Because alterations in microRNA expression can predict the development and progression of several cancers, we investigated whether dysregulation of specific microRNAs can predict RS in CLL patients. Thus, we compared microRNA expression levels in samples from 49 CLL patients who later developed RS with samples from 59 CLL patients who did not. We found that high expression of miR-125a-5p or low expression of miR-34a-5p can predict ~50% of RS with a false positive rate of ~9%. We found that CLL patients predicted to develop RS show either an increase of miR-125a-5p expression (~20-fold) or a decrease of miR-34a-5p expression (~21-fold) compared with CLL patients that are not predicted to develop RS. Thus, miR-125a-5p and miR-34a-5p can be valuable predictor markers of RS and have the potential to provide physicians with information that can indicate the best therapeutic strategy for CLL patients.
      Keywords: Lymphoid Neoplasia, Brief Reports
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-04-845115
      Issue No: Vol. 132, No. 20 (2018)
  • Charcot-Leyden crystal formation is closely associated with eosinophil
           extracellular trap cell death
    • Authors: Ueki, S; Tokunaga, T, Melo, R. C. N, Saito, H, Honda, K, Fukuchi, M, Konno, Y, Takeda, M, Yamamoto, Y, Hirokawa, M, Fujieda, S, Spencer, L. A, Weller, P. F.
      Pages: 2183 - 2187
      Abstract: Protein crystallization in human tissue rarely occurs. Charcot-Leyden crystals (CLCs) were described in various eosinophilic diseases>150 years ago, but our understanding of CLC formation still remains limited. In this study, we demonstrate that CLCs observed in varied inflamed human tissues are closely associated with eosinophil cell-free granules and nuclear envelope/plasma membrane disintegration with release of filamentous chromatin (extracellular traps), typical morphologies of a regulated pathway of extracellular trap cell death (ETosis). During the process of eosinophil ETosis, eccentrically localized cytoplasmic and perinuclear CLC protein (galectin-10) is homogeneously redistributed in the cytoplasm. Rapid (1-2 minutes) formation of intracytoplasmic CLCs was observed using time-lapse imaging. Plasma membrane rupture enabled the release of both intracellularly formed CLCs and soluble galectin-10 that further contributed to formation of CLCs extracellularly, in parallel with the expulsion of free intact granules and extracellular traps. CLC formation and galectin-10 release were dependent on nicotinamide adenine dinucleotide phosphate oxidase activation. To our knowledge, this is the first demonstration of natural formation of CLCs in association with an active physiological process (ie, ETosis). These results indicate that dynamic changes in intracellular localization and release of galectin-10 contribute to CLC formation in vivo and suggest that CLC/galectin-10 might serve as an indicator of ETosis.
      Keywords: Phagocytes, Granulocytes, and Myelopoiesis, Brief Reports, Clinical Trials and Observations
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-04-842260
      Issue No: Vol. 132, No. 20 (2018)
  • Notch signaling mediated by Delta-like ligands 1 and 4 controls the
           pathogenesis of chronic GVHD in mice
    • Authors: Radojcic, V; Paz, K, Chung, J, Du, J, Perkey, E. T, Flynn, R, Ivcevic, S, Zaiken, M, Friedman, A, Yan, M, Pletneva, M. A, Sarantopoulos, S, Siebel, C. W, Blazar, B. R, Maillard, I.
      Pages: 2188 - 2200
      Abstract: Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) and remains an area of unmet clinical need with few treatment options available. Notch blockade prevents acute GVHD in multiple mouse models, but the impact of Notch signaling on cGVHD remains unknown. Using genetic and antibody-mediated strategies of Notch inhibition, we investigated the role of Notch signaling in complementary mouse cGVHD models that mimic several aspects of human cGVHD in search of candidate therapeutics. In the B10.D2->BALB/c model of sclerodermatous cGVHD, Delta-like ligand 4 (Dll4)–driven Notch signaling was essential for disease development. Antibody-mediated Dll4 inhibition conferred maximum benefits when pursued early in a preventative fashion, with anti-Dll1 enhancing early protection. Notch-deficient alloantigen-specific T cells showed no early defects in proliferation or helper polarization in vivo but subsequently exhibited markedly decreased cytokine secretion and enhanced accumulation of FoxP3+ regulatory T cells. In the B6->B10.BR major histocompatibility complex–mismatched model with multi–organ system cGVHD and prominent bronchiolitis obliterans (BO), but not skin manifestations, absence of Notch signaling in T cells provided long-lasting disease protection that was replicated by systemic targeting of Dll1, Dll4, or both Notch ligands, even during established disease. Notch inhibition decreased target organ damage and germinal center formation. Moreover, decreased BO-cGVHD was observed upon inactivation of Notch1 and/or Notch2 in T cells. Systemic targeting of Notch2 alone was safe and conferred therapeutic benefits. Altogether, Notch ligands and receptors regulate key pathogenic steps in cGVHD and emerge as novel druggable targets to prevent or treat different forms of cGVHD.
      Keywords: Immunobiology and Immunotherapy, Transplantation
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-03-841155
      Issue No: Vol. 132, No. 20 (2018)
  • Distinct patterns of clonal evolution in patients with concurrent myelo-
           and lymphoproliferative neoplasms
    • Authors: Kennedy, J. A; Medeiros, J. J. F, Dobson, S. M, Arruda, A, Sukhai, M. A, Stockley, T, Tierens, A, Minden, M. D, Kamel-Reid, S, Dick, J. E, Gupta, V.
      Pages: 2201 - 2205
      Keywords: Myeloid Neoplasia, Lymphoid Neoplasia
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-04-845065
      Issue No: Vol. 132, No. 20 (2018)
  • Increased risk of colon cancer and osteogenic sarcoma in Diamond-Blackfan
    • Authors: Vlachos, A; Rosenberg, P. S, Atsidaftos, E, Kang, J, Onel, K, Sharaf, R. N, Alter, B. P, Lipton, J. M.
      Pages: 2205 - 2208
      Keywords: Red Cells, Iron, and Erythropoiesis, Clinical Trials and Observations
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-05-848937
      Issue No: Vol. 132, No. 20 (2018)
  • Acquired {alpha}-thalassemia associated with myelodysplastic syndromes
    • Authors: Mullen, S; Talaulikar, D.
      Pages: 2209 - 2209
      Keywords: Free Research Articles, BloodWork, Red Cells, Iron, and Erythropoiesis
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-08-867341
      Issue No: Vol. 132, No. 20 (2018)
  • Rituximab prevents long-term relapses in TTP
    • Pages: 2210 - 2210
      Keywords: Free Research Articles, CME article
      PubDate: 2018-11-15T09:00:27-08:00
      DOI: 10.1182/blood-2018-10-878959
      Issue No: Vol. 132, No. 20 (2018)
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