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Blood
Journal Prestige (SJR): 6.434
Citation Impact (citeScore): 7
Number of Followers: 262  
 
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ISSN (Print) 0006-4971 - ISSN (Online) 1528-0020
Published by American Society of Hematology Homepage  [2 journals]
  • Extracellular vesicles in DLBCL provide abundant clues to aberrant
           transcriptional programming and genomic alterations
    • Authors: Rutherford, S. C; Fachel, A. A, Li, S, Sawh, S, Muley, A, Ishii, J, Saxena, A, Dominguez, P. M, Caldas Lopes, E, Agirre, X, Chambwe, N, Correa, F, Jiang, Y, Richards, K. L, Betel, D, Shaknovich, R.
      Abstract: The biological role of extracellular vesicles (EVs) in diffuse large B-cell lymphoma (DLBCL) initiation and progression remains largely unknown. We characterized EVs secreted by 5 DLBCL cell lines, a primary DLBCL tumor, and a normal control B-cell sample, optimized their purification, and analyzed their content. We found that DLBCLs secreted large quantities of CD63, Alix, TSG101, and CD81 EVs, which can be extracted using an ultracentrifugation-based method and traced by their cell of origin surface markers. We also showed that tumor-derived EVs can be exchanged between lymphoma cells, normal tonsillar cells, and HK stromal cells. We then examined the content of EVs, focusing on isolation of high-quality total RNA. We sequenced the total RNA and analyzed the nature of RNA species, including coding and noncoding RNAs. We compared whole-cell and EV-derived RNA composition in benign and malignant B cells and discovered that transcripts from EVs were involved in many critical cellular functions. Finally, we performed mutational analysis and found that mutations detected in EVs exquisitely represented mutations in the cell of origin. These results enhance our understanding and enable future studies of the role that EVs may play in the pathogenesis of DLBCL, particularly with regards to the exchange of genomic information. Current findings open a new strategy for liquid biopsy approaches in disease monitoring.
      Keywords: Lymphoid Neoplasia, e-Blood
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2017-12-821843
      Issue No: Vol. 132, No. 7 (2018)
       
  • Benefits and risks of JAK inhibition
    • Authors: Arcaini, L; Cazzola, M.
      Pages: 675 - 676
      Keywords: Free Research Articles
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-07-858720
      Issue No: Vol. 132, No. 7 (2018)
       
  • Non-zero-sum game of transfusions: EOL in leukemia
    • Authors: Medeiros; B. C.
      Pages: 676 - 678
      Keywords: Free Research Articles
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-06-856336
      Issue No: Vol. 132, No. 7 (2018)
       
  • Moving target PF4 directs HIT responses
    • Authors: Semple, J. W; Kapur, R.
      Pages: 678 - 679
      Keywords: Free Research Articles
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-07-859975
      Issue No: Vol. 132, No. 7 (2018)
       
  • Novel agents for primary central nervous system lymphoma: evidence and
           perspectives
    • Authors: Illerhaus, G; Schorb, E, Kasenda, B.
      Pages: 681 - 688
      Abstract: Primary central nervous system lymphoma (PCNSL) is a rare aggressive extranodal non- Hodgkin lymphoma. Although high remission rates can be achieved with high-dose methotrexate–based immunochemotherapy, risk of relapse and associated death is still substantial in at least a third of patients. Novel agents for treating lymphoid malignancies have substantially enriched treatment options for PCNSL. We herein systematically review the existing clinical evidence of novel agents in treatment of PCNSL, summarize ongoing studies, and discuss perspectives. The body of evidence for novel agents is still limited to noncomparative studies, but the most promising approaches include Bruton kinase inhibition with ibrutinib and immunomodulatory treatment (eg, with lenalidomide). Targeting the mammalian target of rapamycin pathway does not seem to have a meaningful clinical benefit, and evidence of checkpoint inhibition with nivolumab is limited to anecdotal evidence. Future studies should embrace the concept of induction and maintenance therapy as well as the combination of drugs with different mechanisms of action. Selection of patients based on molecular profiling and relapse patterns should be another aspect informing future comparative trials, which are urgently needed to improve prognosis for patients with PCNSL.
      Keywords: Perspectives, Immunobiology and Immunotherapy, Lymphoid Neoplasia, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-01-791558
      Issue No: Vol. 132, No. 7 (2018)
       
  • L-Glutamine for sickle cell anemia: more questions than answers
    • Authors: Quinn; C. T.
      Pages: 689 - 693
      Abstract: In 2017, the Food and Drug Administration approved 2 medications for sickle cell anemia (SCA): hydroxyurea for children and l-glutamine for children and adults. The approval of hydroxyurea was long overdue, but the approval of l-glutamine was a surprise to many. Any effective new treatment for SCA is a welcome advance, but there are few published studies of l-glutamine as a specific treatment for SCA. Accordingly, there are many unanswered questions about its efficacy, safety, and role in current therapy.
      Keywords: Sickle Cell Disease, Red Cells, Iron, and Erythropoiesis, Blood Spotlight, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-03-834440
      Issue No: Vol. 132, No. 7 (2018)
       
  • Aggressive B-cell lymphomas in patients with myelofibrosis receiving
           JAK1/2 inhibitor therapy
    • Authors: Porpaczy, E; Tripolt, S, Hoelbl-Kovacic, A, Gisslinger, B, Bago-Horvath, Z, Casanova-Hevia, E, Clappier, E, Decker, T, Fajmann, S, Fux, D. A, Greiner, G, Gueltekin, S, Heller, G, Herkner, H, Hoermann, G, Kiladjian, J.-J, Kolbe, T, Kornauth, C, Krauth, M.-T, Kralovics, R, Muellauer, L, Mueller, M, Prchal-Murphy, M, Putz, E. M, Raffoux, E, Schiefer, A.-I, Schmetterer, K, Schneckenleithner, C, Simonitsch-Klupp, I, Skrabs, C, Sperr, W. R, Staber, P. B, Strobl, B, Valent, P, Jaeger, U, Gisslinger, H, Sexl, V.
      Pages: 694 - 706
      Abstract: Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 patients with MPN, including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4 (5.8%) of 69 patients receiving JAK1/2 inhibition compared with 2 (0.36%) of 557 with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 patients with MPN. Considering primary myelofibrosis only (N = 216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) vs 1 (0.54%) of 185 control patients. Lymphomas were of aggressive B-cell type, extranodal, or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a preexisting B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1–/– mice: 16 of 24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a preexisting B-cell clone may identify individuals at risk.
      Keywords: Free Research Articles, Myeloid Neoplasia, Lymphoid Neoplasia, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2017-10-810739
      Issue No: Vol. 132, No. 7 (2018)
       
  • Cancer-associated thrombosis in patients with implanted ports: a
           prospective multicenter French cohort study (ONCOCIP)
    • Authors: Decousus, H; Bourmaud, A, Fournel, P, Bertoletti, L, Labruyere, C, Presles, E, Merah, A, Laporte, S, Stefani, L, Piano, F. D, Jacquin, J.-P, Meyer, G, Chauvin, F, for the ONCOCIP Investigators
      Pages: 707 - 716
      Abstract: The need to accurately identify cancer outpatients at high risk of thrombotic complications is still unmet. In a prospective, multicenter cohort study (ONCOlogie et Chambres ImPlantables [ONCOCIP]), consecutive adult patients with a solid tumor and implanted port underwent 12-month follow-up. Our primary objective was to identify risk factors for (1) catheter-related thrombosis, defined as ipsilateral symptomatic upper-limb deep-vein thrombosis with or without pulmonary embolism, and (2) venous thromboembolism other than catheter-related, defined as any symptomatic superficial- or deep-vein thrombosis (other than catheter-related) or pulmonary embolism, and incidental pulmonary embolism. All events were objectively confirmed and centrally adjudicated. Rate assessments integrated competing risk of death. Overall, 3032 patients were included (median age: 63 years; women: 58%). The most frequent cancer locations were breast (33.7%), lung (18.5%), and colorectal (15.6%), cancer being metastatic in 43.2% of patients. Most patients (97.1%) received chemotherapy. By 12 months, 48 (1.6%) patients had been lost to follow-up and 656 (24.6%) had died; 3.8% (n = 111) of patients had experienced catheter-related thrombosis, and 9.6% (n = 276) venous thromboembolism other than catheter-related. By multivariate analysis, use of cephalic vein for catheter insertion predicted catheter-related thrombosis, whereas ongoing antiplatelet therapy was protective; risk factors for venous thromboembolism other than catheter-related were advanced age, previous venous thromboembolism, cancer site, and low hemoglobin level or increased leukocyte count before chemotherapy. In conclusion, this large prospective cohort study showed a high rate of venous thromboembolism in patients with a solid tumor and implanted port. Risk factors for catheter-related thrombosis differed from those for venous thromboembolism not catheter-related. This trial was registered at www.clinicaltrials.gov as #NCT02025894.
      Keywords: Thrombosis and Hemostasis, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-03-837153
      Issue No: Vol. 132, No. 7 (2018)
       
  • Transfusion dependence, use of hospice services, and quality of
           end-of-life care in leukemia
    • Authors: LeBlanc, T. W; Egan, P. C, Olszewski, A. J.
      Pages: 717 - 726
      Abstract: Hospice provides high-quality end-of-life care, but patients with leukemias use hospice services less frequently than those with solid tumors. Transfusion dependence (TD) may hinder or delay enrollment, because hospice organizations typically disallow transfusions. We examined the association between TD and end-of-life outcomes among Medicare beneficiaries with leukemia. From the Surveillance, Epidemiology, and End Results-Medicare database, we selected beneficiaries with acute and chronic leukemias who died in 2001-2011. We defined TD as ≥2 transfusions within 30 days before death or hospice enrollment. End points included hospice enrollment and length of stay, reporting relative risk (RR) adjusted for key covariates. Among 21 033 patients with a median age of 79 years, 20% were transfusion dependent before death/hospice enrollment. Use of hospice increased from 35% in 2001 to 49% in 2011. Median time on hospice was 9 days and was shorter for transfusion-dependent patients (6 vs 11 days; P < .001). Adjusting for baseline characteristics, TD was associated with a higher use of hospice services (RR, 1.08; 95% confidence interval [CI], 1.04-1.12) but also with 51% shorter hospice length of stay (RR, 0.49; 95% CI, 0.44-0.54). Hospice enrollees had a lower likelihood of inpatient death and chemotherapy use and lower median Medicare spending at end-of-life, regardless of TD status. In conclusion, relatively increased hospice use combined with a markedly shorter length of stay among transfusion-dependent patients suggests that they have a high and incompletely met need for hospice services and that they experience a barrier to timely referral. Policy solutions supporting palliative transfusions may maximize the benefits of hospice for leukemia patients.
      Keywords: Transfusion Medicine, Myeloid Neoplasia, Lymphoid Neoplasia, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-03-842575
      Issue No: Vol. 132, No. 7 (2018)
       
  • Dynamic intercellular redistribution of HIT antigen modulates
           heparin-induced thrombocytopenia
    • Authors: Dai, J; Madeeva, D, Hayes, V, Ahn, H. S, Tutwiler, V, Arepally, G. M, Cines, D. B, Poncz, M, Rauova, L.
      Pages: 727 - 734
      Abstract: Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies to platelet factor 4 (PF4)/heparin complexes. PF4 released from platelets binds to surface glycosaminoglycans on hematopoietic and vascular cells that are heterogenous in composition and differ in affinity for PF4. PF4 binds to monocytes with higher affinity than to platelets, and depletion of monocytes exacerbates thrombocytopenia in a murine HIT model. Here we show that the expression of PF4 on platelets and development of thrombocytopenia are modulated by the (re)distribution of PF4 among hematopoietic and endothelial cell surfaces. Binding of PF4 to platelets in whole blood in vitro varies inversely with the white cell count, likely because of the greater affinity of monocytes for PF4. In mice, monocyte depletion increased binding of PF4 to platelets by two- to three-fold. Induction of HIT in mice caused a transient>80-fold increase in binding of HIT antibody to monocytes vs 3.5-fold increase to platelets and rapid transient monocytopenia. Normalization of monocyte counts preceded the return in platelet counts. Exposure of blood to endothelial cells also depletes PF4 from platelet surfaces. These studies demonstrate a dynamic interchange of surface-bound PF4 among hematopoetic and vascular cells that may limit thrombocytopenia at the expense of promoting prothrombotic processes in HIT.
      Keywords: Thrombocytopenia, Platelets and Thrombopoiesis, Thrombosis and Hemostasis
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-02-830737
      Issue No: Vol. 132, No. 7 (2018)
       
  • Self-repopulating recipient bone marrow resident macrophages promote
           long-term hematopoietic stem cell engraftment
    • Authors: Kaur, S; Raggatt, L. J, Millard, S. M, Wu, A. C, Batoon, L, Jacobsen, R. N, Winkler, I. G, MacDonald, K. P, Perkins, A. C, Hume, D. A, Levesque, J.-P, Pettit, A. R.
      Pages: 735 - 749
      Abstract: Distinct subsets of resident tissue macrophages are important in hematopoietic stem cell niche homeostasis and erythropoiesis. We used a myeloid reporter gene (Csf1r-eGFP) to dissect the persistence of bone marrow and splenic macrophage subsets following lethal irradiation and autologous hematopoietic stem cell transplantation in a mouse model. Multiple recipient bone marrow and splenic macrophage subsets survived after autologous hematopoietic stem cell transplantation with organ-specific persistence kinetics. Short-term persistence (5 weeks) of recipient resident macrophages in spleen paralleled the duration of extramedullary hematopoiesis. In bone marrow, radiation-resistant recipient CD169+ resident macrophages and erythroid-island macrophages self-repopulated long-term after transplantation via autonomous cell division. Posttransplant peak expansion of recipient CD169+ resident macrophage number in bone marrow aligned with the persistent engraftment of phenotypic long-term reconstituting hematopoietic stem cells within bone marrow. Selective depletion of recipient CD169+ macrophages significantly compromised the engraftment of phenotypic long-term reconstituting hematopoietic stem cells and consequently impaired hematopoietic reconstitution. Recipient bone marrow resident macrophages are essential for optimal hematopoietic stem cell transplantation outcomes and could be an important consideration in the development of pretransplant conditioning therapies and/or chemoresistance approaches.
      Keywords: Hematopoiesis and Stem Cells, Transplantation
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-01-829663
      Issue No: Vol. 132, No. 7 (2018)
       
  • Unrelated cord blood transplantation in patients with idiopathic
           refractory severe aplastic anemia: a nationwide phase 2 study
    • Authors: Peffault de Latour; R., Chevret, S., Jubert, C., Sirvent, A., Galambrun, C., Ruggeri, A., Gandemer, V., Cornillon, J., Rialland, F., Dalle, J.-H., Forcade, E., Bruno, B., Paillard, C., Rorlich, P. S., Salmon, A., Fürst, S., Sicre de Fontbrune, F., Rubio, M. T., Bay, J.-O., Mohty, M., Larghero, J., Gluckman, E., Socie, G., on behalf of the Francophone Society of Bone Marrow Transplantation Cellular Therapy
      Pages: 750 - 754
      Abstract: Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together>4 x 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 x 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.
      Keywords: Pediatric Hematology, Transplantation, Free Research Articles, Red Cells, Iron, and Erythropoiesis, CME article, Brief Reports, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-01-829630
      Issue No: Vol. 132, No. 7 (2018)
       
  • Heparin-induced thrombocytopenia and thrombosis during high dose melphalan
           and autologous stem cell transplantation
    • Authors: Sarosiek, S; Quillen, K, Sloan, J. M, Brauneis, D, Sanchorawala, V.
      Pages: 755 - 757
      Keywords: Thrombocytopenia, Multiple Myeloma, Platelets and Thrombopoiesis, Thrombosis and Hemostasis, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-03-838672
      Issue No: Vol. 132, No. 7 (2018)
       
  • CCR4 mutations associated with superior outcome of adult T-cell
           leukemia/lymphoma under mogamulizumab treatment
    • Authors: Sakamoto, Y; Ishida, T, Masaki, A, Murase, T, Yonekura, K, Tashiro, Y, Tokunaga, M, Utsunomiya, A, Ito, A, Kusumoto, S, Iida, S, Ueda, R, Inagaki, H.
      Pages: 758 - 761
      Keywords: Immunobiology and Immunotherapy, Lymphoid Neoplasia, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-02-835991
      Issue No: Vol. 132, No. 7 (2018)
       
  • Treatment of IgM-associated immunoglobulin light-chain amyloidosis with
           rituximab-bendamustine
    • Authors: Manwani, R; Sachchithanantham, S, Mahmood, S, Foard, D, Sharpley, F, Rezk, T, Lane, T, Quarta, C, Fontana, M, Lachmann, H. J, Gillmore, J. D, Whelan, C, Hawkins, P. N, Wechalekar, A. D.
      Pages: 761 - 764
      Keywords: Multiple Myeloma, Lymphoid Neoplasia, Clinical Trials and Observations
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-04-846493
      Issue No: Vol. 132, No. 7 (2018)
       
  • Primary cutaneous small/medium CD4+ T-cell lymphoproliferative disorder
    • Authors: Xu, J; Huang, Q.
      Pages: 765 - 765
      Keywords: Free Research Articles, BloodWork, Lymphoid Neoplasia
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-05-850941
      Issue No: Vol. 132, No. 7 (2018)
       
  • Harlequin cells
    • Authors: Hirano, T; Eto, K.
      Pages: 766 - 766
      Keywords: Free Research Articles, BloodWork, Myeloid Neoplasia
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-05-852095
      Issue No: Vol. 132, No. 7 (2018)
       
  • Exflagellation of Plasmodium vivax microgametocytes in human peripheral
           blood
    • Authors: Singh Bhar, V; Agarwal, M.
      Pages: 767 - 767
      Keywords: Free Research Articles, BloodWork, Red Cells, Iron, and Erythropoiesis
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-01-828913
      Issue No: Vol. 132, No. 7 (2018)
       
  • Cord blood transplantation and refractory severe anaplastic anemia
    • Pages: 768 - 768
      Keywords: Free Research Articles, CME article
      PubDate: 2018-08-16T09:00:20-07:00
      DOI: 10.1182/blood-2018-06-860205
      Issue No: Vol. 132, No. 7 (2018)
       
 
 
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