Scarfo I, Ormhoj M, Frigault MJ, et al. Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas. Blood. 2018;132(14):1495-1506.
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

Schuetz C, Neven B, Dvorak CC, et al. SCID patients with ARTEMIS vs RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS-deficient SCID. Blood. 2014;123(2):281-289.
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

Young K, Conley B, Romero D, et al. BMP9 regulates endoglin-dependent chemokine responses in endothelial cells. Blood. 2012;120(20):4263-4273.
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

Extensive Kaposi sarcoma infiltration in bone marrow in a patient with HIV
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Lyapichev, K., Li, S. Tags: Free Research Articles BLOOD WORK Source Type: research

FLT3 pathway is a potential therapeutic target for PRC2-mutated T-cell acute lymphoblastic leukemia
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Zhang, J., Zhang, Y., Zhang, M., Liu, C., Liu, X., Yin, J., Wu, P., Chen, X., Yang, W., Zhang, L., Guo, Y., Zou, Y., Chen, Y., Cao, Y., Cheng, T., Zhu, X. Tags: Lymphoid Neoplasia Letter to Blood Source Type: research

Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease
The intestinal microbiota in allogeneic bone marrow transplant (allo-BMT) recipients modulates graft-versus-host disease (GVHD), a systemic inflammatory state initiated by donor T cells that leads to colitis, a key determinant of GVHD severity. Indole or indole derivatives produced by tryptophan metabolism in the intestinal microbiota limit intestinal inflammation caused by diverse stressors, so we tested their capacity to protect against GVHD in murine major histocompatibility complex–mismatched models of allo-BMT. Indole effects were assessed by colonization of allo-BMT recipient mice with tryptophanase positive or...
Source: Blood - December 6, 2018 Category: Hematology Authors: Swimm, A., Giver, C. R., DeFilipp, Z., Rangaraju, S., Sharma, A., Ulezko Antonova, A., Sonowal, R., Capaldo, C., Powell, D., Qayed, M., Kalman, D., Waller, E. K. Tags: Transplantation Source Type: research

Platelet-derived TLT-1 is a prognostic indicator in ALI/ARDS and prevents tissue damage in the lungs in a mouse model
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) affect>200 000 individuals yearly with a 40% mortality rate. Although platelets are implicated in the progression of ALI/ARDS, their exact role remains undefined. Triggering receptor expressed in myeloid cells (TREM)–like transcript 1 (TLT-1) is found on platelets, binds fibrinogen, and mediates clot formation. We hypothesized that platelets use TLT-1 to manage the progression of ALI/ARDS. Here we retrospectively measure plasma levels of soluble TLT-1 (sTLT-1) from the ARDS Network clinical trial and show that patients whose sTLT-1 levels were&...
Source: Blood - December 6, 2018 Category: Hematology Authors: Morales-Ortiz, J., Deal, V., Reyes, F., Maldonado-Martinez, G., Ledesma, N., Staback, F., Croft, C., Pacheco, A., Ortiz-Zuazaga, H., Yost, C. C., Rowley, J. W., Madera, B., John, A. S., Chen, J., Lopez, J., Rondina, M. T., Hunter, R., Gibson, A., Washingt Tags: Immunobiology and Immunotherapy, Phagocytes, Granulocytes, and Myelopoiesis, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research

Bifunctional PD-1 x {alpha}CD3 x {alpha}CD33 fusion protein reverses adaptive immune escape in acute myeloid leukemia
The CD33-targeting bispecific T-cell engager (BiTE) AMG 330 proved to be highly efficient in mediating cytolysis of acute myeloid leukemia (AML) cells in vitro and in mouse models. Yet, T-cell activation is correlated with upregulation of programmed cell death-ligand 1 (PD-L1) and other inhibitory checkpoints on AML cells that confer adaptive immune resistance. PD-1 and PD-L1 blocking agents may counteract T-cell dysfunction, however, at the expense of broadly distributed immune-related adverse events (irAEs). We developed a bifunctional checkpoint inhibitory T cell–engaging (CiTE) antibody that combines T-cell redir...
Source: Blood - December 6, 2018 Category: Hematology Authors: Herrmann, M., Krupka, C., Deiser, K., Brauchle, B., Marcinek, A., Ogrinc Wagner, A., Rataj, F., Mocikat, R., Metzeler, K. H., Spiekermann, K., Kobold, S., Fenn, N. C., Hopfner, K.-P., Subklewe, M. Tags: Immunobiology and Immunotherapy, Myeloid Neoplasia Source Type: research

Bcor insufficiency promotes initiation and progression of myelodysplastic syndrome
BCOR, encoding BCL-6 corepressor (BCOR), is X-linked and targeted by somatic mutations in various hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice lacking Bcor exon 4 (BcorE4/y) in the hematopoietic compartment developed NOTCH-dependent acute T-cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9 and 10 (BcorE9-10/y), which express a carboxyl-terminal truncated BCOR that fails to interact with core effector components of polycomb repressive complex 1.1. BcorE9-10/y mice developed lethal T-ALL in a similar manner to BcorE4/y mice, whereas BcorE...
Source: Blood - December 6, 2018 Category: Hematology Authors: Tara, S., Isshiki, Y., Nakajima-Takagi, Y., Oshima, M., Aoyama, K., Tanaka, T., Shinoda, D., Koide, S., Saraya, A., Miyagi, S., Manabe, I., Matsui, H., Koseki, H., Bardwell, V. J., Iwama, A. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research

Subclonal TP53 copy number is associated with prognosis in multiple myeloma
Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts (P
Source: Blood - December 6, 2018 Category: Hematology Authors: Shah, V., Johnson, D. C., Sherborne, A. L., Ellis, S., Aldridge, F. M., Howard-Reeves, J., Begum, F., Price, A., Kendall, J., Chiecchio, L., Savola, S., Jenner, M. W., Drayson, M. T., Owen, R. G., Gregory, W. M., Morgan, G. J., Davies, F. E., Houlston, R. Tags: Multiple Myeloma, Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations Source Type: research

Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma
The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (
Source: Blood - December 6, 2018 Category: Hematology Authors: Perrot, A., Lauwers-Cances, V., Corre, J., Robillard, N., Hulin, C., Chretien, M.-L., Dejoie, T., Maheo, S., Stoppa, A.-M., Pegourie, B., Karlin, L., Garderet, L., Arnulf, B., Doyen, C., Meuleman, N., Royer, B., Eveillard, J.-R., Benboubker, L., Dib, M., Tags: Multiple Myeloma, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL
We report here the results of DUO, a global phase 3 randomized study of duvelisib vs ofatumumab monotherapy for patients with relapsed or refractory (RR) CLL/SLL. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (n = 160) or ofatumumab IV (n = 159). The study met the primary study end point by significantly improving progression-free survival per independent review committee assessment compared with ofatumumab for all patients (median, 13.3 months vs 9.9 months; hazard ratio [HR] = 0.52; P
Source: Blood - December 6, 2018 Category: Hematology Authors: Flinn, I. W., Hillmen, P., Montillo, M., Nagy, Z., Illes, A., Etienne, G., Delgado, J., Kuss, B. J., Tam, C. S., Gasztonyi, Z., Offner, F., Lunin, S., Bosch, F., Davids, M. S., Lamanna, N., Jaeger, U., Ghia, P., Cymbalista, F., Portell, C. A., Skarbnik, A Tags: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Reversing anti-factor Xa agents and the unmet needs in trauma patients
Andexanet alfa, a reversing agent for anticoagulants that inhibit factor Xa, has recently been licensed in the United States. We discuss the impact of this licensure on current practice and review in detail the problems of a neglected and growing clinical area: reversing the anticoagulation effect of factor Xa inhibitors in bleeding trauma patients. We identify areas of practice that need research so that care of bleeding trauma patients receiving direct factor Xa inhibitors can be improved. (Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Hunt, B. J., Neal, M. D., Stensballe, J. Tags: Thrombosis and Hemostasis, Blood Spotlight, Clinical Trials and Observations Source Type: research

Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway
The mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B cells. Here, we describe how this process is initiated. We observed wide stable variation in complement activation when PF4/heparin was added to plasma of healthy donors, indicating a responder "phenotype" (high, intermediate, or low). Proteomic analysis of plasma from these healthy donors showed a strong correlation between complement activation and plasma immun...
Source: Blood - December 6, 2018 Category: Hematology Authors: Khandelwal, S., Ravi, J., Rauova, L., Johnson, A., Lee, G. M., Gilner, J. B., Gunti, S., Notkins, A. L., Kuchibhatla, M., Frank, M., Poncz, M., Cines, D. B., Arepally, G. M. Tags: Plenary Papers, Platelets and Thrombopoiesis Source Type: research

Stool can soften GVHD
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Hazenberg, M. D. Tags: Free Research Articles COMMENTS Source Type: research

TLT-1: please release me, let me go
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Senis, Y. A. Tags: Free Research Articles COMMENTS Source Type: research

CiTE antibody for AML
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Rettig, M. P., DiPersio, J. F. Tags: Free Research Articles COMMENTS Source Type: research

How deep is the myeloma iceberg?
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: San-Miguel, J. F., Paiva, B. Tags: Free Research Articles COMMENTS Source Type: research

DUO delivers for duvelisib
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Brown, J. R. Tags: Free Research Articles COMMENTS Source Type: research

Natural, not immune; classical, not alternative
(Source: Blood)
Source: Blood - December 6, 2018 Category: Hematology Authors: Warkentin, T. E. Tags: Free Research Articles COMMENTS Source Type: research

Steensma DP. How I use molecular genetic tests to evaluate patients who have or may have myelodysplastic syndromes. Blood. 2018;132(16):1657-1663.
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

Scheinberg DA. Immune reconstitution and remission in CML. Blood. 2017;129(9):1064-1065.
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

Mixed-phenotype acute leukemia, T/megakaryoblastic
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Authors: Klairmont, M. M., Choi, J. K. Tags: Free Research Articles, BloodWork, Myeloid Neoplasia, Lymphoid Neoplasia BLOOD WORK Source Type: research

TET2 deficiency leads to stem cell factor-dependent clonal expansion of dysfunctional erythroid progenitors
Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Anemia is the defining cytopenia of MDS patients, yet the molecular mechanisms for dyserythropoiesis in MDSs remain to be fully defined. Recent studies have revealed that heterozygous loss-of-function mutation of DNA dioxygenase TET2 is 1 of the most common mutations in MDSs and that TET2 deficiency disturbs erythroid differentiation. However, mechanistic insights into the role of TET2 on disordered erythropoiesis are not fully defined. Here, we show that TET2 deficiency leads initially to stem cell fac...
Source: Blood - November 29, 2018 Category: Hematology Authors: Qu, X., Zhang, S., Wang, S., Wang, Y., Li, W., Huang, Y., Zhao, H., Wu, X., An, C., Guo, X., Hale, J., Li, J., Hillyer, C. D., Mohandas, N., Liu, J., Yazdanbakhsh, K., Vinchi, F., Chen, L., Kang, Q., An, X. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research

Molecular classification of primary mediastinal large B-cell lymphoma using routinely available tissue specimens
Primary mediastinal large B-cell lymphoma (PMBCL) is recognized as a distinct entity in the World Health Organization classification. Currently, the diagnosis relies on consensus of histopathology, clinical variables, and presentation, giving rise to diagnostic inaccuracy in routine practice. Previous studies have demonstrated that PMBCL can be distinguished from subtypes of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures. However, requirement of fresh-frozen biopsy material has precluded the transfer of gene expression–based assays to the clinic. Here, we developed a robust and accurate mol...
Source: Blood - November 29, 2018 Category: Hematology Authors: Mottok, A., Wright, G., Rosenwald, A., Ott, G., Ramsower, C., Campo, E., Braziel, R. M., Delabie, J., Weisenburger, D. D., Song, J. Y., Chan, W. C., Cook, J. R., Fu, K., Greiner, T., Smeland, E., Holte, H., Savage, K. J., Glinsmann-Gibson, B. J., Gascoyne Tags: Lymphoid Neoplasia, Brief Reports Source Type: research

miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels
Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations of MYC or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely miR-...
Source: Blood - November 29, 2018 Category: Hematology Authors: Musilova, K., Devan, J., Cerna, K., Seda, V., Pavlasova, G., Sharma, S., Oppelt, J., Pytlik, R., Prochazka, V., Prouzova, Z., Trbusek, M., Zlamalikova, L., Liskova, K., Kruzova, L., Jarosova, M., Mareckova, A., Kornauth, C., Simonitsch-Klupp, I., Schiefer Tags: Lymphoid Neoplasia Source Type: research

Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia
Genomic studies have recently identified RPS15 as a new driver gene in aggressive and chemorefractory cases of chronic lymphocytic leukemia (CLL). RPS15 encodes a ribosomal protein whose conserved C-terminal domain extends into the decoding center of the ribosome. We demonstrate that mutations in highly conserved residues of this domain affect protein stability, by increasing its ubiquitin-mediated degradation, and cell-proliferation rates. On the other hand, we show that mutated RPS15 can be loaded into the ribosomes, directly impacting on global protein synthesis and/or translational fidelity in a mutation-specific manne...
Source: Blood - November 29, 2018 Category: Hematology Authors: Bretones, G., Alvarez, M. G., Arango, J. R., Rodriguez, D., Nadeu, F., Prado, M. A., Valdes-Mas, R., Puente, D. A., Paulo, J. A., Delgado, J., Villamor, N., Lopez-Guillermo, A., Finley, D. J., Gygi, S. P., Campo, E., Quesada, V., Lopez-Otin, C. Tags: Lymphoid Neoplasia Source Type: research

T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocyto...
Source: Blood - November 29, 2018 Category: Hematology Authors: Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B Tags: Immunobiology and Immunotherapy Source Type: research

EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation
Autologous T cells targeting Epstein-Barr virus (EBV) latent membrane proteins (LMPs) have shown safety and efficacy in the treatment of patients with type 2 latency EBV-associated lymphomas for whom standard therapies have failed, including high-dose chemotherapy followed by autologous stem-cell rescue. However, the safety and efficacy of allogeneic donor-derived LMP-specific T cells (LMP-Ts) have not been established for patients who have undergone allogeneic hematopoietic stem-cell transplantation (HSCT). Therefore, we evaluated the safety and efficacy of donor-derived LMP-Ts in 26 patients who had undergone allogeneic ...
Source: Blood - November 29, 2018 Category: Hematology Authors: McLaughlin, L. P., Rouce, R., Gottschalk, S., Torrano, V., Carrum, G., Wu, M.-F., Hoq, F., Grilley, B., Marcogliese, A. M., Hanley, P. J., Gee, A. P., Brenner, M. K., Rooney, C. M., Heslop, H. E., Bollard, C. M. Tags: Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

How I treat the blast phase of Philadelphia chromosome-negative myeloproliferative neoplasms
The classic Philadelphia chromosome (Ph)–negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem-cell diseases, characterized by activated JAK/STAT signaling and significant phenotypic mimicry, including a propensity for evolution to myeloid blast phase disease. Effective therapeutic options are limited for patients with Ph– MPNs in the blast phase (MPN-BP), and allogeneic stem-cell transplantation is the only known cure. Our increasing understanding of the molecular pathogenesis of this group of diseases, coupled with the increasing availability of targeted agents, has the ...
Source: Blood - November 29, 2018 Category: Hematology Authors: Odenike, O. Tags: How I Treat, Free Research Articles, Myeloid Neoplasia, Clinical Trials and Observations Source Type: research

The current state of sickle cell trait: implications for reproductive and genetic counseling
Sickle cell trait (SCT) is unique among the carrier states that are identified during newborn screening. Unlike other heterozygous states for rare recessive diseases, SCT is exceedingly prevalent throughout regions of the world, making sickle cell disease one of the most common monogenetic diseases worldwide. Because of this high frequency, reproductive counseling is of paramount importance. In addition, unlike other carrier states, SCT seems to be a risk factor for several clinical complications, such as extreme exertional injury, chronic kidney disease, and venous thromboembolism. Increasing knowledge about these clinica...
Source: Blood - November 29, 2018 Category: Hematology Authors: Pecker, L. H., Naik, R. P. Tags: Red Cells, Iron, and Erythropoiesis, Review Articles Source Type: research

Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease
Castleman disease (CD) describes a heterogeneous group of hematologic disorders that share characteristic lymph node histopathology. Patients of all ages present with either a solitary enlarged lymph node (unicentric CD) or multicentric lymphadenopathy (MCD) with systemic inflammation, cytopenias, and life-threatening multiple organ dysfunction resulting from a cytokine storm often driven by interleukin 6 (IL-6). Uncontrolled human herpesvirus-8 (HHV-8) infection causes approximately 50% of MCD cases, whereas the etiology is unknown in the remaining HHV-8-negative/idiopathic MCD cases (iMCD). The limited understanding of e...
Source: Blood - November 29, 2018 Category: Hematology Authors: Fajgenbaum, D. C. Tags: Lymphoid Neoplasia, Review Articles Source Type: research

Ineffective erythropoiesis of TET2 deficiency
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Authors: Wojchowski, D. M. Tags: Free Research Articles COMMENTS Source Type: research

PMBCL: a molecular diagnosis?
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Authors: Lim, M. S. Tags: Free Research Articles COMMENTS Source Type: research

Not so lost in translation: RPS15 mutations in CLL
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Authors: Ljungström, V., Rosenquist, R. Tags: Free Research Articles COMMENTS Source Type: research

An expanding network of cytoskeletal defects
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Authors: Keller, M. D. Tags: Free Research Articles COMMENTS Source Type: research

Targeting EBV-positive B- and T/NK-cell lymphomas
(Source: Blood)
Source: Blood - November 29, 2018 Category: Hematology Authors: Long, H. M. Tags: Free Research Articles COMMENTS Source Type: research

Microgranular variant of acute promyelocytic leukemia with cytoplasmic projections resembling micromegakaryocytes
(Source: Blood)
Source: Blood - November 22, 2018 Category: Hematology Authors: Jiang, W., Lee, S.-H. Tags: Free Research Articles, BloodWork, Myeloid Neoplasia BLOOD WORK Source Type: research

Germline loss-of-function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes
(Source: Blood)
Source: Blood - November 22, 2018 Category: Hematology Authors: Nagata, Y., Narumi, S., Guan, Y., Przychodzen, B. P., Hirsch, C. M., Makishima, H., Shima, H., Aly, M., Pastor, V., Kuzmanovic, T., Radivoyevitch, T., Adema, V., Awada, H., Yoshida, K., Li, S., Sole, F., Hanna, R., Jha, B. K., LaFramboise, T., Ogawa, S., Tags: Myeloid Neoplasia Letter to Blood Source Type: research

Treatment with 5-azacytidine induces a sustained response in patients with angioimmunoblastic T-cell lymphoma
(Source: Blood)
Source: Blood - November 22, 2018 Category: Hematology Authors: Lemonnier, F., Dupuis, J., Sujobert, P., Tournillhac, O., Cheminant, M., Sarkozy, C., Pelletier, L., Marcais, A., Robe, C., Fataccioli, V., Haioun, C., Hermine, O., Gaulard, P., Delarue, R. Tags: Lymphoid Neoplasia, Clinical Trials and Observations Letter to Blood Source Type: research

Reduced incidence of vein occlusion and postthrombotic syndrome after immediate compression for deep vein thrombosis
This study was registered at ClinicalTrials.gov (NCT01429714) and the Dutch Trial registry in November 2010 (NTR2597). (Source: Blood)
Source: Blood - November 22, 2018 Category: Hematology Authors: Amin, E. E., Bistervels, I. M., Meijer, K., Tick, L. W., Middeldorp, S., Mostard, G., van de Poel, M., Serne, E. H., Otten, H. M., Klappe, E. M., Joore, M. A., ten Cate, H., ten Wolde, M., ten Cate-Hoek, A. J. Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research

Transferrin receptor 2 is a potential novel therapeutic target for {beta}-thalassemia: evidence from a murine model
β-thalassemias are genetic disorders characterized by anemia, ineffective erythropoiesis, and iron overload. Current treatment of severe cases is based on blood transfusion and iron chelation or allogeneic bone marrow (BM) transplantation. Novel approaches are explored for nontransfusion-dependent patients (thalassemia intermedia) who develop anemia and iron overload. Here, we investigated the erythropoietin (EPO) receptor partner, transferrin receptor 2 (TFR2), as a novel potential therapeutic target. We generated a murine model of thalassemia intermedia specifically lacking BM Tfr2: because their erythroid cells are...
Source: Blood - November 22, 2018 Category: Hematology Authors: Artuso, I., Lidonnici, M. R., Altamura, S., Mandelli, G., Pettinato, M., Muckenthaler, M. U., Silvestri, L., Ferrari, G., Camaschella, C., Nai, A. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research

IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue notes instances of Burkitt lymphoma/leukemia (BL) with IG-MYC rearrangement displaying a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the molecular pathogenesis of preBLL, we investigated 13 preBLL cases (including 1 cell line), of which 12 were analyzable using genome, exome, and targeted sequencing, imbalance mapping, and DNA methylation profiling. In 5 patients with reads across the IG-MYC breakpoint junctions, we found evidence that the translocation derived from an aberrant VDJ recombination, as is typical f...
Source: Blood - November 22, 2018 Category: Hematology Authors: Wagener, R., Lopez, C., Kleinheinz, K., Bausinger, J., Aukema, S. M., Nagel, I., Toprak, U. H., Seufert, J., Altmüller, J., Thiele, H., Schneider, C., Kolarova, J., Park, J., Hübschmann, D., Murga Penas, E. M., Drexler, H. G., Attarbaschi, Tags: Lymphoid Neoplasia, Brief Reports Source Type: research

Outcome-based interpretation of early interim PET in advanced-stage Hodgkin lymphoma
The HD18 study for patients with newly diagnosed advanced-stage Hodgkin lymphoma (HL) used positron emission tomography (PET) after 2 cycles (PET-2) of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses (eBEACOPP) to guide further treatment. Here, we analyzed the impact of PET-2 results in the context of eBEACOPP according to the Deauville score (DS) in patients treated within the HD18 trial. Residual tissue was visually compared with reference regions according to DS. We analyzed the association between PET-2 uptake and baseline characteristics, progression-fr...
Source: Blood - November 22, 2018 Category: Hematology Authors: Kobe, C., Goergen, H., Baues, C., Kuhnert, G., Voltin, C.-A., Zijlstra, J., Hoekstra, O., Mettler, J., Drzezga, A., Engert, A., Borchmann, P., Dietlein, M. Tags: Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Improving CLL V{gamma}9V{delta}2-T-cell fitness for cellular therapy by ex vivo activation and ibrutinib
The efficacy of autologous (αβ) T-cell–based treatment strategies in chronic lymphocytic leukemia (CLL) has been modest. The V9V2-T cell subset consists of cytotoxic T lymphocytes with potent antilymphoma activity via a major histocompatibility complex–independent mechanism. We studied whether V9V2-T cells can be exploited as autologous effector lymphocytes in CLL. Healthy control V9V2-T cells were activated by and had potent cytolytic activity against CLL cells. However, CLL-derived V9V2-T cells proved dysfunctional with respect to effector cytokine production and degranulation, despite an increased...
Source: Blood - November 22, 2018 Category: Hematology Authors: de Weerdt, I., Hofland, T., Lameris, R., Endstra, S., Jongejan, A., Moerland, P. D., de Bruin, R. C. G., Remmerswaal, E. B. M., ten Berge, I. J. M., Liu, N., van der Stelt, M., Faber, L. M., Levin, M.-D., Eldering, E., Tonino, S. H., de Gruijl, T. D., van Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research

A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia
Ibrutinib is highly efficacious and used at 420 mg/d for treatment of chronic lymphocytic leukemia (CLL). We previously demonstrated a decline in Bruton’s tyrosine kinase (BTK) protein levels in CLL cells after 1 cycle of ibrutinib, suggesting ibrutinib dose could be lowered after the first cycle without loss of biological effect. To test this postulate, a pilot study (NCT02801578) was designed to systematically reduce ibrutinib dosing within the same patient with CLL over the course of three 28-day cycles. After an initial cycle of 420 mg/d, the dose was reduced to 280 mg/d in cycle 2, and then to 140 mg/d in cycle ...
Source: Blood - November 22, 2018 Category: Hematology Authors: Chen, L. S., Bose, P., Cruz, N. D., Jiang, Y., Wu, Q., Thompson, P. A., Feng, S., Kroll, M. H., Qiao, W., Huang, X., Jain, N., Wierda, W. G., Keating, M. J., Gandhi, V. Tags: Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma
The combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) to determine the maximal tolerated dose (MTD) of POM as the primary objective, and overall response rate (ORR), progression-free survival (PFS), and safety profile as secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intol...
Source: Blood - November 22, 2018 Category: Hematology Authors: Tun, H. W., Johnston, P. B., DeAngelis, L. M., Atherton, P. J., Pederson, L. D., Koenig, P. A., Reeder, C. B., Omuro, A. M. P., Schiff, D., ONeill, B., Pulido, J., Jaeckle, K. A., Grommes, C., Witzig, T. E. Tags: Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions
Oral anticoagulants are commonly prescribed but high risk to cause adverse events. Skilled drug interaction management is essential to ensure safe and effective use of these therapies. Clinically relevant interactions with warfarin include drugs that modify cytochrome 2C9, 3A4, or both. Drugs that modify p-glycoprotein may interact with all direct oral anticoagulants, and modifiers of cytochrome 3A4 may interact with rivaroxaban and apixaban. Antiplatelet agents, nonsteroidal anti-inflammatory drugs, and serotonergic agents, such as selective serotonin reuptake inhibitors, can increase risk of bleeding when combined with a...
Source: Blood - November 22, 2018 Category: Hematology Authors: Vazquez, S. R. Tags: Thrombosis and Hemostasis, Review Articles Source Type: research

Anticoagulating patients with high-risk acquired thrombophilias
Antiphospholipid syndrome (APS), heparin-induced thrombocytopenia, and paroxysmal nocturnal hemoglobinuria are 3 acquired thrombophilias that carry a high risk of venous and arterial thromboembolism. Management of these conditions has largely included anticoagulation with a vitamin K antagonist after an initial period of a parenteral anticoagulant, for as long as the thrombotic risk is still present. The available evidence for the use of direct oral anticoagulants (DOACs) is limited and primarily consists of case series and cohort studies, which are summarized in this chapter. Randomized trials evaluating DOACs in patients...
Source: Blood - November 22, 2018 Category: Hematology Authors: Skeith, L. Tags: Thrombosis and Hemostasis, Review Articles Source Type: research

Postthrombotic syndrome: simple prevention
(Source: Blood)
Source: Blood - November 22, 2018 Category: Hematology Authors: Solymoss, S. Tags: Free Research Articles COMMENTS Source Type: research