British Journal of Haematology
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Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura
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We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) ( (Source: British Journal of Haematology)
Source: British Journal of Haematology - November 19, 2009 Category: Hematology Authors: Ellinor I. B. Peerschke, Biree Andemariam, Wei Yin, James B. Bussel Source Type: journals
Successful treatment of autoimmune and lymphoproliferative complications of patients with intrinsic B-cell immunodeficiencies with RituximabEmail this article to a colleague.
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The heterogeneous group of primary immunodeficiencies requires personalized diagnosis and therapy to acheive an optimal outcome for each patient. This was exemplified by two patients with intrinsic B-cell class-switch defects (subclass of Hyper-IgM syndromes), where lymphoproliferation and autoimmunity determined the clinical course for many years due to lack of exact diagnosis. Based on genetics or a novel functional diagnostic approach, a definite individual diagnosis was established for each patient and they started Rituximab therapy. Autoimmune phenomena and generalized lymphadenopathy disappeared and remained well con...
Source: British Journal of Haematology - November 17, 2009 Category: Hematology Authors: Christian Hennig, Ulrich Baumann, Claudia Ilginus, Gerd Horneff, Juergen Foell, Gesine Hansen Source Type: journals
Health-related quality of life following haematopoietic cell transplantation: patient education, evaluation and interventionEmail this article to a colleague.
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Health-related quality of life (QOL) is a vital concern in the pre-treatment consent process and post-treatment care of recipients of haematopoietic cell transplantation (HCT). We propose that comprehensive care of such patients requires an integration of knowledge of the impact of HCT on QOL, assessment of QOL, as well as resources available for intervention. This knowledge may significantly improve patient care when incorporated into daily clinical practice in the transplant setting. As a framework for this approach, this article reviews the literature on QOL after allogeneic and autologous HCT for adults with haematolog...
Source: British Journal of Haematology - November 16, 2009 Category: Hematology Authors: Joseph Pidala, Claudio Anasetti, Heather Jim Source Type: journals
Favourable outcome of pneumonia due to novel influenza A/H1N1 2009 virus in a splenectomised adult patient undergoing therapy for non-Hodgkin lymphomaEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - November 16, 2009 Category: Hematology Authors: Julio García-Suárez, Yolanda Martín, Marta Callejas, Mario Rodriguez-Dominguez, Juan Carlos Galán, Carmen Burgaleta Source Type: journals
Fludarabine, Bortezomib, Myocet® and rituximab chemotherapy in relapsed and refractory mantle cell lymphomaEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - November 16, 2009 Category: Hematology Authors: Enrico Orciuolo, Gabriele Buda, Matteo Pelosini, Mario Petrini Source Type: journals
Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directionsEmail this article to a colleague.
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Progressive degeneration of the central nervous system leading to the loss of neuromotor, neurophysiological and cognitive abilities is the fundamental clinical problem in patients with many inherited metabolic diseases (IMD). Worldwide experience shows that morbidity, quality of life, and survival in these patients can be improved by allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed early in the course of the disease. At present, while available for some conditions, exogenous enzyme replacement therapy is unable to correct cognitive and central nervous system disease because of its in...
Source: British Journal of Haematology - November 16, 2009 Category: Hematology Authors: Vinod K. Prasad, Joanne Kurtzberg Source Type: journals
Myeloma cell-induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast-myeloma hybrid cellsEmail this article to a colleague.
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This study identified a structure that deeply affects this response, because of its impact on the physical organisation of the myeloma cell microenvironment. The proximity between myeloma cells and osteoclasts or osteoblasts was shown to be conditioned by the recently discovered layer of flat cells that separates the osteoclasts and osteoblasts from the bone marrow, by forming a canopy over bone remodelling compartment (BRC). These canopies are frequently disrupted in myeloma, and this disruption correlates with increased proximity and density of myeloma cells. In vitro evidence indicates that this disruption may be due to...
Source: British Journal of Haematology - November 16, 2009 Category: Hematology Authors: Thomas L. Andersen, Kent Søe, Teis E. Sondergaard, Torben Plesner, Jean-Marie Delaisse Source Type: journals
Phase 2 study of two sequential three-drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myelomaEmail this article to a colleague.
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We report results from a phase 2 study of two sequential three-drug combinations. Forty-four previously untreated, symptomatic MM patients received: bortezomib 1·3 mg/m2 (days 1, 4, 8, 11), cyclophosphamide 300 mg/m2 (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21-day cycles, followed by bortezomib 1·0 mg/m2, dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%[ge] very good partial response. Twenty-two patients have undergone stem-cell transplantatio...
Source: British Journal of Haematology - November 16, 2009 Category: Hematology Authors: William I. Bensinger, Sundar Jagannath, Robert Vescio, Elber Camacho, Jeffrey Wolf, David Irwin, Gerardo Capo, Marti McKinley, Phyllis Potts, David H. Vesole, Amitabha Mazumder, John Crowley, Pam Becker, Jacqueline Hilger, Brian G.M. Durie Source Type: journals
Central nervous system T-cell lymphoma in acquired immunodeficiency syndromeEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - November 14, 2009 Category: Hematology Authors: Mihoko Yotsumoto, Kotaro Funato, Yuko Hashimoto, Hiroaki Fujimoto, Katsuyuki Fukutake Source Type: journals
The potential role of epigenetic therapy in multiple myelomaEmail this article to a colleague.
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This review describes the role that epigenetic changes play in the pathogenesis of cancer, concentrating on the plasma cell malignancy multiple myeloma, and highlights recent findings regarding the efficacy of epigenetic therapeutic agents in laboratory studies and clinical trials. DNA methylation is altered in a wide range of cancers with hypermethylation of CpG islands associated with silencing of tumour suppressor genes. Genes found to be silenced by methylation in myeloma samples include VHL, TP53, CDKN2A, and TGFBR2. Myeloma is linked to the overexpression of a histone methylatransferase (MMSET) and inactivating mutat...
Source: British Journal of Haematology - November 13, 2009 Category: Hematology Authors: Emma M. Smith, Kevin Boyd, Faith E. Davies Source Type: journals
Serum granulysin as a possible biomarker of natural killer cell neoplasmsEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - November 13, 2009 Category: Hematology Authors: Masayuki Nagasawa, Kazuyuki Ogawa, Kinya Nagata, Norio Shimizu Source Type: journals
Deciphering the molecular basis of venous thromboembolism: where are we and where should we go?Email this article to a colleague.
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Venous thromboembolism (VTE) is a frequent disease that has a major genetic component of risk. However, known identified genetic risk factors account for (Source: British Journal of Haematology)
Source: British Journal of Haematology - November 13, 2009 Category: Hematology Authors: Pierre-Emmanuel Morange, David-Alexandre Tregouet Source Type: journals
Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia majorEmail this article to a colleague.
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Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients' iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients...
Source: British Journal of Haematology - November 12, 2009 Category: Hematology Authors: Kallistheni Farmaki, Ioanna Tzoumari, Christina Pappa, Giorgos Chouliaras, Vasilios Berdoukas Source Type: journals
Peripheral T-cell lymphoma gene expression profiling and potential therapeutic exploitationsEmail this article to a colleague.
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In conclusion, gene expression profiling is beginning to change the pathological classification, the prognosis profiles and the therapeutic approach in T-cell lymphomas. (Source: British Journal of Haematology)
Source: British Journal of Haematology - November 12, 2009 Category: Hematology Authors: Régis Costello, Carole Sanchez, Thérèse Le Treut, Pascal Rihet, Jean Imbert, Gérard Sébahoun Source Type: journals
microRNA expression in erythropoiesis and erythroid disordersEmail this article to a colleague.
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MicroRNAs are a recently discovered class of small (c. 22 nt) naturally occurring non-coding RNA molecules that regulate gene expression through binding to the un-translated region of target mRNA. MicroRNAs play key roles in many cellular pathways including haematopoiesis and aberrant expression is a common feature of haematological malignancies. Whilst other areas of haematopoiesis have been extensively reviewed the involvement of microRNAs in red cell production (erythropoiesis) and disorders of this pathway is lacking. In this review the rapidly accumulating evidence that points to the major role microRNAs play in both ...
Source: British Journal of Haematology - November 12, 2009 Category: Hematology Authors: Charles H. Lawrie Source Type: journals
Polo-like-kinase 1 (PLK1) as a molecular target to overcome SYK-mediated resistance of B-lineage acute lymphoblastic leukaemia cells to oxidative stressEmail this article to a colleague.
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This study is the first to identify PLK1 as a regulator of SYK tyrosine kinase and a molecular target to overcome SYK-mediated resistance of B-lineage ALL cells to OS. (Source: British Journal of Haematology)
Source: British Journal of Haematology - November 12, 2009 Category: Hematology Authors: Fatih M. Uckun, Zahide Ozer, Sanjive Qazi, Lisa Tuel-Ahlgren, Chen Mao Source Type: journals
Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantationEmail this article to a colleague.
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From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment after a median of 15 and 19 d, respectively. Grade II[ndash]IV acute graft-versus-host disease (GvHD) occurred in 25% of patients and 35% had chronic GvHD. Overall response rate at day 100 was 95% including 46% complete remission (CR). Cumulative incidence of non-relapse mortality at 1 year was 25% [95% confidence interval (CI):...
Source: British Journal of Haematology - November 12, 2009 Category: Hematology Authors: Nicolaus Kröger, Avichai Shimoni, Georgia Schilling, Rainer Schwerdtfeger, Martin Bornhäuser, Arnon Nagler, Axel R. Zander, Marion Heinzelmann, Ronald Brand, Gösta Gahrton, Curly Morris, Dietger Niederwieser, Theo de Witte Source Type: journals
A comprehensive evaluation of the prognostic significance of 13q deletions in patients with B-chronic lymphocytic leukaemiaEmail this article to a colleague.
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Deletion 13q14 on fluorescence in situ hybridization (FISH) analysis is the most common cytogenetic abnormality in chronic lymphocytic leukaemia (CLL), and is a favourable prognostic biomarker when detected as a sole abnormality. We intensively interrogated clinical outcome in 323 consecutive, untreated CLL patients with isolated 13q- identified within 2 years of diagnosis. We also analyzed outcome in 217 additional patients with deletion 11q22.3 or 17p13.1, or trisomy 12, based on whether these occurred in isolation or in conjunction with 13q-. Patients with a heterozygous 13q- and those with a homozygous deletion had sim...
Source: British Journal of Haematology - November 8, 2009 Category: Hematology Authors: Daniel L. Van Dyke, Tait D. Shanafelt, Timothy G. Call, Clive S. Zent, Stephanie A. Smoley, Kari G. Rabe, Susan M. Schwager, Jessica C. Sonbert, Susan L. Slager, Neil E. Kay Source Type: journals
Circulating CD52 and CD20 levels at end of treatment predict for progression and survival in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab (FCR)Email this article to a colleague.
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In this report, blood and bone marrow (BM) cCD52 and cCD20 were measured at response assessment in previously treated (N = 235) patients with CLL who received fludarabine, cyclophosphamide, and rituximab (FCR). Univariate and multivariate statistical models evaluated correlations of pre- and response variables with progression-free (PFS) and overall survival (OS). Response variables included 1996 National Cancer Institute-Working Group (NCI-WG) response, polymerase chain reaction (PCR) for immunoglobulin heavy chain (IGHV) in BM, and cCD52 and cCD20 levels (blood and BM) at response assessment. Using multivariate analysis,...
Source: British Journal of Haematology - November 6, 2009 Category: Hematology Authors: Gheath Alatrash, Maher Albitar, Susan O'Brien, Xuemei Wang, Taghi Manshouri, Stefan Faderl, Alessandra Ferrajoli, Jan Burger, Guillermo Garcia-Manero, Hagop M. Kantarjian, Susan Lerner, Michael J. Keating, William G. Wierda Source Type: journals
Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4+ perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotypeEmail this article to a colleague.
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We have previously shown an expansion of cytotoxic antigen-experienced CD4+T cells (CTLs) that express perforin (PF) in the peripheral blood of patients with B cell chronic lymphocytic leukaemia (B-CLL). Increased frequencies of CD4+CTLs have since been attributed to chronic viral infections, particularly, human cytomegalovirus (HCMV). The present study examined the involvement of CD4+CTLs in responses to HCMV in B-CLL, and characterized their differentiation. We studied 36 HCMV seropositive (SP) and seronegative B-CLL patients and 20 healthy age-matched individuals. The HCMV reactivity of CD4+PF+ and CD4+PF[minus] cells w...
Source: British Journal of Haematology - November 6, 2009 Category: Hematology Authors: James A. Walton, Peter M. Lydyard, Amit Nathwani, Vincent Emery, Arne Akbar, Martin J. Glennie, Nino Porakishvili Source Type: journals
Antigen receptor gene rearrangements reflect on the heterogeneity of adult Acute Lymphoblastic Leukaemia (ALL) with implications of cell-origin of ALL subgroups – a UKALLXII studyEmail this article to a colleague.
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Cytogenetic and molecular investigations of Acute Lymphoblastic Leukaemia (ALL) have identified the existence of distinct clinical subgroups. Molecular monitoring of clonal Immunoglobulin and T cell receptor (IG/TR) gene rearrangements has become an important tool in stratification of therapy of ALL. In order to determine whether certain features of the patient-specific rearrangements could hold further prognostic clues or provide information on the cell of origin of ALL, a comprehensive analysis of structural and biological features (V gene usage, coding frame and mutational status and complementarity-determining region -...
Source: British Journal of Haematology - November 6, 2009 Category: Hematology Authors: Lena Rai, Anouska Casanova, Anthony V. Moorman, Sue Richards, Georgina Buck, Anthony H. Goldstone, Adele K. Fielding, Letizia Foroni Source Type: journals
An increased frequency of 13q deletions detected by fluorescence in situ hybridization and its impact on survival in children and adolescents with Burkitt lymphoma: results from the Children's Oncology Group study CCG-5961Email this article to a colleague.
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Burkitt lymphoma (BL), an aggressive B-cell malignancy, is often curable with short intensive treatment regiments. Nearly all BLs contain rearrangements of the MYC/8q24 region; however, recent cytogenetic studies suggest that certain secondary chromosomal aberrations in BL correlate with an adverse prognosis. In this multi-centre study, the frequency and impact on clinical outcome of del(13q) and +7 in addition to MYC rearrangements as detected by fluorescence in situ hybridization (FISH) in children and adolescents with intermediate and high-risk BL registered on Children's Cancer Group study CCG-5961 were investigated. A...
Source: British Journal of Haematology - November 6, 2009 Category: Hematology Authors: Marilu Nelson, Sherrie L. Perkins, Bhavana J. Dave, Peter F. Coccia, Julia A. Bridge, Elizabeth R. Lyden, Nyla A. Heerema, Mark A. Lones, Lauren Harrison, Mitchell S. Cairo, Warren G. Sanger Source Type: journals
Cytomegalovirus-specific CD8+ T cells targeting different HLA/peptide combinations correlate with protection but at different threshold frequenciesEmail this article to a colleague.
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Cytomegalovirus (CMV) causes significant morbidity and mortality in patients after haematopoietic stem cell transplantation (HSCT). Due to limitations of current antiviral therapies, alternative approaches, involving transfer of donor-derived CMV-specific CD8+ T cells, have been considered. Levels of such cells correlating with protection against CMV infection and disease have only been reported in patients expressing HLA-A*0201 and HLA-B*0702. This is despite an increasing number of reports describing cells targeting CMV peptides presented by other human leucocyte antigens (HLAs). Considering several frequent HLA alleles,...
Source: British Journal of Haematology - November 6, 2009 Category: Hematology Authors: Sandra Giest, Sarah Grace, Alexandra C. Senegaglia, Ricardo Pasquini, Rosa M. Gonzalo-Daganzo, Manuel N. Fernández, Stephen Mackinnon, J. Alejandro Madrigal, Paul J. Travers Source Type: journals
Role of the interaction between Lu/BCAM and the spectrin-based membrane skeleton in the increased adhesion of hereditary spherocytosis red cells to lamininEmail this article to a colleague.
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Lu/BCAM, the unique erythroid receptor for laminin 511/521, interacts with the erythrocyte membrane skeleton through spectrin binding. It has been reported that Hereditary Spherocytosis red blood cells (HS RBC) exhibit increased adhesion to laminin. We investigated the role of Lu/BCAM[ndash]spectrin interaction in the RBC adhesion properties of 2 splenectomised HS patients characterized by 40% spectrin deficiency. Under physiological flow conditions, HS RBC exhibited an exaggerated adhesion to laminin that was completely abolished by soluble Lu/BCAM. Triton extraction experiments revealed that a greater fraction of Lu/BCAM...
Source: British Journal of Haematology - November 5, 2009 Category: Hematology Authors: Emilie Gauthier, Wassim El Nemer, Marie P. Wautier, Olivier Renaud, Gil Tchernia, Jean Delaunay, Caroline Le Van Kim, Yves Colin Source Type: journals
Fusion of PDGFRB to two distinct loci at 3p21 and a third at 12q13 in imatinib-responsive myeloproliferative neoplasmsEmail this article to a colleague.
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We identified four patients who presented with BCR-ABL1 negative myeloproliferative neoplasms and cytogenetically visible abnormalities of chromosome band 5q31-35. Fluorescence in situ hybridization indicated that the platelet-derived growth factor receptor [beta] gene (PDGFRB) was disrupted in all four cases and 5' rapid amplification of cDNA ends identified in-frame mRNA fusions between PDGFRB and WDR48 (3p21), GOLGA4 (3p21) and BIN2 (12q13). Strikingly, all three genes encode proteins involving intracellular trafficking. Imatinib, a known inhibitor of PDGFR[beta], selectively blocked the growth of t(3;5) myeloid colonie...
Source: British Journal of Haematology - November 4, 2009 Category: Hematology Authors: Claire Hidalgo-Curtis, Jane F. Apperley, Anthony Stark, Michael Jeng, Jason Gotlib, Andrew Chase, Nicholas C. P. Cross, Francis H. Grand Source Type: journals
Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemiaEmail this article to a colleague.
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To evaluate minimal residual disease (MRD) after chemotherapy and haematopoietic stem cell transplantation in juvenile myelomonocytic leukaemia (JMML), a locked nucleic acid-allele specific quantitative polymerase chain reaction (LNA-AS-qPCR) was developed for 13 patients (four types of PTPN11 mutation and four types of RAS mutation). The post-transplant MRD detected by LNA-AS-qPCR analysis was well correlated with chimerism assessed by short tandem repeat PCR analysis. Non-intensive chemotherapy exerted no substantial reduction of the tumour burden in three patients. There was no significant difference in the quantity of ...
Source: British Journal of Haematology - October 30, 2009 Category: Hematology Authors: Kazuyuki Matsuda, Kazuo Sakashita, Chiaki Taira, Miyuki Tanaka-Yanagisawa, Ryu Yanagisawa, Masaaki Shiohara, Hirokazu Kanegane, Daiichiro Hasegawa, Keiichiro Kawasaki, Mikiya Endo, Shuhei Yajima, Shinya Sasaki, Keisuke Kato, Kazutoshi Koike, Akira Kikuchi Source Type: journals
Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphomaEmail this article to a colleague.
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Romidepsin has shown promise in the treatment of T-cell lymphomas, and so we evaluated molecular endpoints gathered from 61 patients enrolled on a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma at the National Institutes of Health. The endpoints included histone H3 acetylation and ABCB1 gene expression in peripheral blood mononuclear cells (PBMCs); ABCB1 gene expression in tumour biopsy samples; and blood fetal haemoglobin levels (HbF), all of which were increased following romidepsin treatment. The fold increase in histone acetylation in PBMCs at 24 h was weakly to moderately well correlated with...
Source: British Journal of Haematology - October 29, 2009 Category: Hematology Authors: Susan E. Bates, Zhirong Zhan, Kenneth Steadman, Tomasz Obrzut, Victoria Luchenko, Robin Frye, Robert W. Robey, Maria Turner, Erin R. Gardner, William D. Figg, Seth M. Steinberg, Alex Ling, Tito Fojo, Kin Wah To, Richard L. Piekarz Source Type: journals
Increased levels of tissue factor activity and procoagulant phospholipids during treatment of children with acute lymphoblastic leukaemiaEmail this article to a colleague.
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In conclusion, these data indicate that, in addition to the well-identified increased in coagulation factors and inhibitor deficiencies, the injury of the endothelium could lead to the release of TF and PPL and could contribute to the hypercoagulability of children treated for ALL. (Source: British Journal of Haematology)
Source: British Journal of Haematology - October 29, 2009 Category: Hematology Authors: Pascale Schneider, Patrick Van Dreden, Aurélie Rousseau, Yusra Kassim, Elisabeth Legrand, Jean-Pierre Vannier, Marc Vasse Source Type: journals
Lenalidomide on alternative days is effective in myelodysplastic syndrome with 5q- deletionEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - October 29, 2009 Category: Hematology Authors: Marzia Defina, Michela Rondoni, Alessandro Gozzetti, Lara Aprile, Ida Chitarrelli, Alberto Fabbri, Francesco Lauria, Monica Bocchia Source Type: journals
Severe liver dysfunction from hepatitis C virus reactivation following alemtuzumab treatment for chronic lymphocytic leukaemiaEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - October 29, 2009 Category: Hematology Authors: Parameswaran Anoop, Andy Wotherspoon, Estella Matutes Source Type: journals
WASP plays a novel role in regulating platelet responses dependent on αIIbβ3 integrin outside-in signallingEmail this article to a colleague.
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The most consistent feature of Wiskott Aldrich syndrome (WAS) is profound thrombocytopenia with small platelets. The responsible gene encodes WAS protein (WASP), which functions in leucocytes as an actin filament nucleating agent [ndash]yet[ndash] actin filament nucleation proceeds normally in patient platelets regarding shape change, filopodia and lamellipodia generation. Because WASP localizes in the platelet membrane skeleton and is mobilized by [alpha]IIb[beta]3 integrin outside-in signalling, we questioned whether its function might be linked to integrin. Agonist-induced [alpha]IIb[beta]3 activation (PAC-1 binding) wa...
Source: British Journal of Haematology - October 28, 2009 Category: Hematology Authors: Anna Shcherbina, Jessica Cooley, Maxim I. Lutskiy, Charaf Benarafa, Gary E. Gilbert, Eileen Remold-O'Donnell Source Type: journals
Comprehensive analyses and characterization of haemophagocytic lymphohistiocytosis in Vietnamese childrenEmail this article to a colleague.
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In conclusion, the majority of HLH cases are associated with virus infections in Vietnamese children. Familial HLH is rare. The frequent reactivation and high mortality demands a more appropriate therapeutic regimen in tropical areas like Vietnam. (Source: British Journal of Haematology)
Source: British Journal of Haematology - October 27, 2009 Category: Hematology Authors: Lam T. My, Le B. Lien, Wen-Chuan Hsieh, Toshihiko Imamura, Tran N. K. Anh, Phan N. L. Anh, Nguyen T. Hung, Fan-Chen Tseng, Chia-Yu Chi, Ngo T. H. Dao, Duong T. M. Le, Le Q. Thinh, Tran T. Tung, Shinsaku Imashuku, Tang C. Thuong, Ih-Jen Su Source Type: journals
Frequency of altered monoclonal protein production at relapse of multiple myelomaEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - October 27, 2009 Category: Hematology Authors: Josie A. R. Hobbs, Mark T. Drayson, Katie Sharp, Stephen Harding, Arthur R. Bradwell, Graham P. Mead Source Type: journals
Treatment with deferasirox (Exjade®) effectively decreases iron burden in patients with thalassaemia intermedia: results of a pilot studyEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - October 26, 2009 Category: Hematology Authors: Ersi Voskaridou, Eleni Plata, Maroussa Douskou, Manousos Papadakis, Eleni-Evangelia Delaki, Dimitrios Christoulas, Evangelos Terpos Source Type: journals
Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993Email this article to a colleague.
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The predictive value of molecular minimal residual disease (MRD) monitoring using polymerase chain reaction amplification of clone-specific immunoglobulin or T-cell Receptor rearrangements was analysed in 161 patients with non T-lineage Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group (ECOG) 2993. MRD positivity ([ge]10[minus]4) in patients treated with chemotherapy alone was associated with significantly shorter relapse-free survival (RFS) at several time-points during the first year of therapy. MRD status best...
Source: British Journal of Haematology - October 26, 2009 Category: Hematology Authors: Bella Patel, Lena Rai, Georgina Buck, Sue M. Richards, Yeasmin Mortuza, Wayne Mitchell, Gareth Gerrard, Anthony V. Moorman, Veronique Duke, A. Victor Hoffbrand, Adele K. Fielding, Anthony H. Goldstone, Letizia Foroni Source Type: journals
Insight into the molecular pathogenesis of hairy cell leukaemia, hairy cell leukaemia variant and splenic marginal zone lymphoma, provided by the analysis of their IGH rearrangements and somatic hypermutation patternsEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - October 22, 2009 Category: Hematology Authors: Sarah L. Hockley, Stavroula Giannouli, Alison Morilla, Andrew Wotherspoon, Gareth J. Morgan, Estella Matutes, David Gonzalez Source Type: journals
Growth differentiation factor 15 in anaemia of chronic disease, iron deficiency anaemia and mixed type anaemiaEmail this article to a colleague.
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Recently, the iron and erythropoiesis-controlled growth differentiation factor 15 (GDF15) has been shown to inhibit the expression of hepcidin in [beta]-thalassaemia patients, thereby increasing iron absorption despite iron overload. To access the diagnostic and pathogenic impact of GDF15 in inflammatory anaemia the association of GDF15 expression with serum iron parameters and hepcidin was studied in patients suffering from iron deficiency anaemia (IDA), anaemia of chronic disease (ACD) and ACD subjects with true iron deficiency (ACD/IDA). GDF15 was significantly increased in both ACD and ACD/IDA, but not in IDA subjects ...
Source: British Journal of Haematology - October 21, 2009 Category: Hematology Authors: Igor Theurl, Armin Finkenstedt, Andrea Schroll, Manfred Nairz, Thomas Sonnweber, Rosa Bellmann-Weiler, Milan Theurl, Markus Seifert, Victor J. Wroblewski, Anthony T. Murphy, Derrick Witcher, Heinz Zoller, Günter Weiss Source Type: journals
Lenalidomide in patients with refractory or multiple relapsed Hodgkin lymphomaEmail this article to a colleague.
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - October 21, 2009 Category: Hematology Authors: Boris Böll, Peter Borchmann, Max S. Topp, Mathias Hänel, Katrin S. Reiners, Andreas Engert, Ralph Naumann Source Type: journals
Ontogeny of haematopoiesis: recent advances and open questionsEmail this article to a colleague.
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Unravelling the embryonic origins of the haematopoietic system has been the subject of sustained research for more than a century. Nevertheless, many important questions are still either unanswered or remain a matter of intense debate. Recent progress in mouse and embryonic stem cell model systems as well as imaging and post-genomic technologies has provided new insights into many of these open questions. Here we place into context recent reports on the anatomical site of blood stem cell emergence and, using red blood cells as an example, illustrate how the development of stem cells and the other blood lineages is both tem...
Source: British Journal of Haematology - October 21, 2009 Category: Hematology Authors: Katrin Ottersbach, Aileen Smith, Andrew Wood, Berthold Göttgens Source Type: journals
High resolution SNP array genomic profiling of peripheral T cell lymphomas, not otherwise specified, identifies a subgroup with chromosomal aberrations affecting the REL locusEmail this article to a colleague.
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Little is known about genomic aberrations in peripheral T cell lymphoma, not otherwise specified (PTCL NOS). We studied 47 PTCL NOS by 250k GeneChip single nucleotide polymorphism arrays and detected genomic imbalances in 22 of the cases. Recurrent gains and losses were identified, including gains of chromosome regions 1q32[ndash]43, 2p15[ndash]16, 7, 8q24, 11q14[ndash]25, 17q11[ndash]21 and 21q11[ndash]21 ([ge]5 cases each) as well as losses of chromosome regions 1p35[ndash]36, 5q33, 6p22, 6q16, 6q21[ndash]22, 8p21[ndash]23, 9p21, 10p11[ndash]12, 10q11[ndash]22, 10q25[ndash]26, 13q14, 15q24, 16q22, 16q24, 17p11, 17p13 and...
Source: British Journal of Haematology - October 21, 2009 Category: Hematology Authors: Sylvia Hartmann, Stefan Gesk, René Scholtysik, Markus Kreuz, Stefanie Bug, Inga Vater, Claudia Döring, Sergio Cogliatti, Marie Parrens, Jean-Philippe Merlio, Anna Kwiecinska, Anna Porwit, Pier Paolo Piccaluga, Stefano Pileri, Gerald Hoefler, Ralf Küppe Source Type: journals
Cell cycle and tissue of origin contribute to the migratory behaviour of human fetal and adult mesenchymal stromal cellsEmail this article to a colleague.
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In conclusion, our results suggest that MSC from various sources have different migratory capacities, depending on the tissue of origin. Similar to haematopoietic stem cells, cell cycle contributes to MSC migration, which offers perspectives for modulation of MSC to enhance efficacy of future cellular therapies. (Source: British Journal of Haematology)
Source: British Journal of Haematology - October 21, 2009 Category: Hematology Authors: Marijke W. Maijenburg, Willy A. Noort, Marion Kleijer, Charlotte J. A. Kompier, Kees Weijer, Jaap D. van Buul, C. Ellen van der Schoot, Carlijn Voermans Source Type: journals
Genome wide DNA-profiling of HIV-related B-cell lymphomasEmail this article to a colleague.
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Non-Hodgkin lymphomas (NHL) represent a frequent complication of human immunodeficiency virus (HIV) infection. To elucidate HIV-NHL pathogenesis, we performed a genome-wide DNA profiling based on a single nucleotide polymorphism-based microarray comparative genomic hybridization in 57 HIV-lymphomas and, for comparison, in 105 immunocompetent diffuse large B-cell lymphomas (IC-DLBCL). Genomic complexity varied across HIV-NHL subtypes. HIV-Burkitt lymphoma showed a significantly lower number of lesions than HIV-DLBCL (P = 0·032), whereas the median number of copy number changes was significantly higher in Epstein[ndash]Barr...
Source: British Journal of Haematology - October 13, 2009 Category: Hematology Authors: Daniela Capello, Marta Scandurra, Giulia Poretti, Paola M. V. Rancoita, Michael Mian, Annunziata Gloghini, Clara Deambrogi, Maurizio Martini, Davide Rossi, Timothy C. Greiner, Wing C. Chan, Maurilio Ponzoni, Santiago M. Moreno, Miguel A. Piris, Vincenzo C Source Type: journals
Incidence and reasons for late failure after allogeneic haematopoietic cell transplantation following BuCy2 in acute myeloid leukaemiaEmail this article to a colleague.
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The long-term follow-up is presented for 317 patients with acute myeloid leukaemia who underwent human leucocyte antigen-identical sibling marrow transplants between 1984 and 1995 following preparation with busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Among the 142 (45%) who were alive and leukaemia-free 3 years following transplantation, the leukaemia-free survival at 15 years was 72·8%. The cumulative incidence of late (>3 years beyond transplant) non-relapse mortality at 15 years was 12·9% and of late relapse was 16·5%. None of the variables considered (including age, disease stage, and graft-versus-host disease...
Source: British Journal of Haematology - October 12, 2009 Category: Hematology Authors: Shubham Pant, Mehdi Hamadani, Anthony J. Dodds, Jeffrey Szer, Pamela A. Crilley, Dustin Stevenson, Gary Phillips, Patrick Elder, Ian Nivison-Smith, Belinda R. Avalos, Sam Penza, David Topolsky, Ronald Sobecks, Matt Kalaycio, Brian J. Bolwell, Edward A. Co Source Type: journals
Advances in the understanding of cobalamin assimilation and metabolismEmail this article to a colleague.
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The haematological and neurological consequences of cobalamin deficiency define the essential role of this vitamin in key metabolic reactions. The identification of cubilin-amnionless as the receptors for intestinal absorption of intrinsic factor-bound cobalamin and the plasma membrane receptor for cellular uptake of transcobalamin bound cobalamin have provided a clearer understanding of the absorption and cellular uptake of this vitamin. As the genes involved in the intracellular processing of cobalamins and genetic defects of these pathways are identified, the metabolic disposition of cobalamins and the proteins involved...
Source: British Journal of Haematology - October 11, 2009 Category: Hematology Authors: Edward V. Quadros Source Type: journals
Clinical Practice Guidelines for the management of atypical Haemolytic Uraemic Syndrome in the United KingdomEmail this article to a colleague.
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Atypical haemolytic uraemic syndrome (aHUS) is associated with a poor prognosis with regard to survival at presentation, recovery of renal function and transplantation. It is now established that aHUS is a disease of complement dysregulation with mutations in the genes encoding both complement regulators and activators, and autoantibodies against the complement regulator factor H. Identification of the underlying molecular abnormality in an individual patient can now help to guide their future management. In these guidelines we make recommendations for the investigation and management of aHUS patients both at presentation ...
Source: British Journal of Haematology - October 10, 2009 Category: Hematology Authors: C. Mark Taylor, Sam Machin, Stephen J. Wigmore, Tim H. J. Goodship Source Type: journals
Sequential phase II Southwest Oncology Group studies (S0112 and S0301) of daunorubicin and cytarabine by continuous infusion, without and with ciclosporin, in older patients with previously untreated acute myeloid leukaemiaEmail this article to a colleague.
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Attempts to overcome multi-drug resistance in acute myeloid leukaemia (AML) have been limited by toxicities. To investigate the effect of reducing peak drug levels, we performed sequential phase II studies using continuous infusion daunorubicin and cytarabine without (AD) and then with ciclosporin (ADC) in older patients with AML. Untreated patients (age 56+ years) received daunorubicin (45 mg/m2 per day for 3 d) and cytarabine (200 mg/m2 per day for 7 d), both by continuous infusion, without (S0112, 60 patients) and then with (S0301, 50 patients) the addition of ciclosporin. Complete response (CR) rates were 38% on S0112 ...
Source: British Journal of Haematology - October 10, 2009 Category: Hematology Authors: Thomas R. Chauncey, Holly Gundacker, Mazyar Shadman, Alan F. List, Shaker R. Dakhil, Harry P. Erba, Marilyn L. Slovak, I-Ming Chen, Cheryl L. Willman, Kenneth J. Kopecky, Frederick R. Appelbaum Source Type: journals
A population pharmacokinetic model for pegylated-asparaginase in childrenEmail this article to a colleague.
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We analysed 1221 serum activity measurements in 168 children from the Berlin-Frankfürt-Münster acute lymphoblastic leukaemia studies, ALL-BFM (Berlin-Frankfürt-Münster) 95 and ALL-BFM REZ, in order to develop a pharmacokinetic model describing the activity-time course of pegylated (PEG)-asparaginase for all dose levels. Patients received 500, 750, 1000 or 2500 U/m2 PEG-asparaginase on up to nine occasions. Serum samples were analysed for asparaginase activity and data analysis was done using nonlinear mixed effects modelling (NONMEM Vers. VI, Globomax, Hanouet, MD, USA). Different linear and nonlinear models were teste...
Source: British Journal of Haematology - October 10, 2009 Category: Hematology Authors: Georg Hempel, Hans-Joachim Müller, Claudia Lanvers-Kaminsky, Gudrun Würthwein, Antje Hoppe, Joachim Boos Source Type: journals
Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cellsEmail this article to a colleague.
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The present study explored the impact of two novel criteria; having >95% abnormal plasma cells by flow cytometry at diagnosis and the evolving subtype of the disease, as predictors of progression in 61 smouldering multiple myeloma (SMM) and 311 monoclonal gammopathy of unknown significance (MGUS) patients. Although both criteria were of prognostic value, the risk of progression was better identified by immunophenotyping [Hazard Ratio (HR) 6·2 and 17·2 for SMM and MGUS, respectively] than evolving subtype, which had independent prognostic value only in MGUS (HR 3·6). Immunophenotyping discriminated the different risk of ...
Source: British Journal of Haematology - October 10, 2009 Category: Hematology Authors: Ernesto Pérez-Persona, Gema Mateo, Ramón García-Sanz, María-Victoria Mateos, Natalia de las Heras, Alfonso García de Coca, José M. Hernández, Josefina Galende, Guillermo Martín-Nuñez, Abelardo Bárez, José M. Alonso, Alejandro Martín, Consuelo Source Type: journals
Immunotoxin BL22 induces apoptosis in mantle cell lymphoma (MCL) cells dependent on Bcl-2 expressionEmail this article to a colleague.
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Mantle cell lymphoma (MCL) is an incurable mature B cell proliferation, combining the unfavourable clinical features of aggressive and indolent lymphomas. The blastic variant of MCL has an even worse prognosis and new treatment options are clearly needed. We analysed the effects of BL22, an immunotoxin composed of the Fv portion of an anti- CD22 antibody fused to a 38-kDa Pseudomonas exotoxin-A fragment on four MCL cell lines as well as on primary cells of four MCL patients. Apoptosis induction by BL22 was much more pronounced in MCL cell lines with low Bcl-2 expression (NCEB-1, JeKo-1 and JVM-2) compared to Granta-519 cel...
Source: British Journal of Haematology - October 10, 2009 Category: Hematology Authors: Christian Bogner, Tobias Dechow, Ingo Ringshausen, Michaela Wagner, Madlen Oelsner, Gloria Lutzny, Thomas Licht, Christian Peschel, Thomas Decker Source Type: journals
Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP)Email this article to a colleague.
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Diffuse large B cell lymphoma (DLBCL) is clinically and biologically heterogeneous. In most cases of DLBCL, lymphoma cells co-express vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2, suggesting autocrine in addition to angiogenic effects. We enumerated microvessel density and scored lymphoma cell expression of VEGF, VEGFR1, VEGFR2 and phosphorylated VEGFR2 in 162 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone)-like regimens. VEGFR2 expression correlated with shorter overall survival (OS) independent of International Prognostic I...
Source: British Journal of Haematology - October 10, 2009 Category: Hematology Authors: Dita Gratzinger, Ranjana Advani, Shuchun Zhao, Neha Talreja, Robert J. Tibshirani, Ragini Shyam, Sandra Horning, Laurie H. Sehn, Pedro Farinha, Javier Briones, Izidore S. Lossos, Randy D. Gascoyne, Yasodha Natkunam Source Type: journals
