MedWorm: Hematology

Drug Combo Meets NSCLC Milestone

MedPage Today Hematology/Oncology — Sat, 20 Mar 2010 14:13:05 +0100

Nanoparticle albumin-bound paclitaxel (Abraxane) met a key milestone in a non-small cell lung cancer clinical trial, the drug's maker said. (Source: MedPage Today Hematology/Oncology)

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A non-functioning vitamin D receptor predisposes to leukaemoid reactions in mice

Hematological Oncology — Sat, 20 Mar 2010 00:00:00 +0100

The vitamin D hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D, is not only essential for mineral metabolism but may have important functions beyond calcium homoeostasis. By gene targeting, we have recently generated mice expressing a functionally inactive mutant vitamin D receptor (VDR). After a change in environmental conditions from specific pathogen free (SPF) conditions to a modified barrier system, a high percentage of aged mutant, but not wild-type, mice developed a haematological disorder characterized by splenomegaly, granulocytosis, thrombocytosis and dysplastic changes with displacement of erythropoiesis in bone marrow during the following months. All cases were associated with very high serum levels of the acute phase reaction protein se...

Kaplan-Meier method is inappropriate for estimating cumulative incidence of graft-versus-host disease in the presence of competing events

American Journal of Hematology — Sat, 20 Mar 2010 00:00:00 +0100

No abstract. (Source: American Journal of Hematology)

Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations

Haemophilia — Sat, 20 Mar 2010 00:00:00 +0100

Summary. Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by a lack or decrease of coagulation factor VIII activity. The molecular diagnosis of HA is challenging and a variety of different mutations have been identified throughout the F8 gene. Our aim was to detect the causative mutation in 266 HA patients from Emilia-Romagna region (Italy) and in all suspected carriers. Molecular analysis of F8 in 201 HA patients (152 index cases) was performed with a combination of several indirect and direct molecular approaches, such as long distance polymerase chain reaction, multiplex ligation-dependent probe amplification, denaturing high performance liquid chromatography and direct sequencing. The analysis revealed 78 different mutations, 23 of which were novel, not having been ...

Reduction of imatinib dose and persistence of complete molecular response after p210 multipeptide vaccine in chronic myeloid leukaemia treated with dose escalation for acquired resistance

British Journal of Haematology — Sat, 20 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Dialysis in the poisoned patient

Hemodialysis International — Sat, 20 Mar 2010 00:00:00 +0100

Patients who ingest toxic substances may require extracorporeal removal of the poisons or their toxic metabolites if native renal clearance is not sufficient because of acute kidney injury, acuity of symptoms, or burden of toxin. Here, a case is presented, and the literature on renal replacement therapy in the event of acute intoxication is reviewed. Extracorporeal therapy efficacy is examined in terms of the characteristics of the toxin (molecular size, charge, protein, or lipid binding); the patient (body habitus and volume of distribution); and the process (membrane effects on extraction ratios and sieving, role of blood, and dialysate flow rates). The choice of extracorporeal therapy and hemodialysis prescriptions for specific poisonings are discussed. (Source: Hemodialysis Internation...

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SGO: New Option for Recurrent Ovarian Cancer? (CME/CE)

MedPage Today Hematology/Oncology — Fri, 19 Mar 2010 18:19:19 +0100

SAN FRANCISCO (MedPage Today) -- Women with recurrent or relapsed, platinum-sensitive ovarian cancer had a significantly lower risk of subsequent recurrence and less toxicity when treated with carboplatin and pegylated liposomal doxorubicin (PLD, Doxil) than with standard therapy, data from a large European study showed. (Source: MedPage Today Hematology/Oncology)

SGO: No Lung CA Risk Seen with Estrogen (CME/CE)

MedPage Today Hematology/Oncology — Fri, 19 Mar 2010 17:33:21 +0100

SAN FRANCISCO (MedPage Today) -- Unopposed estrogen therapy (ERT) did not increase lung cancer incidence or mortality risk in the Women's Health Initiative (WHI). (Source: MedPage Today Hematology/Oncology)

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:47 +0100

(Source: Transfusion Medicine Reviews)

Will Publish in Future Issues . . .

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:47 +0100

(Source: Transfusion Medicine Reviews)

Editorial Board

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:47 +0100

(Source: Transfusion Medicine Reviews)

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Journal Club

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:47 +0100

(Source: Transfusion Medicine Reviews)

The Usefulness of Pathogen Inactivation During an Outbreak of the New Strain of Influenza (H1N1)

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:47 +0100

The degree of attention surrounding the pandemic of a new strain of influenza virus (H1N1) has posed major crisis management problems to health care workers worldwide. In the Kansai region of Japan, the number of blood donors has fallen by approximately 40%. This drop in blood donations has been due to an increase in the number of people unwilling to leave their homes as a result of being exposed to and the possible spread of this new strain of influenza. The World Health Organization predicted that the number of blood donors would decrease by 25% in the event of a widespread H1N1 virus outbreak, but the decrease in blood donation in Japan far exceeded this figure. This fact has fulfilled the previously predicted concern that blood transfusions could be significantly impaired in the event ...

Arnault Tzanck, MD (1886-1954)

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:46 +0100

Arnault Tzanck's name is attached to an apparatus he invented that was widely used for transfusing blood in France between the wars, as well a simple test he devised using the microscopic analysis of scrapings from skin cancer lesions, different ganglia, and some forms of dermatitis especially pemphigus. The Tzanck smear is still widely used as a test for herpes, among other diseases. He also experimented with different methods of preserving blood and blood substitutes. Tzanck's most lasting contribution was in the organization of blood transfusion in France that eventually resulted in the creation of the Centre National de Transfusion Sanguine (National Blood Transfusion Center), which was established in 1949 with Tzanck as its first director. In the process, Tzanck educated a whole gener...

A Strategic Approach to the Problems of Providing Rhesus D–Negative Blood Transfusion in Geographic Areas With Low RhD Negativity: A Nigerian Perspective

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:43 +0100

In contrast to the white prevalence, the frequency of rhesus D (RhD) negativity in the Nigerian population ranges from less than 1% to about 6% in the different ethnic population groups across the country. Consequently, there is often a severe scarcity of RhD-negative blood in Nigeria, leading to undue delay in transfusing RhD-negative patients. This situation has led to the prolongation of hospital stays as well as increased morbidity and mortality in affected patients. The problem is compounded by the general unavailability of donor RhD-negative blood, which is partially related to a suboptimal national blood transfusion service. This situation has thus relegated the responsibilities of donor recruitment and blood collection to individual hospital blood banks. This has led to the necessi...

Optimization of Leukocyte Collection and Monocyte Isolation for Dendritic Cell Culture

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:43 +0100

Leukapheresis is the method of choice to collect monocytes for dendritic cell (DC) culture. Improvement of cell separators and cell collection software have enabled the collection of 109 monocytes for the generation of monocyte-derived DCs, which is sufficient to prepare a DC vaccine series. However, leukapheresis works with the technique of differential centrifugation which is not applicable to selectively collect mononuclear cells of similar density. After leukapheresis, thus, additional preparation steps are required to isolate and enrich the desired monocyte population. The cell isolation and cultivation techniques depend on the quality of the original leukocyte harvest due to the monocyte yield and the content of residual erythrocytes and platelets. Monocyte elutriation from the leuka...

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Is There a Role for Autologous/Placental Red Blood Cell Transfusions in the Anemia of Prematurity?

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:43 +0100

Because most extremely preterm infants with birth weight less than 1000 g need red blood cell transfusions, many attempts have been made to collect, process, and store placental blood (ie, umbilical cord blood) for autologous transfusions. Although it is feasible to do this, multiple problems in doing so including insufficient volumes collected, clotting, hemolysis, bacterial contamination, failure to significantly supplant need for allogeneic transfusions, and high costs have led many to question whether, on balance, autologous/placental red blood cell transfusion offers clinically significant benefits. (Source: Transfusion Medicine Reviews)

Blood Still Kills: Six Strategies to Further Reduce Allogeneic Blood Transfusion-Related Mortality

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:42 +0100

After reviewing the relative frequency of the causes of allogeneic blood transfusion-related mortality in the United States today, we present 6 possible strategies for further reducing such transfusion-related mortality. These are (1) avoidance of unnecessary transfusions through the use of evidence-based transfusion guidelines, to reduce potentially fatal (infectious as well as noninfectious) transfusion complications; (2) reduction in the risk of transfusion-related acute lung injury in recipients of platelet transfusions through the use of single-donor platelets collected from male donors, or female donors without a history of pregnancy or who have been shown not to have white blood cell (WBC) antibodies; (3) prevention of hemolytic transfusion reactions through the augmentation of pati...

Masthead

Transfusion Medicine Reviews — Fri, 19 Mar 2010 15:31:42 +0100

(Source: Transfusion Medicine Reviews)

Editorial Board

Experimental Hematology — Fri, 19 Mar 2010 15:31:37 +0100

(Source: Experimental Hematology)

Genetics Add Little to Breast Cancer Risk Prediction (CME/CE)

MedPage Today Hematology/Oncology — Fri, 19 Mar 2010 15:13:06 +0100

The addition of genetic information only modestly improved breast cancer risk assessment in an analysis of 5,600 cases. (Source: MedPage Today Hematology/Oncology)

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Memphis! Join the IMF for a Broadway Theater Party!

International Myeloma Foundation — Fri, 19 Mar 2010 04:00:00 +0100

(Source: International Myeloma Foundation)

Successful treatment of disseminated intravascular coagulation in a child with acute myelogenous leukaemia using recombinant thrombomodulin

British Journal of Haematology — Fri, 19 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Necrobiotic xanthogranuloma, a rare complication of a persistently high paraprotein

British Journal of Haematology — Fri, 19 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

The use of fluid boluses to safely perform extracorporeal photopheresis (ECP) in low-weight children: A novel procedure

Journal of Clinical Apheresis — Fri, 19 Mar 2010 00:00:00 +0100

We present a safe and feasible alternative to the procedure for children who weigh less than 40 Kg, while maintaining a closed loop, sterile system utilizing the UVAR XTS device. A retrospective chart review was performed analyzing the use of fluid boluses (normal saline in those between 20 and 40 Kg, 5% albumin in those under 20 Kg) before ECP. Eleven patients underwent 334 ECP procedures for acute and chronic graft-versus-host disease (n = 9), and for prevention of graft-versus-host disease (n = 2). Volumes of fluid boluses were calculated based on the expected extracorporeal volume during the first draw cycle. Treatments consisted of at least three draw cycles using the 125 mL bowl. The median weight was 28.5 Kg (range 19 to 39); nine of 11 required red cell transfusions to maintain ade...

A large family from Argentina with Prekallikrein deficiency due to a compound heterozygosis (T insertion in intron 7 and Asp558Glu in exon 15): Prekallikrein Cordoba

American Journal of Hematology — Fri, 19 Mar 2010 00:00:00 +0100

No abstract. (Source: American Journal of Hematology)

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Pandemic influenza A (H1N1) virus infections in children with sickle cell disease

Blood — Thu, 18 Mar 2010 16:02:04 +0100

(Source: Blood)

Genetic variations in the heparanase gene (HPSE) associate with increased risk of GVHD following allogeneic stem cell transplantation: effect of discrepancy between recipients and donors

Blood — Thu, 18 Mar 2010 16:02:04 +0100

Graft-versus-host disease (GVHD) is the most common cause of nonrelapse mortality and morbidity after hematopoietic stem cell transplantation (HSCT). The well-documented involvement of heparanase in the process of inflammation and autoimmunity led us to investigate an association between HPSE gene single-nucleotide polymorphisms (SNPs) and the risk of GVHD. The present study indicates a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing acute GVHD. Moreover, the study revealed that discrepancy between recipient and donor in these SNPs may elevate significantly the risk of acute GVHD. This association was statistically significant when the recipients possessed genotype combinations dictating higher levels of heparanase ...

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen–matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipien...

Amino acid residues Arg659, Arg660, and Tyr661 in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Previous studies have shown that ADAMTS13 spacer domain is required for cleavage of von Willebrand factor (VWF). However, the exact amino acid residues within this domain critical for substrate recognition are not known. Epitope mapping of anti-ADAMTS13 immunoglobulin G from patients with thrombotic thrombocytopenic purpura and sequence alignment of the ADAMTS13 spacer domains of human, mouse, and zebrafish with these of human and murine ADAMTS1, a closely related member of ADAMTS family, have provided hints to investigate the role of the amino acid residues between Arg659 and Glu664 of the ADAMTS13 spacer domain in substrate recognition. A deletion of all these 6 amino acid residues (ie, Arg659-Glu664) from the ADAMTS13 spacer domain resulted in dramatically reduced proteolytic activity t...

Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug

Blood — Thu, 18 Mar 2010 16:02:03 +0100

In conclusion, HCQ reversed antiphospholipid-mediated disruptions of AnxA5 on PLBs and cultured cells, and in APS patient plasmas. These results support the concept of novel therapeutic approaches that address specific APS disease mechanisms. (Source: Blood)

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A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement

Blood — Thu, 18 Mar 2010 16:02:03 +0100

The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds complement C5 thereby preventing formation of the cytolytic membrane attack complex of complement. However, in essentially all patients treated with eculizumab, persistent anemia, reticulocytosis, and biochemical evidence of hemolysis are observed; and in a significant proportion, their PNH erythrocytes become opsonized with complement C3. These observations suggest that PNH patients treated with eculizumab are left with clinically significant immune-mediated hemolytic anemia becau...

Role for ADAP in shear flow-induced platelet mechanotransduction

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Binding of platelets to fibrinogen via integrin IIbβ3 stimulates cytoskeletal reorganization and spreading. These responses depend on tyrosine phosphorylation of multiple proteins by Src family members and Syk. Among Src substrates in platelets is adhesion- and degranulation-promoting adapter protein (ADAP), an adapter with potential binding partners: SLP-76, VASP, and SKAP-HOM. During studies of platelet function under shear flow, we discovered that ADAP–/– mouse platelets, unlike ADAP+/+ platelets, formed unstable thrombi in response to carotid artery injury. Moreover, fibrinogen-adherent ADAP–/– platelets in shear flow ex vivo showed reduced spreading and smaller zones of contact with the matrix. These abnormalities were not observed under static conditions,...

Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6

Blood — Thu, 18 Mar 2010 16:02:03 +0100

The transforming and tumor growth–promoting properties of Axl, a member of the Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases (TAMRs), are well recognized. In contrast, little is known about the role of the TAMR ligand growth arrest–specific gene 6 (Gas6) in tumor biology. By using Gas6-deficient (Gas6–/–) mice, we show that bone marrow–derived Gas6 promotes growth and metastasis in different experimental cancer models, including one resistant to vascular endothelial growth factor inhibitors. Mechanistic studies reveal that circulating leukocytes produce minimal Gas6. However, once infiltrated in the tumor, leukocytes up-regulate Gas6, which is mitogenic for tumor cells. Consistent herewith, impaired tumor growth in Gas6–/– mice is r...

An upstream insulator regulates DLK1 imprinting in AML

Blood — Thu, 18 Mar 2010 16:02:03 +0100

DLK1 is an imprinted gene on chromosome 14. Using informative coding single nucleotide polymorphisms, we found DLK1 expression to be monoallelic in normal bone marrow, whereas it was biallelic in 76% of acute myeloid leukemia (AML) overexpressing DLK1 (61% of all AML). Quantitative methylation analysis of 7 cytosine-phosphate-guanosine-rich areas (3 upstream of or within DLK1, the putative intergenic-differentially methylated region and 3 upstream of or within MEG3) revealed a strong association between biallelic DLK1 expression and hypermethylation of a cytosine-phosphate-guanosine-rich region 18 kb upstream of DLK1. Allele-specific methylation analysis of this region revealed the alleles to be differentially methylated in normal bone marrow and monoallelic DLK1 AML, whereas there was inc...

The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma

Blood — Thu, 18 Mar 2010 16:02:03 +0100

The proteasomal pathway of protein degradation involves 2 discrete steps: ubiquitination and degradation. Here, we evaluated the effects of inhibiting the ubiquitination pathway at the level of the ubiquitin-activating enzyme UBA1 (E1). By immunoblotting, leukemia cell lines and primary patient samples had increased protein ubiquitination. Therefore, we examined the effects of genetic and chemical inhibition of the E1 enzyme. Knockdown of E1 decreased the abundance of ubiquitinated proteins in leukemia and myeloma cells and induced cell death. To further investigate effects of E1 inhibition in malignancy, we discovered a novel small molecule inhibitor, 3,5-dioxopyrazolidine compound, 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione (PYZD-4409). PYZD-4409 ind...

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Bortezomib induces apoptosis in primitive chronic myeloid leukemia cells including LTC-IC and NOD/SCID repopulating cells

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Chronic myeloid leukemia (CML) is treated effectively with tyrosine kinase inhibitors (TKIs); however, 2 key problems remain—the insensitivity of CML stem and progenitor cells to TKIs and the emergence of TKI-resistant BCR-ABL mutations. BCR-ABL activity is associated with increased proteasome activity and proteasome inhibitors (PIs) are cytotoxic against CML cell lines. We demonstrate that bortezomib is antiproliferative and induces apoptosis in chronic phase (CP) CD34+ CML cells at clinically achievable concentrations. We also show that bortezomib targets primitive CML cells, with effects on CD34+38–, long-term culture-initiating (LTC-IC) and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells. Bortezomib is not selective for CML cells and induces ...

Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor–related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 105 tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell–derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40%...

Overexpression of caveolin-1 in adult T-cell leukemia

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Caveolin-1 is implicated in the regulation of signal pathways. Adult T-cell leukemia (ATL) is a T-cell malignancy causatively associated with human T-cell leukemia virus type 1 (HTLV-1). To determine the role of caveolin-1 in leukemogenesis, we examined caveolin-1 expression levels in HTLV-1–infected T-cell lines and ATL cells. These cells expressed high levels of caveolin-1 compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Caveolin-1–positive ATL cells were detected in ATL lymph nodes and skin lesions, and caveolin-1 was also detected in the plasma of patients with ATL. Infection of a human T-cell line, an epithelial cell line, and normal PBMCs with HTLV-1 induced caveolin-1 expression. The viral protein Tax transcriptionally activate...

The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas contains templated nucleotide insertions and a major breakpoint region similar to follicular and mantle cell lymphoma

Blood — Thu, 18 Mar 2010 16:02:03 +0100

The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. However, the nucleotide sequence of only one t(14;18)–positive MALT lymphoma has been reported so far. We here report the molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)–positive MALT lymphomas. Similar to the IGH-associated translocations in follicular and mantle cell lymphomas, the IGH-MALT1 junctions in MALT lymphoma showed all features of a recombination signal sequence–guided V(D)J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated nucleotides (T-nucleotides) were identified at the t(14;18)/IGH...

PI3K p110{delta} regulates T-cell cytokine production during primary and secondary immune responses in mice and humans

Blood — Thu, 18 Mar 2010 16:02:03 +0100

In this study, using the isoform-selective inhibitor IC87114, we show that sustained p110 activity is required for interferon- production. Moreover, acute inhibition of p110 inhibits cytokine production and reduces hypersensitivity responses in mice. Whether p110 played a similar role in human T cells was unknown. Here we show that IC87114 potently blocked T-cell receptor–induced phosphoinositide 3-kinase signaling by both naive and effector/memory human T cells. Importantly, IC87114 reduced cytokine production by memory T cells from healthy and allergic donors and from inflammatory arthritis patients. These studies establish that previously activated memory T cells are at least as sensitive to p110 inhibition as naive T cells and show that mouse models accurately predict p110 functi...

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Irradiation and IL-15 promote loss of CD8 T-cell tolerance in response to lymphopenia

Blood — Thu, 18 Mar 2010 16:02:03 +0100

In conclusion, we show that lymphopenia is not sufficient to break CD8 T-cell tolerance. Furthermore, we demonstrate that pretreatment regimens are crucial to circumvent this problem and to optimize adoptive T-cell therapy. (Source: Blood)

Mislocalization of SLP-76 leads to aberrant inflammatory cytokine and autoantibody production

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Central and peripheral tolerance is required to prevent immune responses to self-antigens. We now present a mouse model in which wild-type (WT) SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) has been constitutively targeted to the membrane, where CD4+ T cells become spontaneously dysregulated and develop an inflammatory phenotype. Mice bearing membrane-targeted SLP-76 (MTS) have a partial T-cell lymphopenia and impaired signaling though the mature T-cell receptor. The CD4+ T cells that develop in these mice possess an activated-like phenotype and are skewed toward the inflammatory TH1 and TH17 lineages. MTS mice also spontaneously develop autoantibodies at an early age. To rule out abnormal thymic selection as the sole cause of the MTS phenotype, we expressed WT SLP-76 a...

Free HTLV-1 induces TLR7-dependent innate immune response and TRAIL relocalization in killer plasmacytoid dendritic cells

Blood — Thu, 18 Mar 2010 16:02:03 +0100

A recent report demonstrated that free human T-cell leukemia virus 1 (HTLV-1) could infect plasmacytoid dendritic cells (pDCs). The major role of pDCs is to secrete massive levels of interferon- (IFN-) upon virus exposure; however, the induction of IFN- by HTLV-1 remains unknown. We demonstrate here that cell-free HTLV-1 generated a pDC innate immune response by producing massive levels of IFN- that were inhibited by anti–HTLV-1 antibodies. HTLV-1 induced costimulatory molecules and rapid expression of the apoptotic ligand tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Furthermore, HTLV-1 stimulated pDC-induced apoptosis of CD4+ T cells expressing DR5, transforming pDCs into IFN-producing killer pDCs. We also observed that an endosomal acidification inhibitor ...

Regulation of human NK-cell cytokine and chemokine production by target cell recognition

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Natural killer (NK)–cell recognition of infected or neoplastic cells can induce cytotoxicity and cytokine secretion. So far, it has been difficult to assess the relative contribution of multiple NK-cell activation receptors to cytokine and chemokine production upon target cell recognition. Using Drosophila cells expressing ligands for the NK-cell receptors LFA-1, NKG2D, DNAM-1, 2B4, and CD16, we studied the minimal requirements for secretion by freshly isolated, human NK cells. Target cell stimulation induced secretion of predominately proinflammatory cytokines and chemokines. Release of chemokines MIP-1, MIP-1β, and RANTES was induced within 1 hour of stimulation, whereas release of TNF- and IFN- occurred later. Engagement of CD16, 2B4, or NKG2D sufficed for chemokine release, ...

FOG1 requires NuRD to promote hematopoiesis and maintain lineage fidelity within the megakaryocytic-erythroid compartment

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Nuclear factors regulate the development of complex tissues by promoting the formation of one cell lineage over another. The cofactor FOG1 interacts with transcription factors GATA1 and GATA2 to control erythroid and megakaryocyte (MK) differentiation. In contrast, FOG1 antagonizes the ability of GATA factors to promote mast cell (MC) development. Normal FOG1 function in late-stage erythroid cells and MK requires interaction with the chromatin remodeling complex NuRD. Here, we report that mice in which the FOG1/NuRD interaction is disrupted (Fogki/ki) produce MK-erythroid progenitors that give rise to significantly fewer and less mature MK and erythroid colonies in vitro while retaining multilineage capacity, capable of generating MCs and other myeloid lineage cells. Gene expression profil...

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B cell-specific lentiviral gene therapy leads to sustained B-cell functional recovery in a murine model of X-linked agammaglobulinemia

Blood — Thu, 18 Mar 2010 16:02:03 +0100

The immunodeficiency disorder, X-linked agammaglobulinemia (XLA), results from mutations in the gene encoding Bruton tyrosine kinase (Btk). Btk is required for pre-B cell clonal expansion and B-cell antigen receptor signaling. XLA patients lack mature B cells and immunoglobulin and experience recurrent bacterial infections only partially mitigated by life-long antibody replacement therapy. In pursuit of definitive therapy for XLA, we tested ex vivo gene therapy using a lentiviral vector (LV) containing the immunoglobulin enhancer (Eµ) and Igβ (B29) minimal promoter to drive B lineage–specific human Btk expression in Btk/Tec–/– mice, a strain that reproduces the features of human XLA. After transplantation of EµB29-Btk-LV–transduced stem cells, treat...

Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study

Blood — Thu, 18 Mar 2010 16:02:03 +0100

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by dysregulation of the Fas apoptotic pathway. Clinical manifestations of ALPS include autoimmune cytopenias, organomegaly, and lymphadenopathy. These findings overlap with Evans syndrome (ES), defined by presence of at least 2 autoimmune cytopenias. We hypothesized a subset of patients with ES have ALPS and tested 45 children at 22 institutions, measuring peripheral blood double-negative T cells (DNTs) and Fas-mediated apoptosis. ALPS was diagnosed in 47% of patients tested. Markedly elevated DNTs (≥ 5%) were a strong predictor of ALPS (positive predictive value = 94%), whereas no patients with DNTs less than 2.5% had ALPS on apoptosis testing. Severity of cytopenias and elevated immunog...

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

Blood — Thu, 18 Mar 2010 16:02:02 +0100

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder that can be treated with bone marrow transplantation, immunosuppressive therapy, and high-dose cyclophosphamide. Here, we report long-term follow-up on 67 SAA patients (44 treatment-naive and 23 refractory) treated with high-dose cyclophosphamide. At 10 years, the overall actuarial survival was 88%, the response rate was 71% with the majority being complete, and the actuarial event-free survival was 58% in 44 treatment-naive SAA patients. Patients with refractory SAA fared less well after high-dose cyclophosphamide therapy; at 10 years, overall actuarial survival, response, and actuarial event-free survival rates were 62%, 48%, and 27%, respectively. High-dose cyclophosphamide is highly effective therapy for se...

Targeting the translational machinery as a novel treatment strategy for hematologic malignancies

Blood — Thu, 18 Mar 2010 16:02:02 +0100

The dysregulation of protein synthesis evident in the transformed phenotype has opened up a burgeoning field of research in cancer biology. Translation initiation has recently been shown to be a common downstream target of signal transduction pathways deregulated in cancer and initiated by mutated/overexpressed oncogenes and tumor suppressors. The overexpression and/or activation of proteins involved in translation initiation such as eIF4E, mTOR, and eIF4G have been shown to induce a malignant phenotype. Therefore, understanding the mechanisms that control protein synthesis is emerging as an exciting new research area with significant potential for developing innovative therapies. This review highlights molecules that are activated or dysregulated in hematologic malignancies, and promotes ...

A novel antiphospholipid antibody agent?

Blood — Thu, 18 Mar 2010 16:02:02 +0100

(Source: Blood)

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If Virchow were to meet Newton

Blood — Thu, 18 Mar 2010 16:02:02 +0100

(Source: Blood)

Macrophages give Gas(6) to cancer

Blood — Thu, 18 Mar 2010 16:02:02 +0100

(Source: Blood)

V(D)J recombination and staggered DNA breaks: guilty again

Blood — Thu, 18 Mar 2010 16:02:02 +0100

(Source: Blood)

Cyclophosphamide in aplastic anemia?

Blood — Thu, 18 Mar 2010 16:02:02 +0100

(Source: Blood)

Target recognition-induced NK-cell responses

Blood — Thu, 18 Mar 2010 16:02:02 +0100

(Source: Blood)

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Alpha-type 1-polarized dendritic cells loaded with apoptotic allogeneic myeloma cell line induce strong CTL responses against autologous myeloma cells

Annals of Hematology — Thu, 18 Mar 2010 15:24:25 +0100

Abstract To induce a potent cytotoxic T lymphocyte (CTL) response, various tumor antigens should be loaded onto dendritic cells (DCs). In multiple myeloma (MM), it is difficult to obtain a sufficient number of autologous tumor cells as a source of tumor antigens in the clinical setting. We investigated the feasibility of immunotherapy in patients with MM, using myeloma-specific CTLs generated in vitro by alpha-type 1-polarized DCs (αDC1s) loaded with the ultraviolet B-irradiated allogeneic myeloma cell line, ARH77. αDC1s significantly increased the expression of several costimulatory molecules without differences in loading with tumor antigens. αDC1s showed a high production of interleukin-12 during maturation and after subsequent stimulation with CD40L but were not sig...

SGO: Laparoscopy Passes Staging Test for Uterine Cancer (CME/CE)

MedPage Today Hematology/Oncology — Thu, 18 Mar 2010 14:13:06 +0100

SAN FRANCISCO (MedPage Today) -- Laparoscopic staging of uterine cancer offers a safe and effective alternative standard of care to open surgical staging, results of a multicenter clinical trial showed. (Source: MedPage Today Hematology/Oncology)

Seasonal Variation, Weekly and Daily Rhythm of Transient Ischemic Attack in Hungary

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

(Source: Clinical and Applied Thrombosis/Hemostasis)

Pulmonary Embolism Associated With Protein C Deficiency and Abuse of Anabolic-androgen Steroids

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

We present the case of a 19-year-old male athlete with protein C deficiency who developed proximal deep venous thrombosis and pulmonary embolism while abusing anabolic-androgenic steroids. Anabolic-androgenic steroids have been reported to have anticoagulatory and profibrinolytic effects in patients with protein C deficiency. Despite these antithrombotic effects, the patient developed repeated venous thromboembolism during treatment with low-molecular-weight heparin. The net effect of anabolic-androgenic steroids on the haemostatic system may change from antithrombotic to prothrombotic in male abusers of anabolic steroids with protein C deficiency. (Source: Clinical and Applied Thrombosis/Hemostasis)

Thrombotic Thrombocytopenic Purpura and Sickle Cell Crisis

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

Described is a case of acute chest syndrome in a sickle-cell patient (hemoglobin SS) who also developed signs and symptoms of thrombotic thrombocytopenic purpura, including thrombocytopenia and hemolysis (anemia, elevated lactate dehydrogenase, presence of schistocytes, dark-colored plasma, and elevations in nucleated red blood cells). The ADAMTS13 activity level was normal. Discussed are the diagnosis and therapeutic management issues and the challenges of differentiating the vasoocclusive and hemolytic complications of sickling red blood cells from the thrombotic microangiopathy of thrombotic thrombocytopenic purpura. (Source: Clinical and Applied Thrombosis/Hemostasis)

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Effective Hemostasis During Minor Surgery in a Case of Hereditary Combined Deficiency of Vitamin K-dependent Clotting Factors

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

Combined deficiency of the vitamin K-dependent clotting factors (VKCFD) is a rare bleeding disorder involving defective gamma-carboxylation of coagulation factors II , VII, IX and X as well as natural anticoagulants protein C and protein S. The disease is characterized by a cluster of different, often life threatening, bleeding symptoms occurring both spontaneously and in a surgical setting. In the present paper we describe two different treatment modalities to be used both in a programmed surgical procedure and in an emergency scenario. As this disease is a natural model that resembles oral anticoagulation, our experience discloses a possible rationale in the use of recombinant activated FVII for warfarin reversal. (Source: Clinical and Applied Thrombosis/Hemostasis)

Right Atrial Appendage: Forgotten Part of the Heart in Atrial Fibrillation

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

Atrial fibrillation (AF) is the most common clinically encountered arrhythmia in adults. Because it is associated with an increased risk of atrial thrombus formation and embolism, medical and/or electrical cardioversion is the preferred treatment method in the majority of clinics. Thrombus formation in the setting of AF most commonly occurs in the left atrial appendage (LAA), left atrium (LA), right atrial appendage (RAA), and right atrium in decreasing frequency. In routine transesophageal echocardiographic evaluation for AF, examination is generally limited to LA and LAA. Although relatively rare when compared with the left side, RAA thrombus has also the potential of embolism and should be screened. A case of RAA thrombus in which the LA and LAA were spared is described. The authors aim...

Lipoprotein (a) Levels in Childhood Arterial Ischemic Stroke

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

Lipoprotein (a) is a cholesterol-rich plasma lipoprotein with a lipid composition similar to that of low-density lipoproteins (LDL). Many prospective and case-control studies identified elevated levels of lipoprotein (a) as a risk factor for premature myocardial infarction and stroke. Elevated lipoprotein (a) has been identified as a genetically determined risk factor for stroke in young adults, but only preliminary data are available on its role as a risk factor for ischemic stroke in infants and children.Fifty two children with arterial ischemic stroke and 78 age- and sex-matched healthy children were studied. Data of this study indicate that 26.9% of children with arterial ischemic stroke had high lipoprotein (a) levels in comparison with the age matched healthy control group.Measuremen...

Review: Factor XI Deficiency: Review and Management in Pregnant Women

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

Factor XI deficiency is a rare disease found predominantly in Ashkenazi Jews. There is a poor correlation between factor XI level and bleeding in patients with factor XI deficiency. Individuals with severe factor XI deficiency are usually at risk of excessive bleeding after surgery and injury, particularly when trauma involves tissues rich in fibrinolytic activity. Women with partial or severe deficiency are at risk of excessive uterine bleeding during labor. The unpredictable nature of factor XI deficiency complicates management during pregnancy and delivery. This review gives an overview of the management of pregnant women with factor XI deficiency. (Source: Clinical and Applied Thrombosis/Hemostasis)

PAI-1 and D-Dimer in Type 2 Diabetic Women With Asymptomatic Macrovascular Disease Assessed by Carotid Doppler

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

Asymptomatic diabetic patients with different degrees of macrovascular complications can present different hemostatic changes. At this study, plasminogen activator inhibitor-1 (PAI-1) and D-dimer were evaluated in 12 women without diabetes and 64 type 2 diabetic women. All patients were classified into 3 different categories according to the carotid intima-media thickness (IMT) assessed by Doppler: 25 with <1 mm (normal), 15 with >1 mm and without plaque (intermediate), and 24 with stenosis lower than 50% of the vessel lumen (plaque). The results showed increased plasma D-dimer in type 2 diabetic women with carotid plaque when compared to the other groups. High levels of PAI-1 were observed in all the 3 groups of diabetic women when compared to women without diabetes. Our results sug...

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Factor V Leiden Mutation and Thrombotic Occlusion of Microsurgical Anastomosis After Free TRAM Flap

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

We present a case of a patient with previously diagnosed activated protein resistance caused by heterozygous factor V (position 1691 G->A) Leiden mutation in whom a free transverse rectus abdominis muscle flap was performed. The postoperative course was complicated by repeated thrombosis of both the venous and arterial part of the anastomosis. Immediate thrombectomy and repeated arteriography allowed for partial flap salvage. More data are needed to analyze the impact of hereditary thrombophilia on microvascular anastomosis failure. (Source: Clinical and Applied Thrombosis/Hemostasis)

Clopidogrel Provides Significantly Greater Inhibition of Platelet Activity Than Aspirin When Combined With Atorvastatin After Coronary Artery Bypass Grafting: A Prospective Randomized Study

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:35 +0100

Conclusions: Our results demonstrate that the combination of C + A is more effective than that of ASA + A in inhibiting ADP-mediated platelet aggregation and expression of major platelet receptors after CABG. (Source: Clinical and Applied Thrombosis/Hemostasis)

Plasminogen Activator Inhibitor-1 (PAI-1) Gene 4G/5G Promoter Polymorphism is Seen in Higher Frequency in the Indian Patients With Deep Vein Thrombosis

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

Conclusion: Our study shows the association of 4G allele with DVT in Asian Indian population. The higher prevalence of 4G polymorphism in patients with DVT (compared with controls) seen in our study is in concordance with previous reports from the Caucasian population. (Source: Clinical and Applied Thrombosis/Hemostasis)

MR Molecular Imaging of Thrombus: Development and Application of a Gd-based Novel Contrast Agent Targeting to P-selectin

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

In this study, we report a novel P-selectin-targeted paramagnetic molecular imaging agent and the agent’s potential to sensitively detect occult microthrombi on the intimal surface of endothelium. Platelet clots and blood clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that was improved with increasing gadolinium level. In vivo contrast enhancement under part of circulation conditions was assessed in dogs. The micro-thrombi around the femoral vein of dog demonstrated higher signal intensities than the control clots and the adjacent muscle. Histology was performed on regions likely to contain thrombus as indicated by MRI. These results suggest that molecular imaging of P-selectin-targeted paramagnetic ...

Antiplatelet Therapy Prasugrel: A Novel Platelet ADP P2Y12 Receptor Antagonist

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

Novel adenosine diphosphate (ADP) P2Y12 antagonists, including prasugrel, ticagrelor, cangrelor and elinogrel, are in various phases of clinical development. These ADP P2Y12 antagonists have advantages over clopidogrel ranging from faster onset to greater and less variable inhibition of platelet function. Novel ADP P2Y12 antagonists are under investigation to determine whether their use can result in improved antiplatelet activity, faster onset of action, and/or greater antithrombotic effects than clopidogrel, without an unacceptable increase in hemorrhagic or other side effects. Prasugrel (CS-747; LY-640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet ADP P2Y12 receptor. Preclinical and early phase clinical studies have shown prasu...

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Aptamers Influence the Hemostatic System by Activating the Intrinsic Coagulation Pathway in an In Vitro Chandler-Loop Model

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

In this study, we have performed a comprehensive evaluation of the hemostatic system including coagulation, platelets, complement, and inflammatory activation by using different aptamer concentrations and fresh human whole blood in a well-established flow model. We found that single-stranded aptamers did not have a negative influence on platelets, complement, or inflammation but were able to activate factor XII, kallikrein, and prothrombin in a concentration-dependent manner. Consequently, the influence of aptamers on the coagulation system should be taken into consideration before the use of any aptamer-based drugs in patients. (Source: Clinical and Applied Thrombosis/Hemostasis)

Temporal Patterns of Hospital Admissions for Transient Ischemic Attack: A Retrospective Population-based Study in the Emilia-Romagna Region of Italy

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

This study aimed to explore the existence of a temporal pattern of transient ischemic attack and the possible influence by the most common risk factors. The analysis included all hospital admissions with the ICD9-CM code for TIA, recorded in the database of the Emilia Romagna region of Italy (1998-2006; n = 43642, mean age 76.8 ± 11.5 years, 45.5% males). Transient ischemic attack was most frequent in autumn and winter and less common in spring and summer (P < 0.0001), with the highest number of cases in October and the lowest in February, and also most frequent on Monday (P < 0.0001). This study shows a seasonal and weekly pattern in occurrence of transient ischemic attack, independent of sex and the presence of the most common risk factors. (Source: Clinical and Applied Thro...

Effects of Atenolol or Losartan on Fibrinolysis and von Willebrand Factor in Hypertensive Patients With Left Ventricular Hypertrophy

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

Conclusion: Losartan treatment was associated with preserved fibrinolytic balance compared to a more prothrombotic fibrinolytic and hemostatic state in the atenolol group. These findings suggest different fibrinolytic and hemostatic responses to treatment in hypertensive patients with LVH. (Source: Clinical and Applied Thrombosis/Hemostasis)

Early Discharge of Patients With Venous Thromboembolism: Implications Regarding Therapy

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

The purpose of this investigation is to show trends in the duration of hospitalization of patients with pulmonary embolism (PE) and deep venous thrombosis (DVT). The number of patients discharged from short-stay non-Federal hospitals throughout the United States with a primary diagnostic code for PE or DVT from 1979 through 2005 was obtained from the National Hospital Discharge Survey. By 2005, 13% of patients with PE were discharged in 1 to 2 days, 30% in 3 to 4 days, 26% in 5 to 6 days, and 31% in ≥7 days. Regarding DVT, by 2005, 26% of patients with DVT were discharged in 1 to 2 days, 34% were discharged in 3 to 4 days, 20% were discharged in 5 to 6 days, and 19% were discharged in ≥7 days. The data indicate that large proportions of patients with a primary diagnosis of PE and of ...

Role of Thrombotic Risk Factors in End-Stage Renal Disease

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

Conclusion: The carrier of FVL, TT genotype of C677T, and CC genotype of A1298C polymorphisms may act as risk factors for ESRD. (Source: Clinical and Applied Thrombosis/Hemostasis)

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Optimal Dosing of Intravenous Unfractionated Heparin Bolus in Transient Ischemic Attack or Stroke

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

Early initiation of heparin therapy for treatment of stroke is not only associated with an improved outcome, but also with the risk of hemorrhagic transformation. We compared the efficacy of three unfractionated heparin bolus regimens (0 U/kg, 30 U/kg, or 80 U/kg) in achieving a therapeutic activated partial thromboplastin time over the first 6-hour period in a cohort of 54 patients admitted with transient ischemic attack or stroke. Patients treated with the low bolus dose (30 U/kg) were more often within the therapeutic range for activated partial thromboplastin time at two hours after the initial bolus than patients treated with the other regimens. The percentage of therapeutic activated partial thromboplastin time results within the first six hours of treatment was greater in the group ...

Profiling of Heparin-Induced Thrombocytopenia Antibody Levels in Patients With and Without Diabetes

Clinical and Applied Thrombosis/Hemostasis — Thu, 18 Mar 2010 11:48:34 +0100

Heparin/platelet factor 4 (H:PF4) antibodies are the causative agent in heparin-induced thrombocytopenia (HIT). The antibodies are frequently formed after exposure to heparin, most commonly without any signs of clinical HIT. Heparin-induced thrombocytopenia antibodies have been detected by enzyme-linked immunosorbent assay (ELISA) in individuals who have not been exposed to heparin. It is possible that the antibodies could be elicited by PF4 associated with endogenous, heparin-like glycosaminoglycans (GAGs). This risk would be higher in individuals with endothelial dysfunction and chronic platelet activation. In the setting of an outpatient endocrinology clinic, both diabetic and nondiabetic patients were studied and compared with healthy volunteers. Heparin/platelet factor 4 antibody tite...

Erratum to: The current status and the future of JAK2 inhibitors for the treatment of myeloproliferative diseases.

International Journal of Hematology — Thu, 18 Mar 2010 00:00:00 +0100

Authors: Hitoshi Y, Lin N, Payan DG, Markovtsov V PMID: 20237875 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Mosaic Down syndrome-associated acute myeloid leukemia does not require high-dose cytarabine treatment for induction and consolidation therapy.

International Journal of Hematology — Thu, 18 Mar 2010 00:00:00 +0100

Authors: Kudo K, Hama A, Kojima S, Ishii R, Morimoto A, Bessho F, Sunami S, Kobayashi N, Kinoshita A, Okimoto Y, Tawa A, Tsukimoto I The present study aimed to identify optimal treatment intensity in children with mosaic Down syndrome (DS) and acute megakaryoblastic leukemia (AMKL). A retrospective review of AMKL patients was undertaken to identify mosaic DS children. Between November 1992 and November 2007, seven children were diagnosed as mosaic DS and AMKL. The median age at diagnosis was 29 months (range 4-34 months). Three patients had a past history of transient abnormal myelopoiesis. UPN1-4 were treated with intermediate-dose cytarabine and UPN4 received additional one course of high-dose cytarabine. All of these patients were remained in first CR. UPN5-7 were treated with high-...

Higher expression levels of activation-induced cytidine deaminase distinguish hairy cell leukemia from hairy cell leukemia-variant and splenic marginal zone lymphoma

Leukemia — Thu, 18 Mar 2010 00:00:00 +0100

Authors: S L Hockley, A Morilla, M Else, C Dearden, D Catovsky, G J Morgan, E Matutes & D Gonzalez (Source: Leukemia)

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Gene-specific and global methylation patterns predict outcome in patients with acute myeloid leukemia

Leukemia — Thu, 18 Mar 2010 00:00:00 +0100

Authors: S Deneberg, M Grövdal, M Karimi, M Jansson, H Nahi, A Corbacioglu, V Gaidzik, K Döhner, C Paul, T J Ekström, E Hellström-Lindberg & S Lehmann (Source: Leukemia)

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

Leukemia — Thu, 18 Mar 2010 00:00:00 +0100

Authors: J Davidsson, K Paulsson, D Lindgren, H Lilljebjörn, T Chaplin, E Forestier, M K Andersen, A Nordgren, R Rosenquist, T Fioretos, B D Young & B Johansson (Source: Leukemia)

Wilms’ tumor gene 1 protein represses the expression of the tumor suppressor interferon regulatory factor 8 in human hematopoietic progenitors and in leukemic cells

Leukemia — Thu, 18 Mar 2010 00:00:00 +0100

Wilms’ tumor gene 1 protein represses the expression of the tumor suppressor interferon regulatory factor 8 in human hematopoietic progenitors and in leukemic cells Leukemia advance online publication, March 18, 2010. doi:10.1038/leu.2010.33 Authors: K Vidovic, E Svensson, B Nilsson, B Thuresson, T Olofsson, A Lennartsson & U Gullberg (Source: Leukemia)

Monitoring and treatment of anti-D in pregnancy

Vox Sanguinis — Thu, 18 Mar 2010 00:00:00 +0100

(Source: Vox Sanguinis)

Development of romiplostim for the treatment of patients with chronic immune thrombocytopenia: from bench to bedside

British Journal of Haematology — Thu, 18 Mar 2010 00:00:00 +0100

Immune thrombocytopenia (ITP) is an autoimmune disorder characterised by abnormally low platelet counts ( (Source: British Journal of Haematology)

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SIR: Cryotherapy Conserves the Breast (CME/CE, with video)

MedPage Today Hematology/Oncology — Wed, 17 Mar 2010 19:28:43 +0100

TAMPA (MedPage Today) -- Multiprobe cryotherapy was safe and effective in breast cancer patients and didn't require subsequent surgery to ensure that all tumor cells were killed, researchers reported here. (Source: MedPage Today Hematology/Oncology)

SIR: Microspheres Promising in Liver Cancer (CME/CE, with video)

MedPage Today Hematology/Oncology — Wed, 17 Mar 2010 18:08:56 +0100

TAMPA (MedPage Today) -- Radioactive microspheres may delay progression in liver cancer patients, particularly among those with earlier stages of the disease, researchers here said. (Source: MedPage Today Hematology/Oncology)

SGO: Hint of Chemoprevention Potential for Lynch Syndrome (CME/CE)

MedPage Today Hematology/Oncology — Wed, 17 Mar 2010 14:13:06 +0100

SAN FRANCISCO (MedPage Today) -- Oral contraceptives and medroxyprogesterone acetate (MPA, DepoProvera) may have potential as chemopreventive agents for endometrial cancer in women with Lynch syndrome, biomarker data from a small randomized trial suggest. (Source: MedPage Today Hematology/Oncology)

Hemochromatosis and Hemojuvelin G320V Homozygosity in a Hungarian Woman.

Acta Haematologica — Wed, 17 Mar 2010 00:00:00 +0100

Authors: Várkonyi J, Lueff S, Szűcs N, Pozsonyi Z, Tóth A, Karádi I, Pietrangelo A PMID: 20234129 [PubMed - as supplied by publisher] (Source: Acta Haematologica)

Synchronous Mantle Cell Lymphoma, Chronic Lymphocytic Leukaemia and Melanoma in a Single Lymph Node.

Acta Haematologica — Wed, 17 Mar 2010 00:00:00 +0100

Authors: Addada J, Anoop P, Swansbury JG, Wotherspoon A, Thomas JM, Matutes E PMID: 20234130 [PubMed - as supplied by publisher] (Source: Acta Haematologica)

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Effectiveness of communication campaign on iron deficiency anemia in Kyzyl-Orda region, Kazakhstan: a pilot study

BMC Blood Disorders — Wed, 17 Mar 2010 00:00:00 +0100

Background: In 2004, wheat flour fortification (WFF) with iron was implemented in Kazakhstan as a public health strategy to increase the iron intake of all women of childbearing age and of children. In 2003, before starting the flour fortification program, a communication campaign on health education took place in a region with a high prevalence of iron deficiency anemia (IDA). The present study aimed to evaluate the prevalence of anemia, iron deficiency and IDA before and after the campaign. In addition, knowledge about IDA and its prevention, as well as awareness about fortified wheat flour, was assessed. Methods: The subjects of the study were women aged 15-49 years and children aged 2-14 years. The study was carried out in urban and rural areas of Kyzyl-Orda region in 2003 before (Marc...

Successful cord blood transplantation in a girl with monosomy 7 myelodysplastic syndrome and reduced numbers of B cells.

International Journal of Hematology — Wed, 17 Mar 2010 00:00:00 +0100

This report described unrelated umbilical cord blood transplantation for a 3-year-old girl with myelodysplastic syndrome and monosomy 7. The patient had a prolonged course characterized by recurrent infection and slowly progressive pancytopenia. She had reduced numbers of circulating B cells but no decline in immunoglobulin levels. Chemotherapy was not initially recommended because it was contraindicated due to intercurrent lower respiratory tract infection. After 10 months, the girl achieved hematologic remission after induction chemotherapy. The patient then underwent 2-loci HLA-mismatched unrelated donor cord blood transplantation. The time to neutrophil and platelet engraftment was 12 and 23 days post-transplantation, respectively. Acute graft-versus-host disease following transplantat...

Multicentre phase II study of CyclOBEAP plus rituximab in patients with diffuse large B-cell lymphoma

Hematological Oncology — Wed, 17 Mar 2010 00:00:00 +0100

The R-CHOP regimen has been found to improve the outcome of diffuse large B-cell lymphoma (DLBCL). However, it does not provide a satisfactory treatment outcome in the high-risk group. We previously administered the CyclOBEAP regimen to patients with DLBCL, and reported its safety and efficacy. The R-CyclOBEAP regimen was administered over a total period of 12 weeks, and rituximab 375 mg/m2 was given every 2 weeks. There were 101 eligible patients. CR was achieved in 96 patients (95%). The 5-year overall survival (OS) rate was 85% and progression-free survival (PFS) rate was 76%. When the patients were divided according to the IPI, the 5-year OS and PFS rates did not significantly differ among the risk groups. The 5-year PFS of the germinal centre B-cell group was 80% and that of the non-G...

Artificial contact pathway activation masks the haemostatic potential of rFVIIa and NN1731 in thrombocytopenic whole blood

British Journal of Haematology — Wed, 17 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Transient Visual Loss Triggered by Scuba Diving in a Patient with a Petrous Epidermoid and Combined Thrombotic Risk Factors

Pathophysiology of Haemostasis and Thrombosis — Tue, 16 Mar 2010 23:00:00 +0100

Pathophysiol Haemost Thromb (DOI:10.1159/000297738) (Source: Pathophysiology of Haemostasis and Thrombosis)

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Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

(Source: Biology of Blood and Marrow Transplantation)

Officers and Directors of ASBMT

Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

(Source: Biology of Blood and Marrow Transplantation)

Editorial Board

Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

(Source: Biology of Blood and Marrow Transplantation)

Masthead (Purpose and Scope)

Biology of Blood and Marrow Transplantation — Tue, 16 Mar 2010 15:21:08 +0100

(Source: Biology of Blood and Marrow Transplantation)

Predictive value of pretreatment risk group and baseline LDH levels in MDS patients receiving azacitidine treatment

Annals of Hematology — Tue, 16 Mar 2010 14:49:01 +0100

In conclusion, while the pretreatment risk group and initial LDH levels were both confirmed as important prognostic factors to predict the outcomes for patients treated with azacitidine, more effective therapies are still needed to prevent disease progression. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-010-0921-5Authors Joon Ho Moon, Kyungpook National University School of Medicine Department of Hematology/Oncology, Kyungpook National University Hospital 50 Samduck 2-Ga, Jung-Gu 700-721 Daegu South KoreaShi Nae Kim, Kyungpook National University School of Medicine Department of Hematology/Oncology, Kyungpook National University Hospital 50 Samduck 2-Ga, Jung-Gu 700-721 Daegu South KoreaByung Woog Kang, Kyungpook National University School of Medicine D...

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New Radiation Therapy Controls Lung Tumor Size (CME/CE)

MedPage Today Hematology/Oncology — Tue, 16 Mar 2010 14:00:00 +0100

Early testing of a new radiation treatment in patients with inoperable lung cancer indicates the method effectively controls tumor size and may increase survival time, a study found. (Source: MedPage Today Hematology/Oncology)

Media Downplay Failings of Cancer Treatments (CME/CE)

MedPage Today Hematology/Oncology — Tue, 16 Mar 2010 14:00:00 +0100

When the mainstream media report on cancer treatments, they seldom note that aggressive therapies may fail or cause severe side effects, researchers said. (Source: MedPage Today Hematology/Oncology)

War on Cancer: Some Progress but No Victory

MedPage Today Hematology/Oncology — Tue, 16 Mar 2010 14:00:00 +0100

Despite continued progress, the battle against cancer is far from over, according to two cancer researchers. (Source: MedPage Today Hematology/Oncology)

The Role of Molecular Tests in Acute Myelogenous Leukemia Treatment Decisions

Current Hematologic Malignancy Reports — Tue, 16 Mar 2010 08:53:11 +0100

Abstract The prognosis for patients with acute myelogenous leukemia (AML) is dependent on age, karyotype, and the genetics of the neoplastic cell. The molecular markers with prognostic impact include mutations in FLT3, NPM1, MLL, WT1, c-KIT, and expression levels of BAALC, NM1, ERG, and CXCR4. Gene expression profiles and microRNA expression patterns in AML may prove highly useful in defining the prognosis of AML. Cytogenetic and, increasingly, molecular findings are used in determining the best therapy for AML patients, especially the choice of whether to perform allogeneic stem cell transplantation. Content Type Journal ArticleDOI 10.1007/s11899-010-0049-7Authors Gabriela Motyckova, Dana-Farber Cancer Institute 44 Binney Street Boston MA 02115 USARichard M. Stone, Da...

Control of the proliferation of activated CD4+ T cells by connexins.

Journal of Leukocyte Biology — Tue, 16 Mar 2010 00:00:00 +0100

Authors: Oviedo-Orta E, Perreau M, Evans WH, Potolicchio I As expression of Cxs in cells of the immune system increases upon cellular activation, we investigated whether Cxs and especially CxHcs play a major role during T cell-mediated responses. In particular, we studied the expression of Cx43Hc following CD4(+) T cell stimulation using flow cytometry, real-time PCR, and Western blot analysis. We showed that expression of Cx43 and its phosphorylated isoforms increased in response to the engagement of CD3 and CD28. Cx43Hcs were found to be involved in sustaining proliferation of T cells, as assessed by cell cycle staining, thymidine incorporation assays, and CFSE analysis of cells exposed to mimetic peptide inhibitors of the plasma membrane Cx channels and antibodies generated to an ex...

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Diagnosis of severe Type 1 Gaucher's disease before irreversible damage occurs : is HDL cholesterol the answer?

British Journal of Haematology — Tue, 16 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Fertility preservation after chemotherapy for Hodgkin lymphoma

Hematological Oncology — Tue, 16 Mar 2010 00:00:00 +0100

Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause prolonged azoospermia in 90-100% of men and ovarian failure in 5-25% of women under the age of 30. Non-alkylating chemotherapy, like ABVD, is much less harmful: one-third of male patients develop transient azoospermia, and almost no female patients experience ovarian failure. Age is an important factor for women: females over 30 years have a much higher risk of acute ovarian failure. However, with long-term follow-up the cumulative risk of menopause before the age of 40 becomes the same irrespectiv...

Factor VIII/von Willebrand factor concentrate for treatment of life threatening epistaxis in Glanzmann's thrombasthenia

Haemophilia — Tue, 16 Mar 2010 00:00:00 +0100

(Source: Haemophilia)

Haemophilic arthropathy of the ankle treated by total ankle replacement: a case series

Haemophilia — Tue, 16 Mar 2010 00:00:00 +0100

The objective of this prospective study was to evaluate the mid-term outcome in patients treated with total ankle replacement using an unconstrained three-component ankle implant. Ten haemophilic ankles in eight patients (mean age: 43.2 years, range 26.7[ndash]57.5) treated with total ankle replacement were followed up for a minimum of 2.7 years (mean: 5.6, range 2.7[ndash]7.6). The outcome was measured with clinical and radiological evaluations. There were no intra- or peri-operative complications. The AOFAS-hindfoot-score increased from 38 (range 8[ndash]57) preoperatively to 81 (range 69[ndash]95) postoperatively. All patients were satisfied with the results. Four patients became pain free; in the whole patient cohort pain level decreased from 7.1 (range 4[ndash]9) preoperatively to 0.8...

Balance dysfunction in adults with haemophilia

Haemophilia — Tue, 16 Mar 2010 00:00:00 +0100

Summary. The main focus of lower limb physical performance assessment in people with haemophilia (PWH) has usually been on function, muscle strength and joint flexibility. The impact of haemophilic arthropathy on balance and falls risk is relatively under-explored. The aim of this study was to evaluate balance and related performance in PWH compared with age and gender matched healthy controls. It involved a comprehensive suite of clinical and laboratory measures of static and dynamic balance, mobility, strength, physical activity and falls efficacy completed in 20 PWH (mean age 39.4, 100% male) and 20 controls. Fifty percent of PWH reported falls in the past 12 months. Moderate impairment of balance and related measures were identified in PWH compared with the controls, with an average 35...

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Clinical efficacy and safety of the factor VIII/von Willebrand factor concentrate BIOSTATE® in patients with von Willebrand's disease: a prospective multi-centre study

Haemophilia — Tue, 16 Mar 2010 00:00:00 +0100

This study also provides important insights into dosing regimens with BIOSTATE and the role of monitoring therapy with FVIII:C and VWF:RCo. (Source: Haemophilia)

Molecular basis of factor X deficiency cases from India

Haemophilia — Tue, 16 Mar 2010 00:00:00 +0100

(Source: Haemophilia)

Psychosocial correlates of physical activity in adolescents with haemophilia

Haemophilia — Tue, 16 Mar 2010 00:00:00 +0100

Summary. Boys with haemophilia are now encouraged to exercise and take part in physical activities, but actual measures of time spent in active participation is lacking. The aim of this study was to obtain an objective measure of daily physical activity in boys with haemophilia as compared with healthy controls. The study also aimed to ascertain the social and cognitive factors associated with exercise in this population. Seventeen patients (aged 11[ndash]18 years) with haemophilia were studied and compared with 44 healthy controls (aged 10[ndash]16.5 years). Physical activity was measured by accelerometry. Psychosocial correlates were assessed using validated questionnaires. Measured physical activity levels in subjects with haemophilia were slightly higher than for the control group. Bot...

Advances in understanding the pathogenesis of chronic thromboembolic pulmonary hypertension

British Journal of Haematology — Tue, 16 Mar 2010 00:00:00 +0100

Chronic thromboembolic pulmonary hypertension (CTEPH) comprises organizing thrombotic obstructions in the pulmonary arteries. While roughly 40% of CTEPH cases are not preceded by a venous thromboembolic event, 0·1[ndash]5·1% of acute pulmonary thromboemboli evolve into organized obstructions of the pulmonary artery. In patients with predominantly proximal disease, surgical pulmonary endarterectomy provides a potential cure of the disease. For years, the scientific debate of CTEPH was mainly focused around its thromboembolic nature because of striking dissimilarities to classical venous thromboembolism, for example, the lack of risk factors for venous thrombosis, the lack of clinically apparent pulmonary embolism in many patients, the difficulty to reproduce the disease in animal models o...

Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus

British Journal of Haematology — Tue, 16 Mar 2010 00:00:00 +0100

Tumour lysis syndrome (TLS) is a life-threatening oncological emergency characterized by metabolic abnormalities including hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. These metabolic complications predispose the cancer patient to clinical toxicities including renal insufficiency, cardiac arrhythmias, seizures, neurological complications and potentially sudden death. With the increased availability of newer therapeutic targeted agents, such as rasburicase (recombinant urate oxidase), there are no published guidelines on the risk classification of TLS for individual patients at risk of developing this syndrome. We convened an international TLS expert consensus panel to develop guidelines for a medical decision tree to assign low, intermediate and high risk to patient...

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Anti-thymocyte globulin plus etanercept as therapy for myelodysplastic syndromes (MDS): a phase II study

British Journal of Haematology — Tue, 16 Mar 2010 00:00:00 +0100

Immunosuppressive therapies have proven valuable in treating patients with myelodysplastic syndromes (MDS). We evaluated the combination of equine anti-thymocyte globulin (ATGAM®) and the soluble tumour necrosis factor receptor, etanercept (Enbrel®), in a phase II trial. Twenty-five patients with MDS [4-refractory anaemia (RA), 2-RA with ring sideroblasts, 15-refractory cytopenia with multilineage dysplasia (RCMD), 3-RCMD and ring sideroblasts, 1-RA with excess blasts type 1] in International Prognostic Staging System risk groups low (n = 11) or intermediate-1 (n = 14) were enrolled. All patients were platelet or red cell transfusion-dependent. Nineteen patients completed therapy with ATG at 40 mg/kg per day for four consecutive days, followed by etanercept, 25 mg subcutaneous twice a we...

Flow cytometric scoring system (FCMSS) assisted diagnosis of myelodysplastic syndromes (MDS) and the biological significance of FCMSS-based immunophenotypes

British Journal of Haematology — Tue, 16 Mar 2010 00:00:00 +0100

In the myelodysplastic syndromes (MDS), the haematopoietic cells show various levels of abnormal maturation and differentiation, which can be detected by flow cytometry. Testing the anomalies of stage- or lineage-specific surface antigens in CD34+ blasts can distinguish MDS from non-clonal cytopenic diseases, and also reflect the pathological characteristics of MDS as a class of clonal diseases for providing new clues to basic research. The present study established a flow cytometric scoring system (FCMSS) based on theproportion and antigenic co-expression of CD34+ blasts. This FCMSS showed good sensitivity and specificity (77·8% and 100%) in the assisted diagnosis of low-risk MDS without chromosome anomalies, ringed sideroblasts and excess marrow blasts. Moreover, we explored and reporte...

Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia – an individual patient data meta-analysis involving 5659 children

British Journal of Haematology — Tue, 16 Mar 2010 00:00:00 +0100

Vincristine plus steroid pulses have long been a part of maintenance treatment in many protocols for childhood acute lymphoblastic leukaemia (ALL). A collaborative individual patient data meta-analysis of all randomised trials of the addition of vincristine plus prednisone/prednisolone (VP) pulses in childhood ALL was updated and extended to include trials comparing vincristine plus dexamethasone (VD) pulses to maintenance without pulses. VP pulses improved event-free survival (EFS) (70·1% vs. 62·0% at 5 years; odds ratio (OR) = 0·71; 95% confidence interval (CI) = 0·61[ndash]0·84; P = 0·00004); VD pulses did not have a significant effect (80·9% vs. 79·9% 5 year EFS; OR = 0·94; 95% CI = 0·80[ndash]1·11; P = 0·5). Heterogeneity between groups (VP or VD) was significant (P = 0·0...

Consensus guidelines for the optimal management of adverse events in newly diagnosed, transplant-ineligible patients receiving melphalan and prednisone in combination with thalidomide (MPT) for the treatment of multiple myeloma

Annals of Hematology — Mon, 15 Mar 2010 17:54:34 +0100

Abstract Thalidomide has received approval from the European Agency for the Evaluation of Medicinal Products for the treatment of newly diagnosed multiple myeloma (MM) patients older than 65 years or ineligible for transplant. The results of five phase III trials assessing thalidomide in combination with melphalan and prednisone (MPT) have demonstrated significantly improved response rates compared with melphalan and prednisone (MP) alone. Additionally, two of these studies showed that survival was extended by approximately 18 months in patients treated with MPT compared with MP alone. Thalidomide, in combination with MP, is associated with adverse events (AEs) including peripheral neuropathy and venous thromboembolism. In order to optimize the efficacy of MPT, a...

Response to lenalidomide in patients with myelodysplastic syndrome with deletion 5q: clinical and cytogenetic analysis of a single centre series

Annals of Hematology — Mon, 15 Mar 2010 17:54:33 +0100

Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-010-0932-2Authors Rita Coutinho, University of Barcelona Institute of Hematology and Oncology, Department of Hematology, Hospital Clinic IDIBAPS Villarroel 170 08036 Barcelona SpainDolors Costa, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainAna Carrió, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainConcha Muñoz, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainAna Vidal, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainMohammed Belkaid, University of Barcelona Institute of Hematology and Oncology, Department of Hematology, Hospital Clinic IDIBAPS Villarroel 170 0...

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SGO: Drug Combination Slows Recurrent Ovarian Cancer (CME/CE)

MedPage Today Hematology/Oncology — Mon, 15 Mar 2010 14:13:06 +0100

SAN FRANCISCO (MedPage Today) -- Combination chemotherapy resulted in a longer, progression-free survival (PFS) than did sequential therapy in a randomized clinical trial of patients with recurrent, platinum-sensitive ovarian cancer. (Source: MedPage Today Hematology/Oncology)

Risk Stratification Imperative To Treatment Selection In Patients With AML

Lymphoma / Leukemia News From Medical News Today — Mon, 15 Mar 2010 11:00:00 +0100

Using risk stratification to assist in treatment selection was just one of the focal points at a recent presentation of the NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines™) for Acute Myeloid Leukemia (AML) at the NCCN 15th Annual Conference. B... (Source: Lymphoma / Leukemia News From Medical News Today)

Join our free teleconferences for Myeloma Awareness Month! TODAY Dr.Durie talks about what is on the research horizon.

International Myeloma Foundation — Mon, 15 Mar 2010 04:00:00 +0100

In our continuing efforts to provide the most up to date information available regarding multiple myeloma and to create awareness of this disease, the International Myeloma Foundation is pleased to offer a teleconference series covering the four pillars of the IMF: EDUCATION ? SUPPORT ? RESEARCH - ADVOCACY (Source: International Myeloma Foundation)

Join our free teleconferences for Myeloma Awareness Month! Next up: Dr.Durie talks about what is on the research horizon - March 19

International Myeloma Foundation — Mon, 15 Mar 2010 04:00:00 +0100

Correlation of transient elastography with APRI and FIB-4 in a cohort of patients with congenital bleeding disorders and HCV or HIV/HCV coinfection

Haemophilia — Mon, 15 Mar 2010 00:00:00 +0100

Summary. Patients with inherited bleeding disorders frequently suffer from chronic hepatitis C virus (HCV) mono- or human immunodeficiency virus (HIV)/HCV coinfection. Non-invasive markers for liver fibrosis are warranted for these patients. We tested a large cohort of haemophilic patients with HCV mono- or HIV/HCV coinfection for correlation of transient elastography (TE) with two simple surrogate markers of liver fibrosis and for differences in fibrosis stages according to these markers. We prospectively enrolled HCV-positive patients with congenital bleeding disorders with or without HIV coinfection. Liver function tests and platelet counts were determined and TE was performed. Aspartate aminotransferase-to-platelet ratio index (APRI) and a simple index called FIB-4 were calculated and ...

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Regulation of the human HBA genes by KLF4 in erythroid cell lines

British Journal of Haematology — Mon, 15 Mar 2010 00:00:00 +0100

KLF1/EKLF and related Krueppel-like factors (KLFs) are variably implicated in the regulation of the HBB-like globin genes. Prompted by the observation that four KLF sites are distributed in the human [alpha]-globin gene (HBA) promoter, we investigated if KLFs could also act to modulate the expression of the HBA genes. Among the KLFs tested, only KLF4/GKLF bound specifically to three out of four [alpha]-globin KLF sites. The occupancy of the same sites by KLF4 in vivo was confirmed by chromatin immunoprecipitation assays with KLF4-specific antibodies. In luciferase reporter assays in MEL cells, high levels of the wild type HBA promoter, but not mutated promoters bearing point mutations that disrupted KLF4-DNA binding, were transactivated by over-expression of KLF4. In K562 cells, induced KL...

Anemia management in chronic kidney disease: Intravenous iron steps forward

American Journal of Hematology — Mon, 15 Mar 2010 00:00:00 +0100

No abstract. (Source: American Journal of Hematology)

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease

Bone Marrow Transplantation — Mon, 15 Mar 2010 00:00:00 +0100

Authors: D F Godoi, C R Cardoso, D B Ferraz, P R Provinciatto, F Q Cunha, J S Silva & J C Voltarelli (Source: Bone Marrow Transplantation)

Delayed neutrophil engraftment in cord blood transplantation with intensive administration of mycophenolate mofetil for GVHD prophylaxis

Bone Marrow Transplantation — Mon, 15 Mar 2010 00:00:00 +0100

Authors: A Okamura, M Shimoyama, S Ishii, K Wakahashi, N Asada, H Kawano, Y Kawamori, S Nishikawa, K Minagawa, Y Katayama & T Matsui (Source: Bone Marrow Transplantation)

The impact of novel influenza A (H1N1) after hematopoietic SCT

Bone Marrow Transplantation — Mon, 15 Mar 2010 00:00:00 +0100

Authors: P Patel, K Sweiss, S Shatavi, D Peace, N Clark & D Rondelli (Source: Bone Marrow Transplantation)

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Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience

Bone Marrow Transplantation — Mon, 15 Mar 2010 00:00:00 +0100

Authors: A Verdeguer, C D de Heredia, M González, A M Martínez, J M Fernández-Navarro, J M Pérez-Hurtado, I Badell, P Gómez, M E González, A Muñoz & M A Díaz (Source: Bone Marrow Transplantation)

Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study

Bone Marrow Transplantation — Mon, 15 Mar 2010 00:00:00 +0100

Authors: K Jordan, H H Wolf, W Voigt, T Kegel, L P Mueller, T Behlendorf, C Sippel, D Arnold & H J Schmoll (Source: Bone Marrow Transplantation)

Impact of GvHD on quality of life in long-term survivors of haematopoietic transplantation

Bone Marrow Transplantation — Mon, 15 Mar 2010 00:00:00 +0100

Authors: S Pallua, J Giesinger, A Oberguggenberger, G Kemmler, D Nachbaur, J Clausen, M Kopp, B Sperner-Unterweger & B Holzner (Source: Bone Marrow Transplantation)

Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS

Bone Marrow Transplantation — Mon, 15 Mar 2010 00:00:00 +0100

Authors: Y Morita-Hoshi, S-I Mori, A Soeda, T Wakeda, Y Ohsaki, M Shiwa, K Masuoka, A Wake, S Taniguchi, Y Takaue & Y Heike (Source: Bone Marrow Transplantation)

Top-up transfusions in neonates with Rh hemolytic disease in relation to exchange transfusions

Vox Sanguinis — Mon, 15 Mar 2010 00:00:00 +0100

Conclusion In this study, restrictive ET criteria in neonates with Rh hemolytic disease lead to a reduction of the rate of ET but an increase in the number of top-up transfusions for neonatal anemia. (Source: Vox Sanguinis)

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MiRNA profiling in B non-Hodgkin lymphoma: a MYC-related miRNA profile characterizes Burkitt lymphoma

British Journal of Haematology — Mon, 15 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Guideline for investigation and management of adults and children presenting with a thrombocytosis

British Journal of Haematology — Mon, 15 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585

British Journal of Haematology — Mon, 15 Mar 2010 00:00:00 +0100

This study preclinically evaluated the effects of the 'second generation' pan-HDAC inhibitor JNJ-26481585 on human multiple myeloma (MM) cells from established cell lines and primary MM samples (n = 42). Molecular responses in both groups of MM cells included histone acetylation, a shift in Bcl2-family members towards proapoptotic bias, attenuation of growth and survival pathway activity and Hsp72 induction. Mcl-1 depletion and Hsp72 induction were the most reliable features observed in JNJ-26481585-treated primary MM samples. The drug alone effectively induced myeloma cell death at low nanomolar concentrations. In vitro combination of JNJ-26481585 with anti-myeloma therapeutic agents generally resulted In effects close to additivity. In view of the favourable activity of this novel HDAC-i...

Comparison of intradialytic blood pressure variability between conventional thrice-weekly hemodialysis and short daily hemodialysis

Hemodialysis International — Mon, 15 Mar 2010 00:00:00 +0100

We examined the effect of short daily hemodialysis (SDHD) on intradialytic BP variability relative to conventional thrice-weekly HD (CHD). This is a retrospective cohort study. Subjects were those converted from CHD to SDHD (n=12). All intradialytic BPs were collected on the last month of CHD, and on month 6 of SDHD. Absolute predialysis BP level and intradialytic BP variability were defined as the intercept and average residual terms, respectively, from a mixed-effects linear regression model of time on BP. Dialysis modality was a predictor variable (CHD vs. SDHD). Outcome variables were intradialytic BP variability and hypotension (BP (Source: Hemodialysis International)

Pfizer Halts Trial, Two Others Miss Primary Endpoint

MedPage Today Hematology/Oncology — Sun, 14 Mar 2010 14:13:05 +0100

Pfizer has halted another phase-III trial of figitumumab and two trials of sunitinib in breast cancer failed to show significant improvement in survival. (Source: MedPage Today Hematology/Oncology)

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Cardiac release and kinetics of cytokines after elective bare metal coronary stenting

Journal of Thrombosis and Thrombolysis — Sun, 14 Mar 2010 12:27:11 +0100

Abstract The study was designed to assess the cardiac release kinetics of the cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor-necrosis-factor-α (TNF-α) in patients with significant stenosis of the ramus interventricularis anterior. Ten patients were treated by bare metal stent implantation, 11 patients who underwent a diagnostic coronary angiography without intervention served as a control group. Cytokines paired blood samples were withdrawn from the coronary sinus and a peripheral vein immediately before and 1, 2, 6 h after the intervention. Myocardial ischemia was monitored by means of cardiac lactate metabolism and 12-lead electrocardiogram. After coronary intervention IL-6 gradually increased from a common baseline level of 1.34 ± 1....

Development and utility of a multi-dimensional grid to assess individual mineral metabolism control in hemodialysis patients: A potential aid for therapeutic decision making?

Hemodialysis International — Sun, 14 Mar 2010 00:00:00 +0100

A grid was developed to evaluate control of serum calcium, phosphate, and parathyroid hormone levels in hemodialysis patients, based on guideline recommendations (National Kidney Foundation Kidney Disease Outcomes Quality Initiative and Canadian Society of Nephrology), and its face validity was examined in a representative sample of Canadian patients. A retrospective chart review was undertaken in hemodialysis patients from 7 Canadian units. Patients >18 years, on hemodialysis for [ge]12 months, and [ge]3 parathyroid hormone levels measured [ge]1 month apart were included. The grid classified mineral metabolism control as optimal, suboptimal, or poor (mean of 3 measurements). Medication use, hospitalization, and Emergency Department visits were evaluated in relation to grid occupancy. A se...

FDA Approves Five-Day Dosing Regimen For Dacogen(R) (decitabine) For Injection, Offering A New Outpatient Dosing Option For Myelodysplastic Syndromes

Lymphoma / Leukemia News From Medical News Today — Sat, 13 Mar 2010 09:00:00 +0100

Eisai Inc announced that the U.S. Food and Drug Administration (FDA) has approved a five-day dosing regimen for Dacogen® (decitabine) for Injection to treat patients with myelodysplastic syndromes (MDS), a group of bone marrow diseases that alter the production of functional blood cells... (Source: Lymphoma / Leukemia News From Medical News Today)

Altered phosphorylation of cytoskeleton proteins in sickle red blood cells: The role of protein kinase C, Rac GTPases, and reactive oxygen species.

Blood Cells, Molecules & Diseases — Sat, 13 Mar 2010 00:00:00 +0100

Authors: George A, Pushkaran S, Li L, An X, Zheng Y, Mohandas N, Joiner CH, Kalfa TA The small Rho GTPases Rac1 and Rac2 regulate actin structures and mediate reactive oxygen species (ROS) production via NADPH oxidase in a variety of cells. We have demonstrated that deficiency of Rac1 and Rac2 GTPases in mice disrupts the normal hexagonal organization of the RBC cytoskeleton and reduces erythrocyte deformability. This is associated with increased phosphorylation of adducin at Ser-724, (corresponding to Ser-726 in human erythrocytes), a domain target of protein kinase C (PKC). PKC phosphorylates adducin and leads to decreased F-actin capping and dissociation of spectrin from actin, implicating a significant role of such phosphorylation in cytoskeletal remodeling. We evaluated adducin ph...

RRM1 single nucleotide polymorphism -37C->A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy

Journal of Hematology and Oncology — Sat, 13 Mar 2010 00:00:00 +0100

Conclusions: The RRM1 polymorphism 37C->A correlated with PFS in NSCLC patients treated with gemcitabine-based chemotherapy. No significant correlation was found between PBMC RRM1 mRNA expression and the efficacy of gemcitabine. (Source: Journal of Hematology and Oncology)

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Whole-body MRI for staging Hodgkin lymphoma in a pregnant patient

American Journal of Hematology — Sat, 13 Mar 2010 00:00:00 +0100

No abstract. (Source: American Journal of Hematology)

Impaired lymphocyte mitochondrial antioxidant defences in variegate porphyria are accompanied by more inducible reactive oxygen species production and DNA damage

British Journal of Haematology — Sat, 13 Mar 2010 00:00:00 +0100

In conclusion, lymphocytes from VP women showed impaired expression of mitochondrial antioxidant defences but no significant signs of oxidative stress were evidenced in basal, non-stressing conditions; however, lymphocytes of VP women were more susceptible to producing mitochondrial ROS and to suffering oxidative damage when submitted to stressful situations. (Source: British Journal of Haematology)

Home Specimen Collection Boosts Cervical Cancer Screening (CME/CE)

MedPage Today Hematology/Oncology — Fri, 12 Mar 2010 13:13:06 +0100

Allowing women to collect their own cervicovaginal lavage specimens for human papillomavirus (HPV) testing increased coverage and cervical abnormality detection rates in a community-based cervical cancer screening program, Dutch researchers said. (Source: MedPage Today Hematology/Oncology)

Highlights of the fifth annual platelet colloquium

Journal of Thrombosis and Thrombolysis — Fri, 12 Mar 2010 06:48:24 +0100

Content Type Journal ArticleDOI 10.1007/s11239-010-0468-2Authors Patricia A. French, Left Lane Communications Chapel Hill NC USA Journal Journal of Thrombosis and ThrombolysisOnline ISSN 1573-742XPrint ISSN 0929-5305 (Source: Journal of Thrombosis and Thrombolysis)

MedWorm: Hematology

Drug Combo Meets NSCLC Milestone

A non-functioning vitamin D receptor predisposes to leukaemoid reactions in mice

Kaplan-Meier method is inappropriate for estimating cumulative incidence of graft-versus-host disease in the presence of competing events

Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations

Reduction of imatinib dose and persistence of complete molecular response after p210 multipeptide vaccine in chronic myeloid leukaemia treated with dose escalation for acquired resistance

Dialysis in the poisoned patient

SGO: New Option for Recurrent Ovarian Cancer? (CME/CE)

SGO: No Lung CA Risk Seen with Estrogen (CME/CE)

Contents

Will Publish in Future Issues . . .

Editorial Board

Journal Club

The Usefulness of Pathogen Inactivation During an Outbreak of the New Strain of Influenza (H1N1)

Arnault Tzanck, MD (1886-1954)

A Strategic Approach to the Problems of Providing Rhesus D–Negative Blood Transfusion in Geographic Areas With Low RhD Negativity: A Nigerian Perspective

Optimization of Leukocyte Collection and Monocyte Isolation for Dendritic Cell Culture

Is There a Role for Autologous/Placental Red Blood Cell Transfusions in the Anemia of Prematurity?

Blood Still Kills: Six Strategies to Further Reduce Allogeneic Blood Transfusion-Related Mortality

Masthead

Editorial Board

Genetics Add Little to Breast Cancer Risk Prediction (CME/CE)

Memphis! Join the IMF for a Broadway Theater Party!

Successful treatment of disseminated intravascular coagulation in a child with acute myelogenous leukaemia using recombinant thrombomodulin

Necrobiotic xanthogranuloma, a rare complication of a persistently high paraprotein

The use of fluid boluses to safely perform extracorporeal photopheresis (ECP) in low-weight children: A novel procedure

A large family from Argentina with Prekallikrein deficiency due to a compound heterozygosis (T insertion in intron 7 and Asp558Glu in exon 15): Prekallikrein Cordoba

Pandemic influenza A (H1N1) virus infections in children with sickle cell disease

Genetic variations in the heparanase gene (HPSE) associate with increased risk of GVHD following allogeneic stem cell transplantation: effect of discrepancy between recipients and donors

Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

Amino acid residues Arg659, Arg660, and Tyr661 in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor

Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug

A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement

Role for ADAP in shear flow-induced platelet mechanotransduction

Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6

An upstream insulator regulates DLK1 imprinting in AML

The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma

Bortezomib induces apoptosis in primitive chronic myeloid leukemia cells including LTC-IC and NOD/SCID repopulating cells

Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature

Overexpression of caveolin-1 in adult T-cell leukemia

The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas contains templated nucleotide insertions and a major breakpoint region similar to follicular and mantle cell lymphoma

PI3K p110{delta} regulates T-cell cytokine production during primary and secondary immune responses in mice and humans

Irradiation and IL-15 promote loss of CD8 T-cell tolerance in response to lymphopenia

Mislocalization of SLP-76 leads to aberrant inflammatory cytokine and autoantibody production

Free HTLV-1 induces TLR7-dependent innate immune response and TRAIL relocalization in killer plasmacytoid dendritic cells

Regulation of human NK-cell cytokine and chemokine production by target cell recognition

FOG1 requires NuRD to promote hematopoiesis and maintain lineage fidelity within the megakaryocytic-erythroid compartment

B cell-specific lentiviral gene therapy leads to sustained B-cell functional recovery in a murine model of X-linked agammaglobulinemia

Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

Targeting the translational machinery as a novel treatment strategy for hematologic malignancies

A novel antiphospholipid antibody agent?

If Virchow were to meet Newton

Macrophages give Gas(6) to cancer

V(D)J recombination and staggered DNA breaks: guilty again

Cyclophosphamide in aplastic anemia?

Target recognition-induced NK-cell responses

Alpha-type 1-polarized dendritic cells loaded with apoptotic allogeneic myeloma cell line induce strong CTL responses against autologous myeloma cells

SGO: Laparoscopy Passes Staging Test for Uterine Cancer (CME/CE)

Seasonal Variation, Weekly and Daily Rhythm of Transient Ischemic Attack in Hungary

Pulmonary Embolism Associated With Protein C Deficiency and Abuse of Anabolic-androgen Steroids

Thrombotic Thrombocytopenic Purpura and Sickle Cell Crisis

Effective Hemostasis During Minor Surgery in a Case of Hereditary Combined Deficiency of Vitamin K-dependent Clotting Factors

Right Atrial Appendage: Forgotten Part of the Heart in Atrial Fibrillation

Lipoprotein (a) Levels in Childhood Arterial Ischemic Stroke

Review: Factor XI Deficiency: Review and Management in Pregnant Women

PAI-1 and D-Dimer in Type 2 Diabetic Women With Asymptomatic Macrovascular Disease Assessed by Carotid Doppler

Factor V Leiden Mutation and Thrombotic Occlusion of Microsurgical Anastomosis After Free TRAM Flap

Clopidogrel Provides Significantly Greater Inhibition of Platelet Activity Than Aspirin When Combined With Atorvastatin After Coronary Artery Bypass Grafting: A Prospective Randomized Study

Plasminogen Activator Inhibitor-1 (PAI-1) Gene 4G/5G Promoter Polymorphism is Seen in Higher Frequency in the Indian Patients With Deep Vein Thrombosis

MR Molecular Imaging of Thrombus: Development and Application of a Gd-based Novel Contrast Agent Targeting to P-selectin

Antiplatelet Therapy Prasugrel: A Novel Platelet ADP P2Y12 Receptor Antagonist

Aptamers Influence the Hemostatic System by Activating the Intrinsic Coagulation Pathway in an In Vitro Chandler-Loop Model

Temporal Patterns of Hospital Admissions for Transient Ischemic Attack: A Retrospective Population-based Study in the Emilia-Romagna Region of Italy

Effects of Atenolol or Losartan on Fibrinolysis and von Willebrand Factor in Hypertensive Patients With Left Ventricular Hypertrophy

Early Discharge of Patients With Venous Thromboembolism: Implications Regarding Therapy

Role of Thrombotic Risk Factors in End-Stage Renal Disease

Optimal Dosing of Intravenous Unfractionated Heparin Bolus in Transient Ischemic Attack or Stroke

Profiling of Heparin-Induced Thrombocytopenia Antibody Levels in Patients With and Without Diabetes

Erratum to: The current status and the future of JAK2 inhibitors for the treatment of myeloproliferative diseases.