Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients.

Abstract:

:The outcome of patients with acute myeloid leukemia who are older than 60 years has remained poor because of unfavorable disease characteristics and patient-related factors. The randomized German-Austrian AML Study Group 06-04 protocol was designed on the basis of in vitro synergistic effects of valproic acid (VPA) and all-trans retinoic acid with chemotherapy. Between 2004 and 2006, 186 patients were randomly assigned to receive 2 induction cycles with idarubicin, cytarabine, and all-trans retinoic acid either with VPA or without (STANDARD). In all patients, consolidation therapy was intended. Complete remission rates after induction tended to be lower in VPA compared with STANDARD (40% vs 52%; P = .14) as a result of a higher early death rate (26% vs 14%; P = .06). The main toxicities attributed to VPA were delayed hematologic recovery and grade 3/4 infections, observed predominantly during the second induction cycle. After restricting VPA to the first induction cycle and reducing the dose of idarubicin, these toxicities dropped to rates observed in STANDARD. After a median follow-up time of 84 months, event-free and overall survival were not different between the 2 groups (P = .95 and P = .57, respectively). However, relapse-free-survival was significantly superior in VPA compared with STANDARD (24.4% vs 6.4% at 5 years; P = .02). Explorative subset analyses revealed that AML with mutated Nucleophosmin 1 (NPM1) may particularly benefit from VPA. This trial was registered at www.clinicaltrials.gov as #NCT00151255.

journal_name

Blood

journal_title

Blood

authors

Tassara M,Döhner K,Brossart P,Held G,Götze K,Horst HA,Ringhoffer M,Köhne CH,Kremers S,Raghavachar A,Wulf G,Kirchen H,Nachbaur D,Derigs HG,Wattad M,Koller E,Brugger W,Matzdorff A,Greil R,Heil G,Paschka P,Gaidzik

doi

10.1182/blood-2013-12-546283

subject

Has Abstract

pub_date

2014-06-26 00:00:00

pages

4027-36

issue

26

eissn

0006-4971

issn

1528-0020

pii

blood-2013-12-546283

journal_volume

123

pub_type

杂志文章,多中心研究,随机对照试验

相关文献

BLOOD文献大全
  • Genetic inactivation of TRAF3 in canine and human B-cell lymphoma.

    abstract::Non-Hodgkin lymphomas (NHLs) are the most common cancer to affect pet dogs. In contrast to the many genes whose mutation contributes to lymphomagenesis in humans, relatively little is known about the acquired genetic alterations that lead to canine B-cell lymphomas (cBCLs). We performed a survey of 84 canine NHL tumor...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-10-602714

    authors: Bushell KR,Kim Y,Chan FC,Ben-Neriah S,Jenks A,Alcaide M,Fornika D,Grande BM,Arthur S,Gascoyne RD,Steidl C,Morin RD

    更新日期:2015-02-05 00:00:00

  • NMDA receptor-mediated regulation of human megakaryocytopoiesis.

    abstract::Identification of the regulatory inputs that direct megakaryocytopoiesis and platelet production is essential for the development of novel therapeutic strategies for the treatment of thrombosis and related hematologic disorders. We have previously shown that primary human megakaryocytes express the N-methyl-d-aspartat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-11-3553

    authors: Hitchcock IS,Skerry TM,Howard MR,Genever PG

    更新日期:2003-08-15 00:00:00

  • Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group.

    abstract::In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally wer...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Reiter A,Schrappe M,Ludwig WD,Lampert F,Harbott J,Henze G,Niemeyer CM,Gadner H,Müller-Weihrich S,Ritter J

    更新日期:1992-11-15 00:00:00

  • Utilization of a continuous flow reactor to study the lipoprotein-associated coagulation inhibitor (LACI) that inhibits tissue factor.

    abstract::A microperfusion system containing a glass capillary, the inner surface of which is coated with a phospholipid bilayer containing tissue factor, was used to explore the requirement for factors VIIa and Xa in the complex formed with the lipoprotein-associated coagulation inhibitor (LACI). Various combinations of factor...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gemmell CH,Broze GJ Jr,Turitto VT,Nemerson Y

    更新日期:1990-12-01 00:00:00

  • Defensin promotes the binding of lipoprotein(a) to vascular matrix.

    abstract::Retention of lipoproteins within the vasculature is a central event in the pathogenesis of atherosclerosis. However, the signals that mediate this process are only partially understood. Prompted by putative links between inflammation and atherosclerosis, we previously reported that alpha-defensins released by neutroph...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bdeir K,Cane W,Canziani G,Chaiken I,Weisel J,Koschinsky ML,Lawn RM,Bannerman PG,Sachais BS,Kuo A,Hancock MA,Tomaszewski J,Raghunath PN,Ganz T,Higazi AA,Cines DB

    更新日期:1999-09-15 00:00:00

  • Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy.

    abstract::Chronic myeloid leukemia (CML) with T315I mutation has been reported to have poor prognosis. We analyzed 27 patients with T315I, including 20 who developed T315I after imatinib failure (representing 11% of 186 patients with imatinib failure), and 7 of 23 who developed new mutations after second tyrosine kinase inhibit...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-11-123950

    authors: Jabbour E,Kantarjian H,Jones D,Breeden M,Garcia-Manero G,O'Brien S,Ravandi F,Borthakur G,Cortes J

    更新日期:2008-07-01 00:00:00

  • L-selectin shedding affects bacterial clearance in the lung: a new regulatory pathway for integrin outside-in signaling.

    abstract::Pneumonia induced by Gram-negative bacteria is a common and serious disease associated with high morbidity and mortality. Elimination of bacterial pathogens relies on the recruitment and functions of neutrophils. The adhesion molecule L-selectin has recently been implicated in integrin activation in neutrophils (insid...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019000685

    authors: Cappenberg A,Margraf A,Thomas K,Bardel B,McCreedy DA,Van Marck V,Mellmann A,Lowell CA,Zarbock A

    更新日期:2019-10-24 00:00:00

  • Suppression of cell proliferation and the expression of a bcr-abl fusion gene and apoptotic cell death in a new human chronic myelogenous leukemia cell line, KT-1, by interferon-alpha.

    abstract::A new human leukemia cell line, KT-1, was established from a patient in the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidase and two Philadelphia chromosomes (Ph1) [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22....

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yanagisawa K,Yamauchi H,Kaneko M,Kohno H,Hasegawa H,Fujita S

    更新日期:1998-01-15 00:00:00

  • Notch ligands Delta 1 and Jagged1 transmit distinct signals to T-cell precursors.

    abstract::Signaling through the Notch pathway plays an essential role in inducing T-lineage commitment and promoting the maturation of immature thymocytes. Using an in vitro culture system, we show that 2 different classes of Notch ligands, Jagged1 or Delta1, transmit distinct signals to T-cell progenitors. OP9 stromal cells ex...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-08-3257

    authors: Lehar SM,Dooley J,Farr AG,Bevan MJ

    更新日期:2005-02-15 00:00:00

  • MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival.

    abstract::The molecular mechanisms that underlie T-cell quiescence are poorly understood. In the present study, we report a primary immunodeficiency phenotype associated with MST1 deficiency and primarily characterized by a progressive loss of naive T cells. The in vivo consequences include recurrent bacterial and viral infecti...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-09-378364

    authors: Nehme NT,Schmid JP,Debeurme F,André-Schmutz I,Lim A,Nitschke P,Rieux-Laucat F,Lutz P,Picard C,Mahlaoui N,Fischer A,de Saint Basile G

    更新日期:2012-04-12 00:00:00

  • Prevalence of heterozygotes for hemochromatosis in the white population of the United States.

    abstract::In previous studies, the prevalence of HLA-linked hemochromatosis, thought to be the most common genetic illness in whites, has been estimated by identifying homozygotes in the population. Because not all homozygotes express the disease phenotypically, the accuracy of these estimates is uncertain. We analyzed the dist...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: McLaren CE,Gordeuk VR,Looker AC,Hasselblad V,Edwards CQ,Griffen LM,Kushner JP,Brittenham GM

    更新日期:1995-09-01 00:00:00

  • Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies.

    abstract::Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A cha...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Antin JH,Bierer BE,Smith BR,Ferrara J,Guinan EC,Sieff C,Golan DE,Macklis RM,Tarbell NJ,Lynch E

    更新日期:1991-10-15 00:00:00

  • A test for Fanconi's anemia.

    abstract::A simple and reliable cytogenetic test for Fanconi's anemia (FA) that is based on the hypersensitivity of FA cells to mitomycin C (MC) is described. Equal volumes of whole blood from a patient in whom the diagnosis of FA is suspected and from a normal person of the opposite sex are co-cultured in phytohemagglutinin-co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: German J,Schonberg S,Caskie S,Warburton D,Falk C,Ray JH

    更新日期:1987-06-01 00:00:00

  • Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo.

    abstract::Mig, the monokine induced by interferon-gamma, is a CXC chemokine active as a chemoattractant for activated T cells. Mig is related functionally to interferon-inducible protein 10 (IP-10), with which it shares a receptor, CXCR3. Previously, IP-10 was found to have antitumor activity in vivo. In the present study, muri...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sgadari C,Farber JM,Angiolillo AL,Liao F,Teruya-Feldstein J,Burd PR,Yao L,Gupta G,Kanegane C,Tosato G

    更新日期:1997-04-15 00:00:00

  • Exposure of human megakaryocytes to high shear rates accelerates platelet production.

    abstract::Platelets originate from megakaryocytes (MKs) by cytoplasmic elongation into proplatelets. Direct platelet release is not seen in bone marrow hematopoietic islands. It was suggested that proplatelet fragmentation into platelets can occur intravascularly, yet evidence of its dependence on hydrodynamic forces is missing...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-03-209205

    authors: Dunois-Lardé C,Capron C,Fichelson S,Bauer T,Cramer-Bordé E,Baruch D

    更新日期:2009-08-27 00:00:00

  • NF-kappaB constitutes a potential therapeutic target in high-risk myelodysplastic syndrome.

    abstract::Myelodysplastic syndrome (MDS) is a preneoplastic condition that frequently develops into overt acute myeloid leukemia (AML). The P39 MDS/AML cell line manifested constitutive NF-kappaB activation. In this cell line, NF-kappaB inhibition by small interfering RNAs specific for p65 or chemical inhibitors including borte...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-05-1989

    authors: Braun T,Carvalho G,Coquelle A,Vozenin MC,Lepelley P,Hirsch F,Kiladjian JJ,Ribrag V,Fenaux P,Kroemer G

    更新日期:2006-02-01 00:00:00

  • A new adenoviral helper-dependent vector results in long-term therapeutic levels of human coagulation factor IX at low doses in vivo.

    abstract::We have developed a new helper-dependent (HD) adenoviral vector FTC that contains 3 cis-acting sequences as stuffer DNA: a human fragment of alphoid repeat DNA, matrix-attachment regions (MARs), and the hepatocyte control region enhancer. To determine the most robust human coagulation factor IX (hFIX) expression casse...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.11.3923

    authors: Ehrhardt A,Kay MA

    更新日期:2002-06-01 00:00:00

  • In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation.

    abstract::To investigate whether the migratory ability of peripheral blood-derived CD34+ cells of patients undergoing autologous peripheral blood stem cell transplantation is related to the homing efficiency of these cells, the migration in vitro of these cells was determined and correlated with in vivo hematopoietic recovery. ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.3.799

    authors: Voermans C,Kooi ML,Rodenhuis S,van der Lelie H,van der Schoot CE,Gerritsen WR

    更新日期:2001-02-01 00:00:00

  • Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes.

    abstract::Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a u...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-08-301556

    authors: Piccaluga PP,De Falco G,Kustagi M,Gazzola A,Agostinelli C,Tripodo C,Leucci E,Onnis A,Astolfi A,Sapienza MR,Bellan C,Lazzi S,Tumwine L,Mawanda M,Ogwang M,Calbi V,Formica S,Califano A,Pileri SA,Leoncini L

    更新日期:2011-03-31 00:00:00

  • Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study.

    abstract::Hematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.9.2697

    authors: Joshi DD,Dang A,Yadav P,Qian J,Bandari PS,Chen K,Donnelly R,Castro T,Gascon P,Haider A,Rameshwar P

    更新日期:2001-11-01 00:00:00

  • A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis.

    abstract::The kidney is involved in 70% of patients with immunoglobulin light-chain (AL) amyloidosis, but little is known on progression or reversibility of renal involvement, and criteria for renal response have never been validated. Newly diagnosed patients from the Pavia (n = 461, testing cohort) and Heidelberg (n = 271, val...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-04-570010

    authors: Palladini G,Hegenbart U,Milani P,Kimmich C,Foli A,Ho AD,Vidus Rosin M,Albertini R,Moratti R,Merlini G,Schönland S

    更新日期:2014-10-09 00:00:00

  • The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML.

    abstract::Mutations of the NPM1 gene (NPM1mut) are among the most common genetic alterations in acute myeloid leukemia and are suitable for minimal residual disease detection. We retrospectively investigated the prognostic impact of NPM1mut-based minimal residual disease detection from bone marrow for development of relapse by ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-10-461749

    authors: Shayegi N,Kramer M,Bornhäuser M,Schaich M,Schetelig J,Platzbecker U,Röllig C,Heiderich C,Landt O,Ehninger G,Thiede C,Study Alliance Leukemia (SAL).

    更新日期:2013-07-04 00:00:00

  • Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms.

    abstract::Myeloproliferative neoplasms (MPNs) are a group of clonal disorders characterized by aberrant hematopoietic proliferation and an increased tendency toward leukemic transformation. We used targeted next-generation sequencing (NGS) of 104 genes to detect somatic mutations in a cohort of 197 MPN patients and followed clo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-11-537167

    authors: Lundberg P,Karow A,Nienhold R,Looser R,Hao-Shen H,Nissen I,Girsberger S,Lehmann T,Passweg J,Stern M,Beisel C,Kralovics R,Skoda RC

    更新日期:2014-04-03 00:00:00

  • High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of inflammatory molecules in blood cells.

    abstract::Studies on the role of inflammation in cardiovascular disease focus on surrogate markers like plasma levels of C-reactive protein or interleukins that are affected by several factors. In this study we employ an approach in which the inflammatory mRNA profile of leucocytes is measured directly in a multigene system. We...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-08-3283

    authors: Wettinger SB,Doggen CJ,Spek CA,Rosendaal FR,Reitsma PH

    更新日期:2005-03-01 00:00:00

  • Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations.

    abstract::Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granule components or their fusion machinery, leading to impaired natural killer cell and/or T lymphocyte degranulation and/or cytotoxicity. This may accumulate into a life-threatening condition known as macrophage activation s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-03-494039

    authors: Zhao XW,Gazendam RP,Drewniak A,van Houdt M,Tool AT,van Hamme JL,Kustiawan I,Meijer AB,Janssen H,Russell DG,van de Corput L,Tesselaar K,Boelens JJ,Kuhnle I,Van Der Werff Ten Bosch J,Kuijpers TW,van den Berg TK

    更新日期:2013-07-04 00:00:00

  • BB9 ACEs the HSC compartment.

    abstract::In an effort to discover specific markers to isolate human hematopoietic stem cells, Jokubaitis and colleagues report that the monoclonal antibody BB9 reacts with hematopoietic cells displaying morphologic, phenotypic, and/or functional properties of stem and progenitor cells throughout human ontogeny. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2007-12-126672

    authors: Yoder MC

    更新日期:2008-04-15 00:00:00

  • Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization.

    abstract::The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible fo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-03-631598

    authors: Daniels G,Ballif BA,Helias V,Saison C,Grimsley S,Mannessier L,Hustinx H,Lee E,Cartron JP,Peyrard T,Arnaud L

    更新日期:2015-06-04 00:00:00

  • Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation.

    abstract::We used a sensitive real-time reverse transcription-polymerase chain reaction assay to quantify cyclin D1 mRNA levels in bone marrow samples collected at diagnosis from 74 newly diagnosed multiple myeloma (MM) patients who were randomized to undergo either single or double autologous peripheral blood stem cell transpl...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1182/blood-2002-12-3789

    authors: Soverini S,Cavo M,Cellini C,Terragna C,Zamagni E,Ruggeri D,Testoni N,Tosi P,De Vivo A,Amabile M,Grafone T,Ottaviani E,Giannini B,Cangini D,Bonifazi F,Neri A,Fabris S,Tura S,Baccarani M,Martinelli G

    更新日期:2003-09-01 00:00:00

  • The immunotherapy era of myeloma: monoclonal antibodies, vaccines, and adoptive T-cell therapies.

    abstract::The treatment of multiple myeloma has evolved significantly over the last decades from primarily alkylator-based chemotherapeutic agents with minimal efficacy to the introduction of more effective agents including immune modulators and proteasome inhibitors, which have changed the landscape of therapy for this disease...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2016-05-636357

    authors: Hoyos V,Borrello I

    更新日期:2016-09-29 00:00:00

  • Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome.

    abstract::The effects of immunoglobulin G (IgG) from patients with the antiphospholipid syndrome (APS) upon monocyte activation have not been fully characterized. We carried out a comprehensive proteomic analysis of human monocytes treated with IgG from patients with different manifestations of the APS. Using 2-dimensional diff...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-05-577569

    authors: Ripoll VM,Lambrianides A,Pierangeli SS,Poulton K,Ioannou Y,Heywood WE,Mills K,Latchman DS,Isenberg DA,Rahman A,Giles IP

    更新日期:2014-12-11 00:00:00