Reduction of invasive aspergillosis incidence among immunocompromised patients after control of environmental exposure.

Background: The objective of the study was to assess the impact of the relocation of an adult hematological intensive care unit on invasive aspergillosis (IA) incidence.

Methods: A quasi-experimental study, including a control group and an intervention group that both underwent pretest and posttest evaluations, was conducted in the 3 adult hematological intensive care units (each composed of 14 single rooms) in a university hospital from 14 April 2005 through 1 February 2006. One of these units was relocated from the main building to an adjoining modular construction.

Insight into siderophore-carrying peptide biosynthesis: enterobactin is a precursor for microcin E492 posttranslational modification.

Microcin E492-producing bacteria secrete both unmodified and posttranslationally modified microcins. The modification consists of a C-glucosylated linear trimer of N-(2,3-dihydroxybenzoyl)-l-serine, a catecholate siderophore related to salmochelins and enterobactin. We show here that repression of enterobactin biosynthesis inhibits the acquisition of microcin E492 posttranslational modification, as monitored by high-performance liquid chromatography and mass spectrometry.

Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs.

TLX1 is a homeodomain transcription factor generally associated with a favorable outcome in T-cell acute lymphoblastic leukemia (T-ALL). However, the molecular mechanisms of TLX1 deregulation remain unclear and various transcript levels in the absence of 10q24 abnormalities have been reported. A reproducible and accurate delineation of TLX1(+) T-ALL will be necessary for proper therapeutic stratification.

Proportion of long-term event-free survivors and lifetime of adult patients not cured after a standard acute lymphoblastic leukemia therapeutic program: adult acute lymphoblastic leukemia-94 trial.

Background: In adult acute lymphoblastic leukemia, treatment results generally are expressed in terms of overall survival or disease-free survival at 3 years. In this investigation, the authors attempted to express the results in terms of the proportion of long-term disease-free survivors and in terms of lifetime in patients who developed recurrent disease or died.

Methods: Univariate and multivariate analyses were used to assess the influence of different covariates on the 2 result criteria in 922 participants in the Adult Acute Lymphoblastic Leukemia-94 multicenter trial.

Timed-sequential chemotherapy as induction and/or consolidation regimen for younger adults with acute myelogenous leukemia.

Increasing the intensity of induction chemotherapy has generated considerable recent interest in the treatment of acute myeloid leukemia. Achieving complete remission is a sine qua non condition for prolonged disease-free survival and may affect long-term outcome. In this setting, administering a repeat course of induction shortly after completion of the first course, known as timed-sequential chemotherapy (TSC), has been tested and may lead to an improved long-term outcome.

A silicone-based controlled-release device for accelerated proteolytic debridement of wounds.

A new device for rapid enzymatic debridement of cutaneous wounds has been developed using a controlled-release, silicone-based, dried emulsion. A dehydrated serine protease of the subtilisin family, previously untested for wound debridement, was incorporated into the emulsion. This device exhibited excellent storage stability.

A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia.

This phase 2 study evaluated the efficacy and safety of the oral farnesyltransferase inhibitor tipifarnib in adults with refractory or relapsed acute myeloid leukemia (AML). Patients (n=252) received tipifarnib 600 mg twice a day for 21 days in 28-day cycles. Median age was 62 years; 99 (39%) patients were 65 years or older.

Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial.

In elderly patients with acute myeloid leukemia (AML) treated intensively, no best postremission strategy has emerged yet. This clinical trial enrolled 416 patients with AML aged 65 years or older who were considered eligible for standard intensive chemotherapy, with a first randomization comparing idarubicin with daunorubicin for all treatment sequences. After induction, an ambulatory postremission strategy based on 6 consolidation cycles administered monthly in outpatients was randomly compared with an intensive strategy with a single intensive consolidation course similar to induction.

Autologous stem cell transplantation after complete remission and first consolidation in acute myeloid leukemia patients aged 61-70 years: results of the prospective EORTC-GIMEMA AML-13 study.

Background And Objectives: The optimal post-remission treatment for elderly patients with acute myeloid leukemia (AML) is presently unknown. Recent studies have reported the feasibility of autologous peripheral blood stem cell transplantation (PBSCT) in this population. We evaluate the outcome of this post-remission approach after complete remission (CR) and consolidation in elderly patients included in the EORTC-GIMEMA AML-13 trial.

Autologous hematopoietic stem cell transplantation for adults with acute myeloid leukemia in complete remission: the Edouard Herriot Hospital experience.

We retrospectively assess the long-term outcome and determined prognostic factors correlated with outcomes in adults with acute myeloid leukemia (AML) undergoing autologous hematopoietic stem cell transplantation (HSCT) in our institution over a 19-year period. A total of 78 adults who received autologous HSCT for AML in first complete remission (CR) and of 21 adults in further CR were included in the study. Bone marrow (n = 14) or peripheral blood stem cells (PBSC) (n = 85) transplantation was performed at a median of 2.

Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group.

Purpose: Several phase II studies have suggested that cytarabine (AraC) was not required in the treatment of newly diagnosed acute promyelocytic leukemia (APL) patients receiving all-trans-retinoic acid (ATRA), an anthracycline, and maintenance therapy, and we aimed at confirming this finding in a randomized trial.

Patients And Methods: Newly diagnosed APL patients younger than age 60 years with a WBC count of less than 10,000/microL were randomly assigned to receive either ATRA combined with and followed by three daunorubicin (DNR) plus AraC courses and a 2-year maintenance regimen (AraC group) or the same treatment but without AraC (no AraC group). Patients older than age 60 years and patients with initial WBC count of more than 10,000/microL were not randomly assigned but received risk-adapted treatment, with higher dose of AraC and CNS prophylaxis in patients with WBC counts more than 10,000/microL.

Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study.

The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT).

Initial and late prognostic factors to predict survival in adult acute lymphoblastic leukaemia.

Factors able to predict overall survival in adult patients with acute lymphoblastic leukaemia were assessed according to the period since initiation of the treatment using a Cox proportional hazards model. This period covers successively an initial period during the induction treatment and a consolidation period during the postinduction treatment. From 1994 to 2002, 922 patients with acute lymphoblastic leukaemia (excluding French-American-British L3 subtype) were enrolled in a multicentre protocol and followed, with a mean follow up of 58 months.

Trisomy 8 as sole anomaly or with other clonal aberrations in acute myeloid leukemia: impact on clinical presentation and outcome.

One hundred and fifty-four acute myeloid leukemia patients with trisomy 8 were studied for their clinical and biological characteristics, and treatment outcome. Forty-seven patients presented with trisomy 8 as the sole aberration, 107 with trisomy 8 associated with other cytogenetic abnormalities (13 with favorable, 54 with intermediate, and 40 with unfavorable risk cytogenetics). Overall complete remission (CR) proportion was 48%.

Superiority of an arsenic trioxide-based regimen over a historic control combining all-trans retinoic acid plus intensive chemotherapy in the treatment of relapsed acute promyelocytic leukemia.

There is still no consensus on the best approach for the treatment of relapsing acute promyelocytic leukemia. All-trans retinoic acid plus chemotherapy is hampered by potential mechanisms of resistance, and the safety profile of chemotherapy may be considered as not acceptable before stem cell transplantation. Arsenic trioxide provides an option for these patients.

Parasitism of iron-siderophore receptors of Escherichia coli by the siderophore-peptide microcin E492m and its unmodified counterpart.

Microcin E492 (MccE492) is an antibacterial peptide naturally secreted by Klebsiella pneumoniae RYC492. Initially described as an 84-residue unmodified peptide, it was also recently isolated in a posttranslationally modified form, MccE492m. The production of MccE492m is dependent on the synthesis of enterobactin and the mceABCDEFGHIJ gene cluster.

Long-term follow-up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia.

We report on the outcomes of 53 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS, autografted in first complete remission. Five (9.4%) died from the procedure whereas hematological reconstitution occurred in all the remaining patients.

The role of the K247R substitution in the ABL tyrosine kinase domain in sensitivity to imatinib.

Imatinib mesylate has become the gold standard front-line treatment of chronic myelogenous leukemia through its ability to inhibit ABL tyrosine kinase. Resistance to this inhibition may occur. We investigated the role of the K247R polymorphism in persistent sensitivity.

The prognostic value of cN-II and cN-III enzymes in adult acute myeloid leukemia.

We analyzed the expression of deoxycytidine kinase (dCK), UMP/CMP-kinase (UMP/CMP-K), nucleotide diphosphokinase (NDPK-B) and 5'-nucleotidases cN-II, cN-III, cdN and mdN by quantitative polymerase chain reaction at diagnosis in leukemic blasts from 96 patients with acute myeloid leukemia (AML) treated with ara-C. Our results show that high mRNA levels of cN-II and low mRNA levels of cN-III are correlated with a worse clinical outcome and suggest that these enzymes may have a role in sensitivity to ara-C in AML patients.

Emerging drugs for adult acute lymphoblastic leukaemia.

Although most patients with adult acute lymphoblastic leukaemia (ALL) can achieve a remission when treated with conventional, DNA-damaging chemotherapy, in more than half of all cases the disease relapses and ultimately results in death. Therefore, there is a substantial need for new antileukaemic drugs. Recent advances in the understanding of the molecular alterations in ALL have lead to the identification of new targets and the arrival of molecular-targeted therapies in the clinical setting.

Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype.

Mutation of the nucleophosmin (NPM) gene has been reported as the most frequent mutation in acute myeloid leukemia (AML), especially in the presence of a normal karyotype. In this subgroup of intermediate-risk AML, the identification of other gene mutations (eg, FLT3, CCAAT/enhancer-binding protein-alpha [CEBPA]) has helped to refine the prognosis. This study explored the prevalence and the prognostic impact of NPM mutations in a cohort of 106 patients with normal-karyotype AML.

Expression of heat-shock proteins is associated with major adverse prognostic factors in acute myeloid leukemia.

To identify prognostic factors alternative or additional to drug-resistance and apoptosis proteins, we studied the impact of the expression of heat-shock proteins (HSPs) in 98 newly diagnosed acute myeloid leukemia (AML). HSP27 was expressed by 39%, HSP60 by 26%, HSP70 by 58%, HSP90 by 41%, and HSP110 by 30% of cases. HSP expressions were correlated with that of differentiation antigens (CD34, CD14, CD15, CD33) and that of drug-resistance (MRP, MRK) and apoptosis (Bcl-2) proteins.

Heat shock proteins and acute leukemias.

Heat shock proteins (HSPs) acts as molecular chaperones by helping in the refolding of misfolded proteins and assisting in their elimination if they become irreversibly damaged. HSPs induced by stress treatment have a role in the modulation of apoptosis. The reduction in protein expression levels was correlated with an increased susceptibility to drug-induced apoptosis.

Acute leukemia during pregnancy: a report on 37 patients and a review of the literature.

Background: Acute leukemia (AL) requiring cytotoxic treatment occurring during pregnancy poses a very difficult therapeutic dilemma.

Methods: By means of a mail questionnaire, information on a series of 37 patients with a diagnosis of AL during pregnancy was collected from 13 French centers between December, 1988 and November, 2003.

Results: Thirty-one patients had acute myeloid leukemia (AML), and 6 patients had acute lymphoblastic leukemia (ALL).

[Farnesyltransferase inhibitors: preliminary results in acute myeloid leukemia].

Farnesyltransferase inhibitors (FTIs) are small-molecule inhibitors that selectivly inhibit farnesylation of a number of intracellular substrate proteins such as Ras. Preclinical work has revealed their ability to effectively inhibit tumor growth in vitro and in vivo in animal models across a wide range of malignant phenotypes. Acute myeloid leukemias (AMLs) are appropriate disease targets in that they express relevant biologic targets such as Ras, MEK, AKT, and others that may depend upon farnesyl protein transferase activity to promote cell proliferation and survival.