Search results for "Myeloid"
showing 10 items of 538 documents
Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion.
2012
Abstract In myeloid malignancies, the neoplastic clone outgrows normal hematopoietic cells toward BM failure. This event is also sustained by detrimental stromal changes, such as BM fibrosis and osteosclerosis, whose occurrence is harbinger of a dismal prognosis. We show that the matricellular protein SPARC contributes to the BM stromal response to myeloproliferation. The degree of SPARC expression in BM stromal elements, including CD146+ mesenchymal stromal cells, correlates with the degree of stromal changes, and the severity of BM failure characterizing the prototypical myeloproliferative neoplasm primary myelofibrosis. Using Sparc−/− mice and BM chimeras, we demonstrate that SPARC contr…
AML transformation in 56 patients with Ph- MPD in two well defined populations.
2009
The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders (MPD) have an inherent tendency for transformation into acute myelogenous leukaemia (AML). The long-term rate of leukaemic transformation in unselected MPD patients was studied in well-defined MPD populations in Gothenburg, Sweden and the Cote d'Or area, Burgundy, France, respectively. Over a median observation time of 15 yr, 56 subjects (7%) out of a total of 795 patients with Ph- MPD transformed to AML. The yearly incidence of AML transformation was 0.38% in polycythaemia vera (PV), 0.37% in essential thrombocythaemia (ET) and 1.09% in idiopathic myelofibrosis (IMF). The incidence of AML development was signif…
Leucocytosis and thrombosis at diagnosis are associated with poor survival in polycythaemia vera: a population-based study of 327 patients
2012
Three hundred and twenty-seven patients from two population-based cohorts with an established diagnosis of polycythaemia vera were studied for prognostic risk factors for survival and leukaemia in a long-term survey. The relative survival (RS) was 72% and 46% at 10 and 20 years respectively, from the time of diagnosis. Multivariate analysis identified age >70 years, white blood cell count >13 × 10(9) /l and thrombo-embolism at diagnosis as independent risk factors. Patients with two or three of these factors had a 10 year RS of 26%, compared with 59% and 84% in patients with one and no risk factors, respectively. Age and leucocyte count are the main predicting factors for survival in polycy…
Criteria for defining a complete remission in acute myeloid leukaemia revisited. An analysis of patients treated in HOVON-SAKK co-operative group stu…
2005
Complete remission (CR) in patients with acute myeloid leukaemia (AML) is the primary endpoint for the evaluation of induction treatment and treatment strategies. However, the choice and application of the criteria for a haematological CR can often become a subject of debate because of regeneration more than 5% blasts may be present at the time of response evaluation; platelet and neutrophil recovery may be incomplete and marrow cellularity can vary. This study examined the individual parameters for CR in 1250 adult patients with de novo AML treated according to three successive study protocols. Patients with < or =5% blasts showed the best overall survival (OS) and the lowest relapse risk …
Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann–Steiner and Rubinstein–Taybi syndromes
2020
Lysine-specific methyltransferase 2A (KMT2A) is responsible for methylation of histone H3 (K4H3me) and contributes to chromatin remodeling, acting as “writer” of the epigenetic machinery. Mutations in KMT2A were first reported in Wiedemann–Steiner syndrome (WDSTS). More recently, KMT2A variants have been described in probands with a specific clinical diagnosis comprised in the so-called chromatinopathies. Such conditions, including WDSTS, are a group of overlapping disorders caused by mutations in genes coding for the epigenetic machinery. Among them, Rubinstein–Taybi syndrome (RSTS) is mainly caused by heterozygous pathogenic variants in CREBBP or EP300. In this work, we used next generati…
Immunophenotypical comparison of Gaucher's and pseudo-Gaucher cells.
1996
An immunohistochemical study on bone marrow biopsies and spleens of patients with Gaucher's disease and chronic myeloid leukemia was performed to investigate the immunophenotype of Gaucher's cells and pseudo-Gaucher cells. A panel of antibodies was used which were reactive on paraffin-embedded tissues and directed against different hematopoietic lineage cells. Gaucher's cells and pseudo-Gaucher cells expressed a very similar immunophenotype and displayed an intense reaction for the monocytic antibodies tested, thus confirming their common origin and that they belong to the same system. The expression of HLA-DR antigens was much stronger in Gaucher's than in pseudo-Gaucher cells. This last f…
Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and h…
2000
Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy. Median age was 58 years (range: 18-76 years). Forty-nine patients (45%) achieved a complete remission (CR) after two induction cycles with idarubicin, ara-C, and etoposide, 52% of them aged/=60 years and 35% aged60 years (p=0.06). After two consolidation courses, patients were randomized to four cycles of either high-…
Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia.
2013
Summary Concerns have recently emerged about the quality of generic vancomycin products. Our aim is to analyze serum vancomycin concentrations measured 48 hours after the start of an empirical treatment regimen in patients with acute myeloid leukemia (AML) who received one of the two generic vancomycin products available in France. Patients and methods Seventy-nine AML patients treated with vancomycin during two study periods were included in the study. Our vancomycin dosing regimen was based on the patients’ total body weight adjusted for renal clearance. Results A total of 93 serum vancomycin concentrations were collected: 31 in period 1 and 62 in period 2. In bivariate analysis, the mean…
Safety and Pharmacokinetics of Isavuconazole as Antifungal Prophylaxis in Acute Myeloid Leukemia Patients with Neutropenia: Results of a Phase 2, Dos…
2015
ABSTRACT Isavuconazole is a novel broad-spectrum triazole antifungal agent. This open-label dose escalation study assessed the safety and pharmacokinetics of intravenous isavuconazole prophylaxis in patients with acute myeloid leukemia who had undergone chemotherapy and had preexisting/expected neutropenia. Twenty-four patients were enrolled, and 20 patients completed the study. The patients in the low-dose cohort ( n = 11) received isavuconazole loading doses on day 1 (400/200/200 mg, 6 h apart) and day 2 (200/200 mg, 12 h apart), followed by once-daily maintenance dosing (200 mg) on days 3 to 28. The loading and maintenance doses were doubled in the high-dose cohort ( n = 12). The mean ± …
Allogeneic Hematopoietic Stem Cell Transplantation Following the Use of Hypomethylating Agents among Patients with Relapsed or Refractory AML: Findin…
2018
Patients with primary refractory or relapsed acute myeloid leukemia (RR-AML) have very poor prognosis. Due to limited treatment options, some patients are treated with hypomethylating agents (HMAs) due to their tolerability. Little is known about the role of allogeneic hematopoietic stem cell transplantation (HSCT) following HMA therapy in this setting. We retrospectively analyzed an international cohort of 655 RR-AML patients who received HMA therapy to study patterns and outcomes with HSCT. Only 37 patients (5.6%) patients underwent HSCT after HMA therapy. The conditioning regimen was myeloablative in 57% and nonmyeloablative in 43%. Patients received matched unrelated donor, matched sibl…