Publications by authors named "Magali Donnard"

17 Publications

  • Page 1 of 1

Multicentre pharmacokinetic evaluation of rFVIII-Fc (efmoroctocog alfa) in a real life and comparison with non-extended half-life FVIII concentrates.

Haemophilia 2020 Mar 27;26(2):282-289. Epub 2020 Feb 27.

Laboratoire d'Hémostase Hémobiologie, CHU de Lille, Lille, France.

The use of enhanced half-life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroctocog alfa (rFVIII-Fc) in 114 patients and, in 47 cases, compared them to those previously measured with non-EHL FVIII. The in vivo recovery (IVR) of rFVIII-Fc measured with one stage clotting assay (OSA) and chromogenic assay (CSA) was 2.2 and 2.8 IU/mL per IU/kg, respectively. The median half-life (T ) of rFVIII-Fc was 14.5 hours whatever the FVIII:C assay used, but variable and correlated with preinfusion VWF:Ag levels (r = .76). Both IVR and T were lower in patients under 12 years old (2.4 IU/mL per IU/kg and 11.1 hours, respectively; CSA). PK study of rFVIII-Fc vs non-EHL FVIII showed a T ratio of 1.4 in favour of rFVIII-Fc, regardless of the patient's age. However the relative increase in T with rFVIII-Fc was lower than 30% in one-third of patients evaluated, particularly when the previous FVIII administered was a BHK-derived product. This study therefore suggests that analysis of individual PK profile in response to a specific FVIII concentrate is potentially useful before a switch in haemophilia A patients.
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http://dx.doi.org/10.1111/hae.13946DOI Listing
March 2020

Both CD62 and CD162 antibodies prevent formation of CD36-dependent platelets, rosettes, and artefactual pseudoexpression of platelet markers on white blood cells: a study with ImageStream®.

Cytometry A 2011 Jun 1;79(6):477-84. Epub 2011 Apr 1.

Laboratory of Haematology, CHU Dupuytren, Limoges, France.

Fluorescent labeled monoclonal antibodies (mAbs) against CD36 are routinely used as monocyte, erythroid, or platelet markers in clinical cytometry. CD36 has recently been proposed by various authors as a valuable marker helping to enumerate leukocyte's subpopulations by flow cytometry. However, it is known that binding of CD36 may induce platelet activation and formation of platelet's rosettes on leukocytes, resulting in false expression of platelet markers on white blood cells. To study this phenomenon, we have combined classical flow cytometry and a new quantitative flow imaging technique with the ImageStream(®) analyzer. We show that CD36 ligation induces activation of platelets with CD62 expression and their adhesion on leukocytes due to CD62 and CD162 interactions. Preincubation of whole blood samples with either anti-CD62 or anti-CD162 antibodies could prevent formation of these rosettes. Our approach also emphasizes the fact that immunomorphological analysis of cell events with ImageStream technology is a useful tool to validate the specificity of marker's labeling or to elucidate incoherent results obtained with classical flow cytometry. We thus propose to prevent false platelet labeling on leukocytes by preincubation with either anti-CD62 or anti-CD162 antibodies when using CD36 mAbs.
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http://dx.doi.org/10.1002/cyto.a.21050DOI Listing
June 2011

5-LOX, 12-LOX and 15-LOX in immature forms of human leukemic blasts.

Leuk Res 2008 Nov 18;32(11):1756-62. Epub 2008 Jun 18.

Université de Limoges, Centre National de la Recherche Scientifique, CNRS UMR 6101, Faculté de Médecine, 2 rue Dr. Marcland, 87025 Limoges, France.

Several reports have demonstrated an important role of leukotriene B(4) (LTB(4)) in the immune system. We investigated whether leukemic blasts from acute myeloid leukemic (AML) and acute lymphoid leukemic (ALL) patients produced LTB(4), 12- and 15-hydroxyeicosatetraenoic acids (12-HETE and 15-HETE) and whether these compounds affected blast proliferation and apoptosis. Leukemic blasts from AML M(0-2) and ALL patients expressed 5-LOX, 12-LOX and 15-LOX transcripts. Quantitative polymerase chain reaction indicated that 5-LOX transcripts were far more abundant than 12-LOX and 15-LOX ones. Leukemic blasts expressed 5-LOX activating protein (FLAP) transcripts and produced LTB(4) in response to calcium ionophore. In contrast no 15-HETE production was found. Calcium ionophore-stimulated leukemic blasts produced 12-HETE but also released thromboxane A(2) suggesting that contaminating platelets accounted for the release of these compounds. No significant effect of LTB(4), 12-HETE or 15-HETE could be documented on leukemic blast growth and on their apoptose rate. Results of the present study indicate that immature form of leukemic blasts produce LTB(4). However, the three major lipoxygenase metabolites of arachidonic acid; i.e., LTB(4), 12-HETE or 15-HETE, had no evident effect on their growth and apoptosis. We may speculate that LTB(4)-derived blast cells might initiate, augment or prolong tissue inflammation and damages by affecting the marrow and blood cytokine network.
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http://dx.doi.org/10.1016/j.leukres.2008.05.005DOI Listing
November 2008

"6 markers/5 colors" extended white blood cell differential by flow cytometry.

Cytometry A 2007 Nov;71(11):934-44

Laboratoire d'Hématologie, Hôpital Dupuytren, Limoges, France.

Electronic white blood cell (WBC) differential by standard cytology (hematology analyzer and visual inspection of blood smears) is limited to five types and identification of abnormal cells is only qualitative, often problematic, poorly reproducible, and labour costing. We present our results on WBC differential by flow cytometry (FCM) with a 6 markers, 5 colors CD36-FITC/CD2-PE+CRTH2-PE/CD19-ECD/CD16-Cy5/CD45-Cy7 combination, on 379 subjects, with detection of 12 different circulating cell types, among them 11 were quantified. Detection of quantitative abnormalities of whole leucocytes, neutrophils, eosinophils, basophils, monocytes, or lymphocytes was comparable by FCM and by standard cytology in terms of sensitivity and specificity. FCM was better than standard cytology in detection and quantification of circulating blast cells or immature granulocytes, with a first lineage orientation in the former case. All cases of lymphocytosis, with lineage assignment, were detected by FCM. FCM identified a group of patients with excess of CD16pos monocytes as those having an inflammatory syndrome. WBC differential by FCM is at least as reliable as by standard cytology. FCM superiority consists in identification and systematic quantification of parameters that cannot be assessed by standard cytology such as lineage orientation of blast cells or lymphocytes, and expression of markers of interest such as CD16 on inflammatory monocytes.
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http://dx.doi.org/10.1002/cyto.a.20457DOI Listing
November 2007

Functional platelet-activating factor receptors in immature forms of leukemic blasts.

Leuk Res 2007 Mar 11;31(3):399-402. Epub 2006 Jul 11.

UMR CNRS 6101, Centre National de la Recherche Scientifique, Université de Limoges, France.

Platelet-activating factor (PAF) is a phospholipid mediator with potent immunoregulatory activities on mature leukocytes. PAF modulates leukocyte cytosolic Ca2+ concentration ([Ca2+]i) through a Gq mediated pathway. We highlight, for the first time, Gq transcripts, PAF receptor (PAF-R) transcripts and protein in blast cells of acute myeloid (AML) and lymphoid (ALL) leukemia patients. PAF stimulated [Ca2+]i in leukemic blast cells; PAF effects being prevented by a specific PAF-R antagonist. In conclusion, functional PAF-R are present in blast cells of patients with acute leukemia; a result that could be of physiologic importance regarding the important effect of PAF on leukocytes maturation and functions.
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http://dx.doi.org/10.1016/j.leukres.2006.06.002DOI Listing
March 2007

Platelet-activating factor does not stimulate cAMP formation from immature forms of freshly isolated leukaemic blasts.

Leuk Lymphoma 2005 Jan;46(1):129-31

UMR CNRS 6101, Laboratoire d'Hématologie and Service d'Hématologie Clinique et de Thérapie Cellulaire, CHU Dupuytren, Limoges, France.

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http://dx.doi.org/10.1080/10428190400013092DOI Listing
January 2005

A standardized endogenous megakaryocytic erythroid colony assay for the diagnosis of essential thrombocythemia.

Haematologica 2004 Oct;89(10):1207-12

Laboratoire d' Hématologie of the Centres Hospitaliers Universitaires d'Angers, France.

Background And Objectives: The reliability of assays of endogenous megakaryocytic colony (EMC) and endogenous erythroid colony (EEC) formation for the diagnosis of thrombocytoses remains controversial. We tested the suitability of a recently developed collagen-based assay of EMC formation for the diagnosis of essential thrombocythemia (ET).

Design And Methods: This was a multicenter (8 laboratories) study including 121 patients: 82 with ET and 39 with reactive thrombocytoses (RT). EMC and EEC were assessed in each laboratory in serum-free, cytokine-free, standardized collagen gel assays; bone marrow (BM) and peripheral blood (PB) were tested in parallel.

Results: In PB cultures, only EEC were specific for ET. In BM cultures, both EMC and EEC were specific for ET and present in assays of 77.8% (EMC) and 33.3% (EEC) of ET patients. Altogether, 80.2% of ET patients had BM EMC and/or EEC, whereas none of the patients with RT did.

Interpretation And Conclusions: When performed with BM progenitors for the diagnosis of thrombocytoses, positivity of the standardized EMC/EEC assay in collagen is specific (100%) and detects 80% of ET.
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October 2004

Diagnostic value of serum erythropoietin level in patients with absolute erythrocytosis.

Haematologica 2004 Oct;89(10):1194-8

Laboratories of Hematology of Centre Hospitalier Universitaire, Grenoble, France.

Background And Objectives: The diagnosis of polycythemia vera (PV) is based on clinical and biological criteria defined by either the Polycythemia Vera Study Group (PVSG) or the World Health Organization (WHO). Both the PVSG and WHO PV criteria have proved helpful and are extensively used, yet diagnostic strategies and scheduling of biological investigations vary. We assessed the value of measuring serum erythropoietin (Epo) as a first intention diagnostic test in patients with absolute erythrocytosis (AE).

Design And Methods: Serum and bone marrow (BM) samples of 241 patients with a suspicion of erythrocytosis were collected in 8 hospital centers. One hundred and ninety had an absolute erythrocytosis (116 had PV, 66 had secondary erythrocytosis and 4 had idiopathic erythrocytosis). Serum Epo was assayed (ELISA) in 186. Statistical analysis (ROC curves) was used to define serum Epo thresholds that were specific for PV and secondary erythrocytosis and to analyze the diagnostic value of a low or high serum Epo level.

Results: A large majority of PV patients (87% or 101/116) had a serum Epo level below the normal range in healthy patients (3.3 IU/L), giving this value a specificity of 97% with a 97.8% positive predictive value for the diagnosis of PV. Statistical analysis (ROC curves) defined two thresholds allowing a specific and direct diagnosis of 65.6% (65/99) of untreated PV (Epo < 1.4 IU/L) and 19.7% (13/66) of those with secondary erythrocytosis (Epo > 13.7 IU/L).

Interpretation And Conclusions: Based on these data, we propose that measurement of serum Epo level, a simple, reliable and inexpensive test, should be considered as a first intention diagnostic test for patients with absolute erythrocytosis.
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October 2004

Standardization and comparison of endogenous erythroid colony assays performed with bone marrow or blood progenitors for the diagnosis of polycythemia vera.

Hematol J 2004 ;5(2):161-7

Laboratoire d'Hématologie of the Centre Hospitalier Universitaire (CHU), d'Angers, France.

The reliability of the assay of endogenous erythroid colony (EEC) formation in serum-free, cytokine-free collagen-based media was investigated in a multicentric study including 140 patients with polyglobuly (80 polycythemia vera (PV), 54 secondary erythrocytosis (SE), six idiopathic erythrocytosis (IE)) and 10 healthy donors. In each center, EEC assays were performed in parallel with progenitor cells from bone marrow (BM) and peripheral blood (PB); two commercialized media and 'low' and 'high' cell plating densities were tested. Negativity of EEC assays was considered certain only when sufficient BFU-E growth was obtained in control cultures with cytokines. In the two media, EEC formation was specific - never observed in cultures of healthy donors or SE patients - and comparable. BM EEC assays were positive (presence of eythroid colonies) for 75% ('low' plating) to 100% ('high' plating) of PV patients; PB EEC assays were positive for 83.3% ('low' plating) to 93.7% ('high' plating) of PV patients (differences not significant). Depending on the medium, 86.2-93.7% of patients with a positive BM EEC assay had a positive PB EEC assay. Hence, a standardized collagen-based EEC assay can be performed with either BM or PB progenitors; the EEC assay described here is positive for at least 75% of PV patients when a single EEC assay is performed, and for at least 94% of PV patients when both BM and PB EEC assays are performed.
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http://dx.doi.org/10.1038/sj.thj.6200344DOI Listing
November 2004

Platelet-activating factor and normal or leukaemic haematopoiesis.

Leuk Lymphoma 2003 May;44(5):775-82

UMR CNRS 6101, Faculté de Médecine, 2 rue Dr Marcland, 87025, Limoges, France.

Platelet-activating factor (PAF), a phospholipid mediator with a wide range of actions on mature leukocytes, acts directly during early human haematopoiesis by affecting the growth of haematopoietic progenitors and indirectly, by modulating cytokine synthesis by bone marrow stromal cells. At this time, its role during leukaemic diseases remains speculative. The lack of membrane PAF receptor (PAF-R) on leukaemic blasts suggest that this receptor represents a marker of mature cells and its membrane induction a consequence of cell maturation. While the couple PAF/PAF-R has been largely studied using B cell lines, few results are available using B cells of patients with haematopoietic malignancies casting some doubts concerning the potential role (if any) of this molecule during leukaemic diseases.
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http://dx.doi.org/10.1080/1042819031000067549DOI Listing
May 2003