E Duchayne

Centre Hospitalier Universitaire de Toulouse, Toulouse, Midi-Pyrenees, France

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Publications (56)211.55 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We assessed in a French regional healthcare network the distribution of treatments, prognostic factors and outcome of 334 newly diagnosed acute myeloid leukemia patients aged 60 years or older over a 4-year period of time (2007-2010). Patients were selected in daily practice for intensive chemotherapy (n=115), azacitidine (n=95) or best supportive care (n=124). In these three groups, median overall survival was 18.9, 11.3 and 1.8 months, respectively. In the azacitidine group, multivariate analysis showed that overall survival was negatively impacted by higher age (p=0.010 for one unit increase), unfavorable cytogenetics (p=0.001), lymphocyte count < 0.5 G/L (p=0.015) and higher lactate dehydrogenase level (p=0.005 for one unit increase). We compared the survival of patients treated by azacitidine versus intensive chemotherapy and best supportive care using time-dependent analysis and propensity score matching. Patients treated by intensive chemotherapy had a better overall survival compared to those treated by azacitidine from 6 months after diagnosis, whereas patients treated by azacitidine had a better overall survival compared to those treated by best supportive care from 1 day after diagnosis. This study of “real life” practice shows that there is a room for low intensive therapies such as azacitidine in selected elderly acute myeloid leukemia patients.
    American Journal of Hematology 09/2014; · 4.00 Impact Factor
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    ABSTRACT: Hemophagocytic lymphohistiocytosis is an immune dysregulation characterized by severe organ damages induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Acute myeloid leukemia patients may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infections. In a series of 343 patients treated by intensive chemotherapy over a 5-year period in our centre, we identified 32 patients (9.3%) with fevers, very high ferritin levels, and marrow hemophagocytosis (hemophagocytic lymphohistiocytosis patients). Patients with hemophagocytic lymphohistiocytosis exhibited hepatomegaly, pulmonary or neurological symptoms, liver abnormalities, lower platelet count and higher levels of C-reactive protein as well as prolonged pancytopenia as compared to patients without hemophagocytic lymphohistiocytosis. A microbial etiology was documented in 24 patients: 14 bacterial infections, 9 Herpesviridae infections and 11 fungal infections. Hemophagocytic lymphohistiocytosis treatment consisted of corticosteroids and/or intravenous immunoglobulin along with adapted antimicrobial therapy. Patients with hemophagocytic lymphohistiocytosis had a median overall survival of 14.9 months, significantly lower than patients without hemophagocytic lymphohistiocytosis (22.1 months) (p=0.0016). Hemophagocytic lymphohistiocytosis was significantly associated with a higher rate of induction failures mainly due to deaths in aplasia. Hemophagocytic lymphohistiocytosis can be diagnosed in up to 10% of acute myeloid leukemia patients undergoing intensive chemotherapy and is associated with early mortality. Fever, very high ferritin levels and marrow hemophagocytosis represent the cornerstone of diagnosis. Further biological studies are needed to better characterize and recognize this syndrome in acute myeloid leukemia patients.
    Haematologica 10/2013; · 5.94 Impact Factor
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    ABSTRACT: In acute myeloid leukemia (AML), new strategies assess the potential benefit of genetically targeted therapy at diagnosis. This implies waiting for laboratory tests and therefore a delay in initiation of chemotherapy. We studied the impact of time from diagnosis to treatment (TDT) on overall survival, early death and response rate in a retrospective series of 599 newly diagnosed AML patients treated by induction chemotherapy between the years 2000 and 2009. The effect of TDT was assessed using multivariate analysis. TDT was analyzed as a continuous variable using a specific polynomial function to model the shape and form of the relationship. The median TDT was 8 days (IQR, 4-16) and was significantly longer in patients with white blood cell count (WBC) less than 50 G/L (p<0.0001) and in older patients (p=0.0004). In multivariate analysis, TDT had no impact on overall survival (p=0.4095) as compared to age older than 60, secondary AML, WBC higher than 50 G/L, European LeukemiaNet risk groups and ECOG performance status. Furthermore, TDT was not associated with response rate and early death. Thus, waiting a short period of time for laboratory tests to characterize leukemias better and design adapted therapeutic strategies at diagnosis seems possible.
    Blood 01/2013; · 9.78 Impact Factor
  • Leukemia Research - LEUK RES. 01/2007; 31.
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    ABSTRACT: Several tyrosine kinase genes are involved in chromosomal translocations in chronic myeloproliferative disorders, but there are still uncharacterized translocations in some cases. We report two such cases corresponding to atypical chronic myeloid leukaemia with a t(8;9)(p22;p24) translocation. By fluorescence in situ hybridisation (FISH) on the corresponding metaphases with a bacterial artificial chromosome probe encompassing the janus kinase 2 (JAK2) gene at 9p24, we observed a split for both patients, suggesting that this gene was rearranged. The locus at 8p22 contains different candidate genes including the pericentriolar material 1 gene (PCM1), already implicated in reciprocal translocations. The rearrangement of the PCM1 gene was demonstrated by FISH, for both patients. By RT-PCR, we confirmed the fusion of 3' part of JAK2 with the 5' part of PCM1. Sequence analysis of the chimeric PCM1-JAK2 mRNA suggests that the putative protein displays the coiled-coil domains of PCM1 and the tyrosine kinase domain of JAK2. This new translocation identifies JAK2 as a possible therapeutic target for compounds with anti-tyrosine kinase activity.
    Oncogene 12/2005; 24(48):7248-52. · 8.56 Impact Factor
  • Leukemia Research - LEUK RES. 01/2005; 29.
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    ABSTRACT: We report two infants with acute basophilic leukaemia associated with a t(X;6)(p11;q23) as the sole abnormality. Morphologic evidence of basophilic lineage was provided by light and electron microscopy. Both patients also had a similar presentation on diagnosis, characterized by clinical signs consistent with a hyperhistaminaemia syndrome, i.e. urticarian rashes and gastro-intestinal disorders evocative of peptic ulcer. Immunophenotypes differed in the two patients, one expressing CD24, CD13 and CD33, whereas only CD117 was found in the other.Basophilic acute leukaemia, a rare group among acute leukaemias, might be nonrandomly associated with a specific chromosomal abnormality, t(X;6)(p11;q23). This new entity might also be identifiable by an uncommon clinical presentation and occurrence in infancy.
    British Journal of Haematology 10/2003; 98(1):170 - 176. · 4.94 Impact Factor
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    ABSTRACT: The diagnosis of splenic lymphoma with villous lymphocytes (SLVL) was assessed by a panel of cytologists in a series of 100 patients. Clinical and biological characteristics were analysed in relation to prognosis.SLVL is a chronic B-cell lymphoproliferative disorder characterized by splenomegaly and the presence, in peripheral blood, of lymphocytes with ‘villous’ projections. The cytological diagnosis can be difficult in patients without an absolute lymphocytosis which was observed in 24% of cases. B-cells expressed CD19+, CD20+, CD22+, CD24+ and DBA44+, whereas the expression of CD5, CD10 and CD25 was usually negative.SLVL is a disease of the elderly with a relatively benign clinical course. In the present series the 5-year overall survival was 78%. Deaths in 15 patients were related to disease progression or treatment (nine cases). Patients with a leucocyte count >30 × 109/l or lymphocyte count <4 × 109/l or initially treated with chemotherapy had significantly (P < 0.001) lower overall survival than other patients. From these findings, treatment abstention should be considered in patients with favourable prognostic factors; on the other hand, the efficacy of conventional chemotherapy remains to be evaluated in patients with unfavourable prognostic factors.
    British Journal of Haematology 10/2003; 93(3):731 - 736. · 4.94 Impact Factor
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    ABSTRACT: Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.
    Human Pathlogy 09/2003; 34(8):789-91. · 2.84 Impact Factor
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    ABSTRACT: Mutations of the AML1 gene are frequent molecular abnormalities in minimally differentiated acute myeloblastic leukemia (M0 AML), a rare type of AML. In this retrospective multicenter study, morphologic, immunophenotypical, cytogenetic, and molecular features of 59 de novo M0 AML cases were analyzed and correlated to AML1 mutations. Point mutations of AML1 gene were observed in 16 cases (27%). They were correlated with higher white blood cell (WBC) count (P =.001), greater marrow blast involvement (P =.03), higher incidence of immunoglobulin H/T-cell receptor (IgH/TCR) gene rearrangement (P <.0001), and with a borderline significant lower incidence of complex karyotypes. In the 59 patients, FLT3 mutations were the only significant prognostic factors associated with short survival.
    Blood 02/2003; 101(4):1277-83. · 9.78 Impact Factor
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    ABSTRACT: Since the WHO classification of haematological malignancies recommended the description of global entities, we performed a national M7-AML study to correlate morphological, immunological and cytogenetic features, and to find new clinically relevant M7 entities. This study is based on accurate morphological and immunological study to select pure megakaryoblastic proliferations and to eliminate megakaryocytic participation in haemopathies. We collected 53 cases: 23 adults and 30 children. We confirm the wide heterogeneity of adult M7. In adults, the cytogenetic abnormalities are frequently those of secondary leukaemia while a few patients have a previous history and morphological features of dyshaematopoiesis; their outcome is very poor. Among children, besides the well-known Down syndrome M7, we in particular, studied ten t(1;22) M7 and one OTT-MAL transcript positive case with normal karyotype presenting specific features. We were already aware of their younger age, female and tumoral presentation, but we also found a lower percentage of bone marrow blasts, sometimes without any megakaryoblastic bone marrow involvement, but always, with a dysmegakaryocytopoiesis associated with micromegakaryocytes. They are generally good responders to intensive AML chemotherapy with very long disease-free survivals (DFS). Accordingly, OTT-MAL transcript study, in infant M7 with normal karyotype, is recommended and we feel that this entity should be added to the WHO AML classification.
    Leukemia and Lymphoma 02/2003; 44(1):49-58. · 2.61 Impact Factor
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    ABSTRACT: We report a retrospective immunohistochemical study on bone marrow biopsies of 43 patients with different types of lymphomas showing unusual intrasinusoidal infiltration. Most of these patients presented with splenomegaly (74.4%) and peripheral lymphocytosis (83%). In 20/43 patients, lymphoid infiltrates were not detectable on haematoxylin-eosin sections. After immunohistochemistry on bone marrow biopsies and blood and bone marrow smear examinations, the following diagnoses were made: splenic marginal zone lymphoma with villous lymphocytes (SLVL) in 24 patients, large granular lymphocyte (LGL) leukaemia in 14 patients, hepatosplenic T-cell lymphoma in two patients, anaplastic large cell lymphoma in two patients and intravascular large B-cell lymphoma in one patient. In the presence of intrasinusoidal infiltrates of small lymphocytes, a B-cell phenotype (CD20+, CD76/DBA44+/-) was associated with splenic marginal zone lymphoma whereas intrasinusoidal CD3/CD45RA-positive T-cell infiltrates were strongly suggestive of LGL leukaemia. Intrasinusoidal bone marrow infiltration appears to be a common feature of distinct lymphoma subtypes. Immunohistochemical analysis is essential to detect intrasinusoidal medullary infiltrates (which may be minimal) and should be systematically performed in patients with splenomegaly and peripheral lymphocytosis.
    British Journal of Haematology 01/2003; 119(4):916-22. · 4.94 Impact Factor
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    ABSTRACT: To draw the cytogenetic profile of childhood and adult acute megakaryoblastic leukemia (M7), the Groupe Français de Cytogénétique Hématologique collected 53 cases of M7 (30 children and 23 adults). Compared to other acute myeloid leukemias, M7 is characterized by a higher incidence of abnormalities, a higher complexity of karyotypes, and a different distribution of abnormalities among children and adults. Nine cytogenetic groups were identified: normal karyotypes (group 1), patients with Down syndrome (group 2), numerical abnormalities only (group 3), t(1;22)(p13;q13) or OTT-MAL transcript (group 4), t(9;22)(q34;q11) (group 5), 3q21q26 (group 6), -5/del(5q) or -7/del(7q) or both (group 7), i(12)(p10) (group 8), and other structural changes (group 9). Groups 1, 2, 3, and 4 were exclusively composed of children (except one adult in group 3), whereas groups 5, 6, 7, and 8 were mainly made up of adults. The main clinical and hematologic features of these groups were described. No new recurrent abnormality was identified, but mapping of all breakpoints allowed us to specify several possible hot spots of rearrangement: 17q22-23, 11q14-21, 21q21-22, and 16q21-22-23. Although 90.5% of cases had no documented antecedent hematologic disorder or exposure to chemotherapy or radiotherapy, the morphologic and the cytogenetic findings indicated that M7 might be a secondary leukemia more often than suggested by preceding history, particularly among adults. The concurrent analyses of morphologic and cytogenetic data also led us to assume that the initial precursor involved might be more immature in adult than in childhood M7.
    Blood 08/2002; 100(2):618-26. · 9.78 Impact Factor
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    ABSTRACT: CD4(+)CD56(+) malignancies are rare hematologic neoplasms, which were recently shown to correspond to the so-called type 2 dendritic cell (DC2) or plasmacytoid dendritic cells. This study presents the biologic and clinical features of a series of 23 such cases, selected on the minimal immunophenotypic criteria defining the DC2 leukemic counterpart, that is, coexpression of CD4 and CD56 in the absence of B, T, and myeloid lineage markers. Clinical presentation typically corresponded to cutaneous nodules associated with lymphadenopathy or spleen enlargement or both. Cytopenia was frequent. Circulating malignant cells were often detected. Massive bone marrow infiltration was seen in 20 of 23 (87%) patients. Most tumor cells exhibited nuclei with a lacy chromatin, a blastic aspect, large cytoplasm-containing vacuoles or microvacuoles beside the plasma membrane, and cytoplasmic expansions resembling pseudopodia. Other immunophenotypic characteristics included both negative (CD16, CD57, CD116, and CD117) and positive (CD36, CD38, CD45 at low levels, CD45RA, CD68, CD123, and HLA DR) markers. The prognosis was rapidly fatal in the absence of chemotherapy. Complete remission was obtained in 18 of 23 (78%) patients after polychemotherapy. Most patients had a relapse in less than 2 years, mainly in the bone marrow, skin, or central nervous system. Considering these clinical and biologic features, the conclusion is made that CD4(+)CD56(+) malignancies constitute a genuine homogeneous entity. Furthermore, some therapeutic options were clearly identified. Finally, relationships between the pure cutaneous indolent form of the disease and acute leukemia as well as with the lymphoid/myeloid origin of the CD4(+)CD56(+) malignant cell are discussed.
    Blood 04/2002; 99(5):1556-63. · 9.78 Impact Factor
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    ABSTRACT: This retrospective study reports 15 cases of hemophagocytic syndrome in children treated in our department during a eight-year period. Underlying diseases were acute lymphoblastic leukemia (n = 8) acute myeloblastic leukemia (n = 6) and Burkitt lymphoma (n = 1). Hemophagocytic syndrome was suspected after chemotherapy, in case of an unusual prolonged febrile neutropenia (n = 14) or isolated thrombocytopenia (n = 1). That fever was associated with cutaneous, pulmonary, hematologic, digestive and cardiac signs. Biological disorders included hypoprotidemia, hyponatremia, increased liver enzymes and fibrinopenia. Thrombocytopenia was observed in all patients and was associated with neutropenia for 14 of them. Diagnosis of hemophagocytic syndrome was always confirmed by bone marrow aspiration (infiltration with activated macrophages). Infection was documented in eight children. The treatment of hemophagocytic syndrome relied on steroids and resolution of symptoms occurred within three days of therapy. No recurrence of hemophagocytic syndrome was observed with a median follow up of two years and a half. Such complication should be suspected in cases of prolonged febrile neutropenia and/or thrombocytopenia, and confirmed by bone marrow aspiration. Indeed, steroid therapy is effective and chemotherapy can be then pursued.
    Archives de Pédiatrie 03/2002; 9(2):125-9. · 0.36 Impact Factor
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    ABSTRACT: T-prolymphocytic leukaemia (T-PLL) is a rare disorder with a poor outcome. Presentation features were studied in 78 T-PLL cases. Although 53 patients (group A) presented with typical progressive disease including rapidly increasing leucocytosis, 25 patients (group B) experienced an initial indolent clinical course with stable moderate leucocytosis. The morphology and antigenic profile of abnormal cells were similar in both groups, except for a lower incidence of CD45RO+ CD45RA− pattern in group B. A high incidence of inv(14)(q11;q32), t(14;14)(q11;q32) and i(8)(q10) chromosomal abnormalities were found in both groups. After an initial indolent phase (median 33 months; 6–103 months), 16 group B patients progressed to an aggressive stage with clinical and laboratory features similar to group A. Moreover, median survival after progression was short in both groups. In conclusion, T-PLL may start as an indolent disease similar to that reported in ataxia telangectasia. In this rare genetic disorder, some patients develop stable T-cell clones which progress toward T-PLL-like leukaemia. Moreover, ATM gene mutations have been reported in T-PLL. Thus, both diseases are likely to be closely related.
    British Journal of Haematology 01/2002; 103(2):488 - 494. · 4.94 Impact Factor
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    ABSTRACT: The authors report the case of a ten-year-old girl, who had been treated for a malignant germinal tumour five years before, presenting with a leukaemia-like syndrome associating bone pain, liver and spleen nodules and bone marrow involvement. The cyto-pathological analysis showed undifferentiated cells and CD56 and protein S100 were found as the only positive markers. The child received several subsequent lines of chemotherapy and ultimately died of the disease. Particular cytogenetic abnormalities were observed (iso1q10, iso6p10) and were in favor of an unusual NK cell lymphoma. This analysis revealed a XY genotype (testicular feminization syndrome).
    Archives de Pédiatrie 01/2002; 8(12):1337-40. · 0.36 Impact Factor
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    ABSTRACT: Material and methods. – This retrospective study reports 15 cases of hemophagocytic syndrome in children treated in our department during a eight-year period.Results. – Underlying diseases were acute lymphoblastic leukemia (n=8) acute myeloblastic leukemia (n=6) and Burkitt lymphoma (n=1). Hemophagocytic syndrome was suspected after chemotherapy, in case of an unusual prolonged febrile neutropenia (n=14) or isolated thrombocytopenia (n=1). That fever was associated with cutaneous, pulmonary, hematologic, digestive and cardiac signs. Biological disorders included hypoprotidemia, hyponatremia, increased liver enzymes and fibrinopenia. Thrombocytopenia was observed in all patients and was associated with neutropenia for 14 of them. Diagnosis of hemophagocytic syndrome was always confirmed by bone marrow aspiration (infiltration with activated macrophages). Infection was documented in eight children. The treatment of hemophagocytic syndrome relied on steroids and resolution of symptoms occurred within three days of therapy. No recurrence of hemophagocytic syndrome was observed with a median follow up of two years and a half.Conclusion. – Such complication should be suspected in cases of prolonged febrile neutropenia and/or thrombocytopenia, and confirmed by bone marrow aspiration. Indeed, steroid therapy is effective and chemotherapy can be then pursued.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2002; 9(2):125-129.
  • Leukemia Research 12/2001; 25(11):1023-4. · 2.76 Impact Factor
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    ABSTRACT: Case report. – The authors report the case of a ten-year-old girl, who had been treated for a malignant germinal tumour five years before, presenting with a leukaemia-like syndrome associating bone pain, liver and spleen nodules and bone marrow involvement. The cyto-pathological analysis showed undifferenciated cells and CD56 and protein S100 were found as the only positive markers. The child received several subsequent lines of chemotherapy and ultimately died of the disease.Comments. – Particular cytogenetic abnormalities were observed (iso1q10, iso6p10) and were in favor of an unusual NK cell lymphoma.Conclusion. – This analysis revealed a XY genotype (testicular feminization syndrome).
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2001; 8(12):1337-1340.

Publication Stats

866 Citations
211.55 Total Impact Points

Institutions

  • 1994–2013
    • Centre Hospitalier Universitaire de Toulouse
      • • Service d'Hématologie
      • • Laboratoire d’Hématologie
      Toulouse, Midi-Pyrenees, France
  • 2003
    • Centre Hospitalier Universitaire de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2002
    • Muséum de Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2000
    • Institut Paoli Calmettes
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 1998
    • Centre Hospitalier Universitaire de Nantes
      • Laboratoire d'hématologie
      Naoned, Pays de la Loire, France
  • 1991–1996
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1995
    • Institut Claudius Regaud
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 1992
    • CHU de Lyon - Institut d'hématologie et d'oncologie pédiatrique
      Lyons, Rhône-Alpes, France