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Publications (21)83.13 Total impact

  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2009; 24(1):205-9. · 10.16 Impact Factor
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    ABSTRACT: Given the national therapeutic guidelines in France, halofantrine represents the first line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria in children. But several disadvantages exist using halofantrine in paediatrics. The primary objective of this study is to evaluate the tolerance and the efficacy of mefloquine as the first line treatment of uncomplicated P. falciparum malaria in a paediatric emergency department. The secondary objective of the study is to evaluate whether symptomatic measures may improve the gastrointestinal tolerance of mefloquine. This retrospective observational cohort study includes all the patients who have been treated for acute uncomplicated P. falciparum malaria in the paediatric emergency department of the Hospital Trousseau (Paris, France) in 2003. First line treatment was mefloquine in 35 children. Early vomiting occurred in 22 (63%) cases. All children responded to mefloquine therapy except two children who had persistent vomiting early after mefloquine therapy and required intravenous quinine. Those two children had initial vomiting. Light meal and metopimazine prophylaxis did not precede mefloquine intake in those two children. This study suggests that mefloquine treatment of uncomplicated P. falciparum malaria is effective and well tolerated in children. Furthermore, a light meal and metopimazine prophylaxis preceding mefloquine intake may improve its gastrointestinal tolerance.
    Pathologie Biologie 03/2008; 56(1):21-8. · 1.67 Impact Factor
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    ABSTRACT: To determine whether minimal residual disease (MRD) measured by Wilms' tumor gene 1 (WT1) expression is a prognostic marker in pediatric acute myeloid leukemia (AML), we quantified WT1 transcript by real-time quantitative-polymerase chain reaction in 92 AML at diagnosis and during follow-up. Patients (median age, 6 years; cytogenetics, favorable 27%, intermediate 59%, poor 13%) were treated between 1995 and 2002 and enrolled in Leucémie aiguë Myéloblastique Enfant (LAME) 89/91, LAME 99 pilot study and Acute Promyelocytic Leukemia French collaborative protocols. With a median follow-up of 26 months, event-free survival was 56% with a standard deviation (SD) of 5% and overall survival of 62.5% with an SD of 6%. WT1 copy number was normalized by TATA box binding protein gene transcripts and expressed as WT1/TBP x 1,000 ratio. Median WT1 ratio in normal patient controls was 12 (range, 0 to 57). A level over two SD than normal bone marrow controls (ie, WT1 ratio > 50), was considered as significant overexpression. At diagnosis, WT1 overexpression was detected in 78% of patients (72 of 92 patients; median copy ratio, 2231). The WT1 values were significantly higher (P = .01) in favorable cytogenetics and lower (P < .0001) in M5-FAB subtype, 11q23 rearrangements (P < .001), and infants (P = .003) and demonstrate a strong correlation with fusion transcript AML1-ETO, PML-RARalpha expression. After induction treatment, WT1 ratio was analyzed in 46 of 72 patients and found above 50 in nine of 36 patients and five of 25 patients at D35-50 and 3 to 5 months, respectively. WT1 ratio > 50 after induction is an independent prognostic risk factor of relapse (P = .002) and death (P = .02). WT1 quantification is an informative molecular marker for MRD in pediatric AML and is now performed as prospective analysis in ELAM02 protocol.
    Journal of Clinical Oncology 05/2006; 24(10):1507-15. · 18.04 Impact Factor
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    Leukemia 07/2003; 17(6):1193-6. · 10.16 Impact Factor
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    ABSTRACT: The most frequent oncogenic activation events characterized in childhood T acute lymphoblastic leukemia (T-ALL) result in the transcriptional activation of genes coding for transcription factors. The main genes are TAL1/SCL, a member of the basic region helix-loop-helix gene family, and HOX11L2, a member of the homeobox-containing protein family. To gain insight into the pathogenesis of this type of hematologic malignancy, we analyzed 28 T-ALL samples. SIL-TAL1/SCL fusion was detected in 6 patients; expression of HOX11L2 was observed in 6 patients and of HOX11 in 3 patients. With one exception, these activations did not occur simultaneously in the same patients, and they allowed the subclassification of 50% of the patients. SIL-TAL1 fusion was detected in association with HOX11 expression in one patient and with a t(8;14) (q24;q11) in another. High expression of LYL1, LMO2, or TAL1 was observed mainly in samples negative for HOX11L2 expression. HOX11L1 and HOX11 expression were observed in one instance each, in the absence of detectable chromosomal abnormality of their respective loci, on chromosomes 2 and 10, respectively. HOX11L2 expression was associated with a chromosome 5q abnormality, the location of the HOX11L2 locus in each case tested. Finally, our data show that HOX11L2 expression was a suitable marker for minimal residual disease follow-up and was significantly associated with relapse (P =.02).
    Blood 09/2002; 100(3):991-7. · 9.78 Impact Factor
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    ABSTRACT: Eighty children were treated at the hospital Armand-Trousseau (Paris, France) for a malaria attack from 1999-01-01 to 2000-02-01. The parasites were: Plasmodium falciparum: 87.5%, Plasmodium malariae: 12.6%, Plasmodium ovale: 10%, Plasmodium vivax: 6.3%. Mean age was 8.1 years (range: three months to 15 y). The origin of patients was: West Africa for 60 children, Central Africa for ten children and Comores for seven. Sixty-six patients suffered from common malaria attack and seven children were admitted with a presentation of severe malaria. The severe attacks were cerebral malaria for six cases, associated with severe anemia in five cases; the 7th child had a respiratory distress (ARDS) and died. The other six cases were cured without sequelae. Relapses were observed for eight patients: one after a severe cerebral malaria, six after a common P. falciparum attack, one after a P. ovale attack. Parasitemia was higher than in preceding years (mean 2.9%) and more than 5% in 11 cases, but without clear link with severity. Treatment by halofantrine with a single cure was followed by five relapses. None of those children received an effective prophylaxis during and after travel (55/80 without any prophylaxis). These data emphasize the importance of a good appraisal of criteria of severe malaria and lead to advice hospitalization of children with malaria in temperate zone.
    Archives de Pédiatrie 05/2002; 9(4):371-6. · 0.36 Impact Factor
  • Archives de Pédiatrie 03/2002; 9(4):371-376. · 0.36 Impact Factor
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    ABSTRACT: Methods. – Eighty children were treated at the hospital Armand-Trousseau (Paris, France) for a malaria attack from 1999-01-01 to 2000-02-01.Results. – The parasites were: Plasmodium falciparum: 87.5%, Plasmodium malariae: 12.6%, Plasmodium ovale: 10%, Plasmodium vivax: 6.3%. Mean age was 8.1 years (range: three months to 15 y). The origin of patients was: West Africa for 60 children, Central Africa for ten children and Comores for seven. Sixty-six patients suffered from common malaria attack and seven children were admitted with a presentation of severe malaria. The severe attacks were cerebral malaria for six cases, associated with severe anemia in five cases; the 7th child had a respiratory distress (ARDS) and died. The other six cases were cured without sequelae. Relapses were observed for eight patients: one after a severe cerebral malaria, six after a common P. falciparum attack, one after a P. ovale attack. Parasitemia was higher than in preceeding years (mean 2.9%) and more than 5% in 11 cases, but without clear link with severity. Treatment by halofantrine with a single cure was followed by five relapses. None of those children received an effective prophylaxis during and after travel (55/80 without any prophylaxis).Conclusion. – These data emphasize the importance of a good appraisal of criteria of severe malaria and lead to advice hospitalization of children with malaria in temperate zone.
    Archives de Pédiatrie. 01/2002; 9(4):371-376.
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    ABSTRACT: The gray platelet syndrome (GPS) is a rare congenital bleeding disorder in which thrombocytopenia is associated with increased platelet size and decreased alpha-granule content. This report describes 3 new pediatric cases presenting with the classical platelet abnormalities of GPS within one family with normal parents. Examination of blood smears of the 3 patients demonstrated not only gray platelets, but also gray polymorphonuclear neutrophils (PMNs) with decreased or abnormally distributed components of secretory compartments (alkaline phosphatase, CD35, CD11b/CD18). Secondary granules were also decreased in number as assayed by immunoelectron microscopy. These data confirm that the secretory compartments in neutrophils were also deficient in this family. Megakaryocytes (MKs) were cultured from the peripheral blood CD34+ cells of the 3 patients for 14 days, in the presence of thrombopoietin and processed for immunoelectron microscopy. Although von Willebrand factor (vWF) was virtually undetectable in platelets, vWF immunolabeling was conspicuous in cultured maturing MKs, particularly within Golgi saccules, but instead of being packaged in alpha-granules, it was released into the demarcation membrane system. In contrast, P-selectin followed a more classical pathway. Double-labeling experiments confirmed that vWF was following an intracellular pathway distinct from the one of P-selectin. In these 3 new cases of GPS, the MKs appeared to abnormally process vWF, with secretion into the extracellular space instead of normal alpha-granule packaging. Furthermore, the secretory compartment of another blood cell line, the neutrophil, was also affected in this family of GPS.
    Blood 10/2001; 98(5):1382-91. · 9.78 Impact Factor
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    ABSTRACT: Prospective clinical studies including large numbers of patients have led to the conclusion that co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia (My+ ALL) does not have prognostic significance. However, reports of the frequency of My+ ALL in children vary widely across laboratories using different mAb clones and staining and analysing procedures. Taking two commonly accepted thresholds of positivity for myeloid antigens (20 and 30%), we analysed the immunoreactivity of the most widely employed mAb clones against CD13 (SJ1D1, L138 and My7) and CD33 (My9, P67.6 and D3HL60) and compared the proportions of My+ ALL detected by these clones in childhood ALL. The correlation between myeloid antigen expression and the presence of the t(12;21) translocation was analysed concomitantly in the same samples. The percentage of ALL cases positive for myeloid markers varied significantly depending on the mAb clone and the positive threshold. Among patients with B-ALL, the proportion of CD13+ ALL was significantly lower using SJ1D1 than using L138 or My7, while the proportion of CD33+ ALL was significantly higher for My9 than for P67.6 or D3HL60. Analysis of the co-expression of CD13 and CD33 on B-ALL cells using combinations of mAb clones showed that this frequency was either underestimated by the SJ1D1/D3HL60 or overestimated by the L138/P67.6 and My7/My9 combinations. A correlation between CD13/CD33 positivity and the t(12;21) translocation was uniformly observed in B-ALL patients for a positive threshold of 30%, whereas SJ1D1/D3HL60 detected no correlation between t(12;21) and CD13/CD33 positivity when the threshold was lowered to 20%. These data show that the mAb clones commonly used to detect the CD13 and CD33 surface antigens have variable immunoreactivity against childhood ALL cells, which may partly explain the conflicting reports concerning the prognostic significance of myeloid antigen expression in paediatric ALL and its association with different translocations. The present findings may also be of clinical importance for therapeutic choices.
    Leukemia and Lymphoma 07/2001; 42(1-2):75-82. · 2.61 Impact Factor
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    Leukemia 09/2000; 14(8):1526-8. · 10.16 Impact Factor
  • Pediatric Research 01/1997; 41(5). · 2.67 Impact Factor
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    ABSTRACT: We have developed a simplified fluorescent run-off (FluRO) based IgH PCR strategy in order to facilitate follow-up of large numbers of B-cell precursor (BCP) acute lymphoblastic leukaemias (ALL) in a routine molecular diagnostic laboratory. DNA samples from 26 BCP-ALL and one B-cell line were amplified using IgH FR1 and FR2 consensus primers and analysed in parallel either by ethidium bromide non-denaturing PAGE or, after rendering the PCR products fluorescent with an internal JH consensus primer, by high-resolution analysis on an automated fragment analyser. The latter led to a minimum of one log increase in sensitivity of detection in 62% of alleles from 19 samples (16/28 in FR1; 11/15 in FR2) tested in parallel on log DNA dilutions, and to at least a 10(-2) level of sensitivity of detection in 15/19. The improved resolution allowed an approximate 20% increase in the number of clonal alleles detected, and consequently doubled the incidence of oligoclonality (6/26; 23%). Using these strategies, 6/17 (35%) of children analysed prospectively showed residual IgH positivity in the post induction complete remission bone marrow sample. Both early deaths occurred within this subgroup of patients and of the three of four surviving patients tested, two remained positive 2-3 months later. Although this simplified strategy is, as expected, less sensitive than anti-V-D-J junction specific strategies, it enables detection of a category of 'slow-remitters' which may have prognostic significance at a stage where therapeutic decisions are taken.
    British Journal of Haematology 12/1996; 95(2):281-90. · 4.94 Impact Factor
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    ABSTRACT: Primary myelofibrosis is rare in infants and children; its association with auto-immune markers has only been reported in adults. An 8 month-old girl was admitted because of severe anemia and neutropenia. The marrow aspirate showed dysgranulopoiesis and partial interruption of maturation after the myelocyte level. The bone marrow biopsy revealed reticulinic myelofibrosis. The condition worsened with development of agranulocytosis and thrombocytopenia. Investigations ruled out malignant hemopathy, metastatic infiltration of the marrow and osteopathy. A myelodysplastic syndrome was discussed, but presence of anti-granulocyte auto-antibodies and positive Coombs test led to consider an autoimmune etiology. A corticosteroid therapy was attempted, effective only on the platelet lineage. Addition of intravenous gammaglobulin therapy corrected the problem. After a 24 month-course of the disease, it was necessary to prolong therapy. The efficacy of gammaglobulins may be an additional argument for auto-immunity, although no other auto-immune pattern has been observed in our patient, contrary to reported cases in adults.
    Archives de Pédiatrie 02/1996; 3(1):40-3. · 0.36 Impact Factor
  • Archives de Pédiatrie 01/1996; 3. · 0.36 Impact Factor
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    ABSTRACT: Myelofibrosis of the infant regressive with corticosteroid and intravenous immunoglobulin therapy.Background. —Primary myelofibrosis is rare in infants and children; its association with auto-immune markers has only been reported in adults.Case report. —An 8 month-old girl was admitted because of severe anemia and neutropenia. The marrow aspirate showed dysgranulopoiesis and partial interruption of maturation after the myelocyte level. The bone marrow biopsy revealed reticulinic myelofibrosis. The condition worsened with development of agranulocytosis and thrombocytopenia. Investigations ruled out malignant hemopathy, metastatic infiltration of the marrow and osteopathy. A myelodysplastic syndrome was discussed, but presence of anti-granulocyte auto-antibodies and positive Coombs test led to consider an autoimmune etiology. A corticosteroid therapy was attempted, effective only on the platelet lineage. Addition of intravenous gammaglobulin therapy corrected the problem. After a 24 month-course of the disease, it was necessary to prolong therapy.Conclusion. —The efficacy of gammaglobulins may be an additional argument for auto-immunity, although no other auto-immune pattern has been observed in our patient, contrary to reported cases in adults.
    Archives de Pédiatrie 01/1996; 3(1):40-43. · 0.36 Impact Factor
  • Archives de Pédiatrie 01/1996; 3. · 0.36 Impact Factor
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    ABSTRACT: The hemophagocytic syndrome has previously been reported in different infectious diseases (EBV, CMV, tuberculosis...) but rarely in adults with AIDS and never in children suffering from AIDS. A hemophagocytic syndrome was recognized during the follow-up of 3 children with AIDS. The first, a 9-year-old girl developed an acute EBV coinfection and was treated with shots of corticosteroids and vepesid but died shortly afterwards. The second patient, a 3-year-old girl was infected with Aspergillus fumigatus for which she was given amphotericin B with a rapid improvement. The third patient, an 8-year-old boy had multi-resistant Streptococcus pneumoniae otitis and pneumonitis; his condition improved rapidly with adapted antibiotherapy. The HIV-hemophagocytic syndrome is not exceptional in HIV infection because of the association of immunodeficiency and resulting superinfections. Its diagnosis and treatment should be etiologic. Severe cases without etiology could benefit from chemotherapy. Management and outcome of this potentially lethal syndrome might depend on the identification of a curable infectious cause.
    Archives de Pédiatrie 06/1995; 2(5):442-6. · 0.36 Impact Factor
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    ABSTRACT: Background. — The hemophagocytic syndrome has previously been reported in different infectious diseases (EBV, CMV, tuberculosis…) but rarely in adults with AIDS and never in children suffering from AIDS.Case reports. — A hemophagocytic syndrome was recognized during the follow-up of 3 children with AIDS. The first, a 9-year-old girl developed an acute EBV coinfection and was treated with shots of corticosteroids and vepesid but died shortly afterwards. The second patient, a 3-year-old girl was infected with Aspergillus fumigatus for which she was given amphotericin B with a rapid improvement. The third patient, an 8-year-old boy had multi-resistant Streptococcus pneumoniae olitis and pneumonitis; his condition improved rapidly with adapted antibiotherapy.Discussion. — The HIV-hemophagocytic syndrome is not exceptional in HIV infection because of the association of immunodeficiency and resulting superinfections. Its diagnosis and treatment should be etiologic. Severe cases without etiology could benefit from chemotherapy.Conclusion. — Management and outcome of this potentially lethal syndrome might depend on the identification of a curable infectious cause.
    Archives de Pédiatrie 01/1995; 2(5):442-446. · 0.36 Impact Factor
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    ABSTRACT: We report a novel case of hereditary thrombocytopenia. A chronic thrombocytopenia was noted in a woman with mild hemorrhagic complications as well as in her very young son. A platelet fraction contained giant granules stained in red on blood smears. The number of bone marrow megakaryocytes was increased with many micromegakaryocytes. Since the platelet life span was normal, these results indicated an ineffective platelet production. A constitutional cytogenetic abnormality was detected in the two patients: a deletion of the long arm of chromosome 11. The association of these abnormalities constitute a new disorder: this never described cytological entity is a valuable model for exploring the role of some genes involved in the regulation of thrombopoiesis.
    Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 08/1993; 316(7):698-701.