An Investigation of the Steady-State Pharmacokinetics of Oral Valacyclovir in Immunocompromised Children

Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (±SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11±1.41 and 5.19±1.96 μg/mL, respectively. Corresponding single dose area-under-curve values were 12.14±6.60 and 14.49±4.69h×μg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discusse

Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study

<p>Abstract</p> <p>Background</p> <p>We explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors.</p> <p>Methods</p> <p>Between 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLA-matched sibling.</p> <p>Results</p> <p>Complete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 bone marrow (M1). Overall five-year disease-free survival (DFS) was 42 ± 9.7%. Based on multivariate analysis, two groups showed marked differences in five-year outcome: children with age<10, leukocyte count <100,000/mm³and day-21 M1 marrow had a more favorable prognosis (14 pts: 100% CR, event free survival [EFS]: 57%, overall survival [OS]: 79%), than the high-risk group (22 patients: 55% CR, EFS: 18%, OS: 27%) (p < 0.005). We also observed a non statistically significant difference (p = 0.14) in outcome between these groups for transplanted patients (5-year DFS: 83 ± 14% and 33 ± 15%, respectively).</p> <p>Conclusion</p> <p>Age, leukocyte count and early response to treatment defined by the D21 bone marrow response provide an accurate model for outcome prediction. The combination of available tools such as minimal residual disease assessment with determination of these simple factors could be useful for refining indications for BMT in the current era of tyrosine-kinase inhibitor-based therapy.</p

Household Exposure to Pesticides and Risk of Childhood Hematopoietic Malignancies: The ESCALE Study (SFCE)

International audienceOBJECTIVES: We investigated the role of household exposure to pesticides in the etiology of childhood hematopoietic malignancies. METHODS: The national registry-based case-control study ESCALE (Etude sur les cancers de l'enfant) was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and sex. Maternal household use of pesticides during pregnancy and paternal use during pregnancy or childhood were reported by the mothers in a structured telephone questionnaire. Insecticides (used at home, on pets, or for garden crops), herbicides, and fungicides were distinguished. We estimated odds ratios (ORs) using unconditional regression models closely adjusting for age, sex, degree of urbanization, and type of housing (flat or house). RESULTS: We included a total of 764 cases of acute leukemia (AL), 130 of Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls. Insecticide use during pregnancy was significantly associated with childhood AL [OR = 2.1; 95% confidence interval (CI), 1.7-2.5], both lymphoblastic and myeloblastic, NHL (OR = 1.8; 95% CI, 1.3-2.6), mainly for Burkitt lymphoma (OR = 2.7; 95% CI, 1.6-4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4-11.8), but not nodular sclerosis HL (OR = 1.1; 95% CI, 0.6-1.9). Paternal household use of pesticides was also related to AL (OR = 1.5; 95% CI, 1.2-1.8) and NHL (OR = 1.7; 95% CI, 1.2-2.6); but for AL the relationships did not remain after adjustment for maternal pesticide use during pregnancy. CONCLUSION: The study findings strengthen the hypothesis that domestic use of pesticides may play a role in the etiology of childhood hematopoietic malignancies. The consistency of the findings with those of previous studies on AL raises the question of the advisability of preventing pesticide use by pregnant women

Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg(®)) in children with relapsed/refractory myeloid leukemia

BACKGROUND: Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2(nd )relapse after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases. METHODS: GO was administered alone, at a unit dose of 3–9 mg/m(2), once (3 patients), twice (3 patients), three (5 patients) or five times (1 patient). Mean follow-up was 128 days (8–585 d). RESULTS: There were three complete responses (25%) leading to further curative treatment (SCT). Treatment failed in the other nine patients, and only one patient was alive at the end of follow-up. NCI-CTC grade III/IV adverse events comprised hematological toxicity (n = 12), hypertransaminasemia (n = 2), allergy and hyperbilirubinemia (1 case each). There was only one major adverse event (grade IV allergy). No case of sinusoidal obstruction syndrome occurred. CONCLUSION: These results warrant a prospective trial of GO in a larger population of children with AML

Analyse rétrospective monocentrique des facteurs d'hémostase au cours du traitement des leucémies aigües lymphoblastiques chez l'enfant selon le protocole FRALLE 2000 A

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Thrombopénie constitutionnelle par mutation du gène de l ankyrine 26

Les thrombopénies constitutionnelles constituent un vaste groupe de pathologies, qui ont bénéficié ces dernières années des avancées de la biologie moléculaires et de la génétique, permettant de mieux décrire et de mieux comprendre les entités qui la composent. Cependant presque 50% des thrombopénies constitutionnelles restent non rattachées à un gène causal. Récemment l équipe italienne de Noris et al a mis en évidence un groupe de 12 mutations du gène de l Ankyrine 26 chez 78 patients thrombopéniques chroniques issus de 21 familles. La connaissance de cette nouvelle anomalie génétique est une avancée importante car elle va permettre d établir un diagnostic moléculaire pour des thrombopénies constitutionnelles encore non étiquetées et d avoir une meilleure connaissance tant du potentiel hémorragique de cette pathologique, que de son évolution vers d autres anomalies hématologiques, notamment maligne (leucémie aigüe). Ce travail a pour but de décrire les caractéristiques cliniques et biologiques des 11 patients issus de 5 familles suivis à l hôpital Trousseau chez lesquels une mutation du gène de l Ankyrine 26 a été mise en évidence.Il s agit d une pathologie génétique à transmission autosomique dominante, responsable d une thrombopénie chronique isolée (absence d autre anomalie hématologie ou générale), modérée à sévère, associée à un syndrome hémorragique clinique modéré ou absent.Il semble exister dans ces familles une prédisposition aux pathologies hématologiques malignes (LAM essentiellement, mais aussi LMC, LAL et syndrome myélodysplasiques) : 4 cas au sein des 21 familles italiennes et 1 cas de LMC dans la cohorte de Trousseau.Sur le plan biologique, il n existe pas d atteinte des autres lignées sanguines, et on retrouve des signes marqués de dysmégacaryopoïèse au myélogramme. Par ailleurs l étude des fonctions plaquettaires ne montre pas d anomalies et on retrouve chez ces patients une augmentation importante du taux de TPO plasmatique. La mutation du gène de l Ankyrine 26 est donc une nouvelle entité dans l exploration des thrombopénies familiales à volume plaquettaire normal, et dont le nombre de diagnostic croissant permettra de mieux connaitre les caractéristiques clinico-biologiques et le potentiel évolutif notamment malin.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Spécificités pédiatriques de l'utilisation des antifongiques

La spécificité de l'utilisation des antifongiques chez l'enfant répond tout d'abord à l'épidémiologie particulière des infections fongiques en pédiatrie. La pharmacocinétique de nombreux antifongiques peut varier en fonction de l'âge. Pour certains médicaments, des études sont en cours, mais les données sont encore limitées. Parmi les antifongiques disponibles, ceux ayant une autorisation de mise sur le marché en pédiatrie sont rares. La fréquence des effets secondaires peut être différente chez les enfants par rapport aux adultes, et l'association des antifongiques avec d'autres médicaments doit aussi être prudente en pédiatrie. L'intérêt respectif chez l'enfant des diverses galéniques et conditionnements n'est pas toujours pris en compte, alors que l'impact sur le coût des traitements peut-être important. Ceci encourage à définir, pour chaque situation, une stratégie optimale de prescription des antifongiques en pédiatrie

Soins palliatifs en hématologie-oncologie pédiatrique (enquête de pratique auprès de médecins spécialistes, analyse rétrospective de 33 dossiers, étude de la littérature)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF