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UNLABELLED: The most common diagnosis for pediatric thrombocytopenia is immune thrombocytopenia. Nevertheless, in atypical cases, the hypothesis of an inherited thrombocytopenia has to be investigated. We report a series of cases of a newly described entity, genetic thrombocytopenia with mutation in the ankyrine 26 gene, diagnosed from the exploration of five pediatric cases of thrombocytopenia. This entity is characterized by a moderate thrombocytopenia with normal mean platelet volume, and poorly bleeding. Its transmission is autosomal dominant. Final diagnosis is made by sequencing of a short DNA region of ANKRD26 gene. This pathology can be considered as an hematological malignancy predisposition syndrome. CONCLUSION: We report the first cohort of pediatric patients diagnosed with thrombocytopenia with mutation in the ankyrine 26. The aim is to underline the specificities of this entity in children and bring it to the knowledge of pediatricians who may be in first place to manage these patients. WHAT IS KNOWN: ⢠Genetic thrombocytopenia with mutation in the ankyrine 26 gene is a recently described entity, which seems to be considered as a predisposition for hematologic malignancies. ⢠The first cohort has been reported in 2011, by Noris et al., in 78 Italian adult patients. What is New: ⢠We describe clinical and biological features of the first pediatric cohort diagnosed with genetic thrombocytopenia with mutation in the ankyrine 26 gene. ⢠It seemed important to consider the pediatric specificities of this entity to enable pediatricians to investigate, diagnose, and manage pediatric patients and their families.
Assuntos
DNA/genética , Mutação , Trombocitopenia/genética , Adolescente , Adulto , Repetição de Anquirina , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares , Linhagem , Trombocitopenia/diagnóstico , Trombocitopenia/metabolismoRESUMO
Clinical grading of GI involvement during acute GVHD remains a challenging issue, especially in children. Plasma citrulline, a non-protein amino acid selectively produced and released by enterocytes, is a suitable surrogate endpoint for small intestinal epithelial cell mass, irrespective of the underlying cause of cell loss. Children referred for allogeneic bone marrow transplantation who were free from chronic malabsorption or constitutional disease involving the GI tract were consecutively included in this prospective study. Plasma citrulline and albumin concentration was measured every week between day 7 and day 28 of BMT until resolution of the aGVHD or occurrence of chronic GVHD. In total, 31 children were included between 2008 and 2011. After a CR, citrulline levels fell to a minimum level on day 7 and then increased to reach the initial value on day 28. After day 28, plasma citrulline but not albumin was strongly linked to the occurrence of GI GVHD, the threshold being set at 10 µmol/L. The correlation with clinical grade of GI-aGVHD now needs to be assessed in larger populations. In pediatric patients, citrulline is valuable as a suitable non-invasive marker of GI involvement in acute GVHD.
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Transplante de Medula Óssea/efeitos adversos , Citrulina/sangue , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/diagnóstico , Adolescente , Albuminas/química , Biomarcadores/metabolismo , Criança , Pré-Escolar , Diarreia/diagnóstico , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To determine the predictors of a positive SARS-CoV-2 test in a pediatric ambulatory setting. PATIENTS AND METHODS: We performed a cross-sectional prospective study (November 2020-February 2022) of 93 ambulatory settings in France. We included symptomatic children < 15 years old tested for SARS-CoV-2. For each period corresponding to the spread of the original strain and its variants (period 1: original strain; period 2: Alpha, period 3: Delta; period 4: Omicron), we used a multivariate analysis to estimate adjusted odds ratios (aORs) associated with COVID-19 among age, signs, symptoms or contact, and 95 % confidence intervals (95CIs). RESULTS: Of 5,336 children, 13.9 % (95CI 13.0-14.8) had a positive test. During the first three periods, the positivity rate ranged from 5.6 % (95CI 4.6-6.7) to 12.6 % (95CI 10.8-14.6). The main factors associated with a positive test were contact with an infected adult at home or outside the home (aOR 11.5 [95CI 4.9-26.9] to 38.9 [95CI 19.3-78.7]) or an infected household child (aOR 15.0 [95CI 4.8-47.1] to 28.4 [95CI 8.7-92.6]). By contrast, during period 4, aORs for these predictors were substantially lower (2.3 [95CI 1.1-4.5] to 5.5 [95CI 3.2-7.7]), but the positivity rate was 45.7 % (95CI 42.3-49.2). CONCLUSIONS: In pediatric ambulatory settings, before the Omicron period, the main predictor of a positive test was contact with an infected person. During the Omicron period, the odds of these predictors were substantially lower while the positivity rate was higher. An accurate diagnostic strategy should only rely on testing and not on age, signs, symptoms or contact.
Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , Criança , Adolescente , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos Transversais , Estudos ProspectivosRESUMO
In core binding factors (CBF) acute myeloid leukemia (AML), the disruption of CBFalpha/beta genes impairs normal hematopoietic differentiation and is supposed to cooperate with additional mutations promoting proliferation. The incidence and the prognosis of receptor tyrosine kinase (RTK) c-Kit and FLT3 mutations and Ras mutations were evaluated in 103 pediatric and adult patients with CBF-AML. c-Kit mutations were present in 17% patients. c-Kit exon 8 mutations were more frequent in inv(16) than in t(8;21) subset (20 versus 6%). Only one patient had FLT3-ITD but FLT3-D835 was as frequent as reported in AML population (7%). Ras mutations were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%, P=0.001). RTK mutations were associated with a higher white blood cell count (WBC) (36 versus 21 G/L, P=0.05). FLT3 mutations were significantly associated with a shorter EFS and survival (P<0.0001 and P=0.0002) owing to an excess of early events. c-Kit mutations were associated with a shorter EFS and RFS (P=0.002 and P=0.003) in t(8;21) but not inv(16) patients. As previously observed, Ras mutations did not affect prognosis. Screening for RTK mutations may help to identify patients with a more adverse outcome and thus susceptible to benefit from intensified protocols or RTK inhibitors.
Assuntos
Fatores de Ligação ao Core/genética , Leucemia Mieloide/genética , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Tirosina Quinase 3 Semelhante a fms/genética , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Éxons , Feminino , Humanos , Lactente , Leucemia Mieloide/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced. Five-year overall survival (OS) was 78.2% in LAME89 and 81.4% in ELAM02. OS was significantly lower for the unfavorable cytogenetic risk group in LAME89/91 when compared with intermediate and favorable groups (50% vs 90.6 and 86.4%, P=0.001). This difference was no longer apparent in ELAM02 (80.9% vs 71.3% and 5/5, respectively). Survival improvement for children with unfavorable karyotype was statistically significant (P=0.026) and was due to decrease in relapse risk. Five-year transplantation-related mortality was 6.75% in LAME89/91. In ELAM02, it was 3.2% for patients with a sibling donor and 10.9% with an unrelated donor or cord blood. We conclude that the outcome of children with unfavorable karyotype transplanted in CR1 has improved.
Assuntos
Citogenética , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Criança , Feminino , França , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Cariotipagem , Leucemia Mieloide Aguda/mortalidade , Masculino , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
This article describes the survival after childhood acute leukaemia (AL) and non-Hodgkin's lymphoma (NHL) of French population aged less than 15 years. The French National Registry of Childhood Leukaemia and Lymphoma recorded 3995 cases of acute lymphoblastic leukaemia (ALL), 812 of acute myeloid leukaemia (AML) and 1137 of NHL over the period from 1990 to 2000. Overall survival rates at 5 years were 82% (95% CI 80-83), 58% (95% CI 54-61) and 87% (95% CI 85-89) for ALL, AML and NHL, respectively. Survival after AL increased from 77% (95% CI 75-80) in 1990-1992 to 85% (95% CI 83-87) in 1997-2000 for ALL and from 47% (95% CI 41-54) to 61% (95% CI 55-67) for AML. Among AL cases, children aged 1-4 years had the most favourable prognosis. Down's syndrome was associated with poor survival after ALL. No gender-related variations in survival were in evidence. The results reported herein are similar to those reported by other European registries and clinical trials.
Assuntos
Linfoma não Hodgkin/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Síndrome de Down/mortalidade , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Taxa de SobrevidaRESUMO
From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos Antineoplásicos/normas , Leucemia Mieloide Aguda/terapia , Adolescente , Transplante de Medula Óssea , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Seguimentos , França , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/mortalidade , Indução de Remissão , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
Is it necessary - and possible - to discuss death with a child in palliative phase? How should one approach the subject? A recent Swedish study demonstrated the benefits for parents who discussed with their child his or her imminent death, and raised the question of the role nursing can play to help parents. The mother of one child treated in our unit recently wrote a story 48 hours before the child's death. The story served to broach a number of recurrent questions often raised by dying children and their families: fear of the unknown, of being replaced, the inevitability of death, grief, and fear of being forgotten... The story was given to 13 families with dying children. In order to evaluate the story's impact on families and to determine whether a document which stimulates dialogue should continue to be given to parents, we asked that they fill out a questionnaire. Fifty-five percent of parents answered, and confirmed that the story was experienced as a positive thing and helped parents to talk with their children. This study raises many questions and should be part of a global accompaniment strategy. A review of medical, general and children's literature, as well the results of our study, lead us to conclude that the medical body should lend its full support to families who wish to engage in this dialogue with their children.
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Morte , Narração , Revelação da Verdade , Criança , Humanos , Inquéritos e QuestionáriosRESUMO
PURPOSE: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval). RESULTS: CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups. CONCLUSION: G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Lactente , Recém-Nascido , Masculino , Metotrexato/administração & dosagem , Neutropenia/prevenção & controle , Prednisona/administração & dosagem , Proteínas Recombinantes , Trombocitopenia/prevenção & controle , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
In this study we have identified frequent human leukocyte antigen (HLA)-A, -B, -C,-DRB1, and -DQB1 alleles, frequent HLA-B/C, HLA-DRB1/DQB1 two-allele associations, and the most common HLA-A/B/C/DRB1/DQB1 five-locus haplotypes in a population residing in the Paris, France, area. The study was carried out in 356 families of children awaiting hematopoietic stem-cell transplantation (HSCT), with the selection criterion that haplotypes could be assigned with certainty to both the patient and at least one parent. Parental haplotypes were HLA-A, -B serologically typed, and HLA-C, -DRB1, -DQB1 broadly typed by polymerase chain reaction-sequence-specific oligonucleotide probe. The alleles of the most frequent haplotypes were subsequently defined at a high-resolution level by polymerase chain reaction-sequence-specific primer. The results on the distribution of common alleles and common allele associations demonstrated similarities with the previously published data in Caucasian populations, as expected from the geographic origin of the studied population. More importantly, this study provides the largest listing of common B/C and DRB1/DQB1 associations and of common five-allele haplotypes defined with certainty in a Caucasian population to date. These results can be used to help estimate the likelihood of finding a suitable donor in unrelated HSCT and to delineate search strategies for potential donors.
Assuntos
Alelos , Antígenos HLA/genética , Haplótipos , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , ParisRESUMO
UNLABELLED: Disseminated fusariosis in children is a rare and serious fungal infection, that occurs especially in neutropenic immunosuppressed patients, treated for malignant hemopathy, or bone marrow transplant recipient. Treatment is difficult and mortality is estimated between 50 and 70% in adult patients. CASE REPORT 1: A ten-year-old boy, treated for an acute lymphoblastic leukemia in second relapse, presented a disseminated fusarium spp infection, that occurred during neutropenia. He died due to fusariosis infection in spite of amphotericin B treatment. CASE REPORT 2: A ten-year-old neutropenic girl, treated for an acute myeloïd leukemia, presented disseminated fusariosis, uncontrolled by amphotericin B. Recovery was observed after voriconazole introduction and resolution of neutropenia. Ten months later, she presented a leukemia's relapse, treated by new intensive chemotherapy with secondary prophylaxis by voriconazole, without fusariosis's recurrence. CONCLUSION: Voriconazole, a new triazole agent, seems to be an alternative antifungal agent to amphotericin B for disseminated fusarium infection, either at the acute phase or for secondary prophylaxis.
Assuntos
Fusarium/isolamento & purificação , Hospedeiro Imunocomprometido , Micoses/etiologia , Neutropenia/complicações , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criança , Combinação de Medicamentos , Evolução Fatal , Feminino , Humanos , Leucemia Linfoide/complicações , Leucemia Linfoide/tratamento farmacológico , Leucemia Linfoide/imunologia , Leucemia Mieloide/complicações , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/imunologia , Masculino , Micoses/tratamento farmacológico , Micoses/imunologia , Micoses/microbiologia , Neutropenia/induzido quimicamente , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , VoriconazolRESUMO
PURPOSE: To evaluate how adolescents and young adults cured of acute lymphoblastic leukemia (ALL) treated during childhood have integrated the disease, and possible death related to cancer. Particularly, we have focused on experiences related to diagnosis announcement, hospitalisation and treatments and consequences on their social, psychological and somatic behaviour. PATIENTS: Forty-one patients cured of ALL have been enrolled in the study and answered one interview with clinical psychologist or research nurse. RESULTS: Although 60% of the patients argued that they think rarely of their disease, 10% thought about it every day. Traumatic evidence was detectable in most of them. Physical pain was the most reported stress, mainly during hospitalisation (93%), as well as psychological suffering (83%). Afterwards, the mostly often-reported stress was psychological pain (61%). Sixty-six percent declared that they still experience psychological and health consequences at the time of the interview, in some cases reported as a handicap in their life. In 83% of the cases they considered themselves as cured, nevertheless fear of relapse persisted in 1/3. Ninety percent said they have a pleasant life, 56% did not like to talk about leukaemia and 70% thought they could have died. For 85%, disease has been the most important event of their life and 75% testify to repercussions of the disease on their family (family relationship changes, overprotection, siblings difficulties). CONCLUSION: Most of these patients declared to be 'as the others' and developed life projects, but overcoming the pain experience of the disease remained difficult. This study emphasized the need for long-term continuous information and reinforces the importance of addressing treatment psychological and physical pain mainly after the initial hospitalisation period.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/reabilitação , Qualidade de Vida , Sobreviventes/psicologia , Adaptação Psicológica , Adolescente , Comportamento do Adolescente , Criança , Pré-Escolar , Relações Familiares , Feminino , Nível de Saúde , Humanos , Masculino , Dor/psicologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Prognóstico , Estresse PsicológicoRESUMO
UNLABELLED: Evans' Syndrome (ES) is defined as the combination of immune thrombocytopenia (ITP) and autoimmune haemolytic anemia (AIHA), in the absence of any known underlying etiology. Pathophysiology, epidemiology and outcome remain unclear. POPULATION: Thirty-six children (20 male, 16 female), who were diagnosed in the SHIP french centres (Société d'hématologie et d'immunologie pédiatrique) between 1990 and 2002 with ES, were included in this retrospective study. RESULTS: Median age at diagnosis was 4 years. In 21 children, ES occurred in the setting of consanguinity, family history of autoimmune/inflammatory disease, associated autoimmune disorder or immunoregulatory abnormalities (serum imunoglobulins, peripheral blood lymphocytes subsets, low level of the C3-C4 complement components, nuclear antibodies). Several successive treatments were used in this serie (median: 3, range: 0-10) including corticosteroid therapy (35/36), intravenous immunoglobulins (32/36), immunosuppressive agents (14/36), splenectomy (9/36) and anti CD 20 monoclonal antibodies (6/36). Patients with a low level of serum immunoglobulins were more often non-responders to corticosteroidtherapy/intravenous immunoglobulins and required more frequently further therapy (P=0.03). Three patients died (intracranial bleeding, N=2, Guillain-Barre syndrome; N=1). CONCLUSION: ES was a severe, life-threatening disease, requiring aggressive immunosuppressive therapy in as many as half the patients. Our forthcoming study aims to (i) describe homogeneously-studied and prospectively-analysed cohort of childhood ES, (ii) separate ES from specific immune deficiency (especially fas gene mutations), generalised autoimmune/inflammatory disorders and genetic diseases, (iii) identify well-defined ES subsets, (iv) establish prognostic factors and optimal treatment within these subsets.
Assuntos
Anemia Hemolítica Autoimune/patologia , Púrpura Trombocitopênica Idiopática/patologia , Adolescente , Corticosteroides/uso terapêutico , Idade de Início , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Consanguinidade , Feminino , França , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Masculino , Prognóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Estudos Retrospectivos , Índice de Gravidade de Doença , SíndromeRESUMO
PURPOSE: The pharmacokinetics of DaunoXome were studied during a multicentric phase I-II study performed in children suffering from relapsed acute lymphoblastic leukaemia and treated on a weekly schedule. PATIENTS AND METHODS: A group of 18 patients were studied during the first course of treatment at dose levels between 40 and 120 mg/m2. Blood samples were obtained up to 72 h after infusion. The liposomal and free forms of daunorubicin, as well as daunorubicinol, were separated and quantified by HPLC using fluorometric detection, and data were analysed using a model-independent approach. RESULTS: Unchanged liposomal daunorubicin disappeared from plasma following a monoexponential decay. Its AUC represented 95.8% of the total fluorescent species found in plasma and increased linearly with the dose administered. The elimination half-life was 5.23 h, total plasma clearance 0.344 1/h per m2, and volume of distribution at steady state 2.08 l/m2. Free daunorubicin and daunorubicinol were detected in plasma at all time-points studied. Their AUCs represented, respectively, 2.53% and 1.70% of total fluorescent species and their elimination half-lives were, respectively, 16.6 h and 22.3 h. The daunorubicinol/daunorubicin AUC ratio was 0.82%. CONCLUSIONS: This study is the first to demonstrate that free daunorubicin is present in plasma after DaunoXome administration and that it originates from in vivo release from the liposomes. The pharmacokinetics of free daunorubicin appeared to be comparable to those observed after conventional administration. However, the concentration of daunorubicinol appeared to be lower than that found after conventional administration of daunorubicin.
Assuntos
Antibióticos Antineoplásicos/farmacocinética , Daunorrubicina/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Adolescente , Antibióticos Antineoplásicos/sangue , Antibióticos Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Daunorrubicina/análogos & derivados , Daunorrubicina/sangue , Daunorrubicina/uso terapêutico , Portadores de Fármacos , Feminino , Meia-Vida , Humanos , Lipossomos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recidiva , Fatores de TempoRESUMO
The French National Registry of Childhood Leukaemia and Lymphoma (NRCL) covers the whole French mainland population aged less than 15 years (approximately 11 million children) for all childhood haematopoietic tumours since 1 January 1990, except Hodgkin's disease, which has been registered since 1 January 1999. During the period from 1990 to 1999, 5757 cases of leukaemia, lymphoma and myelodysplastic syndrome were registered in the NRCL, with an average of 2.5 sources per case. The age-standardized incidence rates per million per year were 43.1 for leukaemia (34.3 for acute lymphoblastic leukaemia, 7.1 for acute myeloblastic leukaemia, 0.6 for chronic myeloid leukaemia and 0.5 for chronic myelomonocytic leukaemia), 8.9 for non-Hodgkin's lymphomas and 6.7 for Hodgkin's disease. Down's syndrome was present in 110 cases of acute leukaemia (2.5%) and three cases of non-Hodgkin's lymphoma (0.3%). The incidence of acute lymphoblastic leukaemia showed a typical peak at age 2 years for girls and 3 years for boys. The incidence rates of leukaemia and non-Hodgkin's lymphoma did not show any temporal trends over the 10 year period.
Assuntos
Leucemia/epidemiologia , Linfoma não Hodgkin/epidemiologia , Sistema de Registros , Adolescente , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Incidência , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Fatores Sexuais , Fatores de TempoRESUMO
AIM: To analyse the association between potential environmental exposure to hydrocarbons and the risk of acute childhood leukaemia. METHODS: A hospital based multicentre case control study, stratified on centre, age, and sex, with 280 leukaemia cases and 285 controls was carried out. Data were collected by a standardised interview of the mothers. RESULTS: No clear association was seen between maternal occupational exposure to hydrocarbons during pregnancy and leukaemia, or between residential traffic density and leukaemia. There was an association between dwellings neighbouring a petrol station or a repair garage during childhood and the risk of childhood leukaemia (OR 4.0, 95% CI 1.5 to 10.3), with a duration trend. The association, which appeared particularly strong for acute non-lymphocytic leukaemia (OR 7.7, 95% CI 1.7 to 34.3), was not altered by adjustment for potential confounding factors. CONCLUSIONS: Results showed an association between acute childhood leukaemia and dwellings neighbouring auto repair garages and petrol stations, which are benzene emitting sources. These findings could be due to chance, although the strength of the association and the duration trend are arguments for a causal association.
Assuntos
Exposição Ambiental/efeitos adversos , Hidrocarbonetos/toxicidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/induzido quimicamente , Benzeno/toxicidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Exposição Materna , Razão de Chances , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Características de ResidênciaRESUMO
UNLABELLED: Methotrexate elimination may be delayed by different drugs. Such a delay may produce severe toxic complications. CASE REPORTS: We report two cases of adolescents treated for malignant diseases who presented a delayed methotrexate elimination even though they received ciprofloxacin. The first patient had already received several courses of methotrexate without toxicity before this episode. The second patient tolerated methotrexate when ciprofloxacin was not associated to the treatment. CONCLUSION: High-dose methotrexate-ciprofloxacin association should be avoided.
Assuntos
Anti-Infecciosos/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/farmacocinética , Ciprofloxacina/efeitos adversos , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Ciprofloxacina/farmacocinética , Interações Medicamentosas , Feminino , Humanos , Masculino , Neuroblastoma/tratamento farmacológico , Osteossarcoma/tratamento farmacológicoRESUMO
Incidence of severe candidal infections is rapidly increasing since 15 years and is becoming a major concern in onco-hematology practice, especially due to its poor prognosis in neutropenic patients. Diagnosis of candidemia is suspected in case of persistent fever resistant to a large antibiotherapy and requires to search for secondary locations as cutaneous and hepatosplenic candidal infection. Improvement of yeasts detection in blood culture bottles with specific medium is now helpful but use of specific immunoserodiagnosis or PCR methods is at this point unuseful. Fluconazole and Amphotericine B remain the recommended treatments for candidemia. Indications for "new antifongal drugs" are still limited regarding their high cost and the limited clinical studies.