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1.
Ann Oncol ; 35(6): 559-568, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38142939

RESUMEN

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Óseas , ADN Tumoral Circulante , Osteosarcoma , Humanos , Osteosarcoma/genética , Osteosarcoma/sangre , Osteosarcoma/patología , Osteosarcoma/cirugía , Osteosarcoma/mortalidad , Osteosarcoma/diagnóstico , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Masculino , Femenino , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/sangre , Neoplasias Óseas/cirugía , Neoplasias Óseas/mortalidad , Adulto , Adolescente , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Estudios Prospectivos , Adulto Joven , Niño , Variaciones en el Número de Copia de ADN , Clasificación del Tumor , Persona de Mediana Edad , Secuenciación Completa del Genoma , Supervivencia sin Progresión
2.
Leukemia ; 21(2): 238-47, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17170721

RESUMEN

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.


Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Encefalopatías Metabólicas/inducido químicamente , Metotrexato/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Factores de Edad , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/prevención & control , Niño , Preescolar , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Masculino , Neurotoxinas , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Medición de Riesgo
3.
J Infect ; 76(5): 483-488, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29432826

RESUMEN

OBJECTIVES: Definitive diagnosis of invasive candidiasis (IC) may be difficult to achieve in patients with haematological malignancy (PHM). We aimed to evaluate the performance of BDG for the diagnosis and the follow-up of IC in PHM. PATIENTS AND METHODS: We retrospectively reviewed the serological data of BDG assay in adult and paediatric PHM, who developed candidemia or chronic disseminated candidiasis (CDC) through a 4-year period. Sensitivity and kinetics of BDG were determined for both clinical forms. RESULTS: In a panel of 3027 PHM, incidence rates of candidemia and CDC ranged between 0.74 and 0.77 and 0.30 and 0.44 according to the group of patients. At the time of diagnosis, 43.5% and 73% of cases of candidemia and CDC had a positive BDG assay, respectively. We found a significant correlation between the level of BDG at diagnosis and the outcome of candidemia (p = 0.022). In all cases of CDC, BDG negative results were obtained 2 to 6 months before recovery of the CT-scan lesions. CONCLUSIONS: BDG exhibits a low sensitivity to detect IC in PHM, but its kinetics correlates the clinical outcome. Additional studies are warranted in patients with CDC to evaluate the interest of monitoring BDG levels to anticipate the discontinuation of antifungal maintenance therapy.


Asunto(s)
Candidemia/diagnóstico , Candidiasis Invasiva/diagnóstico , Candidiasis/diagnóstico , Neoplasias Hematológicas/microbiología , beta-Glucanos/sangre , Anciano , Anticuerpos Antifúngicos , Antifúngicos/uso terapéutico , Candida , Candidemia/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Candidiasis Invasiva/tratamiento farmacológico , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Cinética , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad
4.
J Immunother Cancer ; 6(1): 159, 2018 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-30591082

RESUMEN

BACKGROUND: Microphthalmia Transcription Factor (MITF)family translocation renal cell carcinoma (tRCC) is a rare RCC subtype harboring TFE3/TFEB translocations. The prognosis in the metastatic (m) setting is poor. Programmed death ligand-1 expression was reported in 90% of cases, prompting us to analyze the benefit of immune checkpoint inhibitors (ICI) in this population. PATIENTS AND METHODS: This multicenter retrospective study identified patients with MITF family mtRCC who had received an ICI in any of 12 referral centers in France or the USA. Response rate according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. Genomic alterations associated with response were determined for 8 patients. RESULTS: Overall, 24 patients with metastatic disease who received an ICI as second or later line of treatment were identified. Nineteen (82.6%) of these patients had received a VEGFR inhibitor as first-line treatment, with a median PFS of 3 months (range, 1-22 months). The median PFS for patients during first ICI treatment was 2.5 months (range, 1-40 months); 4 patients experienced partial response (16,7%) and 3 (12,5%) had stable disease. Of the patients whose genomic alterations were analyzed, two patients with mutations in bromodomain-containing genes (PBRM1 and BRD8) had a clinical benefit. Resistant clones in a patient with exceptional response to ipilimumab showed loss of BRD8 mutations and increased mutational load driven by parallel evolution affecting 17 genes (median mutations per gene, 3), which were enriched mainly for O-glycan processing (29.4%, FDR = 9.7 × 10- 6). CONCLUSIONS: MITF family tRCC is an aggressive disease with similar responses to ICIs as clear-cell RCC. Mutations in bromodomain-containing genes might be associated with clinical benefit. The unexpected observation about parallel evolution of genes involved in O-glycosylation as a mechanism of resistance to ICI warrants exploration.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Renales/genética , Inmunomodulación/efectos de los fármacos , Neoplasias Renales/genética , Factor de Transcripción Asociado a Microftalmía/genética , Familia de Multigenes , Translocación Genética , Adolescente , Adulto , Anciano , Antineoplásicos Inmunológicos/farmacología , Biomarcadores de Tumor , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Niño , Preescolar , Femenino , Genómica/métodos , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Factor de Transcripción Asociado a Microftalmía/antagonistas & inhibidores , Persona de Mediana Edad , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
5.
Arch Pediatr ; 14(5): 461-6, 2007 May.
Artículo en Francés | MEDLINE | ID: mdl-17306514

RESUMEN

OBJECTIVE: To study the feelings of HIV infected mothers during the perinatal period regarding circumstances of HIV diagnosis, disclosure to partner and fear of contamination. POPULATION AND METHODS: A study based upon personal interviews was carried out from November 2003 to January 2004 upon routine pediatric outpatient visits for infants born to HIV positive mothers. RESULTS: This study included 54 women of which 70% were from Sub-Saharan Africa. Fifty-nine per cent discovered their HIV status during a pregnancy. Seventy-seven per cent of partners were informed of maternal status. Among the women reluctant to inform their partner, the main reasons given were fear of violence and separation. Seventy-two per cent of interviewed women refused their spouses to be informed by the medical staff. Medical care during pregnancy (moral support, delivery) was judged as good by a majority of women (90%) who found the behavior of the staff mostly satisfactory. Final child serology remains the most definitive test for mothers, 47% of whom fear the risk of a potential postnatal contamination of their children. CONCLUSION: In these isolated women, many of whom have recently discovered their HIV status, a multidisciplinary approach including psychosocial support is essential.


Asunto(s)
Infecciones por VIH/psicología , Complicaciones Infecciosas del Embarazo/psicología , África/etnología , Estudios Transversales , Femenino , Francia , Infecciones por VIH/transmisión , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Entrevistas como Asunto , Masculino , Satisfacción del Paciente , Atención Perinatal , Embarazo , Parejas Sexuales , Revelación de la Verdad
6.
Arch Pediatr ; 24(4): 317-326, 2017 Apr.
Artículo en Francés | MEDLINE | ID: mdl-28242151

RESUMEN

BACKGROUND: Considering the remarkable efficacy of the strategies for preventing mother-to-child transmission of HIV infection (PMTCT), failures are rare in high-resource countries and deserve further investigation. Moreover, infants have been found to be at increased risk of viral failure. We analyzed the factors related to the children's environment, including maternal psychological factors that may be associated with viral failure in children diagnosed before the age of 1 year. PATIENTS AND METHODS: Retrospective study of all HIV-infected infants, born in France between July 2003 and July 2013, diagnosed before the age of 1 year, cared for in a single reference center, comparing the group of children in viral success to the group of children presenting at least one episode of viral failure, using data available in their medical, psychological and social files. RESULTS: Out of 1061 infants included in the prospective PMTCT follow-up, eight infants were found HIV-positive and an additional six cases were referred from other centers before the age of 1 year, for a total of 14 children born to 13 mothers. Seven children presented durable optimal viral control (VL<50 c/mL) whereas seven others did not reach or maintain optimal viral control over time. The main difference between the two groups was the presence among the mothers of children with viral failure of severe psychological disorders, leading to treatment adherence problems in the mothers who were aware of their HIV status before pregnancy, and difficulties in giving their children's treatments correctly. CONCLUSIONS: Although seroconversion during pregnancy is responsible for a significant proportion of residual transmission in high-resource countries, severe psychological or psychiatric conditions in HIV-positive mothers play an important role on the risk of both MTC residual transmission and viral failure in their infants.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Femenino , Estudios de Seguimiento , Infecciones por VIH/psicología , VIH-1/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Masculino , Cumplimiento de la Medicación/psicología , Madres/psicología , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento
7.
Bone Marrow Transplant ; 52(1): 80-87, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27595286

RESUMEN

Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucémie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level ⩾350 ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0.001), radiation-based preparative regimen (P=0.035) and recent period of transplantation (P<0.001); 2) in multivariate analysis: older age at transplant in quartiles (Odds Ratio (OR)=7.64, 95% CI: 3.73-15.64 for age >12.7 years and OR=5.36, 95% CI: 2.63-10.95 for age from 8.2 to 12.7 years compared to age < 4.7 years), acute myeloid leukemia (OR=3.23, 95% CI: 1.47-7.13), allogeneic graft (OR=4.34, 95% CI: 2.07-9.12 for alternative donors and OR=2.53, 95% CI: 1.2-5.33 for siblings, compared to autologous graft) and radiation-based conditioning regimen (OR=2.45, 95% CI: 1.09-5.53). Graft-versus-host disease was an additional risk factor for allogeneic graft recipients. In conclusion, IO is a frequent complication in pediatric long-term survivors after transplantation for acute leukemia, more frequently observed in older children, those transplanted from alternative donors or with graft-versus-host disease.


Asunto(s)
Supervivientes de Cáncer , Ferritinas/sangre , Trasplante de Células Madre Hematopoyéticas , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/epidemiología , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante , Factores de Edad , Aloinjertos , Niño , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/epidemiología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Prevalencia , Factores de Riesgo , Donantes de Tejidos
8.
J Clin Oncol ; 12(12): 2614-20, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7989936

RESUMEN

PURPOSE AND METHODS: Between January 1981 and June 1993, 137 children and adolescents were each treated at the Institut Gustave Roussy for an initially nonmetastatic osteosarcoma of the extremities. We report the retrospective analysis of 42 cases of recurrence that occurred in this population. RESULTS: The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 21 months (range, 5 to 60). The site of the first recurrence was limited to the lung in 20 patients, the bone in seven patients, was local in six patients, and was confined to soft tissue in one patient. In eight patients, the first recurrence affected multiple sites. Subsequent recurrences often involved unusual or multiple sites. Management of recurrences included surgery and/or various regimens of second-line chemotherapy, and in one case involved high-dose chemotherapy followed by autologous bone marrow transplantation. Overall survival and event-free survival were, respectively, 36% and 27% at 36 months. At present, 13 patients are alive without evidence of disease. Response of the primary tumor to preoperative chemotherapy, the time between the diagnosis and the first recurrence, and the number of metastatic lesions did not correlate with survival. The survival rate is better in patients with a local or a pulmonary first recurrence. CONCLUSION: The most important prognostic indicator at first recurrence seems to be the possible complete resection of disease. Patients not amenable to surgery and patients with a second or a third recurrence have a poor prognosis. The potential benefit of more aggressive treatments such as high-dose chemotherapy and autologous bone marrow transplantation should be investigated for these patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Osteosarcoma/tratamiento farmacológico , Adolescente , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Extremidades , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Leucovorina/administración & dosificación , Masculino , Metotrexato/administración & dosificación , Recurrencia Local de Neoplasia/terapia , Osteosarcoma/mortalidad , Osteosarcoma/secundario , Osteosarcoma/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Vindesina/administración & dosificación
9.
J Clin Oncol ; 17(9): 2789-95, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10561354

RESUMEN

PURPOSE: We analyzed the clinical features and outcome of patients with radiation-associated osteosarcoma treated during the era of contemporary chemotherapy. PATIENTS AND METHODS: The characteristics and outcome of 23 patients (17 males and six females) treated during childhood or adolescence for a solid tumor who later developed osteosarcomas within the radiation field between 1981 and 1996 were reviewed. RESULTS: The median dose of radiation delivered to the first cancer was 47 Gy. Nineteen patients also received chemotherapy. The median time between radiotherapy and the diagnosis of secondary osteosarcoma was 8 years. Histologic slide review showed conventional central osteosarcoma with various differentiation patterns in 21 cases, together with one case of high-grade surface osteosarcoma and one of periosteal osteosarcoma. The sites of involvement were the craniofacial bones in six cases, the first cervical vertebra in one, the girdle bones in seven, and the extremities of long bones in nine. Three patients had metastatic disease at the diagnosis of osteosarcoma. Palliative therapy was administered to seven patients. The aim of treatment was curative for 16 patients, two of whom underwent amputation without further therapy. Intensive chemotherapy regimens were administered to 14 patients before and/or after surgery. Fifteen patients achieved complete surgical remission. Twelve patients were alive and disease-free at a median follow-up duration of 7.5 years. Overall and event-free survivals at 8 years were 50% and 41%, respectively. CONCLUSION: Patients with radiation-related osteosarcoma and resectable lesions can be cured with surgery and intensive preoperative and postoperative chemotherapy.


Asunto(s)
Neoplasias Óseas/terapia , Neoplasias Inducidas por Radiación/terapia , Neoplasias Primarias Secundarias/terapia , Osteosarcoma/terapia , Adolescente , Adulto , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Óseas/mortalidad , Niño , Preescolar , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Metotrexato/uso terapéutico , Recurrencia Local de Neoplasia , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Neoplasias Inducidas por Radiación/mortalidad , Neoplasias Primarias Secundarias/mortalidad , Osteosarcoma/mortalidad , Dosificación Radioterapéutica , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/radioterapia , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/radioterapia
10.
Clin Cancer Res ; 7(3): 538-43, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11297245

RESUMEN

Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumors. Among angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) appear to be useful markers in adults with cancer. The aim of this pilot study was to determine the levels of VEGF in serum and bFGF in serum and urine of children with solid tumor at diagnosis (as measured by ELISA), and to investigate whether these parameters provide prognostic information. Forty consecutive patients with different types of cancer were prospectively included in this study. Median values of all studied angiogenic factors were higher in patients than in controls (n = 40), and the differences were statistically significant for bFGF in serum and urine: 10 versus 3 pg/ml (P = 0.0004) and 6406 versus 0 pg/g of creatinine (P < 0.0001), respectively. Among patients, median serum values of bFGF and VEGF were higher in children with metastatic disease (n = 14) than in those with localized disease (n = 26). The difference was statistically significant for serum bFGF: 17.5 versus 6 pg/ml (P = 0.02). Serum angiogenic factor levels correlated with outcome. The estimated event-free survival at 3 years was 79% for patients with normal bFGF values (n = 13) versus 42% (n = 26; P = 0.02) for those with high levels, and 71% in case of normal VEGF values (n = 20) versus 38% (n = 19; P = 0.04) for those with high levels. No benefit of normal urinary bFGF values was observed. Our results provide a rationale for exploring the clinical interest of bFGF and VEGF measurements in body fluids of a larger group of children with cancer.


Asunto(s)
Factores de Crecimiento Endotelial/biosíntesis , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Linfocinas/biosíntesis , Neoplasias/sangre , Neoplasias/metabolismo , Neovascularización Patológica , Adolescente , Factores de Edad , Neoplasias Óseas/sangre , Neoplasias Óseas/orina , Estudios de Casos y Controles , Niño , Preescolar , Creatinina/orina , Supervivencia sin Enfermedad , Factores de Crecimiento Endotelial/sangre , Factores de Crecimiento Endotelial/orina , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Humanos , Lactante , Recién Nacido , Linfocinas/sangre , Linfocinas/orina , Masculino , Metástasis de la Neoplasia , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
11.
Arch Pediatr ; 12(11): 1591-9, 2005 Nov.
Artículo en Francés | MEDLINE | ID: mdl-16216482

RESUMEN

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.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/psicología , Leucemia-Linfoma Linfoblástico de Células Precursoras/rehabilitación , Calidad de Vida , Sobrevivientes/psicología , Adaptación Psicológica , Adolescente , Conducta del Adolescente , Niño , Preescolar , Relaciones Familiares , Femenino , Estado de Salud , Humanos , Masculino , Dolor/psicología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Pronóstico , Estrés Psicológico
12.
Arch Pediatr ; 12(7): 1116-9, 2005 Jul.
Artículo en Francés | MEDLINE | ID: mdl-15964527

RESUMEN

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.


Asunto(s)
Fusarium/aislamiento & purificación , Huésped Inmunocomprometido , Micosis/etiología , Neutropenia/complicaciones , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Niño , Combinación de Medicamentos , Resultado Fatal , Femenino , Humanos , Leucemia Linfoide/complicaciones , Leucemia Linfoide/tratamiento farmacológico , Leucemia Linfoide/inmunología , Leucemia Mieloide/complicaciones , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/inmunología , Masculino , Micosis/tratamiento farmacológico , Micosis/inmunología , Micosis/microbiología , Neutropenia/inducido químicamente , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Voriconazol
13.
Bone Marrow Transplant ; 50(11): 1438-44, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26191949

RESUMEN

We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8±5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n=119, or AML, n=51. TBI was carried out in 124 cases; a busulfan-based conditioning was done in 30 patients. Twenty-nine patients developed a MS (17.1%, 95% confidence intervals: 11.7-23.6). The cumulative incidence was 13.4% at 25 years of age and 35.5% at 35 years of age. A higher body mass index (BMI) before transplantation and a growth hormone deficiency were associated with increased MS risk (P=0.002 and 0.01, respectively). MS risk was similar for patients who received TBI or busulfan-based conditioning. The TBI use increased the hyperglycemia risk (odds ratio (OR): 4.7, P=0.02). Women were at the risk of developing increased waist circumference (OR: 7.18, P=0.003) and low levels of high-density lipoprotein cholesterol (OR: 2.72, P=0.007). The steroid dose was not a risk factor. The MS occurs frequently among transplanted survivors of childhood leukemia. Its incidence increases with age. Both intrinsic (BMI, gender) and extrinsic factors (TBI, alkylating agents) contribute to its etiopathogenesis.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Metabólico/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sobrevivientes , Acondicionamiento Pretrasplante/efectos adversos , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Adulto , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Glucemia/análisis , Índice de Masa Corporal , Busulfano/uso terapéutico , HDL-Colesterol/sangre , Terapia Combinada , Femenino , Humanos , Lípidos/sangre , Masculino , Síndrome Metabólico/sangre , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Circunferencia de la Cintura , Irradiación Corporal Total/efectos adversos , Adulto Joven
14.
J Clin Endocrinol Metab ; 84(6): 1949-53, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10372692

RESUMEN

The aim of the study was to investigate how leptin could be involved in catch-up growth of children born with intrauterine growth retardation (IUGR). The study population was made up of 70 newborns with IUGR longitudinally studied during the first 2 yr of life and 35 newborns and 32, 66, and 61 children with normal birth weight aged 3 days, 12 months, and 24 months, respectively. Postnatal patterns of body mass index (BMI) were similar in the 2 groups, but BMI remained significantly lower in IUGR over the study period. In contrast, children born with IUGR aged 1 yr had significantly higher serum leptin levels than normal children (P < 0.0001) independently of BMI. The correlation observed between BMI and serum leptin at birth in both groups and in the control group thereafter disappeared in children born with IUGR. Similarly, sexual dimorphism observed in normal children over the study period was not observed in the IUGR group during the first 2 yr of life. In summary, serum leptin is effective and regulated during the first years of life as it is in older children. Children born with IUGR demonstrate high serum leptin values during the first year of life, with a loss of the regulatory effect of BMI and gender. We suggest that these children develop an adaptative leptin resistance beneficial for their catch-up growth. An alternative hypothesis is that these observations could reflect an adipocyte dysfunction, a consequence of the special time course of adipose tissue development in children born with IUGR.


Asunto(s)
Retardo del Crecimiento Fetal/sangre , Crecimiento/fisiología , Proteínas/metabolismo , Envejecimiento/sangre , Índice de Masa Corporal , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Humanos , Lactante , Recién Nacido , Leptina , Estudios Longitudinales , Masculino , Caracteres Sexuales
15.
Surgery ; 123(1): 51-7, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9457223

RESUMEN

BACKGROUND: This study describes a novel method of intraoperative localization of neuroblastoma with a gamma-detecting probe, to detect in situ tumor binding of radiolabeled 123I- or 125I-metaiodobenzylguanidine (MIBG) and improve the quality of tumor resection. METHODS: Fifty-eight children underwent 66 surgical procedures with intraoperative detection of radiolabeled MIBG. All patients with positive MIBG scintiscans at diagnosis were included in the study. A tumor/background ratio exceeding 2:1 at the time of operation was considered positive, indicating a significant uptake of MIBG, compatible with the presence of malignant cells. The surgeons were requested to evaluate the contribution of the method to the surgical procedure. Sensitivity and specificity of the method with either 123I-labeled MIBG or 125I-labeled MIBG, on the basis of correlations between probe findings and pathologic analysis of 288 resected specimens, were determined. RESULTS: Intraoperative detection was helpful in 65% of surgical procedures, allowing a better definition of tumor limits and extension to locoregional nodes or detection of small and nonpalpable tumors in sites with difficult surgical access, especially during operation for relapse. The detection was not contributory in 35% of the procedures (well-localized tumors, thoracic neuroblastoma for technical reasons, highly differentiated tumors as ganglioneuroma, and tumors with mainly necrosis or fibrosis). The sensitivity of 123I and 125I was the same (91% and 92%), but the specificity of 125I (85%) was significantly higher than that of 123I (55%) (p < 0.005). CONCLUSIONS: First, this study demonstrates the feasibility of intraoperative detection, with radiolabeled MIBG, of neuroblastoma in children. We advocate the use of 125I rather than 123I. Second, the method is useful to improve the quality of macroscopic resection in widespread neuroblastoma with nodal involvement, in sites with difficult access, and in operations for relapse.


Asunto(s)
3-Yodobencilguanidina , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/cirugía , Radiofármacos , 3-Yodobencilguanidina/farmacocinética , Neoplasias Encefálicas/patología , Niño , Preescolar , Femenino , Fibrosis , Cámaras gamma , Humanos , Lactante , Radioisótopos de Yodo/farmacocinética , Metástasis Linfática , Masculino , Monitoreo Intraoperatorio , Necrosis , Metástasis de la Neoplasia , Neuroblastoma/patología , Cintigrafía , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular
16.
Parasite ; 2(3): 263-8, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8520801

RESUMEN

Levels of different acute phase proteins were compared in sera from parasitaemic and non-parasitaemic women living in a Plasmodium falciparum endemic area of Thailand. The ability of their sera to interfere with hepatic stage development of the parasite was examined. Correlations were found between levels of alpha-1 antitrypsin, alpha-2 macroglobulin, hemopexin and the potential of sera to block hepatocyte invasion by the sporozoite.


Asunto(s)
Proteínas de Fase Aguda/inmunología , Malaria/inmunología , Proteínas de Fase Aguda/análisis , Adolescente , Adulto , Animales , Anticuerpos Antiprotozoarios/análisis , Células Cultivadas , Femenino , Humanos , Inmunidad Innata , Hígado/parasitología , Hígado/patología , Malaria/epidemiología , Ratones , Ratones Endogámicos BALB C , Plasmodium falciparum/inmunología , Plasmodium yoelii/inmunología , Tailandia/epidemiología
17.
Arch Pediatr ; 10 Suppl 5: 582s-587s, 2003 Dec.
Artículo en Francés | MEDLINE | ID: mdl-15022785

RESUMEN

Invasive aspergillosis is an opportunistic infection, with frequent lung involvement. High-risk children are allogenic bone marrow recipients, and those with hematological malignancies, aplastic anemia or chronic granulomatous disease. Profound and prolonged neutropenia, and corticosteroid therapy are the most important predisposing factors. Building and demolition works represent the major environmental risk factor. The diagnosis of invasive aspergillosis remains difficult to establish. Clinical manifestations are non-specific. Early thoracic computed tomographic scan shows halo sign in most cases. Subsequently appears the air crescent sign. Galactomannan research by sandwich ELISA can be useful in serum and in bronchoalveolar lavage fluid. Aspergillus DNA detection by PCR is still not standardized. Culture of the organism allows species identification. Aspergillus hyphae can be found at cytological examination, but a biopsy specimen is usually required to affirm tissue damage. A new classification of invasive fungal infections in immunocompromised patients was recently proposed by experts from the European Organization for Research and Treatment of Cancer and from the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. On the basis of host linked criteria, microbiological, clinical and radiological features, invasive aspergillosis is classified as proven, probable or possible. These definitions should not be used to guide clinical practice in therapy, but they will improve the quality of epidemiological data, and help the comparison of clinical trial results.


Asunto(s)
Aspergilosis/clasificación , Aspergilosis/diagnóstico , Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/clasificación , Enfermedades Pulmonares Fúngicas/diagnóstico , Aspergilosis/inmunología , Aspergilosis/fisiopatología , Niño , Humanos , Enfermedades Pulmonares Fúngicas/inmunología , Enfermedades Pulmonares Fúngicas/fisiopatología , Factores de Riesgo
18.
Arch Pediatr ; 7(12): 1274-83, 2000 Dec.
Artículo en Francés | MEDLINE | ID: mdl-11147061

RESUMEN

UNLABELLED: Data on disadvantaged children's health are rare in France. The objectives of this study were to compare the frequency of various health problems according to socioeconomic status and to determine if socially vulnerable children benefit from health checkups more than others. PATIENTS AND METHODS: This cross-sectional study was conducted in 5,733 children who underwent a health checkup in Paris between September and December 1998. Three groups were defined according to family income estimation and status: socially vulnerable, at risk of vulnerability, and standard. RESULTS: Health status of socially vulnerable children is characterized by a higher prevalence of significant overweight (1.2% versus 0.3% in children at risk of vulnerability and 0.4% in the standard group), iron deficiency (25.7% by age ten months versus 16.2% and 10.4%, respectively), and cavities (20.6% by age four years versus 15.6% and 6.4%, respectively). Ametropia are more frequent in children from socially vulnerable or at risk of vulnerability groups, but not often corrected. These children present more psychomotor disorders than the others. Following checkups, management of observed health problems is identical in the three groups. CONCLUSION: Prevalence of studied troubles is higher in children living in low socioeconomic condition. Following checkups, these children have access to health care services in most cases. Long-term evaluation of the benefit of such health examinations should be performed.


Asunto(s)
Servicios de Salud del Niño/estadística & datos numéricos , Accesibilidad a los Servicios de Salud , Estado de Salud , Niño , Estudios Transversales , Caries Dental/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Deficiencias de Hierro , Masculino , Obesidad/epidemiología , Paris/epidemiología , Examen Físico , Factores de Riesgo , Clase Social , Población Urbana
19.
Arch Pediatr ; 9 Suppl 1: 13s-18s, 2002 Apr.
Artículo en Francés | MEDLINE | ID: mdl-11998407

RESUMEN

Ethical dilemmas are regularly encountered in the care of patients infected with HIV (Human Immunodeficiency Virus), especially in issues regarding professional confidentiality and shared information with the child and his/her family as well as among professional health workers. This communicable disease, which can be treated but not yet cured, leads to exclusion, due to the fear of infection, to its severity and induces stigmatisation of affected individuals. It interferes with life projects, sexuality, reproductive health, family life, projection into the future. In HIV paediatrics, practitioners regularly deal with complex situations and need to balance parental authority and children's needs/dependence, respect of patient's confidentiality and hazards to another person's health, potential negative impact of disclosing information and risks attributable to the lack of information.


Asunto(s)
Confidencialidad , Ética Médica , Infecciones por VIH , Revelación de la Verdad , Adolescente , Adulto , Niño , Protección a la Infancia , Salud de la Familia , Femenino , Estado de Salud , Humanos , Masculino , Relaciones Padres-Hijo , Autonomía Personal , Sexualidad
20.
Arch Pediatr ; 6(12): 1271-8, 1999 Dec.
Artículo en Francés | MEDLINE | ID: mdl-10627897

RESUMEN

UNLABELLED: In France, the vaccination program has changed through the last years. We report a study on immunization rates of children who underwent a complete health checkup at a Well Child Clinic in Paris. We studied three groups of children (children at the ages of 10 months, 2 years and 4 years) regarding types of daycare and medical care. PATIENTS AND METHODS: Nine hundred children who underwent a health checkup between April and June 1997 were included in the study. Data were collected from immunization records and parents' interviews. RESULTS: In 10-month-old children, prevalence rates of immunization against diphtheria, tetanus, poliomyelitis and pertussis (DTPP) and immunization against Haemophilus influenzae type b (Hib) disease were 98% and 96%, respectively. Only 1.7% were immunized against measles. Forty-two percent of children had complete or ongoing immunization against hepatitis B. The vaccination coverage for BCG was 94%. In two-year-old children, boostering for DTPP vaccine had been performed by 90%, more than 90% were immunized against measles and 50% had received at least one shot to prevent hepatitis B. At the age of 4 years, 99% were immunized against DTPP, 78% were immunized against Hib disease, 98% against measles and 48% for hepatitis B. All children were immunized with BCG, and 98% were BCG-controlled (22% had tuberculin intradermal reaction). The highest immunization rates were observed in children who had preventive care in 'Maternal and Infantile Protection Centres.' Immunization rates were not influenced by the type of daycare, except for measles in two-year-old children managed by private pediatricians. CONCLUSION: We observed high immunization rates of children who underwent health checkups. Late immunization against measles and low immunization rates against hepatitis B reflect the difficulties encountered in mobilising physicians and families for these vaccinations.


Asunto(s)
Protección a la Infancia , Vacuna contra Difteria, Tétanos y Tos Ferina , Inmunización , Factores de Edad , Vacuna BCG/administración & dosificación , Preescolar , Toxoide Diftérico/administración & dosificación , Femenino , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Hepatitis B/administración & dosificación , Humanos , Inmunización Secundaria , Lactante , Masculino , Vacuna Antisarampión/administración & dosificación , Paris , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Factores Socioeconómicos , Toxoide Tetánico/administración & dosificación , Prueba de Tuberculina , Vacunación , Vacunas Combinadas/administración & dosificación
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