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 ProgresiónRESUMEN
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 JovenRESUMEN
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 EspecificidadRESUMEN
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.
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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 TratamientoAsunto(s)
Leucemia Mieloide Aguda/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Calidad de Vida , Antineoplásicos/efectos adversos , Supervivientes de Cáncer , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Recién Nacido , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
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 TejidosRESUMEN
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.
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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 JovenRESUMEN
OBJECTIVES: To assess whether maternal HIV-positive status negatively affects family construction and the child's psychological environment. Could this be responsible for behavioral problems observed in children infected with or affected by HIV? MATERIAL AND METHODS: Interviews were conducted with 60 HIV+ mothers and their infants during the perinatal period, within 3 months of delivery, collected at the time of a pediatric outpatient visit within a PMTCT program. RESULTS: Half of the 60 mothers did not live with the infant's father, 56% of multiparous mothers were separated from their previous children. Sixty-five percent of the fathers were informed of the mother's HIV-positive status, although 90% of fathers who lived with the mothers were informed. During pregnancy, 80% of mothers reported psychological stress; after delivery, 72% of mothers suffered from not being allowed to breastfeed their infants, 43.5% expressed a fear of transmitting the infection to the child, and 40% avoided contacts with the infant. The impact of the mother's psychological stress and anxiety related to the risk of HIV transmission through breastfeeding and casual contacts were already noticeable in the first mother-child interrelations. CONCLUSIONS: Although the risk of MTC transmission in now very small, psychological troubles related to maternal HIV status may negatively affect the children's well-being and behavior, psychological support should be provided for mothers and children as part of comprehensive services.
Asunto(s)
Ansiedad , Lactancia Materna/psicología , Infecciones por VIH/psicología , Conducta Materna/psicología , Periodo Posparto , Refugiados/psicología , Estrés Psicológico , Adulto , África , Ansiedad/psicología , Composición Familiar , Conflicto Familiar/psicología , Femenino , Francia/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Humanos , Lactante , Conducta del Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Relaciones Madre-Hijo , Embarazo , Refugiados/estadística & datos numéricos , Factores de Riesgo , Medio Social , Apoyo Social , Encuestas y CuestionariosAsunto(s)
Infecciones por VIH/diagnóstico , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/diagnóstico , Embarazo en Adolescencia , Aborto Eugénico , Aborto Inducido , Adolescente , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Francia , Infecciones por VIH/prevención & control , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/terapiaRESUMEN
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 VerdadRESUMEN
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.
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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 RiesgoAsunto(s)
Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Niño , Preescolar , Humanos , LactanteAsunto(s)
Infecciones por VIH/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Francia , Infecciones por VIH/transmisión , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Embarazo , Pubertad , Resultado del TratamientoAsunto(s)
Neoplasias Hematológicas/terapia , Neoplasias/terapia , Sobrevivientes , Actividades Cotidianas/psicología , Adolescente , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Niño , Preescolar , Terapia Combinada/efectos adversos , Femenino , Francia , Neoplasias Hematológicas/psicología , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/psicología , Recurrencia Local de Neoplasia/terapia , Neoplasias/psicología , Grupo de Atención al Paciente , Calidad de Vida/psicología , Radioterapia/efectos adversos , Sistema de Registros , Factores de Riesgo , Rol del Enfermo , Sobrevivientes/psicologíaRESUMEN
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.
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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 PsicológicoRESUMEN
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.
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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 , VoriconazolRESUMEN
GOALS OF WORK: We evaluated piperacillin-tazobactam in association with netilmicin (TN) in the early empirical treatment of neutropenic children, as data are limited in number. PATIENTS AND METHOD: In 1996, an observational study was initiated to assess the efficacy and safety of this association, with a glycopeptide (TNG) if needed. The impact on the bacterial ecology of our unit was also observed. Children were treated for hematological malignancy or solid tumor between September 1996 and December 1998 and presented a febrile neutropenia. RESULTS: There were 148 evaluable febrile neutropenic episodes in 104 patients. Median age was 7 years, 55% of the episodes were fever of unknown origin, 22% were clinically documented and 23% microbiologically documented (27 bacteriemia). A glycopeptide was added in 67 episodes. The initial unmodified treatment was successful in 114 episodes (77%): 75/81 episodes in the TN group and 39/67 in the TNG group. For successful episodes, median treatment duration was 6 days. There were 22 febrile recurrences. These patients, as well as initial failures, always responded to a second-line treatment. One child was considered a failure because he developed a skin rash probably due to piperacillin-tazobactam and required another beta-lactamase. CONCLUSION: This study suggests that piperacillin-tazobactam in association with netilmicin presents a satisfactory efficacy and a good tolerance as empirical therapy for febrile neutropenic children. It allowed us to maintain the bacterial ecology of our unit.
Asunto(s)
Antibacterianos/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Fiebre/inducido químicamente , Fiebre/tratamiento farmacológico , Netilmicina/uso terapéutico , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Adolescente , Antibacterianos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Niño , Preescolar , Quimioterapia Combinada , Inhibidores Enzimáticos/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Netilmicina/administración & dosificación , Ácido Penicilánico/administración & dosificación , Piperacilina , Recurrencia , Tazobactam , Resultado del TratamientoRESUMEN
BACKGROUND: In order to lower the long-term toxicity of chemotherapy for hepatoblastoma patients, a prospective study was designed based on pre-operative chemotherapy combining carboplatin and epirubicin (CE). PROCEDURES: Patients under 16 years of age with an epithelial hepatic tumor diagnosed by ultrasound or CT scan and a high serum alpha-foetoprotein (AFP) level were eligible. Patients were treated with a pre-operative chemotherapy regimen combining carboplatin 600 mg/m(2) and epirubicin 80 mg/m(2). Tumor resectability was assessed after four courses given at 3-week intervals. After surgery, patients were given two more courses of CE. Response was assessed based on a drop in serum AFP and tumor shrinkage. RESULTS: Between July 1988 and August 1995, 27 patients with a hepatoblastoma were included. The initial PRETEXT group according to the SIOPEL classification was: group 2 (5 pts), group 3 (15 pts), group 4 (5 pts), and 2 pts were not assessed. Six patients had lung metastases. Response was partial response (PR) in 20/27 (74%) patients, disease was stable in 3 and 4 had progressive disease (PD). A complete surgical resection was performed in 21 pts. Five-year overall and disease-free survival (DFS) were respectively 56% (95%CI: 37-72%) and 63% (95%CI: 44-78%). During the same time period, 7 pts with a hepatocellular carcinoma were treated according to this protocol. Only one achieved a PR. Toxicity was mostly hematologic with > or =grade 3 leukopenia in 23% of the courses, > or =grade 3 thrombocytopenia in 29% of the courses and anemia in 22%. CONCLUSION: The CE protocol is feasible and efficient in hepatoblastoma. However, only a randomized study will permit a valid comparison of the efficacy of cisplatin and carboplatin for the treatment of these patients.