RESUMEN
BACKGROUND: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). PATIENTS AND METHODS: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. RESULTS: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan-Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. CONCLUSIONS: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755).
Asunto(s)
Antineoplásicos , Neoplasias Óseas , Osteosarcoma , Adolescente , Antineoplásicos/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Niño , Humanos , Radioisótopos de Yodo/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Compuestos de Fenilurea , Quinolinas , Adulto JovenRESUMEN
Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs). This stratification moved forward recently to better define these groups and their correlation to outcome. This new stratification into 7 novel subgroups was helpful to lay foundations and complementary data on the understanding regarding molecular pathways and gene mutations underlying medulloblastoma biology. This review was aimed at answering the recent key questions on MB genomics and go further in the relevance of those genes in MB development as well as in their targeted therapies.
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Neoplasias Cerebelosas/genética , Genómica/tendencias , Meduloblastoma/genética , Mutación/genética , Transducción de Señal/genética , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/terapia , Niño , Genómica/métodos , Humanos , Meduloblastoma/diagnóstico , Meduloblastoma/terapiaRESUMEN
OBJECT: Despite the improvement in the overall management of medulloblastomas in recent years, certain phenomena and in particular postoperative cerebellar swelling remain an enigma. This rare complication, little described in the literature, is nonetheless life threatening for the patients. CASE REPORTS: We report our experience about two children who developed severe cerebellar swelling with hydrocephalus and upward herniation soon after a gross total resection of a fourth ventricle medulloblastoma by a telo-velar approach. Despite rapid management of ventricular dilation and optimal medical intensive treatment of intracranial hypertension, both children died quickly after the surgery. Pathological examination analyses were in favour of anaplastic/large cell medulloblastoma. DISCUSSION: Diffuse cerebellar swelling with upward herniation may occur postoperatively in young children with anaplastic/large cell medulloblastoma with leptomeningeal spread. In the literature, only 4 cases have been so far described with delayed onset of symptoms. Two children survived with an aggressive management (decompressive surgery and early radio-chemotherapy). CONCLUSION: Cerebellar swelling is an unrecognised and sudden complication of posterior fossa surgery for metastatic anaplastic medulloblastoma with leptomeningeal dissemination in young children. An initial less invasive surgical approach could be considered in such cases, in order to prevent this complication with potentially tragic issue, and which cannot be managed with a CSF shunt alone.
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Neoplasias Cerebelosas/cirugía , Cuarto Ventrículo , Hidrocefalia/etiología , Meduloblastoma/cirugía , Complicaciones Posoperatorias/etiología , Neoplasias Cerebelosas/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Niño , Preescolar , Resultado Fatal , Femenino , Cuarto Ventrículo/diagnóstico por imagen , Humanos , Hidrocefalia/diagnóstico por imagen , Hipertensión Intracraneal/diagnóstico por imagen , Hipertensión Intracraneal/etiología , Masculino , Meduloblastoma/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagenRESUMEN
PURPOSE: Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. PATIENTS AND METHODS: Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. RESULTS: After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. CONCLUSION: These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols.
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Neoplasias Cerebelosas/mortalidad , Neoplasias Cerebelosas/terapia , Meduloblastoma/mortalidad , Meduloblastoma/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/líquido cefalorraquídeo , Neoplasias Cerebelosas/patología , Quimioterapia Adyuvante , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Lactante , Masculino , Meduloblastoma/líquido cefalorraquídeo , Meduloblastoma/patología , Metotrexato/administración & dosificación , Neoplasia Residual/patología , Procarbazina/administración & dosificación , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Vincristina/administración & dosificaciónRESUMEN
INTRODUCTION: Diffuse intrinsic pontine gliomas (DIPG) constitute 10-15% of all brain tumors in the pediatric population; currently prognosis remains poor, with an overall survival of 7-14 months. Recently the indication of DIPG biopsy has been enlarged due to the development of molecular biology and various ongoing clinical and therapeutic trials. Classically a biopsy is performed using a stereotactic frame assisted procedure but the workflow may sometimes be heavy and more complex especially in children. In this study the authors present their experience with frameless robotic-guided biopsy of DIPG in a pediatric population. PATIENTS AND METHODS: Retrospective study on a series of five consecutive pediatric patients harboring DIPG treated over a 4-year period. All patients underwent frameless robotic-guided biopsy via a transcerebellar approach. RESULTS: Among the 5 patients studied 3 were male and 2 female with a median age of 8.6 years [range 5 to 13 years]. Clinical presentation included ataxia, hemiparesis and cranial nerve palsy in all patients. MRI imaging of the lesion showed typical DIPG features (3 of them located in the pons) with hypo-intensity on T1 and hyper-intensity signal on T2 sequences and diffuse gadolinium enhancement. The mean procedure time was 56minutes (range 45 to 67minutes). No new postoperative neurological deficits were recorded. Histological diagnosis was achieved in all cases as follows: two anaplastic astrocytomas (grade III), two glioblastomas, and one diffuse astrocytoma (grade III). CONCLUSION: Frameless robotic assisted biopsy of DIPG in pediatric population is an easier, effective, safe and highly accurate method to achieve diagnosis.
Asunto(s)
Astrocitoma/diagnóstico por imagen , Biopsia/métodos , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Glioblastoma/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Neuronavegación/métodos , Robótica , Adolescente , Astrocitoma/diagnóstico , Astrocitoma/patología , Astrocitoma/cirugía , Neoplasias del Tronco Encefálico/diagnóstico , Neoplasias del Tronco Encefálico/patología , Neoplasias del Tronco Encefálico/cirugía , Niño , Preescolar , Femenino , Glioblastoma/diagnóstico , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9â years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27â months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Colorrectales/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Proteínas Adaptadoras Transductoras de Señales/genética , Adenosina Trifosfatasas/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Niño , Preescolar , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Femenino , Humanos , Lactante , Masculino , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/genética , Mutación , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/terapia , Proteínas Nucleares/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
Medulloblastoma are cerebellar tumours belonging to the group of primitive neuroectodermal tumours (PNET) and are the most common malignant brain tumours of childhood. These tumours are rare and heterogeneous, requiring some multicentric prospective studies and multidisciplinary care. The classical therapeutic approaches are based on clinical, radiological and surgical data. They involve surgery, radiation therapy and chemotherapy. Some histological features were added to characterize risk. More recently, molecular knowledge has allowed to devise risk-adapted strategies and helped to define groups with good outcome and reduce long-term sequelae, improve the prognostic of high-risk medulloblastoma and develop new therapeutic tools.
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Neoplasias Cerebelosas/terapia , Meduloblastoma/terapia , Adulto , Neoplasias Cerebelosas/clasificación , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/metabolismo , Quimioterapia Adyuvante , Niño , Discapacidades del Desarrollo/etiología , Predisposición Genética a la Enfermedad , Proteínas Hedgehog/metabolismo , Humanos , Imagen por Resonancia Magnética , Meduloblastoma/clasificación , Meduloblastoma/diagnóstico , Meduloblastoma/metabolismo , Mutismo/etiología , Recurrencia Local de Neoplasia , Cuidados Posoperatorios , Pronóstico , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Proteínas Wnt/metabolismoAsunto(s)
Tronco Encefálico/inmunología , Tronco Encefálico/patología , Proteínas ELAV/sangre , Proteínas ELAV/líquido cefalorraquídeo , Ganglioneuroblastoma/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Femenino , Ganglioneuroblastoma/diagnóstico por imagen , Humanos , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico por imagen , Síndromes Paraneoplásicos del Sistema Nervioso/patología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Lynch syndrome (LS) is an autosomal dominant disorder caused by a defect in one of the DNA mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. In the last 15 years, an increasing number of patients have been described with biallelic mismatch repair gene mutations causing a syndrome referred to as 'constitutional mismatch repair-deficiency' (CMMR-D). The spectrum of cancers observed in this syndrome differs from that found in LS, as about half develop brain tumours, around half develop digestive tract cancers and a third develop haematological malignancies. Brain tumours and haematological malignancies are mainly diagnosed in the first decade of life, and colorectal cancer (CRC) and small bowel cancer in the second and third decades of life. Surveillance for CRC in patients with LS is very effective. Therefore, an important question is whether surveillance for the most common CMMR-D-associated cancers will also be effective. Recently, a new European consortium was established with the aim of improving care for patients with CMMR-D. At a workshop of this group held in Paris in June 2013, one of the issues addressed was the development of surveillance guidelines. In 1968, criteria were proposed by WHO that should be met prior to the implementation of screening programmes. These criteria were used to assess surveillance in CMMR-D. The evaluation showed that surveillance for CRC is the only part of the programme that largely complies with the WHO criteria. The values of all other suggested screening protocols are unknown. In particular, it is questionable whether surveillance for haematological malignancies improves the already favourable outcome for patients with these tumours. Based on the available knowledge and the discussions at the workshop, the European consortium proposed a surveillance protocol. Prospective collection of all results of the surveillance is needed to evaluate the effectiveness of the programme.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Trastornos por Deficiencias en la Reparación del ADN/genética , Neoplasias del Sistema Digestivo/diagnóstico , Neoplasias/diagnóstico , Neoplasias Encefálicas/etiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/tratamiento farmacológico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Trastornos por Deficiencias en la Reparación del ADN/complicaciones , Humanos , Leucemia/diagnóstico , Mutación , Neoplasias/etiología , Vigilancia de la PoblaciónRESUMEN
BACKGROUND: The majority of children under 3 years require anesthesia for radiotherapy. METHODS: This work reports the experience of Paul-Strauss Center over a 4-year period on 15 children and covering 386 general anesthesia. RESULTS AND CONCLUSION: The rate of anesthesia-related complications was low (0.5%) subject to the experience of the anesthesiologists and follow-up recommendations.
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Neoplasias Abdominales/psicología , Neoplasias Abdominales/radioterapia , Anestesia General , Neoplasias Encefálicas/psicología , Neoplasias Encefálicas/radioterapia , Preescolar , Humanos , Lactante , Máscaras Laríngeas , Monitoreo Fisiológico , Radioterapia/efectos adversos , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Foxn1 transcription factor deficit leads to immune deficiency, with hair and nail abnormalities. We report the case of a patient also presenting localized leucoderma. CASE REPORT: A 3-year-old boy underwent thymus transplantation at the age of 9 months for Foxn1 deficiency. He had developed urticaria and autoimmune hypothyroidism after thymus grafting. On examination, he had universal non-scarring alopecia, nail changes (atrophy, partial onycholysis and longitudinal grooves) and leucoderma on both big toes. DISCUSSION: This is the first description of leucoderma occurring in a patient with Foxn1 deficiency, as well as the first report of this pigment abnormality following thymus transplantation. The pathogenic hypotheses discussed were post-graft vitiligo and leucoderma induced by Foxn1 deficiency.
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Factores de Transcripción Forkhead/deficiencia , Factores de Transcripción Forkhead/genética , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/cirugía , Complicaciones Posoperatorias/genética , Timo/trasplante , Vitíligo/genética , Alelos , Alopecia/genética , Preescolar , Exones/genética , Estudios de Seguimiento , Tamización de Portadores Genéticos , Humanos , Lactante , Masculino , Mutación Missense/genética , Uñas Malformadas/genéticaAsunto(s)
Docentes Médicos , Pediatría/educación , Selección de Profesión , Movilidad Laboral , Niño , Francia , Humanos , Selección de Personal , Edición , Investigación , Facultades de MedicinaRESUMEN
AIM OF THE STUDY: The purpose of this study was to report in acute childhood idiopathic thrombocytopenic purpura (ITP) the current practices of French paediatric hematologists and to compare them to recent publications of American and British teams. METHOD: A questionnaire was sent online to the members of the French Society of Pediatric Hematology/Immunology (SHIP). This questionnaire, adapted from a similar american study conducted in 2001, asked 16 questions based on the clinical presentation of a 5-year-old boy referred for an acute ITP. RESULTS: 59/123 SHIP members responded to the survey. In response to question regarding initial treatment, 86% of physicians would be given active treatments and only 9% would rarely or never administer any drug. When asked which agent would be used in case of treatment, 68% would choose to prescribe intravenous immunoglobulins and 32% corticosteroids, nobody recommended the use of anti-D immunoglobulins. Furthermore, 83% would usually hospitalize such a child. CONCLUSION: Finally, this study allowed us to update the current French management of treating pediatric ITP which is almost comparable among this subset of pediatric hematologists, but showed some discrepancies comparatively to the American and British studies.
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Pautas de la Práctica en Medicina/estadística & datos numéricos , Púrpura Trombocitopénica Idiopática/terapia , Corticoesteroides/uso terapéutico , Niño , Francia , Hospitalización , Humanos , Inmunoglobulinas Intravenosas , Sociedades Médicas , Encuestas y CuestionariosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Hepáticas/terapia , Neoplasias/terapia , Neutropenia/terapia , Trasplante de Células Madre , Suero Antilinfocítico/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Busulfano/administración & dosificación , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Lactante , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias/complicaciones , Neoplasias/diagnóstico por imagen , Neutropenia/sangre , Neutropenia/complicaciones , Radiografía , Trasplante HomólogoRESUMEN
OBJECTIVES: Combination of caspofungin and another anti-fungal agent raise expectation of improved efficacy in severe fungal infections including failures to first line therapy. METHODS: We assessed the efficacy and safety of a combination therapy including caspofungin in 17 immunosuppressed or postoperative patients progressive despite standard anti-fungal therapy. RESULTS: The infections included aspergillosis (6), invasive candidiasis (9), mucormycosis (1) and Scedosporium pneumonia (1). Infections had failed one to four prior lines of treatment. The anti-fungal agent combined to caspofungin was either an amphotericin B formulation or an azole. There were 12 favourable responses (71%) and five failures. The survival rate at 3 months was 47%. Eleven patients died within 2-533 days. The causes of death included the initial fungal infection (4), relapse of the infection after switching to oral monotherapy (2), breakthrough aspergillosis (1), and the underlying condition (4). Clinical and renal tolerance were good. Significant hepatic abnormalities were recorded in eight (50%) of the 16 patients evaluable for biological tolerance. CONCLUSION: Caspofungin combined with an azole or with amphotericin B may be of interest in the treatment of serious fungal infections after failure of conventional therapy. Close monitoring of hepatic function is required. These approach should be evaluated in prospective trials.
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Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Fluconazol/administración & dosificación , Fluconazol/uso terapéutico , Micosis/tratamiento farmacológico , Péptidos Cíclicos/administración & dosificación , Péptidos Cíclicos/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anfotericina B/efectos adversos , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Caspofungina , Preescolar , Quimioterapia Combinada , Equinocandinas , Humanos , Lipopéptidos , Persona de Mediana Edad , Péptidos Cíclicos/efectos adversos , Factores de RiesgoRESUMEN
The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos Antineoplásicos/normas , Trasplante de Médula Ósea , Leucemia Mieloide Aguda/terapia , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Idarrubicina/uso terapéutico , Lactante , Recién Nacido , Leucemia Mieloide Aguda/mortalidad , Masculino , Mitoxantrona/uso terapéutico , Inducción de Remisión , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
UNLABELLED: Asparaginase is frequently used in the treatment of lymphoblastic malignancies in children and is a major cause of drug-induced acute pancreatitis. Severe cases of iatrogenic pancreatitis are uncommon but potentially lethal, and represent a diagnostic and therapeutic challenge. PATIENTS AND METHOD: We have retrospectively collected pediatric cases of severe acute pancreatitis induced by asparaginase, having occurred since January 1996 in participating centers from France and Belgium. RESULTS: Eleven patients, between four and 15 years old, have been included. Pancreatitis has been observed in all treatment phases, after 6 to 21 doses of asparaginase, 2 to 16 days after the last injection. Circulatory collapse (5/11), insulin-dependent diabetes (6/11) and pancreatic pseudokysts (7/11) were the major complications. Non-surgical treatment mainly included digestive rest, broad-spectrum antibiotic therapy and prolonged use of morphine. Asparaginase has been eventually reintroduced in three cases, and has caused a recurrence of pancreatitis in two of them. CONCLUSION: Intensive supportive management should enable a favourable outcome in most cases of acute pancreatitis induced by asparaginase in children. There is no way to predict the occurrence of this adverse event. Re-use of asparaginase should probably be ruled out.
Asunto(s)
Asparaginasa/efectos adversos , Pancreatitis/inducido químicamente , Enfermedad Aguda , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Pancreatitis/terapia , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
UNLABELLED: Rarely children with Wilms' tumor develop spinal cord dysfunction by metastatic spread into the epidural space or the cord parenchyma. In the case reported here, the mechanism of spinal compression was different. CASE REPORT: The authors report the clinical course of a 2-month-old boy with retroperitoneal extrarenal Wilms' tumor below the left kidney, characterized with a spinal cord compression developed through the intervertebral foramina. CONCLUSION: Abdominal tumor, usually corresponding to neuroblastoma, may be a nephroblastoma.
Asunto(s)
Neoplasias Renales/complicaciones , Compresión de la Médula Espinal/etiología , Tumor de Wilms/complicaciones , Humanos , Lactante , Masculino , Espacio Retroperitoneal/patologíaRESUMEN
At present, the only recognised prognostic factor for primary osteosarcoma is the histological response to preoperative chemotherapy. Our study was designed to identify new diagnostic markers that could eventually have a prognostic value. A total of 54 patients under 20 years of age with primary osteosarcomas were studied while under treatment by the French Society of Paediatric Oncology OS 94 protocol. Paired normal and biopsy samples were collected. In addition, surgical resection specimens, following preoperative chemotherapy, were obtained in 13 cases. After genomic DNA extraction, an allelotyping analysis targeting microsatellites linked to Rb and p53 genes, and 9p21, 7q31 and 5q21 regions was performed. In all, 94% of the samples at diagnosis showed allelic imbalance and the biopsies were highly rearranged except for the microsatellite targeting 7q31. The same panel was highly informative at surgical resection. Microsatellites investigating Rb, p53 and the 9p21 region were particularly altered without a significant correlation with prognosis. On the other hand, the alteration of the 7q31 locus at diagnosis was significantly correlated with a worse prognosis and a new frequently altered locus, 5q21, was described. In conclusion, this panel allowed us to characterise paediatric osteosarcomas. Correlation of prognosis with the altered 7q31 region could be a useful tool and further studies are required to confirm the importance of 5q21.
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Neoplasias Óseas/genética , Osteosarcoma/genética , Adolescente , Adulto , Biopsia , Neoplasias Óseas/tratamiento farmacológico , Niño , Preescolar , Femenino , Genotipo , Humanos , Masculino , Repeticiones de Microsatélite , Osteosarcoma/tratamiento farmacológico , PronósticoRESUMEN
Topoisomerase genes were analyzed at both DNA and RNA levels in 25 cases of newly diagnosed childhood acute lymphoblastic leukemia (ALL). The results of molecular analysis were compared to risk group classification of children in order to identify molecular characteristics associated with response to therapy. At diagnosis, allelic imbalance at topo-isomerase IIalpha (TOP2A) gene locus was found in 75% of informative cases whereas topoisomerase I and IIbeta gene loci are altered in none or only one case, respectively. By semi-quantitative Polymerase chain reaction, we found a 2.5 to 8-fold TOP2A gene amplification in 72% of the children, which was correlated to gene overexpression in every case. These results show that TOP2A gene amplification is a frequent event in ALL at diagnosis. Interestingly, we also identified a small population of children that do not present TOP2A gene amplification or gene overexpression and who are significantly associated with very high risk classified patients showing glucocorticoid resistance. In conclusion, characterization of TOP2A gene status in childhood ALL at diagnosis provides useful complementary information for risk assessment.