RESUMEN
AIM: Improvement of EFS of children older than 3 years with high risk medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas , Meduloblastoma , Adolescente , Carboplatino/administración & dosificación , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/radioterapia , Neoplasias Cerebelosas/cirugía , Niño , Preescolar , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Humanos , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/radioterapia , Meduloblastoma/cirugía , Cuidados Posoperatorios , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
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
Allogeneic stem cell transplantation (allo-SCT) has become an essential component of the treatment for a variety of diseases in pediatric patients. During the past decades, advances in the transplant technology, availability of hematopoietic stem cells and supportive care not only have resulted in improved outcomes, but also have expanded the transplant options. However, these features have been studied mainly in adult populations. This investigation analyzed changes in patient profile, transplantation, graft characteristics and outcome among 250 children and adolescent patients who received allo-SCT in a single center between 1983 and 2010. In the 2000-2010, compared with the 1983-1999 period, a significantly higher 5-year overall survival (64% versus 52%, P=0.03) was observed together with a significant decrease of non-relapse mortality (27% versus 9%, P=0.0002). The progression-free survival was comparable between the two periods (49% versus 57%; P=0.17). The 5-year cumulative incidence of relapse was 24% between 1983 and 1999, and 34% between 2000 and 2010 (P=0.08). Major advances in supportive care practice have been made over the past decade, resulting in a significant survival benefit for the pediatric population undergoing allo-SCT. However, post-transplant relapse remains the leading cause of failure of this therapeutic approach, and preventing relapse represents a major challenge today.
Asunto(s)
Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Lactante , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Children with B cell non-Hodgkin's lymphoma who have not relapsed 1 year after diagnosis and treatment are generally cured. We report here the results of treatment in 114 children who all had a minimum follow-up of 20 months. The protocol LMB 0281 from the French Pediatric Oncology Society was used. This nine-drug intensive-pulsed chemotherapy was based on high-dose cyclophosphamide, high-dose methotrexate (HD MTX), and cytosine arabinoside (ara-C) in continuous infusion. CNS prophylaxis was with chemotherapy only. No local irradiation was performed. No debulking surgery was recommended. There were 72 patients with stage III lymphoma and 42 patients with stage IV lymphoma or B cell acute lymphocytic leukemia (B-ALL). Among those 42 patients, seven had CNS involvement alone, 21 had bone marrow alone, and 14 had both; 26 had greater than 25% blast cells in bone marrow, 14 of whom had blast cells in blood. The primary site of involvement was the abdomen in 90 patients, the Waldeyer Ring in nine, and various sites in eight; seven patients presented without tumor. Seventy-seven patients are alive with a median follow-up of 2 years and 8 months. Seven patients died due to initial treatment failure, 11 died from toxicity, and 19 died after relapse. Among the 93 patients without initial CNS involvement, only one isolated relapse in CNS occurred. Survival and disease-free survival rates reached 67% and 64%, respectively, for all patients, 75% and 73% for stage III patients and 54% and 48% for stage IV and B-ALL patients. Bone marrow involvement was not an adverse prognostic factor. Contrary initial CNS involvement indicated a bad prognosis with a disease-free survival rate of 19% compared with 76% without CNS disease. This study showed that CNS prophylaxis and local control of the primary tumor can be achieved by intensive chemotherapy alone, without radiotherapy or debulking surgery.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfocitos B/patología , Leucemia Linfoide/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfocitos B/inmunología , Enfermedades de la Médula Ósea/tratamiento farmacológico , Niño , Preescolar , Ensayos Clínicos como Asunto , Esquema de Medicación , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Leucemia Linfoide/sangre , Leucemia Linfoide/mortalidad , Linfoma/sangre , Linfoma/mortalidad , Masculino , Estadificación de Neoplasias , Neoplasias del Sistema Nervioso/tratamiento farmacológico , Virosis/inducido químicamenteRESUMEN
PURPOSE: The in vivo response to prephase corticosteroid therapy for 1 week has been described as a major prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are considered responders and have a better prognosis. This prephase therapy is usually considered as an evaluation of glucocorticoid sensitivity. In fact, it also includes one intrathecal (IT) injection of methotrexate (MTX). In this study, we try to clarify the influence of this injection of IT MTX on the response to the prephase therapy. PATIENTS AND METHODS: This retrospective study analyzed the response to prephase therapy in 1,044 children with ALL entered onto the European Organization for Research and Treatment of Cancer (EORTC) trial 58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was restricted to 732 cases with an initial blast count greater than 1,000/microL. The following variables were tested to analyze response to prephase therapy: age, sex, evaluated risk factor (RF), blast count on day 0, actual dose of prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For statistical analysis, the variable day of IT MTX (D) was stratified into three groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3 if D greater than 6. RESULTS: All variables tested had a significant influence on response to the prephase therapy. This was especially true for IT MTX: 90.4% responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001). Immunophenotype was also a major predictor of response to the prephase: 88% responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a significant influence in B-lineage ALL (96% responders in group 1, 90% in group 2, and 79% in group 3; P < .001), whereas the influence could not be detected in T-lineage ALL. CONCLUSION: These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only. Earlier use of IT MTX leads to a higher percentage of responders.
Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Metotrexato/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Crisis Blástica/tratamiento farmacológico , Crisis Blástica/patología , Recuento de Células , Niño , Preescolar , Femenino , Humanos , Lactante , Inyecciones Espinales , Masculino , Metotrexato/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Prednisolona/administración & dosificación , Estudios RetrospectivosRESUMEN
PURPOSE: The European Organization for Research and Treatment of Cancer 58881 study was designed to test in a prospective multicentric randomized trial the value of high-dose (HD) intravenous (IV) cytarabine (Ara-C) added to HD IV methotrexate (MTX) to reduce the incidence of CNS and systemic relapses in children with increased-risk acute lymphoblastic leukemia (ALL) or stage III and IV lymphoblastic lymphoma treated with a Berlin-Frankfurt-Munster (BFM)-based regimen. PATIENTS AND METHODS: After completion of induction-consolidation phase, children with increased-risk (risk factor > 0.8 or T-lineage) ALL or stage III and IV lymphoblastic lymphoma were randomized to receive four courses of HD MTX (5 g/m(2) over 24 hours every 2 weeks) and four intrathecal administrations of MTX (Arm A) or the same treatment schedule with additional HD IV Ara-C (1 g/m(2) in bolus injection 12 and 24 hours after the start of each MTX infusion) (Arm B). RESULTS: Between January 1990 and January 1996, 653 patients with ALL (593 patients) or lymphoblastic lymphoma (60 patients) were randomized: 323 were assigned to Arm A (without Ara-C) and 330 to Arm B (with Ara-C). A total of 190 events (177 relapses and 13 deaths without relapse) were reported, and the median follow up was 6.5 years (range, 2 to 10 years). The incidence rates of CNS relapse were similar in both arms whether isolated (5.6% and 3.3%, respectively) or combined (5.3% and 4.6%, respectively). The estimated 6-year disease-free survival (DFS) rate was similar (log-rank P =.67) in the two treatment groups: 70.4% (SE = 2.6%) in Arm A and 71.0% (SE = 2.5%) in Arm B. The 6-year DFS rate was similar for ALL and LL patients: 70.2% (SE = 1.9%) versus 76.3% (SE = 5.6%). CONCLUSION: Prevention of CNS relapse was satisfactorily achieved with HD IV MTX and intrathecal injections of MTX in children with increased-risk ALL or stage III and IV lymphoblastic lymphoma treated with our BFM-based treatment protocol in which cranial irradiation was omitted. Disappointingly, with the dose schedule used in this protocol, HD Ara-C added to HD MTX, although well tolerated, failed to further decrease the incidence of CNS relapse or to improve the overall DFS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Citarabina/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Análisis Actuarial , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Sistema Nervioso Central/patología , Niño , Preescolar , Citarabina/efectos adversos , Daunorrubicina/administración & dosificación , Supervivencia sin Enfermedad , Sinergismo Farmacológico , Europa (Continente)/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Infusiones Intravenosas , Inyecciones Espinales , Infiltración Leucémica/epidemiología , Infiltración Leucémica/prevención & control , Masculino , Metotrexato/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Prednisona/administración & dosificación , Análisis de Regresión , Riesgo , Vincristina/administración & dosificaciónRESUMEN
We present here the long-term results of three randomized clinical trials conducted on children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1983 and 1998 by the Children Leukemia Cooperative Group (CLCG) from EORTC. In study 58831/32, the overall event-free survival (EFS) rates (+/- s.e.) at 6 and 10 years were 66% +/- 1.8% and 65% +/- 1.8%, respectively, and the risk of isolated central nervous system (CNS) relapse was 6% +/- 1% and 7% +/- 1%, respectively. In patients with a standard risk of relapse the omission of cyclophosphamide had no adverse effect on disease-free survival rates at 10 years (trial 58831). In medium- and high-risk patients the omission of radiotherapy did not increase the risk of CNS or systemic relapse (trial 58832). In study 58881 (1989-1998) the overall EFS rate at 8 years was 68.4% +/- 1.2% and the risk of isolated CNS relapse was 4.2%+/-0.5%. In this trial which adressed three randomized questions, the following results were obtained: the combination of cytarabine at high doses with methotrexate at high doses during interval therapy did not improve prognosis. The addition of 6-mercaptopurine iv during maintenance increased the risk of late relapse. E. coli asparaginase was more toxic and has a higher efficacy than Erwinia asparaginase. Leukocyte counts >100 x 10(9)/l, specific genetic abnormalities, a poor initial response to steroids or a high level of minimal residual disease at early time points were consistently associated with an adverse prognosis in the 58881 trial.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Supervivencia sin Enfermedad , Humanos , Pronóstico , Recurrencia , Inducción de RemisiónRESUMEN
Forty-six children with juvenile myelomonocytic leukemia (JMML) diagnosed between 1978 and 1993 in 12 centers were retrospectively studied. There is no evidence that any conventional treatment influences the long-term evolution of JMML. Among 28 patients treated without bone marrow transplantation (BMT), 26 died (median survival: 17 months), two are alive, one in complete remission (CR) after intensive chemotherapy. Allogenic BMT is the best treatment: 18 patients underwent BMT, 11 are in CR (at 9, 15, 22, 25, 41, 45, 49, 53, 66, 90 and 108 months). Conditioning regimens using chemotherapy alone may cure some patients (3/6) occasionally despite autologous reconstitution (1/3); if relapse occurs, a second BMT may be curative (2/3). Among the 12 patients conditioned immediately with TBI, six are in CR, one is in relapse, five died (one of them in durable autologus CR from Schwannoma). It is our opinion that splenectomy is of therapeutic value and seems not to have influenced the incidence of infections complications. We found no argument in favor of intensive chemotherapy before conditioning. Results with HLA-matched unrelated donors are satisfactory. One patient relapsed at 4 months after an unrelated BMT and entered a new CR after discontinuation of cyclosporine.
Asunto(s)
Leucemia Mielomonocítica Aguda/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Terapia Combinada , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Hidroxiurea/administración & dosificación , Factores Inmunológicos/uso terapéutico , Lactante , Interferones/uso terapéutico , Isotretinoína/uso terapéutico , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/mortalidad , Tablas de Vida , Masculino , Mercaptopurina/administración & dosificación , Inducción de Remisión , Estudios Retrospectivos , Esplenectomía , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Irradiación Corporal TotalRESUMEN
We report the case of a 19 month old boy referred to our institution because of a pelvic tumor initially identified as an embryonal rhabdomyosarcoma and treated with surgery and chemotherapy. Eight years after the initial surgery, a local tumor recurrence with bone metastasis was found. Histological examination and immunohistochemistry showed a double differentiation with both muscular and neuronal cells. This double differentiation was retrospectively found in the initial tumor, then allowing the diagnosis of malignant ectomesenchymoma also called gangliorhabdomyosarcoma. This rare tumor, occurring mainly during childhood, is composed of neuroblasts and / or ganglion cells and of malignant mesenchymal cells (usually rhabdomyosarcomatous cells).
Asunto(s)
Mesenquimoma/patología , Neoplasias Pélvicas/patología , Rabdomiosarcoma/patología , Neoplasias Óseas/secundario , Diferenciación Celular , Diagnóstico Diferencial , Resultado Fatal , Neoplasias Femorales/secundario , Ganglios/patología , Humanos , Inmunohistoquímica , Lactante , Masculino , Mesenquimoma/tratamiento farmacológico , Mesenquimoma/cirugía , Recurrencia Local de Neoplasia , Neuronas/patología , Neoplasias Pélvicas/tratamiento farmacológico , Neoplasias Pélvicas/cirugía , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/cirugía , Rabdomiosarcoma EmbrionarioRESUMEN
BACKGROUND: Pyknodysostosis is characterized by post-natal onset of short-limbed short stature and generalized hyperostosis. It must be differentiated from osteopetrosis with precocious manifestations in which hyperostosis may crowd the marrow cavity with extramedullary hematopoiesis. CASE REPORTS: A boy, born from consanguineous parents presented with classical features of pyknodysostosis: short-limbed stature, large skull, frontal bossing, wide anterior fontanelle and tendency to fracture. His sister had the same features at the age of 3 months; she had hepatosplenomegaly at the age of 5 months with anemia, erythroblastosis (13%), myelemia and, at 10 months, thrombocytopenia. CONCLUSION: Hyperosostis can be complicated by development of such severe hematological manifestations as classically seen in osteopetrosis. Differential diagnosis between both entities is based upon radioclinical investigation.
Asunto(s)
Disostosis Craneofacial/sangre , Disostosis Craneofacial/genética , Enanismo/genética , Hiperostosis/genética , Osteopetrosis/genética , Disostosis Craneofacial/diagnóstico , Enanismo/sangre , Femenino , Enfermedades Hematológicas/etiología , Hematopoyesis Extramedular , Humanos , Hiperostosis/sangre , Lactante , Recién Nacido , Masculino , Osteopetrosis/sangreRESUMEN
Due to the action of the drugs and the position of the patient, general anaesthesia in a child with a mediastinal tumor can complete the obstruction of the trachea and/or the main bronchi and possibly result in irreversible respiratory failure. The risk is directly linked to the degree of lumen amputation of the trachea, usually evaluated by CT-scan: there is a risk of accident if the degree of lumen amputation is greater than 30%. The case reports underline the value of the flexible fibreoptic bronchoscopy under local anaesthesia. This examination, as well as the CT-scan, allows to evaluate the degree of tracheal compression. Moreover, it carries a lower risk than the CT-scan which requires, in a small child, either general anaesthesia or heavy premedication which could lead to asphyxia. Total obstruction most often occurs with anterior mediastinal tumors. However, even posterior or lateral tumors can extend to an anterior position, especially in the young child. If the obstruction of the lumen is greater than 30% and if general anaesthesia is required, the fibreoptic bronchoscopy allows endotracheal intubation under local anaesthesia before general anaesthesia. We report 5 cases which illustrate the risk of tracheal compression during general anaesthesia in patients with a mediastinal tumor and substantiate the advantages of a flexible fibreoptic bronchoscope in the management of these patients before and during general anaesthesia.
Asunto(s)
Anestesia General/métodos , Enfermedades del Mediastino/complicaciones , Tráquea/fisiopatología , Anestesia General/efectos adversos , Quiste Broncogénico/complicaciones , Broncoscopía/métodos , Niño , Constricción Patológica , Femenino , Tecnología de Fibra Óptica , Humanos , Lactante , Complicaciones Intraoperatorias , Intubación Intratraqueal/métodos , Linfoma/complicaciones , Masculino , Enfermedades del Mediastino/diagnóstico , Insuficiencia Respiratoria/etiologíaAsunto(s)
Cloroquina/farmacología , Malaria/congénito , Plasmodium falciparum/efectos de los fármacos , Adulto , Animales , Antimaláricos/uso terapéutico , Cloroquina/uso terapéutico , Resistencia a Medicamentos , Femenino , Humanos , Recién Nacido , Malaria/tratamiento farmacológico , Malaria/parasitología , Malí , Mefloquina , Plasmodium falciparum/aislamiento & purificación , Quinina/uso terapéutico , Quinolinas/uso terapéuticoAsunto(s)
Proteínas de Unión al ADN/genética , Factor de Transcripción Ikaros/genética , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Transcripción/genética , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Humanos , Lactante , Recién Nacido , PronósticoAsunto(s)
Biomarcadores de Tumor/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Estudios de Casos y Controles , Francia/epidemiología , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , PronósticoRESUMEN
Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected.
Asunto(s)
Biomarcadores de Tumor/análisis , Proteínas Cromosómicas no Histona/análisis , Proteínas de Unión al ADN/análisis , Neoplasias Renales/diagnóstico , Tumor Rabdoide/diagnóstico , Factores de Transcripción/análisis , Adulto , Carcinoma/diagnóstico , Carcinoma/genética , Preescolar , Neoplasias del Plexo Coroideo/diagnóstico , Neoplasias del Plexo Coroideo/genética , Proteínas Cromosómicas no Histona/genética , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Femenino , Eliminación de Gen , Marcadores Genéticos , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ , Lactante , Queratinas/análisis , Neoplasias Renales/genética , Masculino , Mutación Puntual , Estudios Retrospectivos , Tumor Rabdoide/genética , Proteína SMARCB1 , Factores de Transcripción/genética , Vimentina/análisisRESUMEN
AIMS: To examine the clinical and pathological characteristics of supratentorial primitive neuroectodermal tumours (PNETs) in a retrospective series of 18 patients, according to the strict definition of the World Health Organization classification of tumours that excludes other types of malignant embryonal tumours of the brain. METHODS AND RESULTS: Eleven children and seven adults with supratentorial PNETs were diagnosed between 1993 and 2002 and their medical records were reviewed. An immunohistochemical study was performed on formalin-fixed paraffin-embedded tissue of 18 primary tumours and five recurrences with antibodies for neuronal (neuron specific enolase, synaptophysin, neurofilament, chromogranin A), epithelial [epithelial membrane antigen (EMA), cytokeratin], glial [glial fibrillary acidic protein (GFAP)], muscle (desmin, h-caldesmon, alpha-smooth muscle actin, myogenin) differentiation and with two anti-CD99 antibodies. All tumours showed at least one neuronal marker except chromogranin A; a variable number of cells were GFAP+ or EMA+ in 18/23 tumours. Six primary tumours and one recurrence were positive for cytokeratin and/or one muscle antigen except myogenin. CD99 was observed in 33% of the cases. The mean duration of overall survival was 20 months. The estimated overall survival rates were 61% at 1 year, 29% at 2 years, and 18% at 3 years. Two factors of poor prognosis were identified by univariate analysis: a positive cerebrospinal fluid cytology at diagnosis and the absence of complete resection. No distinct immunophenotype was statistically related to survival. CONCLUSIONS: A multidirectional differentiation is a frequent event in supratentorial PNETs but has no apparent influence on the outcome of this aggressive neoplasm.
Asunto(s)
Neoplasias Encefálicas/patología , Tumores Neuroectodérmicos Primitivos/patología , Antígeno 12E7 , Adolescente , Adulto , Antígenos CD/análisis , Neoplasias Encefálicas/metabolismo , Moléculas de Adhesión Celular/análisis , Diferenciación Celular , Niño , Preescolar , Femenino , Proteína Ácida Fibrilar de la Glía/análisis , Humanos , Inmunohistoquímica , Lactante , Masculino , Persona de Mediana Edad , Mucina-1/análisis , Tumores Neuroectodérmicos Primitivos/metabolismo , Proteínas de Neurofilamentos/análisis , Fosfopiruvato Hidratasa/análisis , Pronóstico , Análisis de Supervivencia , Sinaptofisina/análisisRESUMEN
A child, who received successful chemotherapy for pneumoblastoma, developed a myelomonocytic leukemia with translocation t(11;19)(q23;p13) 2 years later. Although this leukemia did not present with features generally associated with therapy-related leukemias, we think this hematologic disease to be secondary to previous chemotherapy. Involvement of chromosome 11q23 is common in acute leukemia and seems to be more significantly related to ANLL in young children (M4 and M5 FAB classification). However, our observation and previous reports suggest that this chromosomal abnormality might be more frequent in therapy-related leukemias. The responsibility of etoposide and cisplatin may be discussed in such secondary malignancies.
Asunto(s)
Cromosomas Humanos Par 11 , Cromosomas Humanos Par 19 , Leucemia Mielomonocítica Aguda/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Primarias Secundarias/genética , Translocación Genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Preescolar , Dactinomicina/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Masculino , Vincristina/administración & dosificaciónRESUMEN
After defining the clinical, roentgenological and anatomic features of the various kinds of hemophilia-related joint disease (acute hemarthrosis, subacute arthritis, and chronic joint disease), we present a study of outcomes in fifty-one hemophiliac children aged 0 to 15 years and followed-up from January 1968 through December 1987 at the Angers Regional University Hospital. Four hundred and sixty-four cases of hemarthrosis were seen. Risk factors for hemarthrosis were severe hemophilia and age between 5 and 15 years, and the joints most often involved were the ankles, knees, and elbows. Sequelae of hemarthrosis were extremely prevalent in this study population: 100% of patients with severe hemophilia and 90% of patients with a factor activity of 3% or less exhibited chronic joint disease by the age of fifteen, with varying degrees of functional impairment. Because a first episode of hemarthrosis is often followed by recurrences in the same joint, we underline the need for prevention and careful treatment of acute episodes, which are the only means for decreasing articular sequelae.
Asunto(s)
Hemartrosis/etiología , Hemofilia A/complicaciones , Enfermedad Aguda , Adolescente , Factores de Edad , Niño , Preescolar , Enfermedad Crónica , Hemartrosis/epidemiología , Humanos , Lactante , Recién Nacido , Recurrencia , Índice de Severidad de la EnfermedadRESUMEN
The case of a ten month old female with initial clinical and histological findings suggestive of inappropriate macrophage activation syndrome is reported. Subsequently, clinical and pathological changes refuted this diagnosis and demonstrated that the patient had Langherans cell histiocytosis. Clinical, laboratory and pathological findings characteristic of each type of histiocytosis are reviewed. Histological and immunohistochemical studies allow to establish the diagnosis of Langherans cell histiocytosis. The finding of erythrophagocytosis in our patient suggests that two types of histiocyte proliferation can coexist in the same individual.