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1.
Haematologica ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33440924

RESUMO

Pediatric-onset Evans syndrome (pES) is defined by both immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) before the age of 18 years. There have been no comprehensive long-term studies of this rare disease, which can be associated to various immunopathological manifestations (IMs). We report outcomes of the 151 patients with pES and more than 5 years of follow-up from the nationwide French prospective OBS'CEREVANCE cohort. Median age at final follow-up was 18.5 (6.8-50.0) years and the median follow-up period was 11.3 (5.1-38.0) years. At 10 years, ITP and AIHA were in sustained complete remission in 54.5% and 78.4% of patients, respectively. The frequency and number of clinical and biological IMs increased with age: at 20 years old, 74% had at least one clinical cIM. A wide range of cIMs occurred, mainly lymphoproliferation, dermatological, gastrointestinal/hepatic and pneumological IMs. The number of cIMs was associated with a subsequent increase in the number of second-line treatments received (other than steroids and immunoglobulins; hazard ratio, 1.4; 95% confidence interval, 1.15-1.60; p = 0.0002, Cox proportional hazards method). Survival at 15 years after diagnosis was 84%. Death occurred at a median age of 18 (1.7-31.5) years, and the most frequent cause was infection. The number of second-line treatments and severe/recurrent infections were independently associated with mortality. In conclusion, longterm outcomes of pES showed remission of cytopenias but frequent IMs linked to high secondline treatment burden. Mortality was associated to drugs and/or underlying immunodeficiencies, and adolescents-young adults are a high-risk subgroup.

4.
Blood ; 134(1): 9-21, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-30940614

RESUMO

Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.


Assuntos
Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Trombocitopenia/genética , Trombocitopenia/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Mutação , Adulto Jovem
5.
Biol Blood Marrow Transplant ; 22(5): 889-94, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26845034

RESUMO

Relapses of acute lymphoblastic leukemia (ALL) early after hematopoietic stem cell transplantations in children are uncommon but associated with a very poor prognosis. Whereas there are no current recommendations for the management of these relapses, the children's quality of life is an important issue. We studied the outcomes, including 1-year overall survival, complete remission, and quality of life, of 19 children with ALL who relapsed within the first year after their transplantation treated in the 5 participating centers between 2000 and 2011 Patients were distributed as follows: supportive care only (group A), outpatient treatment (mainly steroid and vincristine, group B), or intensive inpatient treatment (group C). There were no significant differences in 1-year overall survival (31.5% for the entire cohort) or remission rate for time between transplantation and relapse (< 6 months or 6 to 12 months), transplantation or disease characteristics, or treatment group. However, time spent in hospital (for treatment and complications) significantly differed between treatment groups B and C (20.8% ± 13.0 versus 59.1% ± 32.9, respectively; P < .05). No differences in organ toxicities, school attendance, or Lansky scores were found between treatment groups. Our sample size-limited data indicate, in a prepersonalized medicine era, that children treated with steroid and vincristine have the same prognosis as those treated with intensive therapy, but they may benefit from improved quality of life. Nevertheless, new therapeutic strategies are required and future prospective trials would help to establish recommendations.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tempo de Internação , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Qualidade de Vida , Adolescente , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Taxa de Sobrevida , Fatores de Tempo
6.
Eur J Cancer ; 48(15): 2409-16, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22633624

RESUMO

AIM: This phase II study evaluated efficacy, safety and pharmacokinetics (PK) profile of combination intravenous vinorelbine (VNL) and continuous low doses oral cyclophosphamide (CPM) combination in children and young adults with a recurrent or refractory solid tumour. METHODS: A total of 117 patients (median age, 12 years) within six disease strata received intravenous VNL 25mg/m(2) on days 1, 8 and 15 of each 28-day cycle combined with continuous daily oral CPM 25mg/m(2). Tumour response was assessed every two cycles according to WHO (World Health Organisation) criteria. PK of VNL was investigated in a subset of 18 patients aged 4-15 years. RESULTS: In rhabdomyosarcoma (RMS) (n=50), the best overall response rate (ORR) was 36% with four complete (8%) and 14 partial responses (28%). The best ORR was 13% in Ewing's sarcoma (n=15), 6% in non-RMS soft tissue sarcoma (n=16) and 6% in neuroblastoma (n=16). No response was observed in osteosarcoma (n=10) and medulloblastoma (n=7). The main grade 3/4 toxicity was neutropenia (38%). Other severe toxicities were limited with 3% of peripheral neuropathy and no haemorrhagic cystitis. The PK analysis revealed equivalent blood exposure to VNL between children >4 years and adult series when the VNL dose was based on the body surface area-based dosing. CONCLUDING STATEMENT: In heavily pre-treated children, VNL combined with CPM showed an interesting response rate in RMS and an acceptable toxicity profile supporting further evaluation of these agents in phase III trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Rabdomiossarcoma/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Neoplasias Ósseas/metabolismo , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Recidiva , Rabdomiossarcoma/metabolismo , Sarcoma/metabolismo , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vimblastina/farmacocinética , Vinorelbina , Adulto Jovem
7.
Pediatr Blood Cancer ; 55(4): 757-60, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20589639

RESUMO

Juvenile xanthogranuloma was diagnosed in two infants aged 8 and 2 months with skin lesions, hepatosplenomegaly, and pancytopenia. Disease control was not achieved with first-line vinblastine-steroid-VP16 combination therapy. Two courses of 2-chlorodeoxyadenosine (2CDA) (0.3 mg/kg) and cytosine arabinoside (AraC) (1 g/m(2)) were then administered for 5 days and were followed, after hematological recovery, by maintenance therapy. Both patients had normal complete blood cell counts and no signs of JXG, respectively, 31 and 24 months after diagnosis.


Assuntos
Cladribina/administração & dosagem , Citarabina/administração & dosagem , Doenças Hematológicas/etiologia , Xantogranuloma Juvenil/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Xantogranuloma Juvenil/sangue
8.
Eur J Cancer ; 44(2): 205-15, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18077152

RESUMO

The aim of this study was to describe the overall survival after childhood cancer in France using follow-up data from regional population-based registries. The survival of children (aged under 15 years) diagnosed with a cancer during 1990-1999 was analysed. For all cancers, the survivals were, respectively, 90.3% [89.4-91.3] at 1-year, 75.2% [73.8-76.6] at 5 years and 72.2% [70.7-73.7] at 10 years. During the 1990s, the average improvement in the 5-year survival was +1.2% per year. Adjusted for gender, age, area of residence and stage, children with cancer diagnosed between 1995 and 1999 had a 0.80 reduced risk of dying compared with those whose cancer had been diagnosed between 1990 and 1994. The increase of survival at the population level reflects a global improvement in childhood cancer care. The Paediatric Registries, in association with the French Society of Childhood Cancer, are now collecting data to quantify on a national basis the other events, at least relapse and second cancers.


Assuntos
Neoplasias/mortalidade , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , França/epidemiologia , Humanos , Lactente , Masculino , Mortalidade/tendências
9.
Pediatr Blood Cancer ; 43(7): 749-57, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15390289

RESUMO

BACKGROUND: Cancer is the second most important cause of death for children aged less than 15 years in France, unintentional injuries being the leading cause. The aim of the present study was to estimate the incidence of childhood cancer from six Childhood Cancer Registries covering 32% of France. PROCEDURE: Incident cancer cases diagnosed between 1990 and 1999 in children (0-14 years) resident in the administrative areas covered by each Registry were included. Annual age-standardized rates (ASRs) were adjusted by the world population. The estimated annual percent change (EAPC) was used to measure trend towards changes in the annual age-standardized incidence rate. RESULTS: With 4234 registered cases, the ASRs per million children were 137.5 for all cancers combined, 42.3 for leukemia, 29.1 for central-nervous-system tumors, 15.6 for lymphomas, 14.1 for sympathetic-nervous-system tumors, and 9.1 for renal tumors. The ASR of all cancers combined was slightly higher in males (145.8 per million children) than in females (128.7 per million children) with an M/F ratio of 1.2. No significant incidence trend was observed, with an EAPC of +0.2% [IC 95% (-2.5; +3.0); P = 0.89]. CONCLUSIONS: The estimated incidence rates are similar to those reported in previous studies in European and North American countries. These results will contribute to the development of National Registration of Childhood Cancer in France and support the national research program on childhood cancer.


Assuntos
Neoplasias/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias/classificação , Sistema de Registros , Fatores Sexuais , Tempo
10.
Eur J Pediatr ; 162(12): 863-7, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14648217

RESUMO

Hoyeraal-Hreidarsson syndrome represents a severe variant of dyskeratosis congenita (Zinsser-Cole-Engman syndrome). This X-linked recessive, progressive, multisystemic disorder reported so far in 12 pedigrees is characterised by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, mental retardation, progressive combined immune deficiency and aplastic anaemia. Mutations in the DKC1gene on Xq28 have been identified in the X-linked form of dyskeratosis congenita and in some Hoyeraal-Hreidarsson syndrome patients. We report on two sibs and two other unrelated patients with the striking clinical features of Hoyeraal-Hreidarsson syndrome. Noticeably, all four had early digestive problems, with chronic, bloody diarrhoea and feeding problems causing one of the most difficult problems in the supportive treatment of this uniformly lethal condition. Pathological changes in the proliferative compartment of the digestive mucosa included alterations of the glandular architecture and focal rarefaction of the glands. This aspect seems consistent with altered telomerase function associated with a dyskerin mutation which may decrease the proliferative capacity of digestive epithelial cells. A missense mutation 146 C-->T (Thr49Met) in the DKC1gene was found in two unrelated patients, whereas mutation screening was negative for one single case. The absence of mutations of the DKC1gene in patients with Hoyeraal-Hreidarsson syndrome emphasises the probable implication of one or more other loci.


Assuntos
Proteínas de Ciclo Celular/genética , Diarreia/etiologia , Disceratose Congênita/complicações , Disceratose Congênita/genética , Mutação de Sentido Incorreto , Proteínas Nucleares/genética , Diarreia/patologia , Transtornos da Motilidade Esofágica/etiologia , Humanos , Recém-Nascido , Mucosa Intestinal/patologia , Masculino , Síndrome
11.
Cancer ; 98(2): 349-55, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12872356

RESUMO

BACKGROUND: Less than 5% of neuroblastomas are diagnosed in adolescent patients. Previous studies of patients who were treated with less intensive chemotherapy regimens relative to currently available regimens suggested that adolescents survived longer than younger children, and this finding was related to a lack of myc-N amplification. Those reports prompted the authors to study a cohort of adolescent patients who had been included in more recent trials. METHODS: The authors investigated the presentation, treatment, and outcome in 28 adolescent patients who were enrolled in studies of the French Society of Pediatric Oncology during the period from 1987 to 1999 and who were older than age 10 years at the time they were diagnosed with neuroblastoma. The results were used to compare this subpopulation with a control group of children. RESULTS: None of the six patients with Stage I-II disease either developed recurrent disease or died. At 5 years, disease progression was high (progression-free survival [PFS], 28%) for the 9 adolescents with Stage III disease, but so was survival (overall survival [OS], 86%). The 13 adolescent patients with metastatic neuroblastoma had very poor outcomes (PFS, 18%; OS, 27%). Despite intensive therapy, advanced neuroblastoma appeared to carry a poorer prognosis in adolescent patients compared with children, although patients with Stage III disease had a more indolent course. No difference was found between adolescent patients and children regarding the clinical presentation, treatment schedule, or doses and tolerance of chemotherapy. The incidence of elevated urinary catecholamine metabolite secretion was lower in adolescents compared with children. CONCLUSIONS: Adolescent patients with advanced neuroblastoma had less favorable outcomes compared with children, even if survival in adolescents with Stage III disease seemed longer.


Assuntos
Neoplasias Abdominais/diagnóstico , Neuroblastoma/diagnóstico , Neoplasias Abdominais/terapia , Adolescente , Estudos de Casos e Controles , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neuroblastoma/terapia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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