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2.
Br J Haematol ; 186(5): 741-753, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31124581

RESUMO

Outcomes in childhood T-cell acute lymphoblastic leukaemia (T-ALL) are steadily improving due to intensive therapy. Between 1989 and 2008, 599 children with newly diagnosed T-ALL were enrolled in two successive European Organization for Research and Treatment of Cancer - Children's Leukaemia Group trials (58881 and 58951), both based on the Berlin-Frankfurt-Munster protocol and without cranial irradiation. In the latter trial induction chemotherapy was intensified. The most important randomizations were Medac Escherichia coli asparaginase versus Erwinia asparaginase in trial 58881, and dexamethasone (6 mg/m2 /day) versus prednisolone (60 mg/m2 /day) and prolonged versus conventional asparaginase duration in trial 58951. 8-year event-free survival (EFS) increased from 65·1% to 74·0% in trial 58951. Improvement was most profound for patients with white blood cell (WBC) counts <100 × 109 /l and "good responders" to prephase. Medac E. coli asparaginase was associated with longer EFS [hazard ratio (HR) 0·54, P = 0·0015] and overall survival (HR 0·51, P = 0·0018). Induction therapy with dexamethasone did not improve EFS compared to prednisolone. Remarkably, intensification of central nervous system (CNS)-directed therapy in trial 58951 resulted in fewer bone marrow relapses, while the incidence of CNS relapses remained low. In summary, we showed that adequate asparaginase therapy, intensified induction treatment and intensification of CNS-directed chemotherapy can result in an improvement of outcome in T-ALL patients with good prephase response and initial WBC counts <100 × 109 /l, representing approximately 50% of T-ALL patients.

3.
Int J Cancer ; 145(11): 2907-2916, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30697705

RESUMO

Neuroblastoma (NB) is the most common extra-cranial tumour in children. Little is known about the aetiology of NB. The early age at onset and the embryonic nature suggest a role for perinatal exposures. We conducted a pooled analysis of two French national population-based case-control studies to explore whether there was an association between parental smoking and alcohol consumption and the risk of NB. The mothers of 357 NB cases and 1,783 controls from general population, frequency matched by age and sex, were interviewed on demographic, socioeconomic and perinatal characteristics, maternal reproductive story, and life-style and childhood environment. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. A meta-analysis of our findings with those of previous studies was also conducted. Maternal smoking during pregnancy was slightly more often reported for the cases (24.1%) than for the controls (19.7%) (OR 1.3 [95% CI 0.9-1.7]; summary OR from meta-analysis 1.1 [95% CI 1.0-1.3]. Paternal smoking in the year before child's birth were not associated with NB as independent exposure (OR 1.1 [95% CI 0.9-1.4] but the association was stronger when both parents reported having smoked during pregnancy (OR 1.5 [95% CI 1.1-2.1]. No association was observed with maternal alcohol intake during pregnancy (OR 1.0 [95% CI 0.8-1.4], summary OR from meta-analysis 1.0 [95% CI 0.9-1.2]. Our findings provide some evidence of an association between maternal smoking during pregnancy and NB and add another reason to recommend that women refrain from smoking during pregnancy.

4.
J Pediatr ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30442413

RESUMO

OBJECTIVE: To evaluate the association between medical and social environmental factors and the risk of repeating a grade in childhood leukemia survivors. STUDY DESIGN: A cross-sectional study of childhood leukemia survivors, recruited through the LEA cohort (Leucémie de l'Enfant et de l'Adolescent [French Childhood Cancer Survivor Study for Leukemia]) in 2014. An adjusted logistic regression model was used to identify variables linked to repeating a grade after the diagnosis among the survivors, and the rates of repeating a grade were compared between the survivors and their siblings using a multilevel logistic regression model. RESULTS: The mean age at inclusion of the 855 participants was 16.2 ± 7.0 years, and the mean duration of follow-up from diagnosis to evaluation was 10.2 ± 6.2 years. After disease onset, 244 patients (28.5%) repeated a grade, with a median interval of 4 years (IQR, 2-8 years). Independent factors associated with repeating a grade were male sex (OR, 1.78; 95% CI, 1.21-2.60), adolescence (OR, 2.70; 95% CI, 1.63-4.48), educational support during the treatment period (OR, 3.79; 95% CI, 2.45-5.88), low parental education level (OR, 2.493; 95% CI, 1.657-3.750), and household financial difficulties (OR, 2.62; 95% CI, 1.607-4.28). Compared with siblings, survivors were at greater risk of repeating a grade (OR, 1.87; 95% CI, 1.48-2.35). CONCLUSIONS: The most vulnerable patients seemed to be adolescents and those with parents of low socioeconomic status. Improving the schooling career of leukemia survivors will require that the medical community more carefully consider the social status of patients.

5.
Front Pharmacol ; 9: 00950, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319400

RESUMO

Background: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC has shown its efficacy in adult tumor types such as breast and ovarian cancer and has to some extent been studied in pediatrics. Objective: To assess the anti-tumor activity and toxicity of a four-drug metronomic regimen in relapsing/refractory pediatric brain tumors (BT) with progression-free survival (PFS) after two cycles as primary endpoint. Methods: Patients ≥4 to 25 years of age were included with progressing BT. Treatment consisted of an 8-week cycle of celecoxib, vinblastine, and cyclophosphamide alternating with methotrexate. Kepner and Chang two-steps model was used with 10 patients in the first stage. If stabilization was observed in ≥2 patients, 8 additional patients were recruited. Assessment was according WHO criteria with central radiology review. Results: Twenty-nine patients (27 evaluable) were included in two groups: ependymoma (group 1, N = 8), and miscellaneous BT (group 2): 3 medulloblastoma (MB), 5 high grade glioma (HGG), 11 low grade glioma (LGG), 2 other BT. After first stage, recruitment for ependymoma was closed [one patient had stable disease (SD) for 4 months]. Cohort 2 was opened for second stage since 1 HGG and 3 LGG patients had SD after two cycles. Recruitment was limited to LGG for the second stage and 2 partial responses (PR), 6 SD and 2 progressive disease (PD) were observed after two cycles. Of these patients with LGG, median age was 10 years, nine patients received vinblastine previously. Median number of cycles was 6.8 (range: 1-12). Treatment was interrupted in five patients for grade 3/4 toxicity. Conclusion: This regimen is active in patients with LGG, even if patients had previously received vinblastine. Toxicity is acceptable. Trial Registration: This study was registered under clinicaltrials.gov - NCT01285817; EUDRACT nr: 2010-021792-81.

7.
Haematologica ; 103(4): 645-654, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29351982

RESUMO

The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. Metabolic syndrome was found in 10.3% of patients (mean follow-up duration: 16.3±0.2 years) and 4.5% of controls, (OR=2.49; P<0.001). Patients transplanted with total body irradiation presented the highest risk (OR=6.26; P<0.001); the other treatment groups also showed a higher risk than controls, including patients treated with chemotherapy only. Odd Ratios were 1.68 (P=0.005) after chemotherapy only, 2.32 (P=0.002) after chemotherapy and cranial irradiation, and 2.18 (P=0.057) in patients transplanted without irradiation. Total body irradiation recipients with metabolic syndrome displayed a unique profile compared with controls: smaller waist circumference (91 vs 99.6 cm; P=0.01), and increased triglyceride levels (3.99 vs 1.5 mmol/L; P<0.001), fasting glucose levels (6.2 vs 5.6 mmol/L; P=0.049), and systolic blood pressure (137.9 vs 132.8 mmHg; P=0.005). By contrast, cranial irradiation recipients with metabolic syndrome had a larger waist circumference (109 vs 99.6 cm; P=0.007) than controls. Regardless of the anti-leukemic treatment, metabolic syndrome risk was higher among childhood leukemia survivors. Its presentation differed depending on the treatment type, thus suggesting a divergent pathophysiology. This study is registered at clinicaltrials.gov identifier: 01756599.

8.
Cancer Causes Control ; 28(10): 1125-1132, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28840389

RESUMO

PURPOSE: Neuroblastoma (NB) is an embryonic tumor that occurs almost exclusively in infancy and early childhood. While considerable evidence suggests that it may be initiated during embryonic development, the etiology of NB is still unknown. The aim of this study was to explore whether there is an association between maternal use of household pesticides during pregnancy and the risk of NB in the offspring. METHODS: We conducted a pooled analysis of two French national-based case-control studies. The mothers of 357 NB cases and 1,783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on sociodemographic and perinatal characteristics, childhood environment, and life-style. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. RESULTS: After controlling for matching variables, study of origin, and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with NB (OR 1.5 [95% CI 1.2-1.9]). The most commonly used type of pesticides were insecticides and there was a positive association with their use alone (OR 1.4 [95% CI 1.1-1.9]) or with other pesticides (OR 2.0 [95% CI 1.1-3.4]). CONCLUSIONS: Although there is the potential for recall bias due to the study design, our findings add to the evidence of an association between the household use of pesticides and NB. Until a better study design can be found, our findings add yet another reason why to advise pregnant women to limit pesticide exposure during the periconceptional period.


Assuntos
Exposição Materna , Troca Materno-Fetal , Neuroblastoma/epidemiologia , Praguicidas , Adulto , Estudos de Casos e Controles , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Lactente , Modelos Logísticos , Masculino , Razão de Chances , Gravidez , Fatores de Risco
9.
Haematologica ; 102(10): 1727-1738, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28751566

RESUMO

Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of non-very high-risk patients by comparing prolonged (long-asparaginase) versus standard (short-asparaginase) native E. coli asparaginase treatment in a randomized part of the phase III 58951 trial of the European Organization for Research and Treatment of Cancer Children's Leukemia Group. The main endpoint was disease-free survival. Overall, 1,552 patients were randomly assigned to long-asparaginase (775 patients) or short-asparaginase (777 patients). Patients with grade ≥2 allergy to native E. coli asparaginase were switched to equivalent doses of Erwinia or pegylated E. coli asparaginase. The 8-year disease-free survival rate (±standard error) was 87.0±1.3% in the long-asparaginase group and 84.4±1.4% in the short-asparaginase group (hazard ratio: 0.87; P=0.33) and the 8-year overall survival rate was 92.6±1.0% and 91.3±1.2% respectively (hazard ratio: 0.89; P=0.53). An exploratory analysis suggested that the impact of long-asparaginase was beneficial in the National Cancer Institute standard-risk group with regards to disease-free survival (hazard ratio: 0.70; P=0.057), but far less so with regards to overall survival (hazard ratio: 0.89). The incidences of grade 3-4 infection during consolidation (25.2% versus 14.4%) and late intensification (22.6% versus 15.9%) and the incidence of grade 2-4 allergy were higher in the long-asparaginase arm (30% versus 21%). Prolonged native E. coli asparaginase therapy in consolidation and late intensification for our non-very high-risk patients did not improve overall outcome but led to an increase in infections and allergy. This trial was registered at www.clinicaltrials.gov as #NCT00003728.


Assuntos
Asparaginase/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Criança , Pré-Escolar , Quimioterapia de Consolidação , Proteínas de Escherichia coli/administração & dosagem , Proteínas de Escherichia coli/efeitos adversos , Proteínas de Escherichia coli/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução , Lactente , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
10.
Am J Med Genet A ; 173(8): 2088-2096, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28544599

RESUMO

Individuals with trisomic conditions like Down syndrome and Edwards syndrome are prone to certain types of malignancy. However, for Patau syndrome (constitutional trisomy 13), which occurs in 1/10,000-1/20,000 live births, the tumor profile has not been well characterized. An awareness of susceptibility to malignancies can improve care of affected individuals, as well as further our understanding of the contribution of trisomy to carcinogenesis. Therefore, we conducted an extensive review of the literature; we found 17 malignancies reported in individuals with Patau syndrome. These comprised eight embryonic tumors, three leukemias, two malignant germ cell tumors, two carcinomas, a malignant brain tumor, and a sarcoma. Benign tumors were mainly extragonadal teratomas. The small number of reported malignant tumors suggests that there is not an increased risk of cancer in the context of trisomy 13. The tumor profile in Patau syndrome differs from that observed in Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), suggesting that the supernumerary chromosome 13 could promote particular tumor formations as it does particular malformations. No general and direct relationships of tumor occurrence with organ weight, congenital malformations, histological changes, or presence of tumor suppressor genes on chromosome 13 were observed. However, some tumors were found in tissues whose growth and development are controlled by genes mapping to chromosome 13. Recent reports of successful outcomes following surgical treatment and adapted chemotherapy indicate that treatment of cancer is possible in Patau syndrome.


Assuntos
Neoplasias/fisiopatologia , Síndrome da Trissomia do Cromossomo 13/fisiopatologia , Trissomia/fisiopatologia , Humanos , Neoplasias/complicações , Síndrome da Trissomia do Cromossomo 13/complicações
11.
Leuk Lymphoma ; 58(6): 1433-1445, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27736268

RESUMO

Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis. Interestingly, DFO displayed synergistic activity with three ALL-specific drugs: dexamethasone, doxorubicin, and L-asparaginase. DFO appeared to act through a reactive oxygen species-dependent DNA damage response and potentiated the action of an inhibitor of the PARP pathway of DNA repair. Our results demonstrate that targeting iron metabolism could be an interesting adjuvant therapy for acute lymphoblastic leukemia.


Assuntos
Quelantes de Ferro/farmacologia , Ferro/metabolismo , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , PTEN Fosfo-Hidrolase/deficiência , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Apoptose/efeitos dos fármacos , Asparaginase/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quimioterapia Adjuvante , Dano ao DNA , Desferroxamina/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Expressão Gênica , Humanos , Quelantes de Ferro/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/mortalidade , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Espécies Reativas de Oxigênio/metabolismo , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo
12.
Pediatr Hematol Oncol ; 34(8): 425-427, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29303660

RESUMO

We report the outcome of 27 children with de novo acute megakaryoblastic leukemia (AMKL) (excluding Down syndrome) enrolled in the French multicenter prospective study ELAM02 (2005-2011). There was no difference in gender, initial leukocyte count, CNS involvement, and complete remission rate (88.9%), as compared to other acute myeloid leukemia (AML) subtypes. AMKL patients had a significantly poorer outcome (5-year overall survival 54% [CI 95% 33%-71%] than children with other AML subtypes (5-year overall survival 73% [CI 95% 68%-77%] p = 0.02). Gender, age, CNS leukemia, hyperleukocytosis, complete remission or cytogenetic subgroups were not significant prognostic factors of disease-free survival. AMKL (excluding Down syndrom) remains an AML subgroup with inferior outcome.


Assuntos
Leucemia Megacarioblástica Aguda/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Síndrome de Down , Feminino , França/epidemiologia , Humanos , Lactente , Leucemia Megacarioblástica Aguda/sangue , Leucemia Megacarioblástica Aguda/terapia , Masculino , Estudos Prospectivos , Taxa de Sobrevida
13.
Haematologica ; 101(12): 1603-1610, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27515247

RESUMO

Cardiovascular conditions are serious long-term complications of childhood acute leukemia. However, few studies have investigated the risk of metabolic syndrome, a known predictor of cardiovascular disease, in patients treated without hematopoietic stem cell transplantation. We describe the overall and age-specific prevalence, and the risk factors for metabolic syndrome and its components in the L.E.A. (Leucémie de l'Enfant et de l'Adolescent) French cohort of childhood acute leukemia survivors treated without hematopoietic stem cell transplantation. The study included 650 adult patients (mean age at evaluation: 24.2 years; mean follow-up after leukemia diagnosis: 16.0 years). The prevalence of metabolic syndrome was 6.9% (95% CI 5.1-9.2). The age-specific cumulative prevalence at 20, 25, 30 and 35 years of age was 1.3%, 6.1%, 10.8% and 22.4%, respectively. The prevalence of decreased high-density lipoprotein cholesterol, increased triglycerides, increased fasting glucose, increased blood pressure and increased abdominal circumference was 26.8%, 11.7%, 5.8%, 36.7% and 16.7%, respectively. Risk factors significantly associated with metabolic syndrome in the multivariate analysis were male sex (OR 2.64; 95% CI 1.32-5.29), age at last evaluation (OR 1.10; 95% CI 1.04-1.17) and body mass index at diagnosis (OR 1.15; 95% CI 1.01-1.32). The cumulative steroid dose was not a significant risk factor. Irradiated and non-irradiated patients exhibited different patterns of metabolic abnormalities, with more frequent abdominal obesity in irradiated patients and more frequent hypertension in non-irradiated patients. Survivors of childhood acute leukemia are at risk of metabolic syndrome, even when treated without hematopoietic stem cell transplantation or central nervous system irradiation. A preventive approach with regular screening for cardiovascular risk factors is recommended. clinicaltrials.gov identifier:01756599.


Assuntos
Leucemia/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Sobreviventes , Adolescente , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Leucemia/terapia , Masculino , Prevalência , Radioterapia/efeitos adversos , Radioterapia/métodos , Indução de Remissão , Fatores de Risco , Adulto Jovem
14.
Am J Med Genet C Semin Med Genet ; 172(3): 296-306, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27474103

RESUMO

Constitutional trisomy 18 causes Edwards syndrome, which is characterized by intellectual disability and a particular set of malformations. Although this condition carries high mortality during prenatal and early postnatal life, some of the rare infants who survive the first months develop benign and malignant tumors. To determine the tumor profile associated with Edwards syndrome, we performed a systematic review of the literature. This review reveals a tumor profile differing from those of Down (trisomy 21) and Patau (trisomy 13) syndromes. The literature covers 45 malignancies: 29 were liver cancers, mainly hepatoblastomas found in Japanese females; 13 were kidney tumors, predominantly nephroblastomas; 1 was neuroblastoma; 1 was a Hodgkin disease; and 1 was acute myeloid leukemia in an infant with both trisomy 18 and type 1 neurofibromatosis. No instances of the most frequent malignancies of early life-cerebral tumors, germ cell tumors, or leukemia--are reported in children with pure trisomy 18. Tumor occurrence does not appear to correlate with body weight, tissue growth, or cancer genes mapping to chromosome 18. Importantly, the most recent clinical histories report successful treatment; this raises ethical concerns about cancer treatment in infants with Edwards syndrome. In conclusion, knowledge of the Edwards' syndrome tumor profile will enable better clinical surveillance in at-risk organs (i.e., liver, kidney). This knowledge also provides clues to understanding oncogenesis, including the probably reduced frequency of some neoplasms in infants and children with this genetic condition. © 2016 Wiley Periodicals, Inc.


Assuntos
Neoplasias/etiologia , Trissomia , Carcinogênese , Pré-Escolar , Cromossomos Humanos Par 18 , Humanos , Lactente , Recém-Nascido , Neoplasias/diagnóstico , Neoplasias/patologia , Trissomia/patologia , Síndrome da Trissomía do Cromossomo 18
15.
Int J Cancer ; 139(9): 1936-48, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27342419

RESUMO

Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention.


Assuntos
Anormalidades Congênitas/epidemiologia , Suplementos Nutricionais/estatística & dados numéricos , Neuroblastoma/epidemiologia , Complicações na Gravidez/epidemiologia , Adolescente , Adulto , Peso ao Nascer , Aleitamento Materno , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Entrevistas como Assunto , Modelos Logísticos , Masculino , Gravidez , Complicações na Gravidez/etiologia , Adulto Jovem
16.
J Cancer Surviv ; 10(6): 1058-1066, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27185246

RESUMO

PURPOSE: Our principal aim was to assess the occupational outcomes of French survivors of childhood leukemia, compared to national population. The secondary objective was to identify determinants linked with employment stability after childhood leukemia. METHODS: All survivors aged 15 and over enrolled in the French LEA Cohort (Childhood and Adolescent Leukemia) were included. Occupational data were self-reported. The occupational distributions expected in the cohort for each age range were established based on the distribution in France as reference, and comparisons between observed and expected distributions were performed. Logistic regression model was used to explore determinants of stability of survivors' employment. RESULTS: The questionnaire was completed by 845 eligible survivors (response rate 87.8 %), with a mean age of 22.3 ± 5.4 years and a mean follow-up duration of 14.3 ± 6.3 years. Among the 361 survivors currently in the labor market, 36 (10.0 %) were seeking a job, which is significantly lower than expected (19.3 %) compared to French population. Conversely, among those currently employed, the number of survivors in unstable employment (43.9 %) was significantly higher than expected (33.5 %). Younger age and higher number of late effects were risk factors for unstable employment. CONCLUSIONS: While the employment rate of the young French adult population of childhood leukemia survivors seems rather positive, access to a steady job appears to be compromised for some survivors. IMPLICATIONS FOR CANCER SURVIVORS: A strategy to better identify particular subgroups of survivors at greatest risk for difficulties in their professional achievement will help ensure the development of specific intervention strategies and support procedures.


Assuntos
Emprego/tendências , Leucemia/reabilitação , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Leucemia/mortalidade , Masculino , Fatores de Risco , Sobreviventes , Adulto Jovem
17.
Ann Hematol ; 95(1): 93-103, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26455579

RESUMO

Acute lymphoblastic leukemia of T cell lineage (T-ALL) is an aggressive malignant disease which accounts for 15 % of childhood ALL. T(11;14) is the more frequent chromosomal abnormality in childhood T-ALL, but its prognostic value remained controversial. Our aim was to analyze the outcome of childhood T-ALL with t(11;14) to know if the presence of this translocation is associated with a poor prognosis. We conducted a retrospective study from a series of 20 patients with t(11;14), treated in two consecutive trials from the European Organization for Research and Treatment of Cancer Children Leukemia Group over a 19-year period from 1989 to 2008. There were no significant differences between the 2 consecutive groups of patients with t(11;14) regarding the clinical and biological features at diagnosis. Among 19 patients who reached complete remission, 9 patients relapsed. We noticed 7 deaths all relapse- or failure-related. In the 58881 study, a presence of t(11;14) was associated with a poor outcome with an event-free survival at 5 years at 22.2 % versus 65.1 % for the non-t(11;14) T-ALL (p = 0.0004). In the more recent protocol, the outcome of T-ALL with t(11;14) reached that of non-t(11;14) T-ALL with an event-free survival at 5 years at 65.5 versus 74.9 % (p = 0.93). The presence of t(11;14) appeared as a poor prognostic feature in the 58881 trial whereas this abnormality no longer affected the outcome in the 58951 study. This difference is probably explained by the more intensive chemotherapy in the latest trial.


Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 14/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Translocação Genética/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
18.
Nat Genet ; 47(11): 1334-40, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26457648

RESUMO

Juvenile myelomonocytic leukemia (JMML) is a rare and severe myelodysplastic and myeloproliferative neoplasm of early childhood initiated by germline or somatic RAS-activating mutations. Genetic profiling and whole-exome sequencing of a large JMML cohort (118 and 30 cases, respectively) uncovered additional genetic abnormalities in 56 cases (47%). Somatic events were rare (0.38 events/Mb/case) and restricted to sporadic (49/78; 63%) or neurofibromatosis type 1 (NF1)-associated (8/8; 100%) JMML cases. Multiple concomitant genetic hits targeting the RAS pathway were identified in 13 of 78 cases (17%), disproving the concept of mutually exclusive RAS pathway mutations and defining new pathways activated in JMML involving phosphoinositide 3-kinase (PI3K) and the mTORC2 complex through RAC2 mutation. Furthermore, this study highlights PRC2 loss (26/78; 33% of sporadic JMML cases) that switches the methylation/acetylation status of lysine 27 of histone H3 in JMML cases with altered RAS and PRC2 pathways. Finally, the association between JMML outcome and mutational profile suggests a dose-dependent effect for RAS pathway activation, distinguishing very aggressive JMML rapidly progressing to acute myeloid leukemia.


Assuntos
Redes Reguladoras de Genes/genética , Leucemia Mielomonocítica Juvenil/genética , Mutação , Complexo Repressor Polycomb 2/genética , Transdução de Sinais/genética , Proteínas ras/genética , Acetilação , Doença Aguda , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Progressão da Doença , Feminino , Histonas/metabolismo , Humanos , Lactente , Leucemia Mieloide/genética , Leucemia Mieloide/metabolismo , Leucemia Mielomonocítica Juvenil/metabolismo , Masculino , Metilação , Microscopia Confocal , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Análise de Sequência de DNA/métodos , Análise de Sobrevida , Transcriptoma , Proteínas ras/metabolismo
19.
Br J Haematol ; 168(4): 518-25, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25284463

RESUMO

Cataract was prospectively assessed by serial slip lamp tests in 271 patients included in the Leucémie Enfants Adolescents (LEA) programme, the French cohort of childhood leukaemia survivors. All had received haematopoietic stem cell transplantation (HSCT) after total body irradiation (TBI, n = 201) or busulfan-based (n = 70) myeloablative conditioning regimen. TBI was fractionated in all but six patients. The mean duration of follow-up from HSCT was 10·3 years. Cataract was observed in 113/271 patients (41·7%); 9/113 (8·1%) needed surgery. Cumulative incidence after TBI increased over time from 30% at 5 years to 70·8% and 78% at 15 and 20 years, respectively, without any plateau thereafter. The 15-year cumulative incidence was 12·5% in the Busulfan group. A higher cumulative steroid dose appeared to be a cofactor of TBI for cataract risk, in both univariate and multivariate Cox analysis. In the multivariate analysis, cataract had an impact in two quality of life domains: 'the role limitation due to physical problems' and 'the role limitation due to emotional problems'. These data suggest that with increasing follow-up, nearly all patients who receive TBI, even when fractionated, will suffer from cataract that can impact on their quality of life and that high cumulative steroid dose is a cofactor.


Assuntos
Catarata/etiologia , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Radioterapia/efeitos adversos , Adolescente , Adulto , Bussulfano/uso terapêutico , Catarata/induzido quimicamente , Catarata/epidemiologia , Terapia Combinada , Fracionamento da Dose de Radiação , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Modelos de Riscos Proporcionais , Qualidade de Vida , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Adulto Jovem
20.
J Pediatr Hematol Oncol ; 37(2): 109-16, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24936742

RESUMO

We evaluated the impact of central nervous system irradiation (CNSI) on long-term health status and quality of life (QoL) of childhood lymphoblastic leukemia survivors included in the French L.E.A. (Childhood and Adolescent Leukemia) multicentric cohort. QoL was self-reported in adults and assessed by parents in children and adolescents, using adapted questionnaires. From 2004 to 2009, 630 nongrafted patients were assessed after 11.8±6.3 years from diagnosis. Patients receiving CNSI (18.6%) or chemotherapy alone (81.4%) were compared. The risk of having long-term physical effects was increased with CNSI (odds ratio=3.3; 95% confidence interval, 1.8-5.9), especially regarding growth failure, second tumor, cataract, and overweight. QoL did not differ significantly according to the treatment received, despite a tendency toward lower scores with CNSI in children and adolescents (summary score 63.6±13.3 vs. 71.7±12.4, P=0.14). Compared with French norms, adult survivors had an impaired QoL, especially in mental domains (mental composite score 45.2±9.8 vs. 47.9±2.1, P<0.001). In pediatric survivors, QoL was not impaired and even tended to be higher than population norms (summary score 71.7±12.4 vs. 70.0±4.2, P=0.054), mainly in social and relational domains. In conclusion, QoL seems to be impaired by the trauma of a life-threatening illness in childhood, as well as by the treatment received.


Assuntos
Neoplasias Encefálicas/psicologia , Irradiação Craniana/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Qualidade de Vida , Sobreviventes/psicologia , Doença Aguda , Adolescente , Adulto , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Feminino , Seguimentos , Nível de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Tempo , Adulto Jovem
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