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1.
Pediatr Blood Cancer ; : e28419, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798263

RESUMO

INTRODUCTION: Our objectives were to assess the quality of life (QoL) of parents of childhood leukemia survivors compared with population norms and to identify the determinants of parents' long-term QoL. METHODS: Parents of minors who had survived childhood leukemia participating in the French LEA cohort (Leucémie de l'Enfant et de l'Adolescent-French Childhood Cancer Survivor Study for Leukemia) were asked to complete the French version of the WHOQOL-BREF. Results were compared with age- and sex-matched values from a French reference population. Parents' and survivors' characteristics likely to be associated with QoL, long after the child's leukemia diagnosis, were explored using multivariate analysis. RESULTS: We included 487 parents (mean age 42.9 ± 6.0 years, mean follow-up time from diagnosis 7.3 ± 3.3 years). Compared with the reference population, scores for physical health and social relationships for parents of childhood leukemia survivors were significantly lower (P < 0.001, effect size = 0.24 and P < 0.001, effect size = 0.29, respectively) contrary to scores for psychological health which were significantly higher (P < 0.001, effect size = 0.29). Even if health- and cancer-related characteristics were associated with parents' QoL in some dimensions, the only factor associated with each of the three dimensions (social relationships, physical health, and psychological) in the multivariate analysis was the parent's financial situation. CONCLUSIONS: Long after leukemia diagnosis, the parents reported lower scores in the physical health and social relationship domains. Despite the difficulties of actually influencing socioeconomic characteristics, it is important to consider the social situation of each family in the long-term care of survivors and their families.

2.
Hematol Oncol ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32809224

RESUMO

Over the years, the prognosis of adolescents treated for acute lymphoblastic leukemia (ALL) has improved. However, this age group still represents a challenge with an overall survival (OS) of 60% compared to 85% in younger children. Herein, we report the outcome of adolescents treated in the European Organisation for Research and Treatment of Cancer (EORTC) 58951 clinical trial. EORTC 58951 clinical trial included patients with de novo ALL between 1998 and 2008. For this study, we analyzed data of all adolescents between 15 and under 18. Data from 97 adolescents were analyzed, 70 had B-lineage and 27 had T-lineage ALL. The 8-year event-free survival (EFS) and OS for the B-cell precursor ALL cases were 72.3% (59.4%-81.7%) and 80.8% (67.4%-89.1%), respectively. For the T-lineage, the 8-year EFS and OS were 57.4% (36.1%-74.0%) and 59.0% (36.1%-76.2%), respectively. "B-other" ALL, defined as BCP-ALL lacking any known recurrent genetic abnormalities were more frequent in our adolescent population (52.8%) than in younger children (27.1%). Outcome of adolescents in the EORTC 58951 study is supporting the findings that adolescents have better outcome in pediatric compared to adults' trials. Nevertheless, in pediatric studies, adolescents still have a worse prognosis than younger children. Despite the fact that specific unfavorable characteristics may be linked to the adolescent population, a careful study and characterization of adolescents "B-other" genetic abnormalities in ALL is critical to improve the outcome of this population.

3.
Pediatr Res ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32722662

RESUMO

BACKGROUND: Poor and delayed microbiological documentation of episodes of febrile neutropenia (EFN) deserves improvement. We assessed the impact of a new blood culture (BC) sampling protocol to optimize the diagnosis of bloodstream infection during EFN, compared with standard of care protocol. METHODS: This pre/post intervention included patients who presented an EFN in a pediatric hematology-oncology center. Data were compared between 1-year periods P1 (110 EFN, 53 patients) and P2 (124 EFN, 53 patients). Pre-intervention settings were 1-2 mL of blood cultured per BC set and several samplings over days (multisampling strategy) during period P1 vs. one unique early sampling of a large volume of blood (0.5-60 mL) depending on patient weight during period P2 (single-sampling weight-adapted strategy). Microbial detection and time-to-diagnosis were evaluated. RESULTS: Seventeen EFNs were microbiologically documented in P1 (15.5%) and 26 in P2 (21%). The rate of positive BC sets increased during P2 (10.4% vs. 5.8%). All cases of bacteremia were documented by BC drawn during the first 4 days of fever, and during P2 by samples obtained on the first day of fever. CONCLUSIONS: Bacteremia detection was improved. This proof-of-concept study shows benefits of combining the single-sampling strategy with large weight-adapted blood sampling strategy during EFN. IMPACT: Combination of single-sampling and weight-adapted blood culture strategies showed benefits in the documentation of bloodstream infections during febrile neutropenia.Bacteremia detection was improved in this preliminary study and this warrants further evaluation in the overall pediatric population.We observed no adverse effects associated with the new strategy while overall blood sparing was improved and handling of intravascular devices was reduced.The good tolerance of the blood sampling suggests that the recommended 1% volume limitation in children could be reconsidered.A similar evaluation is justified in the overall pediatric population suspected for bloodstream infection.

4.
Theranostics ; 10(18): 8130-8142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724462

RESUMO

Anthracyclines are key chemotherapeutic agents used in various adult and pediatric cancers, however, their clinical use is limited due to possible congestive heart failure (HF) caused by acute and irreversible cardiotoxicity. Currently, there is no method to predict the future development of the HF in these patients. In order to identify early biomarkers to predict anthracycline cardiotoxicity in long-term survivors of childhood cancer, this longitudinal study aimed to analyze early and late in-vivo regional myocardial anthracycline-induced cardiotoxicity, related to in-vitro cardiac myocytes dysfunction, in a juvenile rat model. Methods: Young male Wistar rats (4 weeks-old) were treated with different cumulative doses of doxorubicin (7.5, 10 or 12.5 mg/kg) or NaCl (0.9%) once a week for 6 weeks by intravenous injection. Cardiac function was evaluated in-vivo by conventional (left ventricular ejection fraction, LVEF) and regional two-dimensional (2D) speckle tracking echocardiography over the 4 months after the last injection. The animals were assigned to preserved (pEF) or reduced EF (rEF) groups at the end of the protocol and were compared to controls. Results: We observed a preferential contractile dysfunction of the base of the heart, further altered in the posterior segment, even in pEF group. The first regional alterations appeared 1 month after chemotherapy. Functional investigation of cardiomyocytes isolated from the LV base 1 month after doxorubicin treatment showed that early in-vivo contractile alterations were associated with both decreased myofilament Ca2+ sensitivity and length-dependent activation. Changes in post-translational modifications (phosphorylation; S-glutathionylation) and protein degradation of the cardiac myosin binding protein-C may contribute to these alterations. Conclusion: Our data suggest that screening of the contractile defaults of the base of the heart by regional 2D strain echocardiography is useful to detect subclinical myocardial dysfunction prior to the development of delayed anthracycline-induced cardiomyopathy in pediatric onco-cardiology.

5.
Bull Cancer ; 107(6): 629-632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-155023

RESUMO

Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/farmacocinética , Antivirais/uso terapêutico , Criança , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Síndrome de Down/epidemiologia , Interações Medicamentosas , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão , Risco , Medição de Risco , Terapia de Salvação , Avaliação de Sintomas
6.
Bull Cancer ; 107(6): 629-632, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32387061

RESUMO

Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/farmacocinética , Antivirais/uso terapêutico , Criança , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Síndrome de Down/epidemiologia , Interações Medicamentosas , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão , Risco , Medição de Risco , Terapia de Salvação , Avaliação de Sintomas
7.
Br J Haematol ; 189(2): 351-362, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31837008

RESUMO

We investigated the long-term outcome, the incidence of second neoplasms (SN) and the rate of late adverse effects (LAE) in children with central nervous system (CNS) negative medium/high-risk de novo acute lymphoblastic leukaemia (ALL), in first complete remission (CR1) at end of late intensification, randomized to receive no cranial radiotherapy (No CRT, n = 92) versus CRT (standard arm, n = 84) in the non-inferiority EORTC 58832 study (1983-1989). Median follow-up was 20 years (range 4-32 years). The 25-year disease-free survival rate (±SE) was 67·4 ± 4·9% without CRT and 70·2 ± 5·0% with CRT. The 25-year incidence of isolated (6·5 ± 2·6% vs. 4·8 ± 2·3%) and any CNS relapse {8·7 ± 2·9% vs. 11·9 ± 3·5%; hazard ratio (HR) 0·71 [95% confidence interval (CI) 0·28-1·79]; test of non-inferiority: P = 0·01} was not increased without CRT. The 25-year SN incidence in CR1 was 7·9 ± 4·6% vs. 11·0 ± 4·2%. The 25-year event-free and overall survival rates were quite similar in both arms [59·5 ± 6·3% vs. 60·5 ± 5·9%, HR 0·94 (95% CI 0·57-1·52), and 78·1 ± 4·3% vs. 78·5 ± 4·5%, HR 1·00 (95% CI 0·53-1·88)]. Omission of CRT was associated with dramatic decrease in CNS and endocrine LAE rates. In conclusion, our data suggest that, with proper systemic and intrathecal CNS prophylaxis, CRT could totally be omitted in CR1 without jeopardizing survival, while decreasing LAE in childhood ALL.

9.
Br J Haematol ; 186(5): 741-753, 2019 09.
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.

10.
Int J Cancer ; 145(11): 2907-2916, 2019 12 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.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neuroblastoma/epidemiologia , Fumar Tabaco/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Exposição Materna/efeitos adversos , Razão de Chances , Exposição Paterna/efeitos adversos , Gravidez , Sistema de Registros , Fumar Tabaco/efeitos adversos
11.
J Pediatr ; 205: 168-175.e2, 2019 02.
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.


Assuntos
Previsões , Nível de Saúde , Leucemia/epidemiologia , Qualidade de Vida , Medição de Risco/métodos , Adolescente , Criança , Estudos Transversais , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Masculino , Fatores de Risco , Fatores Socioeconômicos , Taxa de Sobrevida/tendências , Adulto Jovem
12.
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.

14.
Haematologica ; 103(4): 645-654, 2018 04.
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.


Assuntos
Leucemia/complicações , Síndrome Metabólica/epidemiologia , Sobreviventes , Adulto , Antineoplásicos/uso terapêutico , Estudos de Casos e Controles , Irradiação Craniana , Feminino , França , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Prevalência , Fatores de Risco , Triglicerídeos/sangue , Circunferência da Cintura , Irradiação Corporal Total , Adulto Jovem
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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