Hopital dEnfants de Brabois

Vandœuvre-lès-Nancy, France

Hopital dEnfants de Brabois

Vandœuvre-lès-Nancy, France
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Oudin C.,Hopital de la Timone Enfants | Simeoni M.-C.,Research Unit EA 3279 | Sirvent N.,Nice University Hospital Center | Contet A.,Hopital dEnfants de Brabois | And 10 more authors.
Blood | Year: 2011

We evaluate the prevalence and risk factors of the metabolic syndrome (MS) in young adults surviving childhood leukemia. During the years 2007 to 2008, assessment of MS was proposed to all adults included in the Leucémie de l'Enfant et de l'Adolescent program, a French prospective multicentric cohort of leukemia survivors. Among 220 eligible patients, 184 (83.6%) had complete evaluation. Median age at evaluation and follow-up duration were 21.2 and 15.4 years. Overall prevalence of MS was 9.2% (95% confidence interval, 5.5-14.4). There was no association of MS with sex, age at diagnosis, leukemia subtype, steroid therapy, and central nervous system irradiation. Patients were stratified according to 4 therapeutic modalities: chemotherapy alone (n = 97), chemotherapy and central nervous system irradiation (n = 27), hematopoietic stem cell transplantation (HSCT) without (n = 17) or with (n = 43) total body irradiation (TBI). MS occurred in 5.2%, 11.1%, 5.9%, and 18.6% of them, respectively. The higher risk observed in the HSCT-TBI group was significant in univariate and in multivariate analysis (odds ratio [OR] = 3.9, P = .03). HSCT with TBI was associated with a higher rate of hypertriglyceridemia (OR = 4.5, P=.004), lowlevel of high-density lipoprotein cholesterol (OR = 2.5, P = .02), and elevated fasting glucose (OR = 6.1, P = .04) So, TBI is a major risk factor for MS. Further studies are warranted to explain this feature. © 2011 by The American Society of Hematology.


PubMed | Hopital dEnfants de Brabois, Center Hospitalier Felix Guyon, Assistance Publique des Hopitaux de Paris AP HP, Hopital de Hautepierre and 12 more.
Type: Journal Article | Journal: Nature genetics | Year: 2015

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.


PubMed | University of Strasbourg, University Hospital of Toulouse, St Antoine Hospital, University of Lyon and 14 more.
Type: | Journal: Bone marrow transplantation | Year: 2016

We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced. Five-year overall survival (OS) was 78.2% in LAME89 and 81.4% in ELAM02. OS was significantly lower for the unfavorable cytogenetic risk group in LAME89/91 when compared with intermediate and favorable groups (50% vs 90.6 and 86.4%, P=0.001). This difference was no longer apparent in ELAM02 (80.9% vs 71.3% and 5/5, respectively). Survival improvement for children with unfavorable karyotype was statistically significant (P=0.026) and was due to decrease in relapse risk. Five-year transplantation-related mortality was 6.75% in LAME89/91. In ELAM02, it was 3.2% for patients with a sibling donor and 10.9% with an unrelated donor or cord blood. We conclude that the outcome of children with unfavorable karyotype transplanted in CR1 has improved.Bone Marrow Transplantation advance online publication, 12 December 2016; doi:10.1038/bmt.2016.293.


PubMed | Hopital dEnfants de Brabois, Montpellier University, Groupe Hospitalier Timone, University Hospital of Grenoble and 5 more.
Type: Journal Article | Journal: Journal of cancer survivorship : research and practice | Year: 2016

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.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.The questionnaire was completed by 845 eligible survivors (response rate 87.8%), with a mean age of 22.35.4years and a mean follow-up duration of 14.36.3years. Among the 361 survivors currently inthe 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.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.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.


PubMed | Hopital dEnfants de Brabois, University of Lyon, Trousseau Hospital, University Hospital of Grenoble and 9 more.
Type: Journal Article | Journal: Haematologica | Year: 2016

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. (Leucmie de lEnfant et de lAdolescent) 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.


Amigou A.,French Institute of Health and Medical Research | Amigou A.,University Paris - Sud | Sermage-Faure C.,French Institute of Health and Medical Research | Sermage-Faure C.,University Paris - Sud | And 16 more authors.
Environmental Health Perspectives | Year: 2011

Background: Traffic is a source of environmental exposures, including benzene, which may be related to childhood leukemia. Objectives: A national registry-based case-control study [ESCALE (Etude Sur les Cancers et les Leucémies de l'Enfant, Study on Environmental and Genetic Risk Factors of Childhood Cancers and Leukemia)] carried out in France was used to assess the effect of exposure to road traffic exhaust fumes on the risk of childhood leukemia. Methods: Over the study period, 2003-2004, 763 cases and 1,681 controls < 15 years old were included, and the controls were frequency matched with the cases on age and sex. The ESCALE data were collected by a standardized telephone interview of the mothers. Various indicators of exposure to traffic and pollution were determined using the geocoded addresses at the time of diagnosis for the cases and of interview for the controls. Indicators of the distance from, and density of, main roads and traffic nitrogen dioxide (NO2) concentrations derived from traffic emission data were used. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Results: Acute leukemia (AL) was significantly associated with estimates of traffic NO2 concentration at the place of residence > 27.7 μg/m3 compared with NO2 concentration < 21.9 μg/m3 [OR = 1.2; confidence interval (CI), 1.0-1.5] and with the presence of a heavy-traffic road within 500 m compared with the absence of a heavy-traffic road in the same area (OR = 2.0; 95% CI, 1.0-3.6). There was a significant association between AL and a high density of heavy-traffic roads within 500 m compared with the reference category with no heavy-traffic road within 500 m (OR = 2.2; 95% CI, 1.1-4.2), with a significant positive linear trend of the association of AL with the total length of heavy-traffic road within 500m. Conclusion: This study supports the hypothesis that living close to heavy-traffic roads may increase the risk of childhood leukemia.


PubMed | Hopital dEnfants de Brabois, Montpellier University, Aix - Marseille University, Trousseau Hospital and 6 more.
Type: Journal Article | Journal: Bone marrow transplantation | Year: 2016

Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucmie de lEnfant et de lAdolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level 350ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0.001), radiation-based preparative regimen (P=0.035) and recent period of transplantation (P<0.001); 2) in multivariate analysis: older age at transplant in quartiles (Odds Ratio (OR)=7.64, 95% CI: 3.73-15.64 for age >12.7 years and OR=5.36, 95% CI: 2.63-10.95 for age from 8.2 to 12.7 years compared to age < 4.7 years), acute myeloid leukemia (OR=3.23, 95% CI: 1.47-7.13), allogeneic graft (OR=4.34, 95% CI: 2.07-9.12 for alternative donors and OR=2.53, 95% CI: 1.2-5.33 for siblings, compared to autologous graft) and radiation-based conditioning regimen (OR=2.45, 95% CI: 1.09-5.53). Graft-versus-host disease was an additional risk factor for allogeneic graft recipients. In conclusion, IO is a frequent complication in pediatric long-term survivors after transplantation for acute leukemia, more frequently observed in older children, those transplanted from alternative donors or with graft-versus-host disease.


Charbit-Henrion F.,Hopital Necker Enfants Malades | Chardot C.,Hopital Necker Enfants Malades | Ruemmele F.,Hopital Necker Enfants Malades | Talbotec C.,Hopital Necker Enfants Malades | And 3 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2014

Objective: Anastomotic ulceration (AU) is a rare complication after intestinal resection and anastomosis, described mostly in children. The main symptom is occult bleeding, leading to iron-deficiency anemia, which is life threatening.Methods: The present survey reports a series of patients with AU after intestinal resection in infancy, focusing on predictive factors, medical and surgical treatment options, and long-term outcomes. Eleven patients (7 boys) born between 1983 and 2005 with AU after an intestinal resection and anastomosis in infancy were included in this retrospective review.Results: The diagnosis of AU was often delayed for several years. No predictive factor (including the primary disease, the length of the remnant bowel, and the loss of the ileocaecal valve) could be identified. Numerous treatment options, including antibiotics and anti-inflammatory drugs, proved to be ineffective to induce prolonged remission. Even after surgical resection, relapses were observed in 5/7 children.Conclusions: The mechanism leading to AU remains unknown. Contrary to previous reports with limited follow-up, no medical or surgical treatment could prevent recurrences. Because relapses may occur several years after treatment, long-term follow-up is needed. © 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.


PubMed | Hannover Medical School, Hopital dEnfants de Brabois, Assistance Publique des Hopitaux de Paris AP HP, University of Paris Pantheon Sorbonne and 7 more.
Type: Journal Article | Journal: European journal of medical genetics | Year: 2016

Noonan syndrome is associated with a range of malignancies including acute lymphoblastic leukemia (ALL). However, little information is available regarding the frequency, natural history, characteristics and prognosis of ALL in Noonan syndrome or RASopathies in general. Cross-referencing data from a large prospective cohort of 1176 patients having a molecularly confirmed RASopathy with data from the French childhood cancer registry allowed us to identify ALL in 6 (0.5%) patients including 4/778 (0.5%) with a germline PTPN11 mutation and 2/94 (2.1%) with a germline SOS1 mutation. None of the patients of our series with CFC syndrome (with germline BRAF or MAP2K1/MAP2K2 mutation - n = 121) or Costello syndrome (with HRAS mutation - n = 35) had an ALL. A total of 19 Noonan-ALL were gathered by adding our patients to those of the International Berlin-Munster-Frankfurt (I-BFM) study group and previously reported patients. Strikingly, all Noonan-associated ALL were B-cell precursor ALL, and high hyperdiploidy with more than 50 chromosomes was found in the leukemia cells of 13/17 (76%) patients with available genetics data. Our data suggest that children with Noonan syndrome are at higher risk to develop ALL. Like what is observed for somatic PTPN11 mutations, NS is preferentially associated with the development of hyperdiploid ALL that will usually respond well to chemotherapy. However, Noonan syndrome patients seem to have a propensity to develop post therapy myelodysplasia that can eventually be fatal. Hence, one should be particularly cautious when treating these patients.

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