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International audience; Background: Childhood cancer confront the whole family with a traumatic event. Because brothers and sisters may encounter emotional problems that can remain for a long time and that only few studies have assessed their long-term outcome, our present objectives were to describe the long-term quality of life (QoL) of childhood leukemia survivors' siblings and to explore its determinant. Methods: Brothers and sisters (from 8-year-old) of survivors included in the French LEA Cohort completed a QoL questionnaire (according to their age). Scores were compared with those reported by age- and gender-matched French general population and by survivors. Using a clustering method, siblings were categorized into 3 groups depending on their level of QoL's scores and factors likely to be linked with these clusters were explored with multivariate analyses. Results: We included 689 brothers and sisters (313 minors, 376 adults) and the mean time from diagnosis was 13.2 ± 6.6 years. Minor siblings reported higher QoL scores than general population (p < 0.001), but a lower score for relationship with family than survivors (p < 0.001). In adult siblings, Mental Component Summary score was lower than general population (p < 0.001). Level of siblings' QoL was linked with female gender, but no association was found with cancer-related factors. Conclusion: Brothers and sisters expressed a divergent perception of their long-term QoL depending on their age. To minimize the impact from childhood to adulthood, long-term attention should also be paid to siblings, often referred as “forgotten children”. © 2022 The Authors. Cancer Medicine published by John Wiley and Sons Ltd.

We included 255 patients from the L.E.A. French long-term follow-up cohort. All had received hematopoietic stem cell transplantation (HSCT) and/or testicular radiation for childhood acute leukemia and were older than 18 years at last L.E.A. evaluation. Total testosterone deficiency was defined as a12 nmol/l level or by substitutive therapy, partial deficiency as normal testosterone with elevated luteinizing hormone (10 UI/l). After myeloablative total body irradiation (n = 178), 55.6% had total deficiency, 15.7% partial deficiency, and 28.7% were normal. A 4-6 Gy testicular boost and a younger age at HSCT increased significantly the risk. After a Busulfan-containing myeloablative conditioning regimen (n = 53), 28.3% had total deficiency, 15.1% partial deficiency, 56.6% were normal (62.5% vs. 0% in patients without or with additional testicular radiation). A 24-Gy testicular radiation without HSCT induced total or partial deficiency in 71.4% and 28.6%, respectively (n = 21). Total testosterone deficiency increased the risk of metabolic syndrome: 25% vs. 12.1% in men with partial testosterone deficiency and 8.8% when Leydig cell function was normal (p = 0.031).

International audience; 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.

International audience; 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.

RésuméL’augmentation régulière de la survie des enfants et des adolescents traités pour un cancer permet d’estimer actuellement en France à 50 000 le nombre d’adultes survivant d’un cancer traité avant l’âge de 20ans et qui sont concernés par les possibles effets tardifs de la maladie et des thérapeutiques reçues (chirurgie, chimiothérapie, radiothérapie). Ces complications peuvent se manifester avec des délais variables par des maladies cardiovasculaires, cérébrovasculaires (après irradiation ou chimiothérapie), des troubles neurocognitifs, endocriniens (croissance, fonction thyroïdienne), troubles de la fertilité et des seconds cancers. Le suivi doit être personnalisé, adapté à chaque patient et dépend du type de la tumeur primitive, des traitements anticancéreux administrés mais aussi des facteurs génétiques associés éventuels. Le risque de développer des complications à long terme augmente avec le temps et peut être exacerbé par les comorbidités liées à l’âge et aux facteurs environnementaux (tabac, alcool, obésité). En France, plusieurs régions ou centres de traitement ont mis en place des consultations spécialisées dans ce domaine.SummaryIncreased survival of patients with childhood cancer has resulted in a growing population of survivors. In France approximately 50,000 alive people have been treated before 20years old and, as survivors, are at risk for health problems due to disease or cancer therapy (surgery, chemotherapy, radiotherapy). Complications such as cardiovascular or cerebrovascular disease (after radiotherapy or chemotherapy), neurocognitive deficiency, endocrine disorders (hypopituitary axis, or thyroid dysfunction), gonadal function, and second malignancy can be life-threatening and seriously affect quality of life. Upon discharge former patients should be given ‘passport’, containing a summary of their medical history, treatment (surgery, chemotherapy cumulative doses, characteristics of radiotherapy and organs involved), methods used to preserve fertility, and complications during treatment. Treatments can then be linked to individualized recommendations for follow-up care. The risk of developing long-term complications increases with time and can be aggravated by age-related comorbidity and environmental factors (tobacco, alcohol, obesity). Many regions and treatment centres in France have in place organised long-term follow-up procedures.

Background With the growing rate of childhood cancer cure and the risks of sequelae, long-term follow-up (FU) of survivors is a central issue. Several models have been proven far from satisfactory. Shared care FU is the result of collaboration between general practitioners (GPs) and cancer centers. We sought to demonstrate the feasibility of setting up a shared care program based on the patient-centered education of GPs and to evaluate the impact of this model in an intervention study. Methods We compared the FU care achievement in two childhood cancer survivor cohorts in the same pediatric oncology center, (i) control group (n = 134) and (ii) intervention study cohort (n = 137), after setting up the program. Results The rate of survivors answering the survey and the rate of patients involved in FU by their GPs were higher in intervention study cohort than in baseline one (132/137 vs. 72/134 and 110/132 vs. 13/72; P ≤ 0.0001). The lack of any FU was definitely lower (10/132 vs. 18/72; P = 0.001) in the intervention study cohort. Conclusion In this shared care program, survivors overcame distrust in their GP's knowledge and entered the FU program after their GPs had been involved in patient-centered education. Personalized and incentive-based guidance was very useful in helping survivors to adhere to FU. Support of a dedicated long-term FU team was very useful. A nationwide organization, consideration of special needs in subgroups of survivors and sustained funding are needed to adjust the program in the very long term.

Background To improve outcome and overall survival (OS) in high-risk neuroblastoma, NB96 induction therapy was intensified using sequential high-dose chemotherapy and autologous stem cell rescue. Procedure Twenty children were included in this pilot study undertaken at seven reference centers in France, between May 1995 and October 1996. Induction began with one cycle of conventional chemotherapy followed by six sequential cycles of high-dose chemotherapy comprising two cycles of etoposide 800 mg/m2/day over 3 days, two cycles of cyclophosphamide 2,000 mg/m2/day over 3 days, and two cycles of carboplatin 400 mg/m2/day over 5 days, followed by stem cell rescue. Results Thirteen patients (13/20) received this induction with acceptable toxicity and adequate stem cell harvest. Of these, nine (9/13) underwent surgery according to the protocol, while one patient was given a consolidation regimen prior to surgery. No toxic death was recorded. At the end of induction, complete remission was achieved in 10 cases (50%), with six still alive in July 2009. The 5-year event-free survival and OS were 35 ± 11% and 40 ± 11%, respectively. Conclusion NB96 therapy is feasible and tolerated without lethal toxicity. Nevertheless, given the small sample size and absence of randomization in our study, the effectiveness of this strategy based on metastasis complete response rates and long-term outcome was not superior to other intensive chemotherapy regimens. Pediatr Blood Cancer 2011; 57: 965–971. © 2011 Wiley-Liss, Inc.

Increased survival of patients with childhood cancer has resulted in a growing population of survivors. In France approximately 50,000 alive people have been treated before 20 years old and, as survivors, are at risk for health problems due to disease or cancer therapy (surgery, chemotherapy, radiotherapy). Complications such as cardiovascular or cerebrovascular disease (after radiotherapy or chemotherapy), neurocognitive deficiency, endocrine disorders (hypopituitary axis, or thyroid dysfunction), gonadal function, and second malignancy can be life-threatening and seriously affect quality of life. Upon discharge former patients should be given 'passport', containing a summary of their medical history, treatment (surgery, chemotherapy cumulative doses, characteristics of radiotherapy and organs involved), methods used to preserve fertility, and complications during treatment. Treatments can then be linked to individualized recommendations for follow-up care. The risk of developing long-term complications increases with time and can be aggravated by age-related comorbidity and environmental factors (tobacco, alcohol, obesity). Many regions and treatment centres in France have in place organised long-term follow-up procedures.

An understanding of the pathogenesis of second cancers may help in their prevention. We report on two children who were treated for acute lymphoblastic leukemia (ALL), with an exclusively cranial prophylactic irradiation (18 Gy) and who presented with a thyroid carcinoma (TC) 12 and 13 years later. From a thorough review of the literature of TC after ALL and of radiation-induced TC, a strong case can be made that these tumors are caused by late effects of scattered radiation. The risk is at its highest in small children. After cranial irradiation, patients require clinical monitoring of the thyroid and cervical area for nodules, continued indefinitely. We suggest that, in most cases, an alternative form of neuromeningeal prophylaxis should be offered in small children with ALL.

There is little data available regarding children and adolescents with Hodgkin lymphoma (HL) who relapse after combined-modality treatment, even though they have a substantial chance of cure. The purpose of this national retrospective study was to evaluate the outcome of patients with recurrent/refractory HL and determine adverse prognostic factors. From 1990 to 2006, 70 patients (median age 13·9 years) with refractory (n = 31) or first relapse (n = 39) HL were identified. Median time from end of treatment to relapse was 6 months (3-56). Relapses occurred in irradiated areas in 43/70 patients. Salvage therapy consisted of chemotherapy and 50 patients received high-dose chemotherapy with autologous stem cell transplantation. Radiotherapy was performed in 29 cases, tandem autologous transplantation in five and allograft in three. With a median follow-up of 40 months (2-140), significant prognostic factors were time to progression/relapse and response to therapy before autograft. Event-free survival and overall survival in patients with refractory disease, early relapse and late relapse were 35 ± 9%, 67 ± 11%, 76 ± 10% and 48 ± 11%, 89 ± 7% and 80 ± 10%, respectively. As progression3 months was a major adverse prognostic factor, novel therapeutic approaches are needed for this group of patients. By contrast, patients have substantial chance of long term second remission in case of relapse3 months.

To improve outcome and overall survival (OS) in high-risk neuroblastoma, NB96 induction therapy was intensified using sequential high-dose chemotherapy and autologous stem cell rescue.Twenty children were included in this pilot study undertaken at seven reference centers in France, between May 1995 and October 1996. Induction began with one cycle of conventional chemotherapy followed by six sequential cycles of high-dose chemotherapy comprising two cycles of etoposide 800 mg/m(2)/day over 3 days, two cycles of cyclophosphamide 2,000 mg/m(2)/day over 3 days, and two cycles of carboplatin 400 mg/m(2)/day over 5 days, followed by stem cell rescue.Thirteen patients (13/20) received this induction with acceptable toxicity and adequate stem cell harvest. Of these, nine (9/13) underwent surgery according to the protocol, while one patient was given a consolidation regimen prior to surgery. No toxic death was recorded. At the end of induction, complete remission was achieved in 10 cases (50%), with six still alive in July 2009. The 5-year event-free survival and OS were 35 ± 11% and 40 ± 11%, respectively.NB96 therapy is feasible and tolerated without lethal toxicity. Nevertheless, given the small sample size and absence of randomization in our study, the effectiveness of this strategy based on metastasis complete response rates and long-term outcome was not superior to other intensive chemotherapy regimens.

Shwachman Diamond syndrome (SDS) is a rare multi organ genetic disease bearing a very high risk of haematological complications i.e. MDS/leukaemia and Bone Marrow Failure. The aim of this study is to explore genotype predisposition of the major complications observed in SDS’s patients and to explore prognosis factors of MDS/leukaemia. Methods: Among 90 SDS patients included in the French Severe Chronic Neutropenia Registry, SBDS gene was screened in 63 patients and mutations have been found in 60 patients. Cut-off date was july 30th, 2007. Differences between groups of patients were analysed as survival data, by log rank test. The medical events analysed were: death (n=6), myelodysplasia or acute leukemia (n=6), bone marrow failure (n=6), all hematological events combined (n=12), the use of G-CSF as infectious prophylaxis (n= 11), the necessity of an orthopedic surgery (n=4) and the necessity of nutritional medical support (parenteral or enteral feeding, by mean of gastrostomy (n= 5), intrauterine growth retardation (n=19) and finally, major development retardation if it leads to a specialized school (n=10). Results: Mutations were found in 60 patients (35 males, 25 females) belonging to 54 distinct families (in 6 families, two siblings were genotyped). The median age at last analysis was 10.3 years (0.5yr-38.6 yr). The great majority of patients present the recurrent genotype K62X/C84fs (n=38, 68%) while 19 other mutations were founded, which could be classified in truncating mutations leading to premature stop codons (nonsense, frameshift or splicing defect; n=8) or missense mutations (n=11). We compared patients with truncating mutations on both alleles to compound heterozygous patients carrying at least one missense mutation. Even if differences were observed for the distribution of events between genotype subgroups of patients, none of them raised statistically significance. However, to date, all leukemia has been observed in the group of patients with “truncating” mutations. The genotype of patients with leukemia was [K62X]+[C84fs] in 5 and [C84fs]+[V93fs] in one; while the genotype of patients with BM failure was [K62X]+[C84fs] (n=2), [C84fs]+[624+1G>C], [C84fs]+[C119R], K62X/undetermined, and [C84fs]+[E99fs], [C84fs]+[E44fs]. Among the 6 pairs of siblings tested, four had a similar outcome and two pairs were discordant for the haematological events (leukaemia in one family, Bone marrow failure in the second family). Further, we have analysed genotype, gender, G-CSF therapy and initial Neutrophils and monocytes count, Hemoglobin level, Platelet level as risk factors of Leukemia/MDS. In a multivariate model, none of these features predicts Leukemia/MDS in SDS patients. Conclusion: The genotype of SDS did not appear to be correlated with clinical presentation or outcome. It remains possible than patients without truncating mutations (about 18%) may have a low rate of leukaemia but our survey lack of statistical powerful to demonstrate this hypothesis. We also failed to determine prognostic factors of Leukemia/MDS in SDS patients.