The CRYO-LEA project is based on the association of a biobank of patients from the LEA cohort and their clinical data. Thus, a blood sample is offered to each patient during their LEA consultation. This sample is then sent to the biological resources center affiliated with CRYOSTEM, on which the clinical service receiving the patient depends. For certain patients treated by allogeneic hematopoietic stem cell transplantation (25% of patients), whose peripheral blood cells come from the graft and are therefore of the donor type, a skin biopsy is proposed for culture and freezing of the fibroblasts. This biopsy is then sent to the service of Prof. SOULIER at Paris-St LOUIS Hospital which ensures the isolation of the fibroblasts, their culture, freezing and storage.

Links have now been established between the treatments used and the specific complications, but significant inter-individual variability is observed for the same treatment. In this context, the identification of genetic susceptibilities to a specific late effect associated with treatment is a very promising approach. Improved knowledge about these genetic susceptibilities may help define more personalized therapies that balance the effectiveness of treatment with the risk of late complications. This can facilitate the development of a targeted prevention strategy (that is, better adapted to the patient’s risk), optimizing care according to risk and improving quality of life. The GEN-LEA study focused on four side effects: metabolic syndrome, anthracycline-induced cardiomyopathy, second malignancies, and symptomatic osteonecrosis. The precise identification of patients with each of these late effects in the LEA cohort, as well as their detailed description in terms of variables associated with the patient, disease and treatment will greatly facilitate the study at the genome level. GEN-LEA is driven from the clinical-biological collection CRYO-LEA.

Acute leukemia chemotherapy contains many potentially nephrotoxic molecules, especially when combined with other nephrotoxic treatments to which patients are regularly exposed. This renal risk increases further when performing myeloablative conditioning before allogeneic bone marrow transplantation. The NEPHRO-LEA study will allow a good evaluation of the long-term renal function of patients treated in childhood for acute leukemia, whether or not they received an allogeneic bone marrow transplant. This study is carried out during LEA consultations: arterial pressure, complete blood ionogram, urine ionogram on micturition, urine test strip. Knowledge of potential long-term nephrological sequelae is essential since it will then lead to nephrological care until there unknown of patients currently having the same life expectancy as the general population.

Children with Down’s syndrome have a higher risk of developing acute leukemia in the first years of life and are more prone to acute toxicities from chemotherapy treatments, despite reduced intensity protocols. However, little is known about the long-term fate of patients with Down’s syndrome who recover from leukemia.

The aim of this study is to assess the long-term survival and sequelae in these children. From the patients of the LEA cohort, the results of patients with trisomy 21 will be compared to patients without trisomy 21 matched on age, characteristics of leukemia and treatments received. The results will also be compared in a second step with those of patients with Down’s syndrome without leukemia using data from the literature.

Acute myeloid leukemia in children and adolescents (AML) are rare diseases with a high relapse rate (45%) and an unfavorable prognosis (<70%) despite therapeutic advances. In order to better understand the functioning of these diseases, the CONECT AML network bringing together 12 research teams in France was created in 2017. The DOREMy project, in which LEA is involved, consists in pooling research data from the CONECT AML network and clinical-biological data from treatment. Pooling data will make it possible to better characterize subgroups of rare patients and to establish a response profile to treatments, which will make it possible to adapt the treatment of future patients in order to reduce the rate of relapses and improve the prognosis of pediatric AML.

Osteonecrosis is a long-known complication of leukemia treatments. Thanks to recent consensus definitions, the study of the fate of symptomatic osteonecrosis authenticated by MRI and their management has become relevant to carry out on a large cohort of unselected childhood leukemia. This step is essential for making therapeutic recommendations based on well-conducted studies and not isolated or compiled cases. The main objective is to describe the patients with symptomatic osteonecrosis at their diagnosis, within the current LEA cohort and to identify the risk factors for involvement regardless of the grade and if severe grade and of uni or multifocal involvement. The other objectives are to evaluate the quality of life (at diagnosis and at the last follow-up) according to the joints, to analyze the radiological lesions according to the joints (in the 1st year and at the last follow-up), to define the prognostic criteria radiological deterioration and describe the therapeutic management according to the joints.

The allogeneic hematopoietic stem cell transplant (allo HSC) is the oldest and the best validated of the immunotherapies used in hematology. Graft versus host disease (GvHD), a dysimmune reaction that can occur after allo HSC, severely affects the prognosis of allogeneic patients. The chronic form of GvH (GvHc) is less well described in the pediatric population than in adults, and is the subject of poorly validated treatments. This study proposes to describe GvHc (incidence, modalities of expression, severity, treatment implemented and repercussions on quality of life) in transplant patients before the age of 18 from the French LEA multicenter cohort.

Previous studies have shown a high prevalence of metabolic syndrome in young adults treated for acute childhood leukemia. Metabolic syndrome causes high cardiovascular morbidity and mortality. Our main hypothesis is that the early detection of metabolic syndrome in patients recovered from childhood AML may lead to an appropriate intervention strategy with the aim of reducing its long-term consequences.

The main objective of the MET-LEA study (in connection with the CONECT-AML network) is to assess the effectiveness of the recommendations for the management of metabolic syndrome on the components of the metabolic syndrome after one year of intervention in this specific context. This intervention will be done by monthly telephone coaching by a dietician. The advice given is based on nutritional and physical activity recommendations (NCEP-ATP III). The secondary objective is to search for hepatic impairment (steatosis, NASH, fibrosis) and to assess the impact of dietary management on this type of impairment.

In women, menstrual irregularities, infertility, and even early menopause are significant side effects associated with the use of alkylating drugs and conditioning before hematopoietic stem cell transplantation. As the survival rate of children with leukemia has improved, quality of life is at the forefront in this patient population and infertility remains one of the most life-changing complications. The main objective of this study is therefore to take stock of fertility in women treated for childhood leukemia and included in the LEA cohort. These collected data will be compared with data from the National Institute of Statistics and Economic Studies (INSEE) on the reproduction rate according to the age of the mother, by age group and year of birth.

Few studies are available on the impact of treatments (whether total body irradiation or high dose of alkylating agents) on the anatomy of the uterus depending on the conditioning regimen and pubertal status at the time of conditioning. A more precise analysis of the imaging of the uterus on a homogeneous cohort of patients seems essential to obtain results concerning the impact on the uterus of the alkylating treatments used in conditioning for the transplant of HSC.

The FERTI-LEA study will allow an anatomical study by MRI of the uterus, depending on the conditioning regimen and the pubertal status at the time of the HSC transplant in the women of the LEA cohort, treated for acute leukemia of the child or adolescent.

Progress in the therapeutic management of pediatric leukemia raises concerns about the long-term sequelae of treatments, especially endocrine. Premature ovarian failure (POI) is an integral part of these secondary morbidities, especially after a hematopoietic stem cell transplant for acute leukemia in childhood. A LEA study was recently conducted on testosterone deficiency in male survivors of childhood acute leukemia after treatment with hematopoietic stem cell transplantation and / or testicular irradiation. Our project is to conduct a parallel study on ovarian failure in surviving women. Thus, the main objective is to study the prevalence of premature ovarian failure after hematopoietic stem cell transplantation for acute leukemia in childhood.

Treatment of acute leukemia in childhood or adolescence may affect the oral sphere in the medium to long term, which will differ depending on the age at which the patient was treated and the type of treatment received. The treatments are also at the origin of acquired oral pathologies (caries disease, periodontal disease) which deteriorate the quality of life of patients and which can have local and general repercussions.

The main objective of this pilot study is to take stock of the oral health of the patients included in the LEA cohort. The secondary objectives are to determine the risk factors for oral pathologies, and to describe their possible repercussions on the quality of life.

A consultation in the dental department of Rothschild Hospital, AP-HP, Paris will be systematically offered to patients included in the LEA cohort, during an inclusion or follow-up visit, on the investigator site of Trousseau hospital, AP-HP, Paris.

Depending on the results of this pilot study, if the value of a systematic oral assessment is confirmed, the device could be extended to other investigative centers.

Long after recovery from childhood leukemia, late side effects can affect patients’ health and quality of life. It is therefore necessary to organize very prolonged follow-up of patients, well beyond childhood and adolescence. The justification for this long-term follow-up is now well accepted in the medical community on the grounds of screening, early treatment or even prevention of sequelae. Some patients, however, have no physical sequelae on subsequent assessments and may never have one. Identifying them would allow another type of cure, particularly awaited by many patients, without the need for further monitoring.

The objectives of the present study are to search, using data from the LEA cohort, for the characteristics of a population at very low risk of sequelae and with sufficient follow-up to predict a very low subsequent risk.

The experience of childhood cancer, responsible within the family of significant stress and important consequences on usual family functioning, necessarily impacts the entire family of the sick child, his parents as well as his healthy siblings. Beyond increased hospital attendance, the family is faced with constant uncertainty about the course of the disease and its prognosis, but also the change in the sick child as well as in his physical condition, in its appearance and behavior. Siblings must adapt to these changes, but also to the additional responsibility that may fall to them within the family, to the sometimes less availability of their parents and to different conflicting emotions of fear, anxiety, isolation, jealousy or guilt. These effects, both psychological and social, can persist over time and continue to influence the quality of life of siblings long after treatment ends, even if the sick child is a cancer survivor. To document the quality of life of siblings of patients who self-report acute childhood leukemia as well as their perception of the impact that the family cancer experience has had on their future in the medium and long term, a questionnaire is offered to the siblings.

The LEA long-term follow-up program has recently been opened to patients who were treated in childhood for Hodgkin lymphoma or lymphoblastic lymphoma. This opening of the program, which individually will allow each patient included better access to more structured prevention, will also make it possible to better know and understand the quality of life (in its physical, psychological and social dimensions) in the post-cancer period for these former patients having been treated for childhood lymphoma, in the French context. The HEMiLY project, which will assess the remote impact of pediatric lymphoma and its treatments on quality of life, will identify profiles of patients at risk of impaired quality of life in the long term, to reflect on support strategies that could be proposed in the organization of post-cancer follow-up.

An initial work from the LEA cohort explored the employment rates of former patients compared to those of the general population. It seems relevant to conduct additional work to document the impact of the state of health of former patients on their professional activity when they are in employment.

Thus, the present study will focus on the losses induced (loss of productivity and absenteeism) by this history of pediatric leukemia and its sequelae on the professional activity of cured adult patients.

The LEA program is a follow-up organization structured around the child who has been treated for leukemia, at the initiative of pediatric oncology actors, which seems to meet the main expectations of the inseparable “child-parent” couple. However, a lower participation rate is observed when the former patient has become an adult. The cohort offers the opportunity to reflect on the efficiency of the organization, integrating patient expectations.

The main objective is to identify the organizational factors (expectations, needs, etc.) of non-adherence to organized monitoring among young adults (18-29 years old), in order to optimize adherence to this monitoring.

The structure of the LEA program is mainly based on a strong organization upstream of follow-up visits (invitation of patients, updating of historical and inter-visit data, etc.). Downstream, the link with the ambulatory system is less supervised by the program. However, after the dedicated follow-up visit, it is indeed on an ambulatory basis that the patient must himself organize specialized consultations (with an ophthalmologist, a cardiologist, etc.) and paraclinical examinations (osteodensitometry, thyroid ultrasound, etc.) prescribed for screening for late sequelae. In the absence of knowledge of the care system, identification of competent structures and the difficulty sometimes in organizing the appointment, some patients do not carry out these examinations, even though they have taken the initial step to benefit of the follow-up. As part of the COSIMA project, a personalized intervention will be carried out by an assistant coordinator of follow-up present in the reference center carrying out the follow-up visits, to accompany the patient in the continuity of the LEA visit for the organization of the prescribed screening consultations. This project should allow an increase in the performance of screening examinations for sequelae in subjects participating in the follow-up program and an optimization of the time taken to deal with any sequelae.

The main side effect of vincristine is chemotherapy-induced peripheral neuropathy (CIPN). Long-term CIPN are associated with anxiety and depression. Finally, CIPN remains a problematic side effect associated with a health-related decline in quality of life, as no preventive and effective curative treatment (with the exception of duloxetine) is currently available.

The long-term prevalence of CIPN is not clearly known in childhood leukemia survivors treated with vincristine. In addition, the possible impact of these persistent NHICs on comorbidities and quality of life is not clearly known in this population either.

To answer these questions, a cross-sectional study evaluating the prevalence and long-term severity of CIPN in patients cured of childhood leukemia treated with vincristine, thanks to the French multicenter cohort LEA, will be carried out. This study will combine the results reported by patients (specific questionnaire) and health data from the LEA database, ensuring very good feasibility.

With the improvement in the survival of adolescents and young adults (AYAs) with acute leukemia, there is a growing need to focus on long-term side effects in a population where the poor laboratory characteristics of leukemia occurring at this age frequently contribute to the need for more aggressive treatment. The medical, physical, but also psychosocial problems occurring in adolescents and young adults treated for acute leukemia constitute an important public health priority which has not been sufficiently studied, with significant disparities. The main objective is to study the long-term effects in patients over 15 years of age at diagnosis of acute leukemia by comparing the population of patients over 15 years of age to patients under 15 years of age at diagnosis.

The results of this study will help refine the long-term follow-up required for this specific population.

Data on hearing loss induced by ototoxicity of treatments received in the management of childhood hematologic malignancy are very scarce. Among the previous studies, some report data dating back more than 10 years, from populations sharing solid and hematologic cancers, or focusing on survivors treated with chemotherapy only. None of them explored the impact of hearing loss on the lives of individuals and their families.

This study proposes to document in a specific population of survivors of childhood malignant hemopathies: the prevalence and characterization of hearing loss, as well as the impact of hearing loss on the lives of individuals and their relatives (social integration, psycho-behavioral issues, intra-family relationships).