[Pediatric aphereses (workshop SFGM-TC)]. / Cytaphérèses pédiatriques (atelier SFGM-TC).

Practice of pediatric aphereses - in particular when caring for low-weight children - differs from the practice of adult aphereses, since pediatric aphereses represent low numbers of procedures, which has practical implications in terms of practical training and retraining for involved healthcare personnel, as needed for habilitation and validation of ongoing competencies. A specific training is mandatory in order to ensure both the child and the staff safety during and after collection, as well as ensure high quality of the collected cell product and that its meets predefined specifications that depend on its intended use. Low and very low-weight children deserve a particular attention for a number of procedural and clinical aspects: the nature and quality of venous accesses to ensure proper operation of the cell separator, management of hemodynamic fluctuations in relation with the relative importance of the extracorporeal blood volume as compared to the total blood volume of the child, risks and clinical manifestations of citrate toxicity, minimization of stress during the procedure that may include but is not limited to pharmacological sedation. The full spectrum of competencies needed to deal with these aspects is rarely present within a single team of healthcare professionals; it most often requires the tight combination of expertise drawing from the collection facility, the pediatric department and possibly the pediatric intensive care unit ward, whether from the same or from different institutions. Interactions must be formalized in a document that accurately describes which category of actors is responsible for each category of acts (prescriptions, decisions), depending on their initial qualifications, specific competencies, and affiliations.

Educational outcomes in siblings of childhood leukemia survivors: Factors associated with school difficulties and comparison with general population.

BACKGROUND: To investigate the educational outcomes of siblings of childhood leukemia survivors, explore determinants of school difficulties, and compare the rates of repeating grades between siblings and the general population. METHODS: A cross-sectional study of childhood leukemia survivors' siblings recruited through the Leucémies de l'Enfant et de l'Adolescent cohort, a French long-term follow-up program, was conducted, and education-related data were obtained via self-report questionnaires. Adjusted logistic regression models were used to identify variables associated with school difficulties and time since diagnosis. Rates of repeating a grade in middle school were compared between siblings and the general population of the same generation. RESULTS: A total of 564 siblings with a mean time from diagnosis of 14.1 ± 6.4 years were included, among whom 139 (24.6%) repeated a grade, at an average of 6.4 ± 4.5 years after diagnosis. In multivariate analysis, the risk factors for repeating a grade were older siblings (odds ratio [OR] 2.3, p = 0.006), family financial difficulties (OR 2.8, p = 0.008), and history of repetition in survivors (OR, 2.5, p = 0.001). Sibling hematopoietic stem cell donors were at greater risk of repeating a grade long-term after diagnosis (p = 0.018). Overall, siblings did not have a higher risk of educational delays at the end of middle school than the general population. CONCLUSION: Although the results are reassuring, socioeconomic and cancer-related factors may have an impact on siblings' schooling long after diagnosis. Paying attention to siblings contributes to identifying the most vulnerable families, allowing more attention and appropriate resources to avoid long-term repercussions. Additionally, supportive and targeted interventions can be developed to improve the organization of education and the health care system.

Anthracycline-induced cardiotoxicity on regional myocardial work and left ventricular mechanical dispersion in adolescents and young adults in post-lymphoma remission.

BACKGROUND: Myocardial work (MW) is a new echocardiographic tool with a high sensitivity to detect early and subtle alterations of myocardial function. We aimed to evaluate the late effects of anthracyclines by assessing the global and segmental MW and intraventricular mechanical dispersion from speckle tracking echocardiography in childhood lymphoma survivors (CLS). METHODS: Thirty-one young adults including CLS and age-matched healthy controls were enrolled. All underwent echocardiography including an evaluation of left ventricular (LV) morphology and regional function. We assessed LV longitudinal (differentiating sub-endocardial and sub-epicardial layers), circumferential strains and twist, global and regional MW index (MWI). LV mechanical dispersion was assessed from the time dispersion of LV longitudinal strain, from myocardial wasted work (MWW) and myocardial work efficiency (MWE). RESULTS: The longitudinal strains both at the level of the sub-endocardium and sub-epicardium were reduced in CLS compared to controls. The global MWI was also decreased (1668 ± 266 vs 1870 ± 264%.mmHg in CLS patients and controls, respectively, p < 0.05), especially on the apical segments. An increase of LV intraventricular mechanical dispersion was observed in CLS. MWW and MWE remained unchanged compared to controls. CONCLUSION: Our results strongly support that cardiac remodeling is observed in CLS, characterized by a decrease in MW and an increase in LV mechanical dispersion. The apex is specifically altered, but its clinical significance remains uncertain. MW as a complement to strain seems interesting in cancer survivors to detect myocardial dysfunction at early stage and adapt their follow-up.

Measuring Safety and Outcomes for the Use of Compassionate and Off-Label Therapies for Children, Adolescents, and Young Adults With Cancer in the SACHA-France Study.

Importance: Innovative anticancer therapies for children, adolescents, and young adults are regularly prescribed outside their marketing authorization or through compassionate use programs. However, no clinical data of these prescriptions is systematically collected. Objectives: To measure the feasibility of the collection of clinical safety and efficacy data of compassionate and off-label innovative anticancer therapies, with adequate pharmacovigilance declaration to inform further use and development of these medicines. Design, Setting, and Participants: This cohort study included patients treated at French pediatric oncology centers from March 2020 to June 2022. Eligible patients were aged 25 years or younger with pediatric malignant neoplasms (solid tumors, brain tumors, or hematological malignant neoplasms) or related conditions who received compassionate use or off-label innovative anticancer therapies. Follow up was conducted through August 10, 2022. Exposures: All patients treated in a French Society of Pediatric Oncology (SFCE) center. Main Outcomes and Measures: Collection of adverse drug reactions and anticancer activity attributable to the treatment. Results: A total of 366 patients were included, with a median age of 11.1 years (range, 0.2-24.6 years); 203 of 351 patients (58%) in the final analysis were male. Fifty-five different drugs were prescribed, half of patients (179 of 351 [51%]) were prescribed these drugs within a compassionate use program, mainly as single agents (74%) and based on a molecular alteration (65%). Main therapies were MEK/BRAF inhibitors followed by multi-targeted tyrosine kinase inhibitors. In 34% of patients at least a grade 2 clinical and/or grade 3 laboratory adverse drug reaction was reported, leading to delayed therapy and permanent discontinuation of the innovative therapy in 13% and 5% of patients, respectively. Objective responses were reported in 57 of 230 patients (25%) with solid tumors, brain tumors, and lymphomas. Early identification of exceptional responses supported the development of specific clinical trials for this population. Conclusions and Relevance: This cohort study of the SACHA-France (Secured Access to Innovative Medicines for Children with Cancer) suggested the feasibility of prospective multicenter clinical safety and activity data collection for compassionate and off-label new anticancer medicines. This study allowed adequate pharmacovigilance reporting and early identification of exceptional responses allowing further pediatric drug development within clinical trials; based on this experience, this study will be enlarged to the international level.

Impact of childhood leukemia on siblings: their long-term perception of family functioning and its relationship with their psychosocial characteristics using structural equation modeling.

PURPOSE: In the context of pediatric cancer, siblings' adaptation and needs have been previously investigated; however, research on the long-term consequences on siblings, especially on their family environment, is scarce. We aimed to (1) assess the family functioning (FF) perceived by siblings of childhood leukemia survivors long after diagnosis and (2) explore characteristics likely associated and investigate associations with psycho-behavioral and social factors. METHODS: Childhood leukemia survivors' siblings older than 11 years were recruited through the LEA cohort, a French long-term follow-up program, and completed the family assessment device (FAD). Logistic regression analysis was used to determine factors likely associated with unhealthy functioning in families as perceived by siblings. Structural equation modeling (SEM) was used to examine relationships that predict siblings' perception of FF. RESULTS: We included 605 siblings (mean follow-up time from diagnosis 14.1 ± 6.8 years), of whom 175 (28.9%) perceived unhealthy functioning. SEM showed that older siblings were more likely to perceive problematic functioning (ß = 0.095, p = 0.014). Sex and leukemia burden had indirect effects on FF through mediators. Family financial situation at diagnosis was not associated with the risk of reporting unhealthy functioning. CONCLUSIONS: Our study contributed to identifying siblings at risk of facing family issues and reinforced the need to provide more consideration and suitable resources to avoid late consequences. Often considered as the "forgotten children", future research should focus on developing targeted interventions to facilitate family communication and improve siblings' social support. IMPLICATIONS FOR CANCER SURVIVORS: Overall, results regarding FF perceived by siblings are reassuring and provide new enlightening elements that allow for better support to all families.

Fitness and metabolic response to exercise in young adult survivors of childhood lymphoma.

PURPOSE: Childhood lymphoma survivors (CLSs) are at high risk of reduced daily activity. This work studied metabolic substrate use and cardiorespiratory function in response to exercise in CLSs. METHODS: Twenty CLSs and 20 healthy adult controls matched for sex, age, and BMI took an incremental submaximal exercise test to determine fat/carbohydrate oxidation rates. Resting echocardiography and pulmonary functional tests were performed. Physical activity level, and blood metabolic and hormonal levels were measured. RESULTS: CLSs reported more physical activity than controls (6317 ± 3815 vs. 4268 ± 4354 MET-minutes/week, p = 0.013), had higher resting heart rate (83 ± 14 vs. 71 ± 13 bpm, p = 0.006), and showed altered global longitudinal strain (- 17.5 ± 2.1 vs. - 19.8 ± 1.6%, p = 0.003). We observed no difference in maximal fat oxidation between the groups, but it was reached at lower relative exercise intensities in CLSs (Fatmax 17.4 ± 6.0 vs. 20.1 ± 4.1 mL/kg, p = 0.021). At V̇O2 peak, CLSs developed lower relative exercise power (3.2 ± 0.9 vs. 4.0 ± 0.7 W/kg, p = 0.012). CONCLUSION: CLSs reported higher levels of physical activity but they attained maximal fat oxidation at lower relative oxygen uptake and applied lower relative power at V̇O2 peak. CLSs may thus have lower muscular efficiency, causing greater fatigability in response to exercise, possibly related to chemotherapy exposure during adolescence and childhood. Long-term follow-up is essential and regular physical activity needs to be sustained.

Optical Genome Mapping in Routine Cytogenetic Diagnosis of Acute Leukemia.

Cytogenetic aberrations are found in 65% of adults and 75% of children with acute leukemia. Specific aberrations are used as markers for the prognostic stratification of patients. The current standard cytogenetic procedure for acute leukemias is karyotyping in combination with FISH and RT-PCR. Optical genome mapping (OGM) is a new technology providing a precise identification of chromosomal abnormalities in a single approach. In our prospective study, the results obtained using OGM and standard techniques were compared in 29 cases of acute myeloid (AML) or lymphoblastic leukemia (ALL). OGM detected 73% (53/73) of abnormalities identified by standard methods. In AML cases, two single clones and three subclones were missed by OGM, but the assignment of patients to cytogenetic risk groups was concordant in all patients. OGM identified additional abnormalities in six cases, including one cryptic structural variant of clinical interest and two subclones. In B-ALL cases, OGM correctly detected all relevant aberrations and revealed additional potentially targetable alterations. In T-ALL cases, OGM characterized a complex karyotype in one case and identified additional abnormalities in two others. In conclusion, OGM is an attractive alternative to current multiple cytogenetic testing in acute leukemia that simplifies the procedure and reduces costs.

Symptomatic osteonecrosis in French survivors of childhood and adolescent leukemia: a clinical and MRI study of LEA cohort.

Osteonecrosis (ON) is a known complication of acute leukemia (AL) management, affecting 1%-10% of young patients and resulting in long-term morbidity. Widespread access to MRI over the past decade has allowed earlier detection and more accurate assessment. This study investigated clinical and MRI features of the 129 (2.5%) patients with symptomatic ON retrospectively recruited from the French LEA (Leucémies de l'Enfant et de l'Adolescent, or child and adolescent leukemias) cohort (n = 4,973). We analyzed data concerning ON risk factors, multifocal involvement, severe lesions detected by MRI, and patient quality of life (QoL). ON patients tended to be >10 years old at the time of AL diagnosis (odds ratio [OR]: 22.46; p < 10-6), female (OR: 1.8; p = 0.002), or treated for relapse (OR: 1.81; p = 0.041). They more frequently suffered from other sequelae (p < 10-6). Most necroses involved weight-bearing joints, and they were multifocal in 69% of cases. Double-blinded review of MRIs for 39 patients identified severe lesions in 14, usually in the hips. QoL of adolescents and adults was poor and permanently impacted after onset of ON. In conclusion, age >10 at time of AL diagnosis, female sex, and relapse occurrence were risk factors for multifocal ON; MRI revealed severe ON in a third of the patients considered; and ON was associated with persistently poor QoL affecting multiple domains. Future studies should include prospective data addressing ON management and seek to identify genetic markers for targeted screening enabling early ON detection and treatment.

Ovarian Function and Spontaneous Pregnancy After Hematopoietic Stem Cell Transplantation for Leukemia Before Puberty: An L.E.A. Cohort Study.

Ovarian function impairment and infertility are among the most frequent late effects after hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate ovarian function, occurrence of premature ovarian insufficiency (POI), and spontaneous pregnancy in a large cohort of adult survivor women who had undergone HSCT for leukemia before puberty. We conducted a retrospective observational study in women from the national cohort L.E.A., the long-term French follow-up program after childhood leukemia. The median follow-up duration was 18 years (14.2-23.3) after HSCT. Among 178 women, 106 (60%) needed pubertal induction with hormone substitution treatment, whereas 72 (40%) had spontaneous menarche. After spontaneous menarche, 33 (46%) developed POI, mostly within 5 years of HSCT. Older age at time of HSCT and cryopreservation of ovarian tissue appeared as significant risk factors for POI. More than 65% of patients who underwent HSCT before the age of 4.8 years had spontaneous menarche, and almost 50% didn't have POI at last evaluation, whereas more than 85% with HSCT after the age of 10.9 years didn't have spontaneous menarche and needed induction of puberty with hormone replacement therapy. Twenty-two women (12%) had at least one spontaneous pregnancy, with 17 live-births, 14 miscarriages, 4 legal abortions, and 2 therapeutic abortions. These results add supplementary data to better counsel patients and their families on the chances of ovarian residual function and pregnancy after HSCT, as well as on the potential interest of fertility preservation.

The uterine volume is dramatically decreased after hematopoietic stem cell transplantation during childhood regardless of the conditioning regimen.

OBJECTIVE: To study the impact of hematopoietic stem cell transplantation (HSCT) on the uterine volume of childhood acute leukemia (AL) survivor depending on age at HSCT and the type of myeloablative conditioning regimen. SETTING: Thirteen French University Teaching Hospitals. DESIGN: Prospective cohort study. PATIENT(S): Eighty-eight women who underwent HSCT during childhood or adolescence for AL compared to a control group. INTERVENTION(S): A multicentric prospective national study compared the uterine volume in a cohort of childhood AL survivor adult women treated with HSCT, matched 1:1 to control women. Pelvic magnetic resonance imaging scans included diffusion-weighted imaging sequences. Scans were centralized for a double-blinded reading by 2 radiologists. MAIN OUTCOME MEASURE(S): Uterine volume, uterine body-to-cervix ratio, and apparent diffusion coefficient. RESULT(S): The mean age at HSCT was 9.1 ± 0.3 years with a mean follow-up duration of 16.4 ± 0.5 years. The cohort of 88 HSCT survivor women was composed of 2 subgroups depending on the myeloablative conditioning regimen received: an alkylating agent-based regimen group (n = 34) and a total body irradiation (TBI)-based regimen group (n = 54). Among the 88 women, 77 were considered as having a "correct hormonal balance" with estrogens supplied by hormone replacement therapy (HRT) for premature ovarian insufficiency (POI) or because of a residual ovarian function. In the control group (n = 88), the mean uterine volume was 79.7 ± 3.3 mL. The uterine volume significantly decreased in all HSCT survivor women. After the alkylating agent-based regimen, the uterine volume was 45.3 ± 5.6 mL, corresponding to a significant volume reduction of 43.1% (28.8-57.4%) compared with that of the control group. After TBI, the uterine volume was 19.6 ± 1.9 mL, corresponding to a significant volume reduction of 75.3% (70.5%-80.2%) compared with that of the control group. After the alkylating agent-based regimen, the uterine volume dramatically decreased in women with POI without HRT compared with that in those with a correct hormonal balance (15.2 ± 2.6 vs. 49.3 ± 6 mL). In contrast, after TBI, the uterine volume was similar in all women, with no positive effect of hormonal impregnation on the uterine volume (16.3 ± 2.6 vs. 20.1 ± 2.2 mL, respectively). CONCLUSION(S): The uterine volume was diminished after HSCT, regardless of the conditioning regimen. The physiopathology needs to be further investigated: specific impact of a high dose of an alkylating agent; impact of hormone deprivation around puberty; poor compliance to HRT; or different myometrial impact of HRT compared with endogenous ovarian estrogens? CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov/NCT03583294 (enrollment of the first subject, November 11, 2017; enrollment of the last subject, June 25, 2021).

Brothers and sisters of childhood acute leukemia survivors: Their long-term quality of life and its determinants.

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".

Ex Vivo Model to Assess the Exposure of Patients to Plasticizers from Medical Devices during Pre-CAR-T Cells' Apheresis.

BACKGROUND: The treatment of relapsed or refractory leukemia remains a major problem. Among the new therapeutic approaches, the use of modified T lymphocytes, called chimeric antigen receptor T cells (CAR-T cells), seems promising. The first step of their preparation is leukapheresis, which involves the collection of mononuclear cells from the patient. This medical procedure requires numerous medical devices (MDs) made of plasticized polyvinylchloride (PVC). These compounds can leach out of the devices during contact with the patient's blood. The aim of our study was to evaluate the migration of the plasticizers contained in the MD during a simulated pre-CAR-T cell leukapheresis procedure, and to measure the patient's and their lymphocytes' exposure to them. METHODS: The qualitative and quantitative composition of the MD used for pre-CAR-T cell apheresis was determined by gas chromatography-mass spectrometry (GC-MS). Then, an ex vivo leukapheresis model using an ethanol/water simulant was performed to evaluate the plasticizers' migration under simulated clinical conditions of pre-CAR-T cells' cytapheresis. The plasticizers released into the simulant were quantified by GC-MS. RESULTS: Diethylhexylphthalate (DEHP) was found in the apheresis kit, with amounts ranging from 25% to 59% (g/100 g of PVC). Bis(2-ethylhexyl) adipate was detected at trace levels. A total of 98.90 ± 11.42 mg of DEHP was released into the simulant, corresponding to an exposure dose of 1.4 mg/kg for a 70 kg patient. CONCLUSIONS: Patients undergoing a pre-CAR-T cell apheresis are mainly exposed to DEHP, which can impact their health because of its endocrine disruption effect, but could also lead to a decrease in CAR-T cells' efficiency/quality.

Improved outcome in children compared to adolescents and young adults after allogeneic hematopoietic stem cell transplant for acute myeloid leukemia: a retrospective study from the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC).

BACKGROUND: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, adolescents and young adults after a first allogeneic HSCT for AML. METHODS: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation's time: children (< 15 years, n = 564), adolescent and post-adolescent (APA) patients (15-25 years, n = 647) and young adults (26-40 years; n = 1434). RESULTS: With a median follow-up of 4.37 years (min-max 0.18-14.73 years), the probability of 2-year overall survival (OS) was 71.4% in children, 61.1% in APA patients and 62.9% in young adults (p = 0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for APA patients and 29.4% for young adults-p = 0.0254, and 7.0% for children, 10.6% for APA patients and 14.2% for young adults, p < 0.0001; respectively). Whilst there was no difference between the three groups for grade I to IV acute GVHD CI at 3 months, the chronic GVHD CI at 2 years was higher in APA patients and young adults (31.4% and 36.4%, respectively) in comparison to the children (17.5%) (p < 0.0001). In multivariable analysis, factors associated with death were AML cytogenetics (HR1.73 [1.29-2.32] for intermediate risk 1, HR 1.50 [1.13-2.01] for intermediate risk 2, HR 2.22 [1.70-2.89] for high cytogenetics risk compared to low risk), use of TBI ≥ 8 Grays (HR 1.33 [1.09-1.61]), disease status at transplant (HR 1.40 [1.10-1.78] for second Complete Remission (CR), HR 2.26 [1.02-4.98] for third CR and HR 3.07 [2.44-3.85] for active disease, compared to first CR), graft source (HR 1.26 [1.05-1.50] for Peripheral Blood Stem Cells compared to Bone Marrow) and donor age (HR 1.01 (1-1.02] by increase of 1 year). CONCLUSION: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that APA patients with AML could be beneficially treated with a chemotherapy-based MAC regimen and bone marrow as a stem cells source.

Bone Mineral Density Evolution and Its Determinants in Long-term Survivors of Childhood Acute Leukemia: A Leucémies Enfants Adolescents Study.

This prospective study aimed to analyze determinants that can influence bone mineral density evolution in childhood acute leukemia survivors. Patients included were selected from the long-term follow-up LEA cohort and had dual energy radiograph absorptiometry scan between 10 and 18 years and after the age of 18. All scans were centrally reviewed. Bone mineral density was measured at the lumbar spine, femoral neck, total hip, and whole body, and expressed as z-score. Eighty-nine patients (female 39, lymphoblastic leukemia 68, relapse 25, hematopoietic stem cell transplantation 44, and mean age 15.4 and 20.1 years at the first and second scans, respectively) were studied. The first and second scan z-scores were significantly correlated (P < 10-3). Mean femoral neck and total hip z-scores improved significantly between the first and second scans, whereas no significant evolution occurred at the lumbar spine and whole-body level. On the second evaluation, 14.6% of patients had z-score <-2 at the lumbar spine and 4.3% at the femoral neck level. Gender, type of leukemia, transplantation, relapse, cumulative corticosteroid doses, or growth hormone deficiency did not have any significant impact on z-score variation. Younger age at diagnosis (≤8.5 years) proved an unfavorable risk factor for z-score evolution at the lumbar spine (P = 0.041); the trend did not reach statistical significance for metabolic syndrome (P = 0.054). At the femoral neck, both were associated with unfavorable z-score evolution (P = 0.003 and 0.025, respectively). Patients treated at a younger age and those with metabolic syndrome seem to be at higher risk of bone mineral density decline and should benefit from specific interventions.

Testosterone deficiency in men surviving childhood acute leukemia after treatment with hematopoietic stem cell transplantation or testicular radiation: an L.E.A. study.

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 a <12 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).

Peripheral blood stem cell collection in children with extremely low body weight (≤8 kg). What have we learned over the past 25 years and where are the limits?

Hematopoietic progenitor cells-apheresis (HPC-A) collection is now a routine procedure for autologous hematopoietic stem cell transplantation. Here we present our 25 years' experience of HPC-A collection in children weighing 8 kg or less, with a focus on the evolution of our standard operating procedures, and the safety limits for these young patients, in the Pediatric Apheresis Unit of Clermont-Ferrand University Hospital (France). Fifteen children weighing 8 kg or less underwent 26 HPC-A collections over 25 years. Median CD34+ cell yield by leukapheresis was 4.4 106 /kg. No procedure-related complications were encountered during or after the collection. No patient had profound thrombocytopenia or anemia that needed post-collection transfusions. Our experience in pediatric oncology patients who underwent HPC-A collections shows that this procedure can be performed even in the smallest of children with no increase in toxicity provided all precautions are taken to ensure that the procedure is carried out under the ideal conditions.

Quality of life in parents of childhood leukemia survivors. A French Childhood Cancer Survivor Study for Leukemia study.

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.

[Access to fertility preservation for adolescents and young adults aged 15 to 24 years with cancers in Auvergne, France]. / Accès à la préservation de la fertilité des adolescents et jeunes adultes de 15 à 24 ans atteints de cancers en Auvergne, France.

INTRODUCTION: Cancers of adolescents and young adults have particular epidemiological specificities. The improvement in their survival should be accompanied by an increased consideration of the treatments' side effects, among which the potential decrease in fertility. The objective of the study was to describe the access to fertility preservation of these patients at the University Hospital of Clermont-Ferrand over a period of 3 years. METHODS: During this retrospective descriptive study, various socio-demographic and clinical data were collected. RESULTS: One hundred and fifty new cases of cancers were diagnosed in patients aged 15 to 24 years. Forty-four percent received at least one fertility consultation, 29 % for girls and 58 % for boys (P<0.001). The number of cases that did not result in fertility preservation was significantly higher for girls than boys (P=0.005). Fertility preservation was mainly achieved by cryopreservation of ovarian tissue in female adolescents, ovocytes in young women and sperm in boys. DISCUSSION: We observed sex disparities in access to fertility preservation. Despite the existence of recommendations, progress remains to be made. The establishment of clinico-biological platforms should allow a better awareness of patients and professionals, and thus promote access to fertility preservation techniques for young patients with cancer.

Childhood Leukemia Survivors and Metabolic Response to Exercise: A Pilot Controlled Study.

BACKGROUND: Leukemia is the most common cancer in pediatrics, with many late effects such as higher risk of dyslipidemia, insulin resistance, obesity, and metabolic syndrome. The objective of this work was to investigate substrate oxidation during submaximal exercise in survivors of childhood acute leukemia. METHODS: A total of 20 leukemia survivors and 20 healthy children were matched by sex, age, and Tanner stage. They all took a submaximal incremental exercise test to determine fat and carbohydrate oxidation rates. RESULTS: Cardiorespiratory fitness was significantly lower in leukemia survivors, with lower relative VO2 peaks (p < 0.001), lower heart rate values (p = 0.02), and lower exercise power (p = 0.012), whereas rest metabolism and body mass index did not differ between the two groups. During exercise, upward of heart rate relative to VO2 peak was significantly higher (p < 0.001) in childhood leukemia survivors. We found lower carbohydrate and fat oxidation rates (p = 0.07) in leukemia survivors compared with healthy children, and also a significantly lower relative maximal fat oxidation rate (p = 0.014). CONCLUSION: Despite impaired physical fitness and metabolic response to exercise, childhood leukemia survivors remained sensitive to physical activity interventions, and could readily adapt to submaximal exercise intensity.

Metabolic response to exercise in childhood brain tumor survivors: A pilot controlled study.

BACKGROUND/OBJECTIVES: Survival rates in children diagnosed with malignant brain tumors exceed 70%. A higher risk of dyslipidemia, central obesity, and insulin resistance has been reported among these children. We investigated substrate utilization during submaximal exercise. DESIGN/METHODS: Ten brain tumor survivors and 10 healthy children were matched by sex, age, and Tanner stage. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates. RESULTS: The relative oxygen volume (VO2 ) peak was significantly higher in the control group than in the survivors of childhood brain tumors (43.3 ± 11.9 and 32.4 ± 10.2 mL/kg /min, P = .04). At the same relative exercise intensity, there was no difference in the carbohydrate or lipid oxidation rate between the two groups, or in the maximal fat oxidation (MFO) rate, or in the heart rate or percentage of VO2 peak to reach MFO. Healthy children achieved MFO at significantly higher muscular power than did brain tumor survivors (47.9 ± 20.8 and 21.8 ± 9.6 W, P = .003). CONCLUSION: Because child brain tumor survivors are less physically fit than healthy children, and substrate utilization during submaximal exercise is not different, physical activity should be promoted for child brain tumor survivors.