A French Cohort of Childhood Leukemia Survivors: Impact of Hematopoietic Stem Cell Transplantation on Health Status and Quality of Life

AbstractThe late effects and quality of life (QoL) in childhood acute leukemia survivors were compared between hematopoietic stem cell transplantation (HSCT) recipients and patients who underwent conventional therapy. The study included 943 patients, 256 of whom underwent HSCT (27.1%). Medical visits were conducted to detect the occurrence of physical late effects. Based on patient age, different questionnaires were used to assess QoL. To evaluate the association between HSCT and each type of late effect or QoL dimension, the appropriate multivariate regressions were performed. QoL mean scores were compared with those obtained for age- and sex-matched French control subjects. Of all the survivors, 674 (71.5%) had at least 1 late effect, with the risk being 5.0 CI95 (3.0-8.6) times higher for transplantation survivors. For child survivors, scoring of QoL showed no significant differences between the treatment groups. The adult HSCT survivors reported lower physical dimension QoL scores than chemotherapy survivors. Compared with French norms, the survivor group reported a significantly lower mental composite score; however, the physical composite score showed no significant difference. Thus, transplanted survivors have a high risk of developing late effects, resulting in a decreased physical well-being in adulthood. However, long after treatment completion, childhood leukemia survivors report that effects on psychological well-being are more important than they are in physical QoL dimensions

Intérêt du dosage de la procalcitonine sérique dans les neutropénies fébriles de l'enfant

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Intérêt de la purge du greffon autologue dans le traitement des neuroblastomes à haut risque

La contamination des greffons autologues a été incriminée au début des années 90 comme étant un des facteurs favorisant la rechute de certains cancers (sein, neuroblastome, hémopathies,...) après chimiothérapie à haute dose suivie d'autogreffe de cellules souches hématopoïetiques. Afin de diminuer cette contamination tumorale, la purge de greffon autologue a été développée à partir de cette période dans certains centres d'oncologie comme Clermont-Ferrand et Nançy. L'objectif de cette étude a été d'analyser l'intérêt d'une telle stratégie dans le devenir à long terme des enfants atteints de neuroblasmes à haut risque. 46 enfants âgés de 2 mois à 11 ans (âge médian 2,5 ans) et atteints de neuroblasmes à haut risque furent traités de 1993 à 2007 par chimiothérapie à haute dose suivie d'autogreffe de cellules souches hématopoïetiques d'origine périphériques préalablement purgées par immunosélection positive des cellules CD34+. Une médiane de 6,5.10 puissance 6 cellules CD34+/kg [0,8-23,7] furent réinjectées après chimiothérapie à haute dose par busulfan+melphalan. La prise de greffe fut effective pour l'ensemble des patients, avec des médianes de sortie d'aplasie pour les polynucléaires neutrophiles (>0,5G/L) à J12 [9-47], et des taux de plaquettes > 50G/L avec autonomie transfusionnelle à J44 [12-259]. Les complications post-greffes furent essentiellement infectieuses et d'évolution favorable sous traitement sauf pour un patient décédé de pneumopathie interstitielle non documentée à J56 post-greffe. La survie sans évènement et la survie globale à 12 ans furent de 46% et 52% respectivement, avec une médiane de suivie à 81 mois. Les facteurs de bon pronostic des neuroblastomes à haut risque étaient dans cette étude : absence de maladie résiduelle dans le greffon pré-purgé, et traitement par l'Acide13-cis Rétinoïque. L'analyse des taux de survie d'une cohorte française de 54 patients extraite des registres de greffes sur la même période a permis de mettre en évidence une survie globale à 3 ans en faveur des patients ayant bénéficié d'un greffon purgé (OS purgés à 62% vs non purgés à 50% ; p=0,04). Ces données confirment la faisabilité des greffes de cellules souches hématopoïétiques périphériques immunosélectionnées CD34+ chez l'enfant atteint de neuroblastome, avec l'obtention d'une survie globale comparable, voire supérieure, aux séries publiées n'ayant pas bénéficié d'une purge de grffon. Une étude prospective randomisée testant l'intérêt de la purge de greffon dans le neuroblastome permettrait la confirmation de ces résultats, mais serait en pratique difficilement réalisable sur une durée raisonnable compte tenu de la fréquence des cas de neuroblastome. Seule une étude française de cas appariés sur l'âge et la période de traitement permettrait de conclure, avec une valeur statistique plus significative.CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Diabète et thérapie cellulaire (état actuel et perspectives)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Lactobacillus rhamnosus Meningitis following Recurrent Episodes of Bacteremia in a Child Undergoing Allogeneic Hematopoietic Stem Cell Transplantation▿

We report a case of meningitis due to Lactobacillus rhamnosus in a child undergoing allogeneic hematopoietic stem cell transplantation for acute leukemia. Four episodes of bacteremia involving strains with pulsotypes identical to that of the cerebrospinal fluid isolate preceded meningitis. After several courses of clindamycin, no relapse occurred during the patient follow-up

Childhood cancer survival in France, 1990-1999.

ERMAInternational audienceThe aim of this study was to describe the overall survival after childhood cancer in France using follow-up data from regional population-based registries. The survival of children (aged under 15 years) diagnosed with a cancer during 1990-1999 was analysed. For all cancers, the survivals were, respectively, 90.3% [89.4-91.3] at 1-year, 75.2% [73.8-76.6] at 5 years and 72.2% [70.7-73.7] at 10 years. During the 1990s, the average improvement in the 5-year survival was +1.2% per year. Adjusted for gender, age, area of residence and stage, children with cancer diagnosed between 1995 and 1999 had a 0.80 reduced risk of dying compared with those whose cancer had been diagnosed between 1990 and 1994. The increase of survival at the population level reflects a global improvement in childhood cancer care. The Paediatric Registries, in association with the French Society of Childhood Cancer, are now collecting data to quantify on a national basis the other events, at least relapse and second cancers

Cancer incidence among children in France, 1990-1999.

International audienceBACKGROUND: Cancer is the second most important cause of death for children aged less than 15 years in France, unintentional injuries being the leading cause. The aim of the present study was to estimate the incidence of childhood cancer from six Childhood Cancer Registries covering 32% of France. PROCEDURE: Incident cancer cases diagnosed between 1990 and 1999 in children (0-14 years) resident in the administrative areas covered by each Registry were included. Annual age-standardized rates (ASRs) were adjusted by the world population. The estimated annual percent change (EAPC) was used to measure trend towards changes in the annual age-standardized incidence rate. RESULTS: With 4234 registered cases, the ASRs per million children were 137.5 for all cancers combined, 42.3 for leukemia, 29.1 for central-nervous-system tumors, 15.6 for lymphomas, 14.1 for sympathetic-nervous-system tumors, and 9.1 for renal tumors. The ASR of all cancers combined was slightly higher in males (145.8 per million children) than in females (128.7 per million children) with an M/F ratio of 1.2. No significant incidence trend was observed, with an EAPC of +0.2% [IC 95% (-2.5; +3.0); P = 0.89]. CONCLUSIONS: The estimated incidence rates are similar to those reported in previous studies in European and North American countries. These results will contribute to the development of National Registration of Childhood Cancer in France and support the national research program on childhood cancer

Pediatric Acute Lymphoblastic Leukemia Articles and Brief Reports Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol

The online version of this article has a Supplementary Appendix. Background The prognosis of patients with relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a long-term, follow-up retrospective study to address the outcome of patients with ETV6/RUNX1-positive leukemia relapses. Design and Methods Among the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified in the low or intermediate risk groups. The median follow-up after relapse was 54.2 months. All but three received second-line salvage therapy and 16 underwent allogeneic transplantation. Results ETV6/RUNX1 had a strong effect on overall survival after relapse (3-year survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases the relapses were late, early combined or isolated extramedullary relapses. The 5-year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus 31.2% when the relapse occurred earlier). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome. Conclusions We found an excellent outcome for patients with ETV6/RUNX1-positive leukemia relapses that occurred more than 36 months after diagnosis. The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1-positive leukemia

Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.

International audienceRelapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ≥10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention

Cohort Profile: The French Childhood Cancer Survivor Study For Leukaemia (LEA Cohort)

International audienceThe main aim of the Leucémies de l'Enfant et l'Adolescent (LEA) project (Childhood and Adolescent Leukaemia) is to study the determinants (medical, socioeconomic, behavioural and environmental) of medium- and long-term outcomes of patients treated for childhood acute leukaemia (AL). The LEA study began in 2004 and is based on a French multicentric prospective cohort. Included are children treated for AL since January 1980 (incident and prevalent cases), surviving at month 24 for myeloblastic AL and lymphoblastic AL grafted in first complete remission or at month 48 for lymphoblastic AL not grafted in first complete remission. Information is collected during specific medical visits and notably includes the following data: socioeconomic data, AL history, physical late effects (such as fertility, cardiac function and metabolic syndrome) and quality of life. Data are collected every 2 years until the patient is 20 years old and has had a 10-year follow-up duration from diagnosis or last relapse. Thereafter, assessments are planned every 4 years. In active centres in 2013, eligible patients number more than 3000. The cohort has already included 2385 survivors, with rate of exhaustiveness of almost 80%. Data access can be requested from principal coordinators and must be approved by the steering committee