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Résumé Introduction Les enfants et adolescents atteints de cancer sont pris en charge en France par des équipes pluri-professionnelles au sein de centres spécialisés d’onco-hématologie pédiatrique, labellisés par l’Institut national du cancer, qui travaillent en réseau avec des centres de pédiatrie de proximité. Le diplôme inter-universitaire d’oncologie pédiatrique (DIUOP) propose une formation à l’onco-hématologie maligne pédiatrique comprenant un enseignement théorique, un stage dans un service validant et un projet de recherche soutenu devant un jury. Méthode Nous avons adressé un questionnaire aux diplômés pour connaître leur situation professionnelle actuelle et avons recherché sur PubMed tous les articles publiés. Résultats De 2000 à 2011, le DIUOP a formé 290 médecins spécialistes : 242 pédiatres, 21 chirurgiens et 19 radiothérapeutes, 8 ayant une autre spécialité telle que l’imagerie, l’hématologie ou l’anatomo-pathologie. Quatre-vingt-douze étaient titulaires d’un diplôme obtenu à l’étranger : en Europe (50 %), en Afrique et au Proche-Orient (42 %) et en Amérique du Sud (8 %). Cent quatre-vingt-dix-sept des 266 diplômés (74 %) ont répondu au questionnaire. Quatre-vingt-dix pour cent prenaient en charge des enfants et adolescents atteints de cancer. Pour ceux exerçant en France, ils travaillaient principalement dans les établissements impliqués dans l’organisation des soins définie par la circulaire DHOS (Direction de l’hospitalisation et de l’organisation des soins) de 2004. Soixante-neuf articles, soit un mémoire sur 4, avaient été publiés dans une revue avec un facteur d’impact médian de 3,5 (0–22,6) dont 85 % en langue anglaise. Conclusion Le DIUOP est la seule formation européenne en langue française offrant une formation professionnalisante, multidisciplinaire, de qualité et complète aux spécialistes impliqués dans la prise en charge des cancers de l’enfant et de l’adolescent. Summary Introduction According to the European Society of Pediatric Oncology (SIOPE) standard of care guidelines, high-quality care of children and adolescents with cancer needs to be delivered by well-trained multidisciplinary teams in specialist centers working with designated shared-care local centers in a so-called hub-and-spoke model. The Diplôme Inter-Universitaire d’Oncologie Pédiatrique (DIUOP) is the only European training program in pediatric oncology in French for all physicians involved in care of patients with pediatric malignancies. In agreement with the SIOPE syllabus, the DIUOP is composed of training courses (120 h), on-site practical training in a specialist center, and a research project to be defended before an examining board. Method All graduates received a questionnaire to describe their current professional position. A comprehensive PubMed analysis retrieved all papers published form DIUOP research projects. Results From 2000 to 2011, 290 physicians were trained: 242 pediatricians, 21 surgeons, and 19 radiation therapists. Eight had another specialty including imaging, hematology, and pathology. Ninety-two were initially trained outside of France: 50% in Europe (mainly in Italy, Belgium, and Switzerland), 42% in Africa and the Middle East, and 8% in South America. Of the 266 graduates, 74% answered the questionnaire, and 90% of them take care of children and adolescents with cancer. Sixty-nine articles, i.e., one out of four research projects, were published in 34 journals with a median impact factor of 3.5 (0–22.6), 85% in English. Conclusion DIUOP is the only French-speaking European education program providing a high-quality, professionalizing, and comprehensive multidisciplinary training program for French and international specialists taking care of children and adolescents with cancer. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)±high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m2/week (LD MTX, n=81) or HD MTX at 1.5 g/m2/2 weeks × 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m2/2 weeks × 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16–18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.Leukemia (2007) 21, 238–247. doi:10.1038/sj.leu.2404495; published online 14 December 2006 [ABSTRACT FROM AUTHOR]

Focuses on the quantitative analysis of messenger RNA TEL/ANL1 fusion transcripts by real-time polymerase chain reaction assay in childhood acute lymphoblastic leukemia. Reason for the introduction of a reference sample to define the quantitation limit; Possibility of comparing the relative efficacy of treatment of patients.

Objectifs: répertorier les lymphomes de Burkitt (LBu) survenant après transplantation d’organe et analyser leurs particularités. Sujets/matériels et Méthodes: Après contact avec les services pédiatriques de greffe d’organe en France et avec le Registre National des Hémopathies de l’Enfant, 13 cas de LBu prouvés histologiquement, de moins de 18 ans (a), ont été répertoriés entre 1997 et 2007, puis analysés rétrospectivement. Résultats: 11 cas étaient évaluables : 9 garçons, 2 filles. Les transplantations étaient rénales [2 patients (pts)] et hépatiques (9 pts). L’âge médian à la greffe était de 14 mois (m) (foie), de 8a 7 m (rein). La séroconversion EBV est survenue à une médiane de9 m après la greffe, et de 20 m avant le LBu. Au diagnostic, les greffés rénaux avaient une clairance moyenne de 50 ml/min/1,73 m2, 3 greffés hépatiques présentaient un rejet chronique. Le délai de survenue médian du LBu était de 2 à 9 m (foie), de 1a 11 m (rein). Les stades du lymphome étaient : stade III (6 pts), stade IV (1 pt), LAL L3 (4 pts). 10/11 pts avaient une charge virale sanguine EBV élevée au diagnostic. Le traitement immunosuppresseur a été diminué dans tous les cas (pas de rejet observé), 3 pts ont reçu du rituximab sans efficacité. 10/11 pts ont été traités selon le protocole LMB 96 ou LMB 2001. 3 pts ont été dialysés au diagnostic (1 greffé rénal) mais un est décédé de syndrome de lyse à J2 de traitement. Les complications infectieuses comprennent des septicémies bactériennes documentées (5 pts), des atteintes fongiques (aspergillose pulmonaire, candidose hépatique : 2 pts), 1 abcès pulmonaire (1 pt). 1 pt a présenté une toxicité neurologique sévère de l’aracytine à haute dose. Les 9 pts effectivement traités par le LMB sont en rémission complète avec un recul médian de 4 a. Le pt traité par un protocole moins intensif (prednisone, cyclophosphamide) est décédé en rechute. Conclusions: Le lymphome de Burkitt de l’enfant transplanté peut être guéri par un traitement intensif de type LMB mais les complications infectieuses peuvent être plus fréquentes et sévères. Le lymphome et sa prise en charge semblent avoir peu d’influence sur le greffon (toxicité directe, rejet). Nous remercions vivement les médecins et chirurgiens des centres de greffe pour leur collaboration. [Copyright &y& Elsevier]

Abstract: Purpose. – To evaluate how adolescents and young adults cured of acute lymphoblastic leukemia (ALL) treated during childhood have integrated the disease, and possible death related to cancer. Particularly, we have focused on experiences related to diagnosis announcement, hospitalisation and treatments and consequences on their social, psychological and somatic behaviour. Patients. – Forty-one patients cured of ALL have been enrolled in the study and answered one interview with clinical psychologist or research nurse. Results. – Although 60% of the patients argued that they think rarely of their disease, 10% thought about it every day. Traumatic evidence was detectable in most of them. Physical pain was the most reported stress, mainly during hospitalisation (93%), as well as psychological suffering (83%). Afterwards, the mostly often-reported stress was psychological pain (61%). Sixty-six percent declared that they still experience psychological and health consequences at the time of the interview, in some cases reported as a handicap in their life. In 83% of the cases they considered themselves as cured, nevertheless fear of relapse persisted in 1/3. Ninety percent said they have a pleasant life, 56% did not like to talk about leukaemia and 70% thought they could have died. For 85%, disease has been the most important event of their life and 75% testify to repercussions of the disease on their family (family relationship changes, overprotection, siblings difficulties). Conclusion. – Most of these patients declared to be ''as the others'' and developed life projects, but overcoming the pain experience of the disease remained difficult. This study emphasized the need for long-term continuous information and reinforces the importance of addressing treatment psychological and physical pain mainly after the initial hospitalisation period. [Copyright &y& Elsevier]

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) is a very useful technique for the imaging of lymphomas in the adult population. It provides unique information about the behaviour of malignant cells and contributes to more accurate staging of the illness and better assessment of response to therapy. The purpose of this study was to evaluate the usefulness of FDG PET in childhood lymphoma compared with conventional imaging methods (CIMs) and clinical data. Between July 1998 and August 2001, 42 FDG PET examinations were performed using a dedicated PET system (27 examinations) or a hybrid coincidence PET system (15 examinations) for initial tumour staging (n=7), restaging (n=5) or assessment of response to therapy or residual masses (n=30) in 27 children with Hodgkin's disease (HD) (n=20) or non-Hodgkin's lymphoma (NHL) (n=7). FDG PET results were compared with CIM findings and clinical data. Since 2000, a standardised questionnaire for evaluation of the clinical impact of FDG PET on both staging and therapy has been sent to the 16 referring physicians and 13 have replied. In all children, FDG PET was performed without any side-effects. FDG PET was found to be very sensitive (Se=12/12) for staging and restaging of the illness, showing more lesions than CIMs, with a 50% patient upstaging rate (6/12). It was very accurate for monitoring response to therapy and for characterisation of residual masses. False-positive results were observed in two NHL patients with thymic uptake and one false-negative result was obtained in a patient whose NHL relapsed 1 month after a negative FDG PET. The questionnaire emphasised the impact of FDG PET on clinical management, which was modified on the basis of the FDG PET results in 23% of patients. As previously demonstrated in the adult population, FDG PET appeared to be a very sensitive imaging technique for staging and restaging of lymphoma in children and was very useful for monitoring the response to... [ABSTRACT FROM AUTHOR]

Autoimmune haemolytic anaemia commonly has a severe course in young children, thus requiring multiple immunosuppressive treatments. Five children with refractory idiopathic autoimmune haemolytic anaemia, and one child with the disease after bone-marrow transplantation, were treated with rituximab-a monoclonal antibody against CD20. Tolerance of the treatment was good. However, circulating Bcells were absent and hypogammaglobulinaemia was seen for 9 months after treatment. All patients remained in complete remission 15-22 months after the start of rituximab therapy. Corticosteroids and immunosuppressive drugs were stopped or their dose markedly reduced. We suggest that rituximab could be a valuable treatment for autoimmune haemolytic anaemia, although a long-lasting but transient B-cell deficiency develops. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses rapid childhood T-ALL growth in xenograft models related to mature phenotype and NF-kB pathway activation without poor prognosis.

Constitutional dominant loss-of-function mutations in the SPRED1 gene cause a rare phenotype referred as neurofibromatosis type 1 (NF1)-like syndrome or Legius syndrome, consisted of multiple café-au-lait macules, axillary freckling, learning disabilities and macrocephaly. SPRED1 is a negative regulator of the RAS MAPK pathway and can interact with neurofibromin, the NF1 gene product. Individuals with NF1 have a higher risk of haematological malignancies. SPRED1 is highly expressed in haematopoietic cells and negatively regulates haematopoiesis. SPRED1 seemed to be a good candidate for leukaemia predisposition or transformation. We performed SPRED1 mutation screening and expression status in 230 paediatric lymphoblastic and acute myeloblastic leukaemias (AMLs). We found a loss-of-function frameshift SPRED1 mutation in a patient with Legius syndrome. In this patient, the leukaemia blasts karyotype showed a SPRED1 loss of heterozygosity, confirming SPRED1 as a tumour suppressor. Our observation confirmed that acute leukaemias are rare complications of the Legius syndrome. Moreover, SPRED1 was significantly decreased at RNA and protein levels in the majority of AMLs at diagnosis compared with normal or paired complete remission bone marrows. SPRED1 decreased expression correlated with genetic features of AML. Our study reveals a new mechanism which contributes to deregulate RAS MAPK pathway in the vast majority of paediatric AMLs. [ABSTRACT FROM AUTHOR]

Leukemia-initiating/repopulating cells (LICs), also named leukemic stem cells, are responsible for propagating human acute leukemia. Although they have been characterized in various leukemias, their role in T-cell acute lymphoblastic leukemia (T-ALL) is unclear. To identify and characterize LICs in T-ALL (T-LIC), we fractionated peripheral blood cell populations from patient samples by flow cytometry into three cell fractions by using two markers: CD34 (a marker of immature cells and LICs) and CD7 (a marker of early T-cell differentiation). We tested these populations in both in vitro culture assays and in vivo for growth and leukemia development in immune-deficient mice. We found LIC activity in CD7+ cells only as CD34+CD7− cells contained normal human progenitors and hematopoietic stem cells that differentiated into T, B lymphoid and myeloid cells. In contrast, CD34+CD7+ cells were enriched in LICs, when compared with CD34−CD7+ cells. These CD34+CD7+ cells also proliferated more upon NOTCH activation than CD34−CD7+ cells and were sensitive to dexamethasone and NOTCH inhibitors. These data show that CD34 and CD7 expression in human T-ALL samples help in discriminating heterogeneous cell populations endowed with different LIC activity, proliferation capacity and responses to drugs. [ABSTRACT FROM AUTHOR]

Summary: The association of lymphoma and autoimmune manifestations has been predominantly studied in adults affected by non-Hodgkin lymphoma. Few publications exist in the literature concerning Hodgkin lymphoma, particularly in children and adolescents. The objectives of this study were to define the characteristics of the link between Hodgkin disease and autoimmunity in childhood. The present 25-year retrospective study was conducted in all centers affiliated with the French Society of Paediatric Oncology (SFCE). Eleven children with Hodgkin disease presented manifestations of disimmunity preceding or following their diagnosis. Four patients had thrombocytopenic purpura, the remaining 7 each had a different autoimmune pathology: lupus syndrome, antiphospholipid syndrome with transient ischemic attack, Evans syndrome, leukocytoclastic vasculitis, autoimmune hemolytic anemia, autoimmune thyroiditis, and juvenile idiopathic arthritis. Lymphoma relapse occurred in 3 patients. Two children died, death being directly attributed to the autoimmune disease in 1 case. Our data suggest that development of autoimmunity is related to significant morbidity. Possible pathophysiological mechanisms include lymphocyte proliferation secondary to chronic inflammation, cell-mediated immune deficiency in Hodgkin disease, molecular mimetics, and antineoplastic phenomena are discussed. A study with a larger patient population is needed to identify the group of children at high risk of autoimmunity for whom additional investigations and modified therapy may be indicated. [ABSTRACT FROM AUTHOR]

Summary: The occurrence of eight cases of adrenal deficit in children hospitalized for acute lymphoblastic leukemia (ALL) led us to conduct a prospective study from May 2006 to May 2007 to better characterize this corticoid-induced adrenal deficit. Forty of the 48 patients hospitalized for ALL were given a low-dose Synacthen test (1μg), a mean 7 days after the induction phase. An adrenal deficit was diagnosed in 27 patients (67.5%). No significant clinical or hematological difference was identified between the “with deficit” (n =27) and “without deficit” (n =13) groups. The diagnosis of adrenal deficit was not more common for children who had received dexamethasone (13/19) or prednisone (14/21), or for those who had (19/29) or had not (8/11) experienced corticoid toxicity during induction. The clinical signs suggesting adrenal deficit were identical in the two groups and none of the children presented an acute episode. In biological terms, only hypoprotidemia was significantly more common in patients with adrenal deficit (p =0.0004). Of 13 patients with a deficit at the end of the induction who had received a 2nd low-dose Synacthène® test before intensification no. 1, 3 weeks on average after the end of corticotherapy, only two still had a deficit. Thus, corticoid-induced adrenal deficit is a common complication in children treated for ALL, although it is not highly symptomatic. Most of these children recover normal adrenal function before intensification no. 1, but it does not eliminate the risk of a secondary deficit after other courses of corticotherapy. Systematic repeated Synacthène® tests in common practice among children treated for ALL does not seem justified. However, the results of this study encouraged us to propose a hydrocortisone substitution to children treated for ALL in the event of stress. [Copyright &y& Elsevier]

Summary: Secondary causes of thrombocytopenia as immunologic thrombopenia purpura, or ITP, are far more common than inherited causes, which even as a group, are rare. Nevertheless, diagnosis is important and progress made in uncovering the molecular basis of these disorders has contributed greatly to our knowledge of these diseases. Inherited thrombocytopenias are a heterogeneous group of disorders. Different criteria have been suggested to classify the forms, such as the inheritance mechanism and the platelet volume as well as the associated platelet dysfunctions or clinical abnormality. This paper describes the clinical and biological data, and current knowledge of the molecular findings of inherited thrombocytopenia, allowing a diagnostic approach to these diseases. [ABSTRACT FROM AUTHOR]

The article discusses about the T-cell acute lymphoblastic leukemia (T-ALL). It is a heterogenous disease and targets the T cells during their differentiation. four different pathway alterations are necessary to induce leukemic progression which includes overexpression of transcription factors, activation of receptors or deregulation of cell cycle mediators. Results including charts of the experiment for T-ALL is also presented.

A letter to the editor is presented that discusses extensive mutational status of genes and clinical outcome in pediatric acute myeloid leukemia.

NALP proteins, also known as NLRPs, belong to the CATERPILLER protein family involved, like Toll-like receptors, in the recognition of microbial molecules and the subsequent activation of inflammatory and immune responses. Current advances in the function of NALPs support the recently proposed model of a disease continuum bridging autoimmune and autoinflammatory disorders. Among these diseases, hereditary periodic fevers (HPFs) are Mendelian disorders associated with sequence variations in very few genes; these variations are mostly missense mutations whose deleterious effect, which is particularly difficult to assess, is often questionable. The growing number of identified sporadic cases of periodic fever syndrome, together with the lack of discriminatory clinical criteria, has greatly hampered the identification of new disease-causing genes, a step that is, however, essential for appropriate management of these disorders. Using a candidate gene approach, we identified nonambiguous mutations in NALP12 (i.e., nonsense and splice site) in two families with periodic fever syndromes. As shown by means of functional studies, these two NALP12 mutations have a deleterious effect on NF-κB signaling. Overall, these data identify a group of HPFs defined by molecular defects in NALP12, opening up new ways to manage these disorders. The identification of these first NALP12 mutations in patients with autoinflammatory disorder also clearly demonstrates the crucial role of NALP12 in inflammatory signaling pathways, thereby assigning a precise function to this particular member of an emerging family of proteins whose putative biological properties are currently inferred essentially through in vitro means. [ABSTRACT FROM AUTHOR]

Abstract: Is it necessary — and possible — to discuss death with a child in palliative phase? How should one approach the subject? A recent Swedish study demonstrated the benefits for parents who discussed with their child his or her imminent death, and raised the question of the role nursing can play to help parents. The mother of one child treated in our unit recently wrote a story 48 hours before the child''s death. The story served to broach a number of recurrent questions often raised by dying children and their families: fear of the unknown, of being replaced, the inevitability of death, grief, and fear of being forgotten… The story was given to 13 families with dying children. In order to evaluate the story''s impact on families and to determine whether a document which stimulates dialogue should continue to be given to parents, we asked that they fill out a questionnaire. Fifty-five percent of parents answered, and confirmed that the story was experienced as a positive thing and helped parents to talk with their children. This study raises many questions and should be part of a global accompaniment strategy. A review of medical, general and children''s literature, as well the results of our study, lead us to conclude that the medical body should lend its full support to families who wish to engage in this dialogue with their children. [Copyright &y& Elsevier]

From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60±4 and 48±4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52±4% for non-allografted patients and 57±7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT−) than in patients randomized for MT (77.6±8 vs 59±8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.Leukemia (2005) 19, 2082–2089. doi:10.1038/sj.leu.2403867; published online 25 August 2005 [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to assess the efficacy and adverse effects of 2-chlorodeoxyadenosine (2-CdA) and cytosine arabinoside (Ara-C) in children with refractory Langerhans cell histiocytosis (LCH) and haematopoietic dysfunction. Ten patients, with a median age at diagnosis of 0.5 years, were enrolled in this study. Treatment comprised at least two courses of Ara-C (1000mg/m2/d) and 2-CdA (9mg/m2/d) administered for 5d every 4 weeks; subsequent median follow-up was 2.8 years (range 0.03–6.4 years). Among the 7 patients who received at least two courses of therapy, disease activity decreased in 6 patients, and control of disease was achieved in all patients after a median delay of 5.5 months. All patients suffered World Health Organisation (WHO) grade 4 haematological toxicity. Two septic deaths occurred shortly after administration of the first course of 2-CdA/Ara-C; a third patient was withdrawn from the trial after the first course and subsequently died following haematopoietic stem cell transplantation. This series is small, but we conclude that 2-CdA and Ara-C combined chemotherapy probably has major activity in childhood refractory Langerhans cell histiocytosis. [Copyright &y& Elsevier]

Abstract: Disseminated fusariosis in children is a rare and serious fungal infection, that occurs especially in neutropenic immunosuppressed patients, treated for malignant hemopathy, or bone marrow transplant recipient. Treatment is difficult and mortality is estimated between 50 and 70% in adult patients. Case report 1. – A ten-year-old boy, treated for an acute lymphoblastic leukemia in second relapse, presented a disseminated fusarium spp infection, that occurred during neutropenia. He died due to fusariosis infection in spite of amphotericin B treatment. Case report 2. – A ten-year-old neutropenic girl, treated for an acute myeloïd leukemia, presented disseminated fusariosis, uncontrolled by amphotericin B. Recovery was observed after voriconazole introduction and resolution of neutropenia. Ten months later, she presented a leukemia''s relapse, treated by new intensive chemotherapy with secondary prophylaxis by voriconazole, without fusariosis''s recurrence. Conclusion. – Voriconazole, a new triazole agent, seems to be an alternative antifungal agent to amphotericin B for disseminated fusarium infection, either at the acute phase or for secondary prophylaxis. [Copyright &y& Elsevier]

Abstract: With the progress of foetal ultrasonography, diagnosis of foetal tumors can be made before birth. We report five cases of prenatally detected neuroblastoma of the adrenal glands. Diagnosis was made during the third trimester in all cases. At birth no clinical sign related to the tumor was present, and urinary catecholamines were within normal ranges. On ultrasound scans the tumor was cystic in 1 case, solid in 2 cases and of mixed echogenicity in 2 cases. All children were operated on without pre or postoperative chemotherapy. In each setting the tumor was a stade neuroblastoma according to the Evans classification. All children are alive and disease-free with a follow-up of 32 months at 14 years. [Copyright &y& Elsevier]

Leukemia (2003) 17, 1193-1196. doi:10.1038/sj.leu.2402914 [ABSTRACT FROM AUTHOR]

Determines the expression of CD13 or CD33 on leukemic cells based on the immunoreactivity of six different clones. Surface expression of CD13 on acute leukemia cells; Surface expression of CD33 on acute leukemia cells; Co-expression of CD13 and CD33 on acute leukemia cells; Correlation between expression of myeloid antigens and presence of TEL AML1.

Many cutpoints have been proposed to categorize continuous variables in childhood acute lymphoblastic leukaemia (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age), and have been used to define therapeutic subgroups. This variation in the choice of cutpoints leads to a bias called the 'Will Rogers phenomenon'. The aim of this study was to analyse variations in the relative risk of relapse or death as a function of continuous prognostic variables in childhood ALL and to discuss the choice of cutpoints. We studied a population of 1545 children with ALL enrolled in three consecutive protocols named FRALLE 83, FRALLE 87 and FRALLE 89. We estimated the risk of relapse or death associated with different values of each continuous prognostic variable by dividing the sample into quintiles of the distribution of the variables. As regards age, a category of children under 1 year of age was distinguished and the rest of the population was divided into quintiles. The floated variance method was used to calculate the confidence interval of each relative risk, including the reference category. The relation between the quantitative prognostic factors and the risk was monotonic for each variable, except for age. For the white blood cell count (WBC), the relation is log linear. The risk associated with WBC values in the upper quintile was 1.9 times higher than that in the lower quintile. The peripheral blast cell count correlated strongly with WBC (correlation coefficient: 0.99). The risk increased with the haemoglobin level, and the risk in the upper quintile was 1.3 times higher than that in the lower quintile. The risk decreased as the platelet count increased: the risk in the lower quintile was 1.2 times higher than that in the upper quintile. The risk increased gradually with increasing age above one year. The small subgroup of patients (2.5% of the population) under 1 year of age at diagnosis had a risk 2.6 times higher than the... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning an investigation on the possibility of receptor interleukin 3 alpha-chain expression within the subgroup of immature T-acute lymphoblastic leukemia to identify cases that could benefit from diphtheria toxin fused to variant human interleukin 3 therapy.

Presents a letter to the editor related to acute lymphoblastic leukemia.

Examines the incidence of acute megakaryoblastic leukemia in children. Total cases reviewed in the study; Distinctive features of the leukemia; Lack of data about the genes involved in the disease.

Objectifs: En 2003 la SFCE a proposé des recommandations MDH03 de prise en charge des lymphomes de Hodgkin de l’enfant. 3 groupes: GMH1stades favorables, GMH2 intermédiaires et GMH3 avancés. Les patients étaient évalués par TDM après 4 cures. En cas de réponse < 75 %, chimiothérapie complémentaire. Pour tous, radiothérapie complémentaire 20Gy IF ± boost. Patients et méthodes: Enregistrement prospectif. 470 patients dont 407 ayant des données exploitables. Age médian 14 ans, 191 filles. Stades IA n = 19;IB n = 8;IIA n = 131;IIB n = 58;IIIA n = 41; IIIB n = 42;IVA n = 45; IVB n = 63;13 %E. Résultats: GMH1 n = 89(22 %), GMH2 n = 181(45 %), GMH3 n = 137(33 %). GMH1: 88 % de bons répondeurs (BR) après 4xVBVP. GMH2:83 % BR après 4xCOPP/ABV. GMH3:94 %BR après 3xOPPA. 4 % des pts ont eu un boost. Recul médian de 32 mois (0-67), 9/407 pts sont décédés. OS à 5 ans 96 %(+/-2 %) (GMH1 100 %, GMH2 94 %, GMH3 95 %). EFS 86 %(+/-2 %) (GMH1 97 %, GMH2 81 %, GMH3 86 %). 2 % des pts réfractaires. Conclusion: Les recommandations MDH03 ont été largement appliquées, avec des résultats encourageants. 60 % des pts ont reçu < 160mg/m2 d’anthracyclines et irradiation 20Gy. Depuis 2008, la SFCE est associée au protocole EURONET PHL-C1 qui évalue l’abstention de radiothérapie pour les BR à 2 cures et randomise la dacarbazine/procarbazine. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the occurrence of clathrin-assembly protein-like lymphoid-myeloid (CALM) fusion in acute megakaryoblastic leukemia.

Objectifs L’augmentation de la prescription de carbapénèmes (CBP) liée au grand nombre de patients colonisés à entérobactéries sécréteurs de b-lactamase à spectre étendu (EBLSE) en hémato-oncologie pédiatrique devenant préoccupante, il convenait de savoir comment celle-ci pourrait être diminuée. Matériels et méthodes Nous avons réalisé une étude rétrospective, dans un service français d’Hémato-Oncologie pédiatrique chez les patients colonisés à EBLSE traités pour des pathologies malignes entre 2008 et 2012. Résultats principaux Une colonisation à EBLSE a été retrouvée chez 9,5% des patients. La consommation de CBP n’a cessé d’augmenter alors que l’incidence de colonisation diminuait en 2012 (p<0,05). Seulement huit infections documentées à EBLSE ont été rapportées, dont trois en contexte d’aplasie. Deux étaient colonisés et se sont infectés au germe de leur portage. L’évolution a été favorable bien que le relais par CBP ait été fait après documentation bactériologique chez six patients. Conclusions L’attente des résultats bactériologiques avant de prescrire des CBP chez un patient colonisé à EBLSE en aplasie fébrile paraissant difficile, une rétrogradation rapide de l’antibiothérapie en l’absence de documentation serait envisageable pour permettre une épargne des CBP. [ABSTRACT FROM AUTHOR]

Objectifs: L’existence d’une hyperdiploïdie est retrouvée dans 25 %-30 % des LAL de la lignée B de l’enfant, et peut être associée à des réarrangements géniques de la voie Ras. L’objectif de cette étude rétrospective est de décrire ces anomalies et leur rôle pronostic éventuel dans ce groupe phénotypique. Patients et Méthodes: 113 pts pris en charge pour une LAL avec hyperploïdie à l’hôpital Trousseau entre 2000 et 2008 ont été répertoriés. Une analyse de mutation concernant les gènes FLT3, NRAS et PTPN11 a été réalisée associée à l’étude de l’expression du gène FLT3 par RQ-PCR. Résultats: Des mutations des gènes FLT3, NRAS et PTPN11 ont été retrouvées chez 24,3 % (n = 25) des patients. Il n’a pas été mis en évidence d’association entre ces mutations et âge, sexe, hyperleucocytose, corticosensibilité, MRD et EFS. Nous avons retrouvé une surexpression de FLT3 dans ce groupe comparées aux autres groupes cytogénétiques (p < 0,0001). Cette surexpression est reliée à un meilleur pronostic, permettant une stratification de l’ EFS suivant l’expression du gène FLT3 (p = 0,04). Conclusion: Notre étude confirme la relative fréquence des mutations de FLT3, NRAS et PTPN11 dans les LAL hyperdiploïdes et le rôle de la voie RAS dans les évènements génomiques successifs associés à la leucémogenèse des LAL de l’enfant. [ABSTRACT FROM AUTHOR]

L’association d’un syndrome lymphoprolifératif et de manifestations auto-immunes a été surtout étudiée dans le cadre des lymphomes non Hodgkiniens de l’adulte. Rares sont les publications concernant la maladie de Hodgkin, en particulier chez l’enfant. Les objectifs de cette étude étaient de définir les caractéristiques de cette association et de rechercher des facteurs prédictifs et pronostiques de l’évolution afin d’améliorer la prise en charge thérapeutique de la maladie de Hodgkin chez l’enfant. Une étude rétrospective portant sur les vingt cinq dernières années est réalisée auprès des centres membres de la Société Française des Cancers de l’Enfant. Nous rapportons dix cas d’enfants porteurs d’une maladie de Hodgkin présentant des manifestations dysimmunitaires apparues avant le diagnostic ou au décours du traitement. Il s’agit de quatre purpuras thrombopéniques idiopathiques, un syndrome lupique, un syndrome des anticorps anti-phospholipides avec accident ischémique transitoire, un syndrome d’Evans, une vascularite leucocytoclasique, une anémie hémolytique auto-immune et une thyroïdite auto-immune. Trois enfants ont au moins rechuté une fois et deux sont décédés, dont l’un directement d’une pathologie auto-immune associée (syndrome lupique). Nous constatons une morbidité importante et des difficultés thérapeutiques liées à l’auto-immunité. Les mécanismes physiopathologiques pouvant expliquer cette association sont également discutés. Afin de définir une population à risque pour laquelle des examens complémentaires et des adaptations de traitement seraient nécessaires, une étude comportant un plus grand nombre de patients est indispensable. [Copyright &y& Elsevier]

La néphroblastomatose (NBL) est un processus prolifératif qui s’associe volontiers avec des néphroblastomes bilatéraux. La SFCE a proposé une approche thérapeutique homogène combinant chimiothérapie et chirurgie. La chimiothérapie était systématique et prolongée, et la chirurgie indiquée seulement en cas de néphroblastome, certain ou suspect, sur les données de l’imagerie, lors du diagnostic ou de la surveillance. Cette étude rétrospective a pour but d’évaluer les indications et les techniques chirurgicales dans l’évolution de la NBL. Patients: En 29 ans (01/1979-12/2007), 23 enfants ont été pris en charge pour NBL, 10 garçons et 13 filles avec un âge médian de 12 mois (6 mois–5 ans). Il s’agissait d’une NBL bilatérale (20) ou unilatérale (3). L’indication chirurgicale était portée uniquement en présence d’un néphroblastome, certain ou suspect, associé à la NBL, soit d’emblée au moment de la prise en charge initiale (29 reins), soit lors de la surveillance (6 reins : 2 masses stables pendant la chimiothérapie et 4 apparues ou progressant après la chimiothérapie). Résultats: Sur 35 reins opérés, une chirurgie conservatrice a été réalisée pour 27 reins (77 %) et une néphrectomie totale pour les 8 autres. Les 23 enfants ont dû être opérés, d’un seul rein (11 enfants) ou des 2 reins (12); il s’agissait histologiquement de 31 néphroblastomes et 4 nodules résiduels de restes néphrogéniques. Parmi les néphroblastomes, 7 étaient de haut risque, 18 de risque intermédiaire et 6 de bas risque. Avec un suivi médian de 4,5 ans (4 mois–15 ans), une récidive est survenue chez 6 enfants (26 %) dont 4 haut risque et 2 intermédiaire, tous après chirurgie conservatrice. Une récidive locale isolée est survenue chez 3 enfants et une récidive avec métastases chez 3 autres. Quatre enfants sont décédés (début de traitement avant 1983 pour 3). Une insuffisance rénale modérée (1) et/ou une hypertension artérielle (2) étaient présentes dans 2 cas. Conclusion: L’incidence du néphroblastome dans l’évolution de la NBL est élevée dans notre expérience de centre chirurgical. Les masses apparaissant ou progressant sous chimiothérapie sont fortement suspectes de néphroblastome. La récidive paraît fréquente après chirurgie conservatrice dans les néphroblastome de haut risque. [Copyright &y& Elsevier]

Investigates the determination of myeloid antigen expression in children with acute lymphoblastic leukemia (My+ALL). Analysis on the immunoreactivity of My+ALL; Surface expression of CD13 on acute leukemia cells; Interrelation between myeloid antigen expressions and the presence of TEL-AML1.