Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

[Sickle cell disease and invasive osteoarticular Salmonella infections]. / Drépanocytose et salmonelloses invasives ostéo-articulaires.

Non-typhi Salmonella are responsible for severe invasive infections in children with sickle cell disease, with osteoarticular locations that can affect short- and long-term outcomes. We describe the cases of 2 children with sickle cell disease who presented paucisymptomatic Salmonella osteoarticular infections on returning from North Africa. Progression was favorable in both cases after appropriate systemic antibiotic therapy, although one Salmonella was multidrug-resistant. Invasive salmonellosis remains rare in France, but, because of its severity, it should be suspected in any patient with sickle cell disease presenting fever, especially in the context of recent trips in Africa countries. Early clinical diagnosis is essential to start appropriate empirical treatment without waiting for bacteriological results.

[Childhood cancer incidence and survival rates in the Rhône-Alpes regional paediatric registry 1987-1999]. / Les cancers de l'enfant de la région Rhône-Alpes: incidence et survie 1987-1999.

UNLABELLED: Cancer is rare in children, and pediatric malignancies represent only 1% of all cancers. OBJECTIVES: The cure rate is high and increasing, and ongoing data collection is therefore warranted. MATERIALS AND METHODS: Here we report the incidence and survival rates of childhood cancers between 1987 and 1999 in the Rhône-Alpes region of France. RESULTS: A total of 1945 cases were recorded during the study period, with an average of 149.6 new cases per year. The approximate incidence rate was 134.1/10(6) per year and the age-standardized incidence rate was 139.2/10(6) per year. The histological distribution and 5-year survival rates were respectively 30.2 and 73% for leukemia, 12.3 and 91.6% for lymphoma, 24.7 and 60.1% for CNS tumors, 9.1 and 71.1% for neuroblastoma, 2.5 and 94.1% for retinoblastoma, 5.8% and 89.9% for renal tumors, 1 and 75% for liver tumors, 6.1 and 60.9% for bone tumors, 4.1 and 58.6% for soft-tissue tumors, 1.1 and 71% for germ cell tumors, and 2.4 and 85.1% for carcinomas. CONCLUSION: The overall survival rate was 75%. Long-term treatment complications warrant further studies of children who survive into adulthood.

[Belated decompensation of an Imerslund-Grasbeck disease]. / Décompensation tardive d'une maladie d'Imerslund-Grasbëck.

Imerslund-Gräsbeck disease is an autosomic recessive disease characterised by a megaloblastic anemia due to a vitamin B12 deficiency and by a moderate proteinuria without kidney failure. It is caused by the malabsorption of Cobalamin-intrinsic factor complex bringing into play cubulin and other proteins (megaline, amnioless), some mutations of which are described at present. We report herein the observation of a child whose diagnosis was made belatedly during an acute decompensation with biological hemophagocytic syndrome. Its evolution was marked by the appearance of neurological disorders at the beginning of the vitamin B12 substitution treatment. These disorder regressed as the dosage was increase. The purpose of this observation is to recapitulate the main characteristics of this disease and to review the current data.

[Bernard-Soulier syndrome revealed by major neonatal thrombocytopenia]. / Syndrome de Bernard-Soulier révélé par une thrombopénie sévère en période néonatale.

Bernard-Soulier syndrome (BSS) is a congenital autosomal recessive bleeding disorder characterised by giant platelets, the lack of thrombocytopenia or a moderate one, prolongation of skin bleeding time, and absent platelet aggregation in response to ristocetin. We report a case of BSS revealed by major neonatal thrombocytopenia. A newborn was admitted for thrombocytopenic purpura initially believed to be due to a maternal auto-immune thrombocytopenia. Because of the persistence of the thrombopenia till the age of 7 months despite therapy by corticosteroids and immunoglobulins, and because of the detection of anti-1b antiplatelets antibodies after transfusion, BSS diagnosis was evoked. In such a situation of major thrombocytopenia, the main therapeutic measure is prevention. Therapy by DDAVP may be used after the age of 3 years in situations of high haemorrhagic risk. This case report underlines the importance of a precise diagnosis in front of a maternal thrombocytopenia and the possibility of antenatal diagnosis of BSS.

[Opsoclonus-myoclonus syndrome associated with non-metastatic neuroblastoma. Long-term survival. Study of the French Society of Pediatric Oncologists]. / Syndrome opsoclonus-myoclonus associé au neuroblastome non métastatique. Suivi à long-terme. Etude de la Société française d'oncologie pédiatrique.

UNLABELLED: Opsoclonus-myoclonus is a rare syndrome characterized by multidirectional chaotic eye movements, myoclonus and ataxia. In children, it could be a paraneoplastic syndrome in association with neuroblastoma, usually with a high survival rate, but having a high frequency of neurologic and psychologic sequelae. OBJECTIVES: The aim of this study was to describe oncologic outcome (prospectively) and neurologic outcome (retrospectively) in children with non-metastatic neuroblastoma, and to determine its best treatment. PATIENTS AND METHODS: Data were collected on 21 children diagnosed with localized neuroblastoma and opsoclonus-myoclonus between 1990-1999 from the French Society of Pediatric Oncology institutions. RESULTS: Median age at diagnosis was 18 months. Location of the tumor was abdominal in 14 cases, thoracic in three cases, pelvic in three cases, and cervical in the last case. There was a majority of small tumors with a maximal diameter < 5 cm in 13 cases. Only four tumors were initially considered as unresectable tumors and received first-line chemotherapy. Complete macroscopic resection was performed in 20 cases (four after primary chemotherapy). Nine children received chemotherapy. Twenty children remained in first complete remission, and one relapsed and died (the unique NMYC amplified case). Treatment for opsoclonus-myoclonus varied widely. Only one child received no medical treatment for opsoclonus-myoclonus, because of complete resolution of neurologic symptoms after exclusive surgery. The following agents were used: corticosteroids in 18 cases, intravenously immune globulin in five cases, and antiepileptic drugs in seven cases. Ten patients experienced relapses of opsoclonus-myoclonus symptoms, mainly related to the decrease of steroid therapy (5/10). Ten of 16 assessable children had persistent neurologic deficits including speech delay or cognitive deficits (8/16), ataxia (6/16), motor delay (2/16), and behavioral problems (2/16). There is no correlation between neurologic outcome, and either age at diagnosis or duration of neurologic symptoms, or type of treatment of the tumor, particularly chemotherapy. CONCLUSION: Persistent neurologic deficits are characteristic for children with neuroblastoma and opsoclonus-myoclonus. Neurologic outcome seems unrelated to the treatment of neuroblastoma, which should exclusively be conducted according to oncological criteria. The treatment of opsoclonus-myoclonus should be standardized, mainly based on high-dose hydrocortisone, with a very low decreasing dosage, associated to intravenously immune globulin in severe cases. A biological immunologic work-up of the disease and cautious neurologic and psychologic standardized follow-up should be performed.

Solid alveolar rhabdomyosarcoma of the thorax in a child.

AIMS: This case illustrates the difficulties and pitfalls of diagnosis of alveolar rhabdomyosarcoma in its solid variant and in an unusual primary location, the mediastinum. CASE DETAILS: A 9-year-old boy presented with a primary thoracic tumour associated with metastasis in the left sacroiliac joint. Bronchial and mediastinal biopsies showed a malignant neoplasm with a solid sheet-like pattern of small round cells with a high nuclear to cytoplasmic ratio associated with little or no fibrosis usually evocative of a peripheral neuroectodermal tumour (PNET) at this age. Immunohistochemical positive staining with vimentin (80% of tumour cells), desmin (20%) and titin (30%) antibodies was suggestive of a rhabdomyosarcoma. In addition, all neural cell adhesion molecule (NCAM) markers tested were positive as well as MIC2, a marker for the Ewing family of sarcomas. There was no rhabdomyoid differentiation at ultrastructural examination. Molecular analysis with RT-PCR amplification of RNA isolated from the tumour demonstrated the presence of a PAX3/FKHR fusion transcript, product of a t(2;13) reciprocal translocation, a genetic marker specific for alveolar rhabdomyosarcoma. CONCLUSIONS: The diagnostic methodology of a small round cell tumour of the child must now include immunohistochemical study and molecular biology to confirm the diagnosis of alveolar rhabdomyosarcoma, in a solid and undifferentiated variant.

Malignant peripheral nerve sheath tumor arising in a "de novo" ganglioneuroma: a case report and review of the literature.

A case of a "de novo" ganglioneuroma showing a large area of malignant peripheral nerve sheath tumor (MPNST) is described. The tumor arose in an 11.5-year-old girl with neither stigmata nor family history of von Recklinghausen's neurofibromatosis. In addition, the patient had no previous history of a neuroblastoma or radiation therapy. This report provides new evidence that, although rare, the spontaneous development of an MPNST in a benign ganglioneuroma can occur. Immunohistochemical and electron microscopy studies supported the finding that the spindle cell component was of nerve sheath origin.