[Recurrence of congenital diaphragmatic hernia]. / Une récidive de hernie diaphragmatique congénitale.

Through the case report of a child who had had a congenital diaphragmatic hernia (cdh) and then relapsed 8 months after initial surgery, the various risk factors related to a cdh, its pre- and postnatal management as well as some long-term complications are discussed.

Par le biais du cas clinique d'un enfant qui a été opéré d'une hernie diaphragmatique congénitale (HDC) et qui a récidivé 8 mois plus tard, les différents facteurs de risques liés à la HDC, sa prise en charge ante et post-natale ainsi que quelques possibles complications à long terme sont discutés.

[Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations in children]. / Le cas clinique du mois. Maladie de Rendu-Osler et malformations artério-veineuses pulmonaires chez l'enfant.

Hereditary hemorrhagic telangiectasia is a constitutional vascular dysplasia characterized by chronic epistaxis, mucocutaneous and visceral telangiectasias and arteriovenous malformations. Apart from family screenings, the disease is rarely diagnosed during the pediatric age given the late advent of typical clinical symptoms. Nevertheless, arteriovenous malformations are sometimes already present at a young age with significant morbidity risk. Therefore, it is important to establish an early diagnosis. We describe two pediatric cases of hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations with divergent clinical presentation.

La maladie de Rendu-Osler, ou télangiectasies hémorragiques héréditaires, est une dysplasie vasculaire constitutionnelle. Elle se caractérise par des épistaxis spontanées et récidivantes, des télangiectasies cutanéo-muqueuses et viscérales et des malformations artério-veineuses. En dehors d'un dépistage familial, cette maladie est rarement diagnostiquée à l'âge pédiatrique étant donné l'apparition tardive des symptômes cliniques typiques. Cependant, les malformations artério-veineuses sont parfois présentes dès le plus jeune âge avec des risques importants de morbidité, d'où l'importance d'un diagnostic précoce. Nous décrivons deux cas pédiatriques de maladie de Rendu-Osler et de malformations artério- veineuses pulmonaires avec des présentations cliniques très différentes.

Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG.

Between November 1990 and November 1996, EORTC Children Leukemia Group conducted a randomized trial in de novo acute lymphoblastic leukemia and lymphoblastic non-Hodgkin's lymphoma patients using a Berlin-Frankfurt-Munster protocol to evaluate the monthly addition of intravenous 6-mercaptopurine (i.v. 6-MP) (1 g/m(2)) to conventional continuation therapy comprising per oral MTX weekly and 6-MP daily. Only during the first 18 months of the randomization period, 6-MP p.o. was interrupted for 1 week after each i.v. 6-MP. A total of 877 patients was randomized to either no i.v. 6-MP (Arm A) or additional i.v. 6-MP (Arm B). A total of 217 relapses (91 in Group A vs 128 in Group B) and 13 deaths in CR (5 vs 8) were reported; a total of 134 patients (55 vs 79) died. The median follow-up was 7.6 years. At 8 years, the disease-free survival rate was lower (P=0.005) in Arm B (69.1% (s.e.=2.2%)) than in Arm A (77.9% (s.e.=2.0%)), and the hazard ratio was 1.45 (95% CI 1.12-1.89). In conclusion, as delivered in this study, i.v. 6-MP was detrimental to event-free survival.

Treatment of childhood autoimmune haemolytic anaemia with rituximab.

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.

[Immune deficiencies: diagnosis, management, some perspectives]. / Déficits immunitaires primaires: diagnostic, prise en charge, quelques perspectives.

Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.

Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organization for Research and Treatment of Cancer 58881 randomized phase III trial.

PURPOSE: The European Organization for Research and Treatment of Cancer 58881 study was designed to test in a prospective multicentric randomized trial the value of high-dose (HD) intravenous (IV) cytarabine (Ara-C) added to HD IV methotrexate (MTX) to reduce the incidence of CNS and systemic relapses in children with increased-risk acute lymphoblastic leukemia (ALL) or stage III and IV lymphoblastic lymphoma treated with a Berlin-Frankfurt-Munster (BFM)-based regimen. PATIENTS AND METHODS: After completion of induction-consolidation phase, children with increased-risk (risk factor > 0.8 or T-lineage) ALL or stage III and IV lymphoblastic lymphoma were randomized to receive four courses of HD MTX (5 g/m(2) over 24 hours every 2 weeks) and four intrathecal administrations of MTX (Arm A) or the same treatment schedule with additional HD IV Ara-C (1 g/m(2) in bolus injection 12 and 24 hours after the start of each MTX infusion) (Arm B). RESULTS: Between January 1990 and January 1996, 653 patients with ALL (593 patients) or lymphoblastic lymphoma (60 patients) were randomized: 323 were assigned to Arm A (without Ara-C) and 330 to Arm B (with Ara-C). A total of 190 events (177 relapses and 13 deaths without relapse) were reported, and the median follow up was 6.5 years (range, 2 to 10 years). The incidence rates of CNS relapse were similar in both arms whether isolated (5.6% and 3.3%, respectively) or combined (5.3% and 4.6%, respectively). The estimated 6-year disease-free survival (DFS) rate was similar (log-rank P =.67) in the two treatment groups: 70.4% (SE = 2.6%) in Arm A and 71.0% (SE = 2.5%) in Arm B. The 6-year DFS rate was similar for ALL and LL patients: 70.2% (SE = 1.9%) versus 76.3% (SE = 5.6%). CONCLUSION: Prevention of CNS relapse was satisfactorily achieved with HD IV MTX and intrathecal injections of MTX in children with increased-risk ALL or stage III and IV lymphoblastic lymphoma treated with our BFM-based treatment protocol in which cranial irradiation was omitted. Disappointingly, with the dose schedule used in this protocol, HD Ara-C added to HD MTX, although well tolerated, failed to further decrease the incidence of CNS relapse or to improve the overall DFS.

New dysostosis showing multilevel absence of vertebral pedicles: unique developmental anomaly of vertebral arches?

We report on an apparently normal child who shows hypopaplasia of the vertebral pedicles and posterior arches of several cervical, thoracic, and lumbar vertebrae with normally fused spinous apophyses, hypoplastic sacrum, lumbar epidural lipomatosis, synostoses of some cervical vertebral disks, and sacral spina bifida. The most likely mechanism is an abnormal differentiation of the spinal processes, due most probably to an absence of differentiation in cartilage of the dense mesenchyme forming their most anterior part. Because the anomalies affect multiple levels, we highly suspect a genetic basis to this unusual dysostosis affecting the development of the posterior sclerotomes.

Stroke and cerebral infarcts in children infected with human immunodeficiency virus.

OBJECTIVE: To study the causes of stroke and cerebral infarcts in children infected with the human immunodeficiency virus (HIV)-type 1. DESIGN: Case series. PATIENTS: Four of 380 HIV-infected children followed up in a 10-year period in our department who had a stroke with evidence of cerebral infarcts on radiological imaging. RESULTS: The four patients were severely immunodepressed, but their clinical status and outcome were different. Aneurysmal dilation of major cerebral arteries and thrombosis of these arteries or of small cortical vessels were discovered in two patients. Both patients had a history of frequent infections and had suffered repeated neurological events that resulted in severe clinical deterioration or death. An infectious causative agent was strongly suspected but was not detected. The other two patients had a more favorable outcome. An isolated cerebrovascular thrombosis was found in one patient, while in the other, HIV-1-related focal necrosis was suggested by the lack of permanent cerebrovascular abnormalities or thrombosis and by signs of necrosis in biopsy specimens of the brain. CONCLUSION: Stroke and cerebral infarcts in HIV-1 infected children have different causes and different prognoses.