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Glioblastomas and medulloblastomas are models for studying the implication of growth factors and oncogenes in tumor development. Amplification and/or hyperexpression of oncogenes result in products that may mimic growth factors and/or their receptors; cells may demonstrate autocrine and/or paracrine activity. Prognostic implications of such findings are suggested.

Alexander disease, or hypoproconvertinemia is a rare autosomic recessive coagulation disorder. The features include familial and/or personal history of bleeding, with an abnormal prothrombin period and a normal activated partial thromboplastin period. Coagulation and genetic studies allow subclassification with prognosis incidence for this disease. The authors report on a case of one family with Alexander disease.

Medulloblastoma is a frequent brain tumor in childhood. Recent advances in histogenesis, management of early and late side-effects, and prognosis are discussed in this review.

Treatment modalities of childhood brain tumors are associated with adverse neuropsychologic sequelae that may be manifested years after therapy. Based on recent published studies, the authors review the etiological factors, the symptoms and the evolutive features of these disorders and their management.

Despite great histological polymorphism, clinical features of supratentorial brain tumors are mainly limited to neurological deficit, and focal epilepsy and/or symptoms secondary to raised intracranial pressure. The treatment relies on surgery and radiotherapy; chemotherapy has not yet demonstrated its efficacy. Failures are explained by the limitation of neurosurgery, and by the toxicity of the radiotherapy that precludes the use of high dosages. Some good vital results are hampered by neuropsychic sequellae.

The authors review the literature concerning chromosomal abnormalities in childhood brain tumors: medulloblastomas, ependymomas, and gliomas of low and high grade. Though these technics require further development, they highlight the role of cytogenetic modification in oncogenesis of brain tumors.

Objectif Rapporter les resultats de l’etude TGM 95 (Societe francaise des cancers de l’Enfant) concernant les tumeurs germinales malignes (TGM) de l’ovaire en insistant sur la prise en charge chirurgicale. Materiel et methode De Janvier 1995 a Decembre 2005, 79 patientes ont ete traitees suivant le protocole TGM 95. L’age median au diagnostic etait de 11,6 ans [11 mois – 20 ans]. Soixante sept filles (85 %) ont eu une chirurgie premiere dont 16 fois en urgence (24 %). Dans 58 % des cas (46) le chirurgien etait un pediatre. La coelioscopie a ete utilisee 10 fois avec 7 conversions. Il y a eu 26(33 %) ruptures pre et ou per-operatoires, toutes volumineuses et friables, qui ont, toutes sauf une, recu une chimiotherapie post operatoire. Resultats et Discussion Dans 13 cas (16.5 %) il n’y a pas eu de dosage preoperatoire des marqueurs. Dans 8 cas (10 %) il n’y a pas eu d’exploration de la cavite abdominale. Il n’y a aucun renseignement concernant une eventuelle ascite dans 27 cas (34%). Il y a eu 5 kystectomies (6.5 %) qui ont toutes ete reprises pour annexectomie, 24 ovariectomies unilaterales (32.2 %), 44 annexectomies unilaterales (60 %) et 1 ovariectomie bilaterale (1.3 %). Quatre patientes avec chirurgie initiale complete ont recu secondairement une chimiotherapie pour une reascension des marqueurs. Six patientes (7.5 %) ont rechute (5 rechutes locoregionales, 1 rechute pulmonaire). Trois patientes sont decedees, une apres rechute, une seconde d’une leucose, la troisieme d’un accident. Conclusion Le pronostic des TGM de l’ovaire est excellent. Cependant une prise en charge chirurgicale plus rigoureuse (dosage des marqueurs, exploration abdominale complete avec prelevement d’ascite, geste chirurgical adapte…) devrait permettre d’ameliorer encore le pronostic et peut etre d’eviter une eventuelle chimiotherapie post operatoire.

13553 Background: New drugs are strongly needed in childhood cancers, particularly in metastatic tumors. Temozolomide (TMZ) and Topotecan (TPT) have shown activity in several pediatric cancers. Resistance to alkylating agents due to MGMT expression, MMR deficiency or microsatellite instability may be overcome through the combination with topoisomerase I inhibitors. The combination of TPT with TMZ has never been given in patients and our objective was to determine the recommended dose (RD) in children. Methods: The study was conducted in 9 centers of the SFCE Pharmacology Group. TMZ was administered orally followed by TPT as a 30 minutes intravenous infusion for 5 consecutive days every 28 days. Dose escalation was performed in a classical 3+3 methodology starting at 100 mg/m2 TMZ and 0.75 mg/m2 TPT. Dose-limiting toxicity (DLT) was evaluated after the first cycle. Pharmacokinetic parameters were studied during the 1st cycle Results: Sixteen patients, median age 8.5 years (range 3–19), were enrolled betwee...

From August 1985 to April 1988, 17 patients have been allografted in France for TM. Fourteen (82%) are alive, 10 (58%) are cured and 4 in autologous reconstitution. Three died, 2 of whom after a second transplantation, and 2 due to CMV interstitial pneumonia. Ten of 17 were conditioned by cyclophosphamide (Cy: 200 mg/kg) and busulfan (Bu: 14 mg/kg): 10 are alive, 6 cured and 4 in autologous reconstitution. Five received Cy (200 mg/kg) Bu (16 mg/kg) +/- total lymphoid irradiation (TLI) (3 patients): 2 patients are cured (one after hepatic veno-occlusive disease), and 3 died. For 2 patients, conditioning included total body irradiation: both are cured. Graft versus host (GVH) reaction prevention included: 4 T cell depletion (with additional prevention in 3; 2 are cured, one is in autologous reconstitution, 1 died); 5 cyclosporine alone (2 cured, 2 autologous reconstitution, 1 dead) and 8 cyclosporine + methotrexate (6 cured, 1 autologous reconstitution, 1 dead). Four of 12 evaluable patients presented a less than or equal to 2 grade acute GVHd. None had received a T cell depleted marrow. Bone marrow transplantation is the only curative treatment currently available for TM patients with HLA identical donors. It should be proposed to any young patient before iron overload is established. Optimal conditioning includes Cy (200 mg/kg) + Bu (14 mg/kg). The best protocol for GVHd prevention remains to be defined.

Thirty-one patients, 13 adults and 18 children, were included in a phase II study of combined treatment with CDDP 40 mg/m2 and VP16 100 or 200 mg/m2 for 5 days. Fourteen patients were primary refractory to front-line treatment and 17 were treated at relapse (9 on therapy, 8 off therapy). Four were low-grade follicular lymphomas, 7 intermediate grade lymphomas, and 20 high grade lymphomas. One of the 14 primary refractory cases responded (CR) whereas 3 PR and 10 CR were observed among the 17 relapses. Toxicity was acceptable. 9 patients are still alive after bone marrow transplantation (median survival, 16 months). This combination is an effective salvage regime before autologous bone marrow transplantation for relapsed NHL, but cannot be recommended for progression on front-line therapy.

9543 Background: Temozolomide has been shown moderately effective in pediatric high-grade glioma (HGG). By decreasing the activity of MGMT, principal mechanism of resistance to temozolomide, cisplatin may increase the activity of this alkylating agent. Methods: Patients aged 4 to 21y with HGG outside the brainstem were treated at diagnosis or at relapse every 28 days with a combination of cisplatin 80 mg/m2 intravenously on day-1 and temozolomide 200 mg/m2 orally on days 2–6, according to the pediatric phase I recommendations. Patients treated at diagnosis had to proceed to involved field radiotherapy after the chemotherapy window. According to initial response, patients were offered additional courses, up to seven. We considered that this combination would be of interest if the response rate was superior or equal to 20%, using a two-stage Simon design in 3 cohorts: evaluable non measurable (infiltrative) at diagnosis (cohort A1); measurable disease (nodular) at diagnosis (A2); recurrent disease (B). The primary endpoint was complete or partial response after two courses, confirmed by central review. Up to 29 evaluable pts were to be entered in each cohort. If fewer than 4/29 responses were observed, it would be concluded that the combination is ineffective. Results: 56 pts were entered from 10/2003 through 07/2006 in 25 centers. One was excluded after central pathology review and 3 due to insufficient radiology work-out. 42 had grade III and 13 grade IV gliomas, including 21 tumors with oligodendroglial features. No response was observed in the first 11 pts in cohort A1 and in the first 12 pts in cohort B. Two partial and 4 minor responses were confirmed in 29 pts of cohort A2 leading to a 7% response rate (95% CI, 1–23%). Median time to progression was 1.7, 7.1 and 6.9 months in cohorts A1, A2 and B, respectively. Toxicity was manageable except in pts with large infiltrative lesions who did not tolerate hydration. Conclusion: CISTEM combination has insufficient efficacy in pediatric compared to adult HGG despite efficient down-regulation of MGMT activity. To overcome resistance to temozolomide in children and adolescents, one may need to target other known resistance mechanisms such as mismatch-repair deficiency. [Table: see text]

9003 Background: Imatinib mesylate inhibits selectively specific activations of the platelet-derived growth factor receptor (PDGFR), c-KIT and BCR/ABL tyrosine kinases and is approved for the treatment of chronic myeloid leukemia and gastro-intestinal stromal tumors (GIST). This study evaluated efficacy of imatinib in solid childhood tumors. Methods: Phase II study of imatinib as single agent in children and adolescents with refractory or relapsing solid tumor expressing at least one of the receptors. Patients were to be treated at 340 mg/m2, a dose escalation allowed to 440 mg/m2 after 2 months in case of insignificant improvement. C-KIT, PDGFRα and β expression was determined on archive tissue sections by immunohistochemistry prior to study entry. Gene mutations, pharmacokinetics, pharmacogenetics, and positron emission tomography imaging were assessed. Results: 36 patients, 21 boys, median age 13.7 years (2.2–22.5 y), 12 with brain tumors, 6 fibromatosis, 8 mesenchymal/bone tumors, and 10 other solid tumors, including 1 GIST and 3 chordoma, were treated at 340 mg/m2 daily during a total of 168 months (median 1.9 month/patient, range 0.5–19). 18/36 expressed c-KIT, 10 PDGFRα, 21 PDGRβ; 12 expressed more than one receptor. Ten patients were escalated to 440 mg/m2 due to lack of efficacy. During the 1st month, 17 patients experienced mild toxicity (grade 1 and 2) related to study treatment: gastro-intestinal (n=22), face edema (n=7), asthenia (n=5), tumor induration (n=2), skin toxicity (n=2), thrombocytopenia (n=1). No partial or complete response was observed; 5 patients (2 fibromatosis, 1 GIST, 1 medulloblastoma, 1 pseudo-inflammatory tumor) experiencing durable stable disease have been under treatment for more than 12 months. Interesting tumor stabilization during 10 and 7 months, respectively, was achieved in a brain stem glioma and a renal carcinoma. Glucose uptake on 18FDG PET scan was reduced in a chordoma, although the child progressed and died due to disease. Pharmacokinetic and genetic data are currently evaluated. Conclusions: Imatinib as single agent was well tolerated, but—as used in our study —failed to show measurable anti-tumor effects according the standard criteria in the pediatric malignancies studied. No significant financial relationships to disclose.

8548 BACKGROUND Bifocal tumours represent 7–12 % of primary cerebral germ cell tumours and are mostly germinomas. The treatment of non metastatic germinomas includes either craniospinal irradiation (CSI) or chemotherapy with focal RT. BIG still represent a challenge. Should they be treated as localized or metastatic disease? This study aims to evaluate the outcome of treatment of BIG treated by chemotherapy followed by localized radiation to tumour bed in non metastatic disease METHODS The data of 118 patients included from 1990–1999 in the SFOP-TGM-TC 90–92 protocol for intracranial germ cell tumours were reviewed. The treatment of patients with germinomas (80 patients) included 2 cycles of alternating carboplatine/Etoposide and Ifosfamide /Etoposide followed by focal RT (40 Gy) delivered to initial target in localised diseases or CSI in metastatic patients. RESULTS 12/118 germ cell tumours had bifocal disease: 2/38 in the secreting group, 10/80 in the non secreting germinoma group. Two of these 10 were ...

Inactivation of both alleles of the retinoblastoma susceptibility gene ( RB1 ), localised on chromosome band 13q14, is the crucial event for the development of retinoblastoma, a malignant tumour that originates from embryonal retinal cells.1, 2 Germinal mutation of one allele leads to a predisposition to retinoblastoma. Tumour development is initiated by inactivation of the second allele. In most families, the tumour predisposition segregates as an autosomal dominant trait with high (90%) penetrance3 and affected subjects usually develop bilateral multifocal tumours. Rare instances of familial retinoblastoma with low penetrance and variable expressivity have been described. In such families, patients develop retinoblastoma later than classical familial cases, there is a high rate of unilateral cases, and phenotypically normal obligate carriers are observed.4 A family with several cases of retinoblastoma has been identified (fig 1). Four members of the family were affected; three had unilateral retinoblastoma (III.5, IV.12, and IV.13), diagnosed at 12, 12, and 24 months, respectively, and one had bilateral retinoblastoma (IV-6), which developed at 11 months. Thus, with the exception of patient IV.13, the age of onset was not delayed compared to an average of less than 12 months in the majority of familial retinoblastoma. There were no cases of spontaneous osteosarcoma in this family, a secondary tumour recurrently found in patients with predisposition to retinoblastoma.5 However, the retinoblastoma of patient IV.6 was treated by radiotherapy (45 Gy) and 10 years later an osteosarcoma occurred in the irradiated field. It is well established that a germline mutation in the RB1 gene dramatically increases the probability of developing a radiation induced osteosarcoma.6 After ophthalmic examination of unaffected family members, no case of retinoma/retinocytoma, which may represent benign proliferation or tumour regression, was found. Altogether, these observations suggest the presence of a germline RB1 mutation linked to incomplete …

PURPOSE: To tailor postinduction therapy for stage 4 neuroblastoma in children who are older than 1 year at diagnosis according to status after induction. PATIENTS AND METHODS: From March 1987 to December 1992, 99 patients who were consecutively admitted were included in the Lyon-Marseille-Curie East of France (LMCE)3 strategy. After induction with the French Society of Pediatric Oncology NB87 regimen and surgery, patients who were in complete remission immediately proceeded to consolidation therapy with vincristine, melphalan, and fractionated total-body irradiation (VMT). All other patients underwent a postinduction strategy before VMT, either an additional megatherapy regimen or further chemotherapy with etoposide/carboplatin. RESULTS: The progression-free survival (PFS) is 29% at 7 years from diagnosis, which compares favorably with that of a similar cohort of 72 patients previously reported by our group (LMCE1; PFS of 20% at 5 years and 8% at 14 years, P = .004). In the multivariate analysis, only age younger than 3 years at diagnosis (P = .0085) and achievement of complete or very good partial remission after NB87 and surgery (P = .00024) remained significant. The PFS of the 87 patients who were included in the postinduction strategy was significantly better than that of the comparable 62 patients on the LMCE1 study (32% v 11% at 7 years; P = .005). CONCLUSION: The progressive improvements in the LMCE results over the last 10 years suggest that improvements in supportive care measures and increases in each component of this strategy (induction, postinduction, consolidation) may all contribute to increased survival rates.

Summary Aggressive fibromatosis (also known as desmoid tumors) arise from musculo-aponeurotic tissues and are histologically benign. They are however locally aggressive. Local relapse occurs in 20 to 100% of treated patients and is specially frequent following incomplete resection. We report 9 cases of children treated at Leon Berard Center between 1979–1991 by surgery and post operative treatment. Patients and methods Between 1979 and 1991, 9 children (7 male, 2 female) with aggressive fibromatosis were treated at Leon Berard Center. Ages ranged from 24 to 204 months. Five were seen at first relapse and 4 were treated in first intent. All specimens were reviewed by the Department of Pathology, (histological confirmation of aggressive fibromatosis was confirmed in all cases). Involved sites of disease include: limbs (4), supraclavicular (2), face (2) and sacrum (1). Initial surgery consisted of wide excision in 7 patients with a macroscopic residual disease, and a microscopic residual disease in 2 cases. Despite partial surgery in 5/9 patients who were treated at other institutions, no further post-operative treatment was proposed and these patients were referred at Centre Leon Berard with local recurrences following first surgical resection. All of them underwent a record surgery at time of relapse. Four patients were referred for initial diagnosis of desmoid tumors and had an incomplete surgery. Four children were treated with postoperative radiation, 2 with radiation and chemotherapy, 1 child with radiation therapy, chemotherapy and endocrine therapy and 1 with endocrine therapy alone. Results: Local control Six patients relapsed within 4 to 12 months from surgery. Three were controlled. Among the controlled patients, 1 received radiation therapy alone (45 Gy), the second received chemora-diation (Ifosfamide, Vincristin, Adriamycin + 45 Gy); the third received Tamoxifen (20 mg/m 2 ). Second surgery was performed on the 6 patients who failed locally: macroscopic complete resection was performed but with positive margin in 3 cases. Gross residual disease was present in two cases, the last one achieved microscopically complete resection. No additional treatment was administered to the child who underwent a complete resection; he is alive at 10 years follow up. Adjuvant treatment was delivered to 5 patients: radiation therapy alone (2 pts); chemoradia-tion and TAM (2); chemotherapy alone (1). Survival All but one patients are still alive with a 93 months median follow up. Seven of 9 children are free of recurrence at last review. Nevertheless, one is still alive but with active disease. The last one died of disease 28 months after the initial surgery by locally uncontrolled tumor. Conclusion Primary treatment is surgical resection and should be as complete as possible. This is difficult to achieve. No patient in our study was completely resected. Most of children relapsed after the initial surgery and patients may died as a consequence of locally uncontrolled tumor. Theses findings confirm that fibromatosis are aggressive tumor which warrant aggressive therapy. Local control may be achieved with adjuvant ″aggressive″ treatment such as radiotherapy.

Summary. Between 1981 and 1985. 50 patients, mainly children and adolescents, with advanced B-cell lymphoma were entered on a protocol comprising eight drugs: cyclo-phosphamide. vincristine, prednisolone. high dose methotrexate. adriamycin. BCNU. cytosine arabinoside and thioguanine. Treatment to the central nervous system consisted of intrathecal methotrexate and cytosine-arabinoside in association with high dose methotrexate without irradiation. Data was collected prospectively with regard to response rate, treatment related complications and survival. Histology was reviewed in all referred cases and in 21 there was supportive evidence from immunological and cytogenetic studies. The overall complete response rate was 86%: 31/36 stage III and 12/14 stage IV. There were four treatment related deaths. The overall disease-free survival is 75% with a median follow up of 32 months. In the group of stage IV patients 5/7 with only marrow involvement, 2/4 with isolated CNS involvement and 1/3 with combined CNS and marrow infiltration survive. All the patients with CNS involvement at presentation underwent consolidation treatment with high dose chemotherapy and bone marrow transplant. These results demonstrate the very high curability of B-cell lymphoma using intensive multiagent therapy even with advanced abdominal disease. Bone marrow infiltration does not appear to be an adverse prognostic factor in isolation from bulk disease or CNS involvement. There remain, however, two groups of patients in whom further intensification of therapy is indicated, namely, those with initial CNS involvement, especially in combination with marrow infiltration, and those with extensive multiorgan involvement at presentation who fail to achieve remission with initial therapy. For the other patients, the large majority, a reduction in the intensity and duration of therapy is currently under study.

On 80 occasions 4 iliac biopsy trephines and 4 iliac aspirations were performed in 37 children with neuroblastoma at various stages of the disease. In 38 of these procedures, tumour cells were detected. In 24% of cases, both trephines and aspirates were positive, whereas in 63% neuroblastoma cells were detected only on the trephines and in 13% only on the aspirates. In addition, in 37% of the stagings, only one out of the 8 investigations was abnormal. Only in one of 33 pathological cases, was BM involvement diagnosed on trephine imprint. No involvement was ever observed on tibial and sternal aspirates without iliac involvement. Immunological studies with two monoclonal antibodies HSAN 1-2 and UJ13A were performed on 56 occasions. Cytohistological and immunological studies were concordant in 39. In 3 studies, the antigens recognized by the two monoclonal antibodies were not expressed by the initial tumour and in 3 additional studies immunological results were falsely negative; but in 11 cases monoclonal antibodies identified residual malignancy despite normal cytohistology. From this study, biopsies appear more helpful to detect malignant cells than aspirates. Immunological staining clearly leads to a better definition of tumour cells in aspirates.

We report the results of a French multicentric pilot study of remission induction therapy in metastatic neuroblastoma. Thirty-five successive unselected patients entered the study over 1 year and were treated by alternating sequences of cisplatin/VM-26 (PE) and vincristine/cyclophosphamide/doxorubicin (CADO). Three courses of each sequence were delivered. Disease reevaluation was extensive, with special focus on bone marrow status. Using strict criteria, 24 patients (68%) achieved a good partial response (GPR), which comprised normalization of bone marrow, and ten (28%) achieved a partial response (PR), and one progressed. The overall response rate was 96%. Thirty-two patients underwent surgery, and complete macroscopic removal of the primary was achieved in 21 (65%). After completion of induction and surgery, six patients (17%) were in complete remission (CRm), without evidence of any residual disease; nine (26%) were in very good partial remission (VGPRm; same as CRm except persistence of nonpathologically evaluable improved bone scan), and 19 (51%) were in partial remission (PRm). Toxicity was acceptable, and no treatment-related deaths occurred. These results show no substantial improvement compared with those previously reported with similar but nonalternating regimens. We advocate a two-category concept (response, remission) to describe initial therapy results in metastatic neuroblastoma and emphasize the need to assess bone marrow by an extensive evaluation.

Using the adhesive tumor cell culture system, we studied the effect of epidermal growth factor (EGF) on 16 primary and 7 metastatic fresh human tumors of the nervous system cultured in serum-free and serum-supplemented media at low cell density. In serum-free conditions, EGF significantly enhanced the growth of glial tumor cells. This positive effect was less pronounced for metastases to the brain. No significant enhancement was observed for the other tumor types (primitive neuroectodermal tumors and various tumors of neuroepithelial/mesenchymal origin). The addition of serum obscured this effect of EGF, even at the lowest cell densities. In 7 tumors, the simultaneous addition of platelet-derived growth factor did not enhance the EGF response. Subtypes of brain tumors respond to EGF in vitro under serum-free conditions.

The chromosomal anomaly t(4;11) is closely related to a specific type of acute leukemia: occurrence in young children, hyperleukocytosis with a particular immunologic phenotype, and poor response to therapy. Allogeneic bone marrow (BM) transplantation has been done in a few cases. We report a case in which a complete remission was obtained after intensive therapy. Because no donor was available, an autologous BM transplantation was performed after purge ex vivo of the BM collection by Asta-Z. Relapse occurred at day 45.

Anti HbS antibody levels were retrospectively studied in 31 children who received at least 4 immunisations with HEVAC vaccine. Results were as follow: 305 mUI/l (6 immunocompetent patients), 263 mUI/l (4 patients with solid tumors of therapy), 26 mUI/l (16 acute leukemias receiving intermittent reinduction therapy), 0.7 mUI/l (3 acute leukemias on maintenance therapy), 0 mUI/l (2 patients allografted for severe aplastic anemia, on immunosuppressive therapy). Antibody levels of patients who received immunisation during reinduction therapy were not correlated with intervall between immunisation and previous or next reinduction, not correlated with intervall from start of therapy, but seemed inversely correlated to age at time of diagnosis and at time of immunisation.

A 13 years old girl is admitted for severe chronic anemia. Few blood sac looking like lesion are discovered. A Blue Rubber Bleb Nevus Syndrome is confirmed discovery of multiple intestinal angioma. No deep lesion is discovered otherwise. Clinical characteristics, nosology and evolutive trend of this rare syndrome are recalled.

Cytogenetic studies using constitutive heterochromatin variations represent one of the best method in documentation of allogeneic bone marrow transplantation (BMT). Sex mismatched transplants are evaluated by gonosomal examination. In sex matched patients, several banding techniques are performed before BMT to detect autosomal polymorphism in donor and recipient. Can be informative: chromosomes 3 and 4 centromere, acrocentric centromere and satellites, chromosomes 1, 9 and 16 secondary heterochromatic constriction. Authors describe their methodology for these studies and results about 81 patients.

Neutropenia developed in 3 pediatrics patients during treatment with oxacillin. The time of onset ranged from 18 to 24 days after beginning treatment with dose of 150 mg/kg/24 h. Concomitant symptoms were fever and rashes. During treatment with oxacillin it is necessary to monitor blood cell count every week.

We studied the effects of prolonged pancuronium administration in 10 neonates under assisted ventilation for hyaline membrane disease. Pancuronium bromide was administered from the time of intubation with a load dose of 0.1 mg/kg followed by a continuous infusion of 0.03-0.07 mg/kg/h. Tolerance, especially cardiovascular, was excellent after 72 to 525 h of therapy (mean 173 h). Oxygen needs, incidence of mechanical complications and the general evolution of idiopathic respiratory distress were not significantly affected by muscle relaxation. The benefits of systematic pancuronium administration during respiratory intensive care in neonates with hyaline membrane disease appear to be of little value when considering the necessary constraints (corneal, cutaneous, vesical and tracheal supervision).

A 5,9 year old girl presented a severe and acute auto-immune hemolytic anemia, unresponsive to steroids, treated by 10 plasma exchanges, immunosuppressive agents and splenectomy. Despite an anticoagulant treatment, occurrence of multiple thrombosis. Unusual evolution of Mycoplasma serological tests.

Acute methotrexate intoxication occurred in 4 patients despite adequate alkaline hyperhydration and classical folinic acid rescue. Three of these patients had no previous risk factor. Charcoal haemoperfusion with haemodialysis was promptly instituted and the methotrexate blood levels rapidly decreased, avoiding further renal damage and multisystemic involvement. Chemotherapy could subsequently be performed in 3 of the 4 patients without delay and toxicity. Charcoal haemofiltration appears to be an excellent treatment of methotrexate intoxication.

Authors report the case of a 19 year old metastatic Ewing's sarcoma, prophylactically treated for suspected tuberculosis by Rifampicin and INH. Hepatic failure was induced by accidental overdose of INH. A high dose containing VCR protocol associated, lead to a coma with convulsions and severe motor peripheral neuropathy partially regressive. Neurological incidents of VCR, INH and their association are reviewed.