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Resume Introduction Le purpura thrombopenique immunologique (PTI) de l’enfant se caracterise par un syndrome hemorragique cutaneo-muqueux variable, le plus souvent modere et une evolution habituellement spontanement favorable. L’hemorragie intracrânienne (HIC) est une complication exceptionnelle mais d’une gravite extreme. Peu de donnees sont disponibles dans la litterature concernant les facteurs de risque, les circonstances de survenue et la prise en charge de cet accident dramatique. Patients et methodes Quatorze observations d’HIC compliquant un PTI aigu de l’enfant ont ete etudiees retrospectivement sur une periode de 20 ans (1993 a 2013) en France. Resultats Au moment de la survenue de l’HIC, tous les enfants avaient une thrombopenie severe (plaquettes Conclusion L’HIC est une complication grave et imprevisible du PTI, que le traitement precoce ne permet sans doute pas d’eviter. Les signes evocateurs d’HIC doivent etre systematiquement recherches. Leur presence necessite une prise en charge en urgence, reposant entre autre sur l’association classique d’immunoglobulines, de corticoides et de transfusions de plaquettes. La place des agonistes du recepteur de la thrombopoietine reste a preciser.

The optic nerve glioma is a relatively rare pathology in children and only a few cases have been described in infants. This paper reports the symptoms of this exceptional case in a 4-month-old child and reviews the differential diagnoses at this age. Finally, we discuss the diagnosis and therapeutic possibilities.

International audience; 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/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 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.

Resume Les performances de deux trousses de detection rapide de l'antigene rotavirus ont ete comparees sur des selles recues au laboratoire de virologie du CHU de Clermont-Ferrand entre septembre 2002 et mai 2003. Cinq cent douze selles ont ete analysees par la trousse immunochromatographique Diarlex® MB (ICG) et par la trousse immunoenzymatique IDEIATM Rotavirus (EIA). Les echantillons donnant des resultats discordants ont ete observes en microscopie electronique (ME) et les dossiers cliniques correspondants reexamines. Sur 512 echantillons, 155 (30,3 %) etaient positifs et 332 (64,8 %) negatifs avec les deux trousses. Les resultats etaient contradictoires dans 25 cas (4,88 %), soient 24 enfants et un adulte, la trousse EIA donnant davantage de resultats positifs. L'examen en ME, possible retrospectivement pour 15/25 echantillons discordants, a confirme la presence de rotavirus dans 7/14 selles positives seulement en EIA, et un echantillon positif seulement en ICG. Le reexamen des 25 observations cliniques a montre la presence de signes de GEA dans tous les cas. L'analyse statistique montre une concordance excellente entre les deux trousses (kappa = 0,89, IC95 % = [0,85–0,93]) malgre un sous-depistage du test ICG par rapport au test EIA (p

Purpose: To clarify treatment strategy for lymphocyte-predominant Hodgkin’s lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin’s lymphoma or were not treated beyond initial adenectomy. Patients and Methods: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. Results: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% ± 10% (SA, 42% ± 16%; CT, 90% ± 8.6%; P < .04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P < .05). Conclusion: Although based on a small number of patients, our study showed that (1) no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2) complementary treatment diminishes relapse frequency but has no impact on survival.

In extracorporeal photopheresis (ECP) collected cells are treated by 8 methoxypsoralen and UVA (PUVA) which induced apoptosis. The mechanism of action of reinfused cell is unclear. A vaccination model postulates an efficient presentation of apoptotic alloreactive cells to the patient immune system. The efficiency may depend upon a predominence of apoptotic alloreactive cells after PUVA. Such selectivity could result from their activation. We studied apoptosis in resting and PHA-activated lymphocytes. Both were equally susceptible. Changes in early apoptosis were possibily missed. We evaluated the effect of preincubation before PUVA. During preincubation monocyte could affect lymphocytes susceptibility to apoptosis as an increase of number of apoptotic cells was observed after 72 hours in stimulated and resting cells. Our findings do not preclude a selectivity of other PUVA effects since expression of membrane marker also targets to PUVA is modified by activation.

PURPOSE: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 × 109/L and platelet count was > 100 × 109/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval). RESULTS: CDI was significantly increased in the G-CSF group compared with the non–G-CSF group (mean ± 95% confidence interval, 105 ± 5% v 91 ± 4%; P < .001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups. CONCLUSION: G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.

Resume En depit des avancees dans le traitement medical des cancers et de l'augmentation constante des taux de survie, le cancer de l'enfant reste une epreuve psychologique et existentielle a la fois pour les jeunes patients et leurs parents. Les professionnels doivent garder a l'esprit deux idees centrales concernant les enfants et adolescents qui souffrent de cancer : 1) le cancer est une maladie qui menace le pronostic vital et induit de ce fait des reactions emotionnelles, cognitives et comportementales ; 2) l'impact du diagnostic de cancer chez les jeunes patients depend de leur niveau de developpement psycho-affectif. La situation de ces enfants et adolescents qui ont a faire face a la fois a la maladie et a son traitement releve d'une prise en charge au sein d'une unite specialisee. Les recommandations recentes du plan cancer insistent sur le soutien psychologique et psychiatrique qui doit etre propose a ces enfants et l'interet de developper des etudes evaluant l'impact psychologique du cancer sur les jeunes patients et leur famille.

PURPOSE To evaluate growth, thyroid function, puberty, cardiac function, and the incidence of cataracts in children who received allogeneic bone marrow transplantation (BMT) for acute myeloblastic leukemia (AML) in first complete remission (CR) after a preparation with or without total-body irradiation (TBI). PATIENTS AND METHODS Among 45 children studied, 26 received busulfan-cyclophosphamide (Bu-Cy) in preparation for transplantation and 19 received TBI. TBI was fractionated in nine cases and delivered as a single dose in 10. Four children in the Bu-Cy group and none in the TBI group had received prior cranial radiation. The mean follow-up duration after BMT was 5.9 years for the whole group. RESULTS The mean cumulative changes in height SD score (SDS) were -0.86 at 3 years and -1.56 at 5 years in the TBI group, whereas these changes were only -0.05 and -0.17 in the Bu-Cy group (P < .01 at 3 and 5 years). The 6-year probability of hypothyroidism was 9% +/- 8% in the Bu-Cy group and 43% +/- 15% after TBI (P < .02). Pubertal development after Bu-Cy was assessable in two girls and five boys: both girls had primary ovarian failure, whereas Leydig cell function appeared to be preserved in the five boys. One child who had received anthracycline when he was less than 1 year old developed cardiac dysfunction 4 years after Bu-Cy. The 6-year probability of cataracts was 70% +/- 13% in the TBI group and 0% after Bu-Cy. CONCLUSION The use of Bu-Cy represents an alternative transplant cytoreductive regimen for children with AML in first CR, which can reduce the risk of posttransplant growth impairment, thyroid dysfunction, Leydig cell damage, and the incidence of cataracts.

PURPOSE To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.

Rhabdomyosarcoma is an extremely virulent rare tumor whose early diagnosis considerably improves survival and visual prognosis. We report the case of a 2-year-old child with levator palpebrae superioris muscle rhabdomyosarcoma revealed by a sudden and isolated blepharoptosis. Initially, clinical and imaging investigations did not show any abnormality but a painful tumor with some hematoma quickly developed, so the investigations were repeated. The CT-scan showed an extra-conal tumor that had developed at the superior part of the orbit. Histology confirmed the diagnosis of embryonic rhabdomyosarcoma. Because of its results, treatment consisting of chemotherapy associating ifosfamide, vincristine, actinomycin and orbital radiotherapy of 40 Gy with a local addition of 10 Gy were administrated with successful results after a 3-year-follow-up.

Few studies have characterized the rotaviruses observed in repeated infections in the same patient. Rotavirus serotypes and electrophoretypes were determined from faecal samples of 24 children hospitalized between 1984 and 1989 in a Clermont-Ferrand hospital and who had had repeated rotavirus shedding. The patients were aged between 3 days and 4 years. Fifty infections were recorded. Of the 48 serotypes obtained, 18 were serotype 1 (37.5 %), 10 serotype 2 (20.8 %) and 20 serotype 4 (41.7 %). Serotype 3 was not found. Seven serotype 2 infections were characterized during rehospitalization. Six patients had two subsequent infections with the same serotype.

The optic nerve glioma is a relatively rare pathology in children and only a few cases have been described in infants. This paper reports the symptoms of this exceptional case in a 4-month-old child and reviews the differential diagnoses at this age. Finally, we discuss the diagnosis and therapeutic possibilities.

The immunomodulatory effect of extracorporeal photochemotherapy (photopheresis) coupled with its efficacy in lymphocytic skin diseases provides a rationale for its use for erosive lichen planus. We report two cases of chronic oral erosive and corticoresistant lichen planus successfully treated with photopheresis.Case 1. A 61-years-old man had erosive oral lichen planus for four years. Oral steroids were contra-indicated due to iatrogenic pancreatitis. After nine photopheresis sessions, subjective improvement occurred and the oral lesions were stabilized. Case 2. A 17-years-old woman presented corticodependent oral and genital erosive lichen planus and cutaneous lesions. After seven sessions of photopheresis, the patient was able to eat again and the pain decreased. After 20 sessions, the cutaneous lichen planus disappeared and complete remission of the mucous lesions was obtained without corticotherapy.These two cases, together with 23 other cases reported elsewhere, strongly suggested the value of photopheresis in the treatment of erosive lichen planus. However, relapses after treatment withdrawal appear extremely frequent.

In 10 years, the neonatal autoimmune enteropathy has been individualized from other causes of neonatal severe protracted diarrheas as a syndrome called Ipex for Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked. Thanks to linkage analyses in affected families, this rare paediatric syndrome with fatal outcome has been correlated to mutations of the foxp3 gene. Homozygous loss of function of foxp3 gene results in the absence of development of a crucial subpopulation of lymphocytes with CD4+CD25+ phenotype, called regulatory T-cells. The study of these lymphocytes allows a better understanding of the immune system homeostasis and of the physiopathology of Ipex syndrome, which is a prerequisite for treatment. Achieving ex vivo manipulation of such lymphocytes will end up on promising applications of cell therapy.

The ability of two commercially available diagnosis rapid assays in detecting rotavirus antigen was compared in a prospective study conducted from September 2002 to May 2003. Five hundred and twelve faecal specimens were studied by IDEIA Rotavirus enzyme immunoassay test (EIA) and Diarlex MB immunochromatographic test (ICG). Specimens giving discrepant results were examined by electron microscopy (EM) and clinical data reconsidered. Out of 512 stool specimens, 155 (30.3%) were positive and 332 (64.8%) negative with the two assays. Discrepant results were obtained for 25 (4.88%) specimens (24 children, 1 adult), with EIA giving more positive results. The retrospective examination by EM, possible for fifteen stools on the 25 that gave discrepant results, confirmed the presence of rotavirus in 7/14 stools which were positive only by EIA and in the stool specimen that was found positive only by ICG. The 25 clinical observations re-examination showed the presence of GEA signs in all cases. The statistical analysis shows an excellent concordance between the EIA and the ICG tests (kappa = 0.89, IC(95%) = [0.85-0.93]) in spite of the underestimation of ICG test in comparison with EIA test (P0.0001).

We report the data of CD34 + cell immunoselection from peripheral blood after G-CSF-alone mobilization (10 μg/kg/d s.c.) in nine children with neuroblastoma (median age 4.5 years (2-8), median body weight 16kg (10-20). Leukaphereses were carried out on a Cobe Spectra separator and two consecutive harvests (4 blood volumes processed) were used for immunoselection on a Ceprate TM column. The yield of CD34 + cells in the purified fraction was 50% (23-80), with a median number of 2.8 x 10 6 CD34 + cells/kg (1-9.4). All patients were reinfused with selected CD34 + cells after busulfan 600 mg/m 2 + melphalan 180 mg/m 2 and achieved successful haemopoietic recovery.

Scleromyxedema is the consequence of a dermal infiltration by mucine, commonly associated with a monoclonal gammapathy of unknown significance.A 46 year-old woman was hospitalized for a scleromyxedema with a bilateral macular edema and a restricted pulmonary syndrome. A quite complete cutaneous response and a complete ocular and pulmonary response were obtained after 12 extracorporeal photopheresis courses and 4 flashes of prednisolone (17 months follow-up).There is no consensus on guidelines for the treatment of scleromyxedema. Steroids and melphalan are usually indicated. However these drugs induce severe side-effects. In the absence of controlled studies concerning the efficiency of the different drugs used in scleromyxedema, the main advantage of photopheresis lies in the safety of this procedure.

Among 2752 patients with acute leukemia who had recurrent leukemia after autograft in remission and were reported to the EBMT, 94 underwent an allogeneic bone marrow transplant and 74 received a second autograft. Recipients of HLA-mismatched related or unrelated bone marrow had an increased transplant-related mortality (TRM, P = 0.017) and a decreased leukemia-free survival (LFS, P = 0.03), compared to recipients of HLA matched related or unrelated bone marrow. Outcome in recipients of HLA-compatible related or unrelated bone marrow was compared to those receiving a second autograft. TRM at 2 years was 51 +/- 8% in recipients of matched allografts and 26 +/- 6% following a 2nd autograft (P0.05). Two-year LFS was 27 +/- 7% and 35 +/- 6% in the two groups, respectively (NS). Multivariate analysis in these two groups showed that TRM was increased in patients who were in 2nd or later remission at 1st autograft (P0. 05) and allograft recipients (P0.05). Relapse was more common in patients with ALL (P0.001), above 25 years of age (P0.02), autograft performed later than 1991 (P0.05), and in second autografts (P0.05). LFS was decreased in patients25 years of age (P0.01), if the interval from first autograft to relapse was 8 months or less (P0.01) and if TBI was used at first autograft (P0.05).

A subgroup of children with ALL remains at high risk of relapse despite the administration of intensive chemotherapeutic protocols and may benefit from allogeneic BMT. The cytoreductive regimen used most often combines TBI with cyclophosphamide. Nevertheless, miscellaneous long-term sequelae have been consequent upon radiotherapy, especially in young children. This retrospective multicentric study analyzes the outcome of children with ALL under 4 years of age receiving an HLA-genoidentical BMT following a radiation-free preparative regimen. A busulfan-based regimen with cyclophosphamide or melphalan +/- etoposide +/- cytarabine was given to 21 children (median age: 28 months, range 6-48). Sixteen patients with initial poor prognostic factors were transplanted in first complete response (CR) and five patients in relapse or second CR. With a median follow-up of 47 months, the results show an overall 4-year DFS of 61.1%. Leukemic recurrence was observed in eight patients. The preparative regimen was well-tolerated and there were no transplant-related deaths. A busulfan-based BMT preparative regimen may be a therapeutic alternative to TBI-containing regimens in young children. Efforts are currently aimed at reducing the relapse rate in these children by optimizing the tumoricidal potential of chemotherapy and the graft-versus-leukemia effect of allogeneic BMT.

We evaluated (i) the stability of a mixture of the three anti-cancer agents used for the treatment of leukemia, namely etoposide, cytarabine and daunorubicine, in 5% glucose, and (ii) its compatibility towards various materials during an infusion protocol as performed for therapeutic purposes in hospital practice. Etoposide and cytarabine were assayed by high-performance liquid chromatography with a C18 type column and UV detection. Daunorubicine was assayed by visible spectrophotometry. The stability study showed all three anti-cancer drugs to be stable in 5% glucose solution, both alone and mixed. Best conservation was obtained by keeping bottles containing the mixture in the dark at room temperature. During the infusion protocol used in clinical practice, etoposide, cytarabine and daunorubicine were stable and compatible with the various materials present in the infusion sets and extension tubing (polyvinyl chloride, polyethylene) and catheters (silicone). Observed variations in concentration did not exceed 10% of initial concentrations of each drug, though we would advocate changing infusion sets and extension tubing daily.

Gastric tumours are exceptional in children and are usually discovered due to digestive tract bleeding or after palpation of a mass in the abdomen. Appropriate exploratory techniques are need to correctly localize the lesions in the stomach. Nevertheless, the absence of any particular signs can mask the polymorphic nature of the lesions that can only be determined by pathologic examinations. The extent of the surgical exeresis and prognosis depend on the nature of the pathological process.

Malignant tumors of pleural origin are rare in childhood and difficult to diagnose. We report a case in a white 11 1/2-year-old girl who presented with a bulky tumour in the basal left lung field. There was an area of osteolysis at the ventral extremity of the 9th left rib allowing excision of the tumor by lateral thoracotomy. Macroscopically the operation was satisfactory. Despite two complementary excisions, chemotherapy with Vin-Caepi and consolidation chemotherapy followed by bone-marrow autograft, left pleural metastases appeared two years later. A second operation, a new course of chemotherapy with stage IV SIOP MMT, followed by a second bone-marrow graft and mediastinal radio-therapy, resulted in remission. At the time of this report, after three and a half years of evolution, the child's condition is satisfactory and she leads a normal life without treatment. A probable diagnosis of pleural mesothelioma was arrived at by elimination. This kind of tumour, without specific markers, is difficult to distinguish from small-round-cell tumors. Evolution is unpredictable and often rapidly fatal. Although these tumors generally have a weak response to chemo- and radiotherapy, we think that close follow-up and active therapy, rapidly initiated at the slightest sign, can improve the quality of life of the patients and increase their survival.

78 consecutive cases of PCP have been analysed: 59 (75.6%) cases were associated with HIV infection and 19 (24.4%) cases were associated with solid tumors and hematologic malignancies at advanced stage of the disease and renal transplantation. It could suggest primary prevention for such patients.

Lorsque le cancer de l’enfant surgit, cela entraine un bouleversement majeur des liens intrafamiliaux (Guex, 2005). De nombreux acteurs de soins se concentrent alors sur l’enfant malade et sur ses parents (Norberg, Lindblad et Boman, 2004). Prendre en consideration les freres et soeurs de l’enfant traite pour un cancer est une necessite du fait de leur isolement et de leur souffrance face a la situation difficile que traverse leur famille (Bass, Trocme, Laverger, 2005). L’equipe soignante et de psycho-oncologie du Centre Regional de Cancerologie et Therapie Cellulaire Pediatrique (CRCTCP) de Clermont-Ferrand se preoccupe des repercussions du cancer d’un enfant sur ses freres et soeurs. Ainsi, un groupe fratrie a ete mis en place avec pour objectif d’offrir une prise en charge psychologique de groupe, aux freres et soeurs d’un enfant actuellement en soins dans le service. Quel est l’interet d’une prise en charge de groupe pour les fratries ? Comment animer un tel groupe ? Quelles recommandations peut-on retirer de notre experience Clermontoise ? L’objectif de cette presentation est, a partir de notre experience, d’etablir des recommandations sur la prise en charge groupale de la fratrie d’un enfant traite pour un cancer.

In order to evaluate the effect of intensive combined chemotherapy in pediatric brain tumors, we designed a phase II study of high-dose busulfan and thiotepa followed by bone marrow transplantation (BMT) in children with measurable recurrent brain tumors. As alkylating agents, busulfan and thiotepa were expected to exhibit a steep dose effect and no overlapping extramedullary toxicity. Moreover, both drugs have an excellent distribution into the central nervous system in humans. Since May 1988, 20 children (median age 6 years) have been treated. Busulfan (150 mg/m2/day x 4) given orally was followed by thiotepa (350 mg/m2/day x 3), given as a 1 h i.v. infusion. Cryopreserved bone marrow was reinfused 48 h after completion of chemotherapy. Tumor response was assessed by computed tomography and magnetic resonance imaging 4 to 6 weeks after BMT. Five partial responses were observed (three of six medulloblastomas, one of five ependymomas, one of two primitive neuroectodermal tumors); two patients with medulloblastoma and one with brain stem tumor achieved an objective response. Ten patients had stable disease and one progressive disease. One patient is not evaluable because of early toxic death. Toxicity was high in terms of aplasia and cutaneous, hepatic and neurological complications. The overall response rate of 26% is encouraging since all patients had disease refractory to all conventional therapies.

Allogeneic bone marrow transplantation (BMT) is currently an established therapy for hematological malignancies. Twenty years of experience has demonstrated that curability comes from both tumor ablation due to conditioning regimen and immunological therapy from the allogeneic graft [1]. This allogeneic effect, called graft-versus-leukemia effect, has been individualized in retrospective studies looking at the impact of graft-versus-host disease on patient outcome [2]. Furthermore, experience with T cell depletion of the graft has been successful in abolishing graft-versus-host disease but has been associated with a high rejection and relapse rate [3]. This experience has confirmed the immunological nature of the graft-versus-leukemia effect and the importance of T cells in the mechanism. Besides toxicity, allogeneic BMT is limited by the lack of suitable donors. This is the reason why autologous BMT has been frequently proposed as an alternative.

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.

An 11 year-old boy was treated for acute promyelocytic leukemia (ALM3) with chemotherapy according to the LAME 86 protocol (aracytin and rubidomycin). The first complete remission was consolidated by two autologous bone marrow transplantations. Following autologous graft, a persistent thrombocytopenic purpura appeared. Autoimmune origin was indicated by a decrease in platelet survival time and by the presence of high levels of antiplatelet antibodies.

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.

Introduction Nous rapportons le cas d’un nourrisson de 4 mois atteint d’un gliome du nerf optique gauche se presentant sous la forme d’une d’exophtalmie unilaterale gauche rapidement evolutive. Objectifs et Methodes Cet enfant, initialement adresse pour buphtalmie gauche faisant suspecter un glaucome congenital unilateral, et presentant une polyangiomatose associee (un angiome cyrano de la pointe du nez et un angiome de la region scapulaire), souffre en realite d’une exophtalmie d’evolution tres rapide. L’examen ophtalmologique complet retrouve au niveau de l’œil gauche une exophtalmie importante, une exotropie avec quasi ophtalmoplegie, une amblyopie profonde et au fond d’œil un œdeme papillaire. Devant ce tableau clinique, nous realisons une echographie en mode B, une IRM et plusieurs biopsies de la lesion tumorale. Resultats L’echographie met en evidence une masse hypo-echogene confirmee par l’IRM qui retrouve une tumeur intra-orbitaire s’etendant, le long du nerf optique, en intra crânien et affleurant le chiasma optique. L’etude anatomopathologique des biopsies conclut a un gliome du nerf optique gauche type astrocytome pilocytique. Sous corticotherapie a fortes doses, l’aspect du fond d’œil se normalise et un relais par chimiotherapie selon le protocole SFOP est debute. L’evolution a 6 mois note une stabilisation tumorale sans toutefois retrouver des signes de regression. Discussion L’apparition brutale d’une exophtalmie n’est pas le mode de decouverte habituel du gliome du nerf optique. Le diagnostic de tumeur vasculaire retro orbitaire gauche devait etre ecarte chez ce patient par la realisation d’une echographie mode B et d’une IRM. La prise en charge medico-chirurgicale en urgence est primordiale et conditionne le pronostic visuel. Conclusion Le diagnostic de gliome du nerf optique chez le nourrisson est rare et notre cas montre la possibilite des tableaux atypiques, tant sur le mode de decouverte que sur le mode evolutif. La possibilite d’envahissement du chiasma optique puis de bilateralisation conditionne gravement le pronostic visuel et justifie une prise en charge urgente dans laquelle l’IRM semble desormais incontournable.

Introduction Nous rapportons le cas d’un rhabdomyosarcome du muscle orbiculaire superieur gauche se presentant sous la forme d’un ptosis unilateral isole d’apparition brutale chez un enfant de deux ans mettant en jeu les pronostics vital et fonctionnel. Objectifs et Methodes L’enfant est amene en consultation pour une ptose de la paupiere superieure gauche d’apparition brutale avec une paupiere froide sans deficit neurologique, ni tumefaction ou autre anomalie. Devant ce tableau sont realises un bilan sanguin, une ponction lombaire et un scanner cerebral qui sont normaux et aboutissent a une surveillance simple. Nous le revoyons 24-48 heures plus tard en urgence pour apparition d’une tumefaction palpebrale majeure, douloureuse associee a un hematome orbitaire. Le bilan morphologique est complete et montre une tumeur extra-conique s’insinuant a la partie superieure du globe en le refoulant sans l’envahir. Une biopsie est alors organisee en urgence. Resultats L’analyse histologique pose le diagnostic de rhabdomyosarcome du muscle orbiculaire gauche. Discussion Il s’agit d’une presentation atypique, representant conformement a la litterature 6 % des modes de decouverte des rhabdomyosarcomes a localisation ophtalmologique. Cependant devant une ptose palpebrale d’apparition brutale et isolee il est necessaire d’eliminer le diagnostic de rhabdomyosarcome palpebral. Conclusion La decouverte d’un rhabdomyosarcome par un ptosis palpebral d’apparition brutale et isolee est une circonstance rare. Toutefois il faut savoir evoquer ce diagnostic afin d’instaurer en urgence une pris en charge carcinologique precoce pour un meilleur benefice sur les plans vital et amblyopique.

78 consecutive cases of PCP have been analysed: 59 (75,6%) cases were associated with HIV infection and 19 (24,4%) cases were associated with solid tumors and hematologic malignancies at advanced stage of the disease and renal transplantation. It could suggest primary prevention for such patients.

Twenty-one patients with advanced Wilms' tumor entered a phase II study with high-dose ifosfamide (3 g/m2 over two days every 15 days). Mesna and hyperhydration were associated with minimal bladder toxicity. After two courses, five partial responses and six complete responses were observed. Ten patients did not respond. The median duration of response was 2 months (range, 1 to 7). Therapy was delayed because of leukopenia for 1 or 2 weeks in only three cases. Fever and infection were not observed. Seven patients presented with hematuria, three of whom were among the 17 patients coadministered mesna, which did not interfere with subsequent therapy.

Children with B cell non-Hodgkin's lymphoma who have not relapsed 1 year after diagnosis and treatment are generally cured. We report here the results of treatment in 114 children who all had a minimum follow-up of 20 months. The protocol LMB 0281 from the French Pediatric Oncology Society was used. This nine-drug intensive-pulsed chemotherapy was based on high-dose cyclophosphamide, high-dose methotrexate (HD MTX), and cytosine arabinoside (ara-C) in continuous infusion. CNS prophylaxis was with chemotherapy only. No local irradiation was performed. No debulking surgery was recommended. There were 72 patients with stage III lymphoma and 42 patients with stage IV lymphoma or B cell acute lymphocytic leukemia (B-ALL). Among those 42 patients, seven had CNS involvement alone, 21 had bone marrow alone, and 14 had both; 26 had greater than 25% blast cells in bone marrow, 14 of whom had blast cells in blood. The primary site of involvement was the abdomen in 90 patients, the Waldeyer Ring in nine, and various sites in eight; seven patients presented without tumor. Seventy-seven patients are alive with a median follow-up of 2 years and 8 months. Seven patients died due to initial treatment failure, 11 died from toxicity, and 19 died after relapse. Among the 93 patients without initial CNS involvement, only one isolated relapse in CNS occurred. Survival and disease-free survival rates reached 67% and 64%, respectively, for all patients, 75% and 73% for stage III patients and 54% and 48% for stage IV and B-ALL patients. Bone marrow involvement was not an adverse prognostic factor. Contrary initial CNS involvement indicated a bad prognosis with a disease-free survival rate of 19% compared with 76% without CNS disease. This study showed that CNS prophylaxis and local control of the primary tumor can be achieved by intensive chemotherapy alone, without radiotherapy or debulking surgery.

In four children from the same family, we have observed an association of mental retardation, dwarfism, hypertelorism, facial clefting and urogenital abnormalities. Clinical and laboratory data suggest that it is a previously undescribed genetic syndrome, ie, a pleiotropic autosomal recessive trait.

Two brothers presented with hemophagocytic reticulosis with neonatal onset. Early clinical and biological symptoms included pallor, hepatosplenomegaly and anemia, thrombocytopenia. Evolution was lethal in both cases, at 5 months and 13 days of age, respectively. Diagnosis was confirmed in both by the pathologic findings: diffuse lymphohistiocytic cellular proliferation with hemophagocytosis and atrophy of the lymphoid tissue. The diagnostic difficulties of this disease in the neonatal period are emphasized.

A case of extraskeletal Ewing's sarcoma arising in right lumbar region with involvement of epidural space is described in a 16 years old girl. The diagnosis of Ewing's sarcoma was done from cytochemical and electron microscopic studies which showed intra-cellular glycogen granules whereas cytologic and immunological analysis eliminated lymphoid malignancies. This case emphasized the interest of these techniques, adjunctive to routine light microscopic examination for the pursuit of a specific diagnosis in the small round cell neoplasm.