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J Lemerle

Publications and source records attributed to J Lemerle.

At least 37 records · Page 2Linked to original sources
PubMed1996

Genetic transmission of susceptibility to cancer in families of children with soft tissue sarcomas.

BACKGROUND: This article presents analysis of clinical and family data for 239 patients with childhood soft tissue sarcoma (STS) treated at the Institut Gustave Roussy in Villejuif. METHODS: A molecular study was performed to detect germline p53 mutations in the 44 families in which at least 1 relative developed cancer before the age of 46 or in which the proband had a second neoplasm. Mutations were found in five families. Standardized incidence ratio calculation and segregation analysis were used to study cancer occurrence in 4448 relatives, including first- and second-degree relatives and first cousins. RESULTS: An excess of brain tumors was observed in all relatives, and of breast carcinoma and STS in first-degree relatives of patients with STS. An excess of breast carcinoma was observed only in young mothers of patients with rhabdomyosarcoma. This excess might be mostly linked to the presence of a germline p53 mutation because it was no more significant when excluding families in which such a mutation existed. No association between breast carcinoma in the mother and rhabdomyosarcoma of the genitourinary tract in the proband was observed. This should be kept in mind when developing a screening strategy for breast carcinoma in mothers of patients with STS. Segregation analysis showed evidence for transmission of an autosomal dominant gene with complete penetrance by the age of 84. The genetic component was explained primarily by p53 germline mutations. CONCLUSIONS: These results show that most relatives of patients with STS are at the same risk for cancer as the general population.

Adult↗
PubMed1996

Busulfan disposition and hepatic veno-occlusive disease in children undergoing bone marrow transplantation.

Hepatic veno-occlusive disease (HVOD) is a frequent life-threatening toxicity in patients undergoing bone marrow transplantation (BMT) after the administration of a high-dose busulfan-containing regimen. Recent studies have shown that the morbidity and mortality of HVOD may be reduced in adults by pharmacologically guided dose adjustment of busulfan. We analyzed the pharmacodynamic relationship between busulfan disposition and HVOD in 61 children (median age, 5.9 years) with malignant disease. Busulfan, given at a dose ranging from 16 mg/kg to 600 mg/m2, was combined with one or two other alkylating agents (cyclophosphamide, melphalan, thiotepa). Only 3 patients received the standard busulfan/cyclophosphamide (BUCY) regimen. A total of 24 patients (40%) developed HVOD, which resolved in all cases. A pharmacokinetics study confirmed the previously reported wide interpatient variability in busulfan disposition but did not reveal any significant alteration in children with HVOD. The mean area under the concentration-time curve (AUC) after the first dose of busulfan was higher in patients with HVOD (6,811 +/- 2,943 ng h ml-1) than in patients without HVOD (5,760 +/- 1,891 ng h ml-1., P = 0.10). This difference reflects the higher dose of busulfan given to patients with HVOD. No toxic level could be defined and, moreover, none of the toxic levels identified in adults were relevant. The high incidence of HVOD in children given 600 mg/m2 busulfan may be linked to the use of more intensive than usual high-dose chemotherapy regimens and/or drug interactions. Before the prospective evaluation of busulfan dose adjustment in children, further studies are required to demonstrate firmly the existence of a pharmacodynamic relationship in terms of toxicity and allogeneic engraftment, especially when busulfan is combined with cyclophosphamide. The maximal tolerated and minimal effective AUCs in children undergoing BMT are likely to depend mainly upon the disease, the nature of the combined high-dose regimen, and the type of bone marrow transplant.

Adolescent↗
PubMed1996

Cancers in relatives of children with non-Hodgkin's lymphoma.

We undertook a family study of children treated at the Institute Gustave-Roussy in France to investigate a familial aggregation of cancer in the families of children with non-Hodgkin's lymphoma (NHL). We obtained family dat for 284 children with NHL. Using the Standardized Incidence Ratio, we compared the observed and expected number of families with at least one proband relative affected by cancer at a young age (before 46 years). We found a small but non-significant excess of all tumors in first-degree relatives (SIR = 1.3, 95% CI = 0.7-2.3) explained by a small but non-significant excess of hematological malignancies (SIR = 1.5, 95% CI = 0.2-5.5), particularly Hodgkin's disease and leukemia, and of osteosarcoma (SIR = 7.5, 95% CI = 0.1-41.4). This is probably a lower bound of the SIR, because the expected number of families was estimated from cancer incidence in France between 1978 and 1982, whereas most cancers occurred before this period. Other tumors were not in excess in first-degree relatives.

Adolescent↗
PubMed1996

[Adrenocortical carcinoma in children: retrospective study of 54 cases].

BACKGROUND: Adrenal tumors rarely occur in childhood. Their criteria for malignancy, as well as the effects of chemotherapy remain poorly defined. POPULATION: Fourty-five children (median age: 4 years) with an adrenal tumor diagnosed between 1973 and 1993 were included in this study. RESULTS: Seventy-six percent of the children showed various degrees of virilization. Tumor was palpable in 57%. Most patients (80%) had local disease, 7% loco-regional disease and 13% distant metastases. Forty-five children underwent an apparently complete surgical resection. Recurrence occurred 2 to 17 months after surgery in 18 of them (40%). Twenty-four children received medical treatment (o.p'-DDD or chemotherapy) and one-third had a tumoral response. The overall 5 year survival rate was 49%. CONCLUSIONS: Adrenocortical neoplasms have a poor prognosis in childhood. Complete resection is the only effective and potentially curative treatment. Currently no effective chemotherapy exists, and the value of adjuvant therapy remains unproven. Multicentric studies are underway to evaluate the efficacy of therapeutic approaches.

Adolescent↗
PubMed1995

Incidence of bone marrow involvement in Ewing's sarcoma: value of extensive investigation of the bone marrow.

PURPOSE: Bone marrow (BM) status is a critical matter when intensified chemotherapy with bone marrow rescue is proposed to improve the survival of patients with poor prognosis Ewing's sarcoma (ES): metastatic or relapsing disease. A systematic bone marrow investigation was performed in all the patients with newly diagnosed ES or relapsing ES to assess their BM status. PATIENTS AND METHODS: From January 1985 to February 1989, 59 untreated patients and five patients at the time of relapse had a bone marrow investigation under general anesthesia: two BM biopsies and two BM aspirates until May 1986, then two BM biopsies and 10 BM aspirates. The classical method of smearing each BM aspirate was compared to cytocentrifugation of the pool of BM samples after gradient density separation. RESULTS: The BM was involved in 13 of 59 untreated patients. BM was the single site of metastatic spread in only one patient but was involved in 52% of the patients with metastatic disease at other sites. This involvement was focal in several patients and frequent discrepancies were noted between the aspirates and biopsies at the various sites explored. The number of positive cases of BM involvement discovered by the two methods is somewhat limited. However preliminary results indicate a superior rate of positive smears with the pool technique which did however fail to detect involvement in some cases. CONCLUSIONS: The present study indicates that 1) BM involvement is a frequent event in metastatic ES (52%); 2) is often multifocal and therefore requires extensive BM investigation; and 3) further investigation of the pool technique to facilitate the BM screening is warranted.

Adolescent↗
PubMed1995

[End of treatment and "recovery"].

Complete recovery is now frequent in children with cancer. However, despite recovery, the disease and the treatment may induce, for many years, severe psychological impairments such as learning disabilities, emotional problems, abnormal behaviour, affective disorders, disturbances of social and familial relatedness. Study of the psychological processes accompanying, first the cancer and its treatment, then the time of recovery, help to define the interventions that will help the child to overcome his/her psychological difficulties without long-term secondary effects.

Child↗
PubMed1995

[Use of intravenous midazolam in status epilepticus in children].

BACKGROUND: Status epilepticus is usually treated by benzodiazepines such as diazepam or clonazepam in association with phenytoin and phenobarbital. Midazolam (MDZ) is a recently developed short-elimination half-life benzodiazepine. CASE REPORTS: Four children, aged 3 days to 4 years, were hospitalized in the pediatric intensive care unit for life-threatening illness and developed status epilepticus. They were given an i.v. bolus dose of 300 to 500 micrograms/kg of MDZ immediately followed by a continuous i.v. infusion at the dose of 100 to 300 micrograms/kg/h. All seizures stopped within 1 hour after the bolus dose administration. No acute adverse events of MDZ were noted. Withdrawal symptoms in one patient were controlled by progressive reduction of MDZ doses. Neurologic sequelae were noted in three children, secondary to their primitive illness. CONCLUSIONS: High doses of MDZ are effective for treating refractory status epilepticus; optimal dosage and duration of treatment remains to be determined.

Anti-Anxiety Agents↗
PubMed1995

[Pediatric aspects of anthracycline cardiotoxicity and practical implications for prevention].

Discovered during the sixties, anthracycline antibiotics are today widely used anti-cancer drugs. Their potentially fatal cardiac toxicity, which is related in part to the total cumulative dose, has been described since 1967. The aim of this paper is to describe their biological and clinical toxic effects on the heart, especially of children, and to propose prevention guidelines. The mechanisms of cardiac toxicity, with their destructive consequences on functional myocytes reserve, are shortly recalled. Acute, sub-acute and chronic clinical aspects of anthracycline's cardiomyopathy are the subject of a literature review. In Pediatric Oncology, the prolonged survival usually observed allows delayed congestive heart failure to occur by myocardial reserve insufficiency, as hemodynamic needs are quickly increasing, especially at the end of the somatic growth. Furthermore, the frequency of cardiac abnormalities is increasing with time after therapy, reaching about half of the explored patients after 15 years. The main known methods to prevent such a toxicity are reviewed. The parcimonious use of anthracyclines is already seen in children. Every method to decrease the maximal plasma concentration of the drug (weekly schedule or prolonged infusion) has to be considered. The active cardioprotectant agent such as ICRF-187, is in clinical development. Detection, prevention, and therapy of cardiac abnormalities, which are likely to precede delayed heart failure, still remains a difficult problem in these more and more numerous children to be cured of cancer.

Antibiotics, Antineoplastic↗
PubMed1995

Melanoma arising de novo in childhood: experience of the Gustave-Roussy Institute.

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case. The disease was localized for 10 patients at presentation (stage I), six had proven nodal metastasis (stage II) and one patient had nodal and breast metastases. The median thickness of the primary lesion was 2.89 mm (range 0.64-10). Five tumours were at level III on Clark's index, eight at level IV and four at level V. Six cases were classified as superficial spreading, two as unclassified radial growth, three nodular, three with Spitzoid cells, and three were unclassified. Two patients presented local recurrence with an initial unclassified melanoma, with a thickness greater than 2.5 mm. At a median follow-up time of 7 years, two patients had died from recurrent disease, and one patient had died from a second malignancy.

Adolescent↗
PubMed1995

[Male fertility after chemotherapy during childhood].

Chemotherapy has considerably improved the prognosis of solid tumours in children, but may have very adverse effects, particularly on fertility. A study was conducted at the Gustave Roussy Institute to identify the toxic effect of chemotherapy on male fertility. At present, 205 patients, treated during childhood have entered the study. Basal FSH-LH have been assayed to assess possible germ cell damage although azoosperia can not be eliminated. Results were normal in 127 patients (62%) and increased basal FSH levels were found in 78 (38%). Endocrine function was not altered: all patients were either impubertal or intrapubertal at diagnosis and subsequently achieved normal puberty. Multivariate analysis revealed an obvious toxic effect of 2 alkylating drugs: cyclophosphamide and procarbazine. No toxic effect was observed for vincristine, dohorubicin or actinomycin D. Age and pubertal status at diagnosis were not correlated with toxic effects. At present, no conclusion for other drugs may be made but results high dose metotrexate are promising. For lomustine and cisplatin, less favourable, though nonsignificant, results have been obtained. Complete recovery is possible several years later.

Adolescent↗
PubMed1994

Radiotherapy in the SIOP (International Society of Pediatric Oncology) nephroblastoma studies: a review.

For decades radiation has generally been accepted as a valuable supplement to surgery in the treatment of Wilms' tumor; unfortunately, it may produce undesirable late effects. It turned out, however, that when treatment is adjusted to known variables, the risk for late sequelae can be diminished in some groups of children. SIOP clinical trials have been based on children with unilateral tumors of standard histology and free of metastasis at diagnosis. The first two clinical trials, SIOP-1 (started in 1971) and SIOP-2 (started in 1974), established the beneficial effect (such as less ruptures, lower stage) of preoperative radiation and actinomycin D (AMD) in SIOP-2, with all children having radiation therapy either preoperatively, postoperatively, or both. In the SIOP-5 trial (started in 1977), preoperative radiation therapy and AMD were compared with preoperative chemotherapy resulting in only 50% of children having radiation. The result permitted disuse of preoperative radiation in the SIOP-6 trial (started in 1980), where only one-third of the patients received postoperative radiation therapy. At present, in the SIOP-9 trial (started in 1987), fewer than 20% of children are having radiotherapy. The survival rates meanwhile have been increasing steadily from 64% in SIOP-1 to 84% in SIOP-6 for stages I, II, and III combined.

Adolescent↗
PubMed1994

Pure dysgerminoma of the ovary in childhood: treatment results and sequelae.

Thirty-five children with pure dysgerminoma of the ovary were all treated at the Institut Gustave Roussy (IGR) from 1956-1985. The median follow-up is 8.5 years. The crude 5-year survival rate is 94.1% (+/- 4.1). The disease-free 5-year survival rate is 81.8% (+/- 6.7). Fourteen patients who had stage I disease were treated by unilateral salpingooophorectomy and prophylactic radiotherapy (20 Gy) to ipsilateral iliac, lumbar-aortic, and subclavicular lymph nodes. All are alive without sequelae. Eighteen patients with stage II and III disease were treated by surgery and radiotherapy (30-40 Gy) to the tumor volume. All are alive but radio-induced sequelae are severe. Five relapses of stage I, II, and III tumors occurred and were cured by a second line treatment. Two of the three patients with stage IV disease died. Four patients received a cisplatinum-containing regimen for disseminated disease or because of a relapse before radiotherapy. Three achieved a complete response of measurable tumor. Given the high efficacy of this kind of chemotherapy and the severe sequelae induced by abdomino-pelvic irradiation, we propose initial chemotherapy for widespread disease and radiotherapy in the event of residual tumor.

Adolescent↗
PubMed1994

Negative 123-meta-iodobenzyl-guanidine imaging in Ewing's sarcoma of bone.

The role of radiolabeled meta-iodobenzyl-guanidine (mIBG) is established in the detection and the staging of neuroblastoma. We designed a study of mIBG scanning for patients with Ewing's sarcoma, a tumor for which a neuroectodermic origin has been proposed. We explored 15 children with round cell sarcoma of bone by a whole body scan carried out 24 hours after injection of 123-I mIBG. No patient demonstrated significant uptake either at the site of the primary or at the sites of metastases. These results suggest that despite its neural histogenesis Ewing's sarcoma is a member of the nonneuroblastoma neural crest tumors, which does not produce or store adrenergic metabolites.

3-Iodobenzylguanidine↗
PubMed1994

Safety, tolerability, efficacy and plasma concentrations of tropisetron after administration at five dose levels to children receiving cancer chemotherapy.

In a double-blind, placebo-controlled, escalating dose study, 44 children receiving cancer chemotherapy of various degrees of emetogenicity were randomly allocated to once-daily treatment with tropisetron 0.05 mg/kg (6 patients), 0.10 mg/kg (5 patients), 0.20 mg/kg (6 patients), 0.33 mg/kg (6 patients), 0.50 mg/kg (6 patients) or placebo (15 patients). All doses of tropisetron were well tolerated; no tropisetron recipient discontinued treatment because of intolerance and no adverse effect could be plausibly correlated to tropisetron administration. Therapeutic plasma concentrations of tropisetron (> 3 ng/ml) were present for 9 h after administration of doses of 0.10 mg/kg or more. Tropisetron at doses of at least 0.20 mg/kg was significantly more effective in preventing vomiting than lower tropisetron doses or placebo, both in terms of treatment failure (> four vomits) (P = 0.015) and patient and investigator efficacy ratings (P = 0.04 for investigator rating; P = 0.035 for patient rating). Further comparative studies of the efficacy of tropisetron in chemotherapy-induced emesis in children are warranted.

Adolescent↗
PubMed1994

The French Wilms' tumour study: no clear evidence for cancer prone families.

Wilms' tumour of the kidney is known to occur in Beckwith-Wiedemann syndrome. It has also been described in four cancer prone families displaying Li-Fraumeni syndrome but it is not usually considered to be part of this syndrome. In order to detect particular familial cancer aggregations associated with this tumour, we studied the cancer incidence and mortality among relatives of the 501 Wilms' tumour patients in the French Wilms' Tumour Study. We found no familial association with breast cancer or soft tissue sarcomas which are the most common cancers in the Li-Fraumeni syndrome. However, we found two significant familial associations of Wilms' tumour with bone cancers on the one hand and with brain tumours on the other hand. These associations could reflect a small proportion of families segregating for some susceptibility gene. This should then be confirmed at the molecular level.

Adolescent↗
PubMed1994

Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy.

PURPOSE AND METHODS: Between January 1981 and June 1993, 137 children and adolescents were each treated at the Institut Gustave Roussy for an initially nonmetastatic osteosarcoma of the extremities. We report the retrospective analysis of 42 cases of recurrence that occurred in this population. RESULTS: The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 21 months (range, 5 to 60). The site of the first recurrence was limited to the lung in 20 patients, the bone in seven patients, was local in six patients, and was confined to soft tissue in one patient. In eight patients, the first recurrence affected multiple sites. Subsequent recurrences often involved unusual or multiple sites. Management of recurrences included surgery and/or various regimens of second-line chemotherapy, and in one case involved high-dose chemotherapy followed by autologous bone marrow transplantation. Overall survival and event-free survival were, respectively, 36% and 27% at 36 months. At present, 13 patients are alive without evidence of disease. Response of the primary tumor to preoperative chemotherapy, the time between the diagnosis and the first recurrence, and the number of metastatic lesions did not correlate with survival. The survival rate is better in patients with a local or a pulmonary first recurrence. CONCLUSION: The most important prognostic indicator at first recurrence seems to be the possible complete resection of disease. Patients not amenable to surgery and patients with a second or a third recurrence have a poor prognosis. The potential benefit of more aggressive treatments such as high-dose chemotherapy and autologous bone marrow transplantation should be investigated for these patients.

Adolescent↗
PubMed1994

Prognostic value of MDR1 gene expression in neuroblastoma: results of a multivariate analysis.

The prognostic value of the MDR1 gene expression in neuroblastoma (NB) was assessed in a multivariate analysis performed in a series of 84 patients (pts) taking into account the main known clinical and biological factors of the disease, i.e., age, stage, MYCN genomic content and DNA ploidy index. Twenty seven children were < 1 year (yr), 13 presented with stage I and II, 7 with stage IV-S, 17 with stage III and 47 (56%) with stage IV. Tumor specimens were obtained from involved bone marrow (n = 12) or surgical primary tumor specimens (n = 72). MDR1 gene expression was measured by Northern hybridization technique and expressed in arbitrary units (a. u.) (Goldstein et al., 1989). Analysis of MYCN genomic content and DNA ploidy index were performed by Southern blot hybridization technique and flow cytometry, respectively. Out of 84 tumor specimens 19 (23%) showed MYCN amplification (> 3 copies/haploid genome). In 24 cases (29%) no detectable MDR1 gene transcript was found (0 a.u.) whereas 42 (50%) had a value in the range 1-30 a.u., and 18 (21%) a value beyond 30 a.u.. High transcript levels were found in localized as well as in metastatic NB (NS). No significant correlation between MDR1 gene expression, age, stage, or MYCN genomic content was found In univariate analysis stage IV, age > 1 yr, MYCN amplification, diploid DNA content and high MDR1 gene transcript levels were significantly related to an increased risk of death. In multivariate analysis only stage IV, MYCN amplification and MDR1 overexpression remained significantly associated with an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗