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D Frappaz

Publications and source records attributed to D Frappaz.

At least 73 records · Page 4Linked to original sources
PubMed1997

N-Myc gene amplification is a major prognostic factor in localized neuroblastoma: results of the French NBL 90 study. Neuroblastoma Study Group of the Société Francaise d'Oncologie Pédiatrique.

PURPOSE: To assess the relevance of N-Myc gene amplification (NMA) as a prognostic factor in localized neuroblastoma (NB) and to evaluate whether less intensive adjuvant treatment is advisable in infants without NMA. PATIENTS AND METHODS: Assessment of NBs included clinical and imaging data to allow tumor-node-metastasis (TNM) staging, biologic determinations (N-Myc gene analysis), and standard histology and work-up to eliminate metastatic spread (metaiodobenzylguanidine [MIBG] scintigraphy and extensive bone marrow staging). Resectability was defined according to imaging findings. Chemotherapy was indicated in children older than 1 year at diagnosis who had postoperative residual disease or lymph node (LN) involvement, in infants with NMA, or as primary treatment in children with an unresectable NB, including dumbbell tumors. Radiotherapy was recommended in children older than 1 who presented with persistent gross residual disease at the end of therapy. RESULTS: Between 1990 and 1994, 316 consecutive children who presented with a localized NB were registered in the NBL 90 study. The median age was 12 months, and 42 patients had dumbbell tumors (13%). NMA was found in 22 of 225 assessable children (10%) and correlated with adverse prognostic indicators such as age older than 1 year, an abdominal primary tumor, a large tumor (T3), and unresectability. Among 186 children who had primary excision, five died of surgery-related complications. Primary chemotherapy was given to 130 patients, which allowed removal of the tumor in all but four. The 5-year overall survival (OS) and event-free survival (EFS) rates were, respectively, 91% and 84% with a median follow-up time of 36 months. The outcome of infants and older children was similar (P = .2). EFS of patients with resectable tumors was slightly better than with unresectable primary tumors (EFS, 89% v 78%; P = .02). In dumbbell NBs, neurologic recovery was achieved in 74% of cases that presented with symptoms, and initial laminectomy was avoided in 75% of children. In a univariate analysis, large tumors, high neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, positive LNs, macroscopic residue, and NMA adversely influenced outcome. In the multivariate analysis, NMA was the most powerful unfavorable predictive indicator: OS and EFS rates for these children were 36% and 32%, compared with 98% and 90% in nonamplified tumors (P < .001). CONCLUSION: Our data confirm the overall good prognosis of localized NBs, even when unresectable. NMA is the most relevant adverse prognostic factor in localized NBs, and more intensive treatment should be investigated in these patients. Prospective studies of other biologic factors are warranted to tailor therapy more accurately. The EFS of children who underwent primary surgery was excellent, and further justifies elimination of adjuvant treatment provided they have no NMA. Despite the elimination of postoperative therapy, infants with non-NMA tumors have an excellent outcome, which suggests that initial chemotherapy can be further reduced in case of unresectable NBs.

Adolescent↗
PubMed1997

[Cutaneous Kaposi disease disclosing acquired immunodeficiency syndrome in a child].

INTRODUCTION: Kaposi's sarcoma associated with acquired immunodeficiency syndrome is uncommon in children and cutaneous localizations are rare. We report a case of pediatric cutaneous Kaposi's sarcoma that revealed a human immunodeficiency virus infection. OBSERVATION: An 8-years-old girl native of the Ivory Coast, with normal statural and psychomotor development, presented cutaneous Kaposi's sarcoma after varicella. The serodiagnosis was positive for type 1 human immunodeficiency virus and CD4 lymphocytes count was 9/mm3. A tonsil localization of Kaposi's sarcoma occurred and bleomycin was a short time effective. A relapse of cutaneous Kaposi's sarcoma with digestive, pulmonary and neurological symptoms was transitorily controlled by the association prednisone-vinblastine-doxorubicin, but death occurred with recurrence of pharyngeal Kaposi's sarcoma. DISCUSSION: The review of literature shows that in pediatric acquired immunodeficiency syndrome, failure to thrive, encephalopathy and opportunistic infections are common. On the other hand, Kaposi's sarcoma is unusual and cutaneous localizations are especially observed when the contamination is postnatal and late. In our case the contamination is presumed perinatal and the human immunodeficiency virus infection was asymptomatic until 8 years old. Kaposi's sarcoma was the cause of the most presenting symptoms and of death, without demonstrated opportunistic infections.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A 5-year (1990-1994) neuroblastoma screening feasibility study in France. Methodology and preliminary observations.

INTRODUCTION: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990-1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26,000 births per year). METHODS: Vanillylmandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffé's kinetic method on Technicon RA-XT. VMA and HVA were expressed as microgram/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. RESULTS AND DISCUSSION: The overall participation rate for the 5-year period was 82.2%. Out of 105,293 infants tested from 128,126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty-five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastomas as it is presently being followed up.

Chromatography, High Pressure Liquid↗
PubMed1996

The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients--results of the NBL 90 Study of the French Society of Pediatric Oncology.

BACKGROUND: Neuroblastoma is the most common malignant cause of spinal compression in the pediatric population. More than 30% of patients who are impaired prior to treatment remain impaired after the completion of therapy. Those who do not improve after decompressive laminectomy may go on to develop severe delayed spinal deformities. METHODS: To decrease the long term sequelae of routine neurosurgical intervention for all intraspinal extensions of neuroblastoma, the French NBL 90 Study was formulated to use chemotherapy as a first-line treatment for all nonmetastatic neuroblastomas with intraspinal extension. Neurosurgical decompression and excision was recommended only for patients demonstrating rapid neurologic deterioration. RESULTS: The overall survival of the 42 patients registered was 97%. Initial neurologic impairment was present in 27 patients (64%), including 11 with paraplegia. Thirty-two patients received chemotherapy as first-line treatment. Complete regression of the intraspinal component was observed in 13 patients and partial regression of greater than 50% of the initial volume in 5 patients. Of 19 evaluable patients presenting with a neurologic deficit and treated with primary chemotherapy, recovery was completed in 11 and partial in 3. Four patients failed to recover from long-standing pretreatment paraplegia. Only one patient worsened during therapy, and recovered completely after emergent neurosurgical intervention. Seven patients underwent initial neurosurgical procedures; six had a neurologic deficit and five recovered completely, including all three who presented with acute onset of paraplegia. Three patients had extraspinal surgery as exclusive treatment. Six patients (15%) suffered severe neurologic sequelae. Only one of the patients who underwent surgery required spinal stabilization for progressive deformity, but follow-up is limited. CONCLUSIONS: By treating patients with dumbbell neuroblastoma initially with chemotherapy, the authors were able to reduce the size of the intraspinal mass in 58% of patients, improve partial neurologic deficits in 92%, and avoid neurosurgical decompression in 60%. Neurologic deficits also improved in 83% of patients requiring emergent neurosurgical intervention.

Adolescent↗
PubMed1996

[Prolonged remission in a child with late brain metastasis of retinoblastoma].

BACKGROUND: Outcome of patients with retinoblastoma is strongly related to the extent of the disease at diagnosis. Thus, prognosis of extra-ocular retinoblastoma is poor and metastases to central nervous system are usually fatal. CASE REPORT: An 8-year-old child presented with a late recurrence of bilateral retinoblastoma. Initial treatment had associated enuclation of the left eye and radiation therapy on the right. At time of tumour recurrence, clinical examination showed cervical lymph nodes. There was a large frontal metastasis on the CT scan and bone marrow examination showed a minimal involvement by malignant cells. The patient achieved complete remission with high dose etoposide and carboplatin; he subsequently underwent massive chemotherapy followed by bone marrow rescue, and received additional radiation therapy on the frontal and cervical areas. He is well, five years after relapse. CONCLUSIONS: This case highlights efficacy of chemotherapy in advanced retinoblastomas. Intensive chemotherapy is a promising and potentially curative approach in the management of advanced or metastatic retinoblastomas.

Brain Neoplasms↗
PubMed1996

[Wilms tumor and Bloom syndrome].

UNLABELLED: Bloom syndrome is characterized by growth failure, skin anomalies with sun sensitivity, minor anatomic defects, excessive chromosomic fragility and usually severe immune deficiency. The chromosome fragility predisposes these children to the development of hematologic malignancies and solid tumors. CASE REPORT: Morgan, a 4-year-old boy with Bloom syndrome, developed a Wilms tumor. Chemotherapy was poorly tolerated. Two years later, the child died from an uncontrolled progressive disease. CONCLUSION: This is the fourth reported case of Wilms tumor occurring in a child with Bloom syndrome. This possibility requires repeated abdominal ultrasonography in such patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[School at the end of life. What objectives what hope?].

BACKGROUND: School intervention programs for children and adolescents with cancer have been developed in France during the last years. Their primary objective is to improve the pschychosocial adaptation of these children to normal life through school integration. These programs are however inadequate for these children who will ultimately die from their disease and may require a specific school intervention. MATERIAL AND METHODS: School data from 30 children requiring palliative care were prospectively collected. School interest, its evolution and specific adaptations according to the child's status were analysed. RESULTS: Sixty per cent of the children showed a continuous desire for school education throughout their life's end. Reading, mathematics and computer work were the most favorite topics. Physical disability and fatigue may change their request during the evolution of the disease. School refusal occurred in 40% of the children and is mainly due to other extra-academic topics, or related to uncontrolled pain. CONCLUSION: Objectives of life's end school are different from educational programs proposed for children with cancer. They must be part of palliative care and have to be defined as a specific entity.

Adolescent↗
PubMed1996

Management of paediatric lymphoma.

The high cure rate obtained in most paediatric lymphomas allows an optimistic vision of future treatments, with decreased primary late effects observed in patients who have completed therapy: decreased cognitive functional impairment, reproductive dysfunction, poor social adaptation, and risk of second malignancies. The deleterious effects of radiation therapy on neurocognitive functions is now well documented (Meadows et al, 1981) but, apart from rare acute toxicities (Sasazaki et al, 1992), reports on those following high-dose methotrexate are scarce, and sometimes discordant (Jannoun and Chessels, 1987; Robertson et al, 1992). Longer follow-up evaluation is warranted before definitive conclusions concerning the relationship between computed tomography scan findings and clinical outcome can be reached. The reproductive function of males is much more severely altered than that of females (Jaffe et al, 1988). Several reports have demonstrated the major dose-dependent toxicity of alkylating agents on male fertility. Male patients receiving more than 9 g/m2 of cyclophosphamide have a particularly high risk of sterility (Aubier et al, 1989) and children with less than 4 g/m2 of cyclophosphamide, a very low risk Patte et al, 1996a). Women treated before the age of 20 who do not receive abdominal irradiation usually have normal reproductive function, although early puberty (Quigley et al, 1989) and early menopause (Byrne et al, 1992) have been documented. The risk of a second malignancy is not as great as in children with a solid tumour or Hodgkin's disease (Anderson et al, 1993). The risk is higher in patients treated with alkylating agents (Lemerle et al, 1989). With the increasing cure rate, a social problem may arise for adults who "have had cancer'. The increased awareness by politicians and health insurance companies should help to solve, at least partially, this new problem (Monaco, 1987). As cure rates increase, emerging concerns involve the familial repercussions of this heavy treatment (Lansky et al, 1978; Cairns et al, 1979). At this stage, there is no demonstrated deleterious effect from treatment for the progeny of cured children (Mulvihill et al, 1987; Stein, 1993). Cure of children with lymphoma is a reality, and one should think in terms of "complete cure' when facing a distressed child with a heavy tumour burden arriving for diagnosis (Schweisguth, 1979). Since 1980, the progress of molecular biology techniques has permitted the precise molecular characterization of gene alterations (oncogenes, immunoglobulins, and T-cell receptor genes) involved in the process of malignant transformation of normal lymphocytes (Bhatia et al, 1996; Williams et al, 1996). In parallel, treatment of malignant NHL of childhood has improved dramatically. The progress in molecular biology has not led to a modification of the clinical management of NHL of childhood which remains mainly empirical. Precise cytohistological classification of lymphomas has resulted in the characterization of low- and high-risk patients requiring distinct therapeutic approaches. The major goals of the next few years will be to increase the cure rates of those patients with CNS and bone marrow involvement at diagnosis, probably through an intensification of chemotherapy (increase in the dose or intensity of the chemotherapy); to define precisely subgroups of good-prognosis patients requiring less aggressive treatment that would decrease the risk of long-term events; and to salvage previously heavily treated patients at relapse. The precise analysis of gene alterations in lymphoma cells of a given patient may have important clinical applications in this respect (Bhatia et al, 1996).

Adolescent↗
PubMed1996

Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma. Proposal for a common methodology of analysis. SENSE group.

BACKGROUND: The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases. AIM OF THE REVIEW: To confirm one or the other hypothesis, and eventually identify biological factors possibly responsible for the initiation and progression of the disease, it is of utmost importance that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to both methodological reliability and feasibility, and the conditions of tissue storage for further analysis of these biological markers. CONCLUSION: The standardized biological evaluation of neuroblastoma will allow to collect sufficient data for multivariate analysis; such analysis is now fundamental if one wants to clearly define the respective impacts of biological abnormalities on neuroblastoma progression.

Biomarkers, Tumor↗
PubMed1996

Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas.

PURPOSE: In contrast to other human tumors, a repression of the cell-surface glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually correlates to N-myc amplification. We thus compared the prognostic value of both markers in the initial staging of 121 children treated for neuroblastoma in collaborative institutions. METHODS: Frozen samples were analyzed by a rapid and well-standardized technique of immunostaining with monoclonal antibodies (MoAbs) against epitopes in the CD44 constant region. RESULTS: In this retrospective series, CD44 was expressed on 102 specimens and strongly correlated with favorable tumor stages and histology, younger age, and normal N-myc copy numbers. In univariate analysis, CD44 expression and normal N-myc were the most powerful markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(-6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant prognostic discrimination in subgroups of patients with or without N-myc-amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was not discriminant. In multivariate analysis of five factors, ie, N-myc amplification, CD44 expression, age, tumor stage, and histology, the only independent prognostic factors of event-free survival were CD44 expression and tumor stage. CONCLUSION: The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.

Antibodies, Monoclonal↗
PubMed1996

[Unusual relapse for neuroblastoma. Case of an intracranial relapse].

The usual sites of initial metastatic deposits in neuroblastoma are osteo-medullary. With modern therapies including megatherapy and hematopoietic rescue, prolonged survival is obtained. However, unusual metastatic sites are more and more often described during the prolonged evolution of these patients such as brain metastases. A case of isolated intracerebral metastatic relapse is reported here in a patient who had received 4 months before a megatherapy in first complete remission. Pathogeny and therapeutical implications are discussed.

Adrenal Gland Neoplasms↗
PubMed1995

Allogeneic bone marrow transplantation for lysosomal storage diseases. The European Group for Bone Marrow Transplantation.

Patients with lysosomal storage disorders have visceral, skeletal, and neurological abnormalities and a limited life expectancy. Bone marrow transplantation has been used to correct the metabolic defects and leads to metabolic improvements in most patients. However, the long-term effect of such therapy is uncertain. We analysed the data from 63 patients transplanted for lysosomal storage diseases. The transplant-related mortality was 10% if an HLA-identical sibling marrow donor was available (n = 40) and 20-25% if mismatched tissue was used. Data on the effect of bone marrow transplantation on biochemical and clinical disease variables were available in 29 of the 63. 28 had a follow-up duration of 1.0-10.2 years; 1 patient died of disease progression in the first year after stable engraftment. 13 patients who had severe neurological symptoms at the time of transplantation showed disease progression. Engraftment of bone marrow in 5 patients with non-neuronopathic Gaucher's disease led to complete disappearance of symptoms. 11 patients had skeletal symptoms because of various mucopolysaccharidoses (MPSs). There was stabilisation of the skeletal lesions during the observation period of 1.4-6.4 years, but none of the patients showed significant regression of the skeletal symptoms. The visceral features (hepatosplenomegaly, cardiac hypertrophy, and upper airway obstruction) in these patients abated after transplantation. We could not evaluate the biochemical and clinical variables in 34 patients because of graft rejection, transplant-related mortality, or follow-up of less than 1 year. There were significant beneficial effects of bone marrow transplantation in patients with non-neuronopathic Gaucher's disease. Stabilisation of disease was observed in patients with MPS-I and MPS-II; this potential benefit needs to be confirmed by longer follow-up. Bone marrow transplantation was not effective if severe neurological symptoms were already present at the time of transplantation.

Adolescent↗
PubMed1995

Sensitive detection of numerical and structural aberrations of chromosome 1 in neuroblastoma by interphase fluorescence in situ hybridization. Comparison with restriction fragment length polymorphism and conventional cytogenetic analyses.

Chromosome I abnormalities are indicators of prognosis in neuroblastoma (NB) but are not yet routinely exploited because conventional methods are technically demanding. We evaluated the pertinence of interphase cytogenetics fluorescence in situ hybridization (FISH) for the analysis of chromosome I in NB, compared with conventional methods. Deletion of Ip was detected in 8 of 9 cell lines analyzed by both FISH and restriction fragment length polymorphism (RFLP), but was evidenced in only 2 cases by conventional cytogenetics, painting analysis being required to reveal the other cases. The chromosome I number evaluated by FISH reflected the total chromosome modal number obtained by cytogenetics. Twenty-eight specimens obtained from ultrasound-guided punctures, surgical biopsies of the primary tumor and bone-marrow aspirates were studied by FISH on frozen cytocentrifuged smears; 12 had a chromosome I trisomy and 16 a disomy. Requirements for a reliable control analysis of Ip deletion by RFLP were met in only 23 cases. The retention of 2 alleles was observed in 15 cases and Ip deletion in 7, by both techniques. In one case, an interstitial deletion of Ip was evidenced only by RFLP, and one of 5 cases analyzed only by FISH had a Ip deletion. Although FISH might be improved by using additional probes, it presents major advantages for routine exploitation. Determining Ip deletion in individual cells makes it possible to analyze small and heterogeneous tumoral specimens; the technique requires only a few hours and can easily be standardized in non-specialized laboratories. The number of chromosome I homologues per cell might serve as a rapid screening for ploidy.

Biopsy↗
PubMed1995

[Follow-up of allogenic bone marrow graft with DNA polymorphisms. Use of two minisatellite MS31 and MS43 probes. Comparison with data of chromosomal polymorphisms].

OBJECTIVES: Allogenic bone marrow transplantation is widely used to treat many diseases of the haemopoietic system as well as metabolic disorders. Follow-up is essential to assess acceptance, rejection or post-graft relapse. This study was undertaken to evaluate the usefulness of the minisatellite probes MS31 and MS43 used as a routine follow-up test after bone marrow transplantation. METHODS: Twenty receivers of allogenic bone marrow transplants were followed-up. Two monoclonal minisatellite probes, MS31 and MS43, were used for comparison with the classical polymorphism methods. RESULTS: Fourteen cases of total chimeras, 3 cases of rejections and 3 cases of mixed chimeras were observed with the molecular probe techniques. In 19 of the 20 cases, this technique gave results compatible with classical polymorphism results. CONCLUSIONS: The minisatellite probes MS31 and MS43 were found to be sensitive, effective tests for bone marrow transplants which can be used in routine follow-up.

Adolescent↗
PubMed1995

Evaluation of CD44 prognostic value in neuroblastoma: comparison with the other prognostic factors.

CD44 gene products are potential markers of aggressiveness in different tumour models, a result which prompted us to study clinical neuroblastoma (NB) specimens. CD44 expression was determined by immunostaining of 52 tumour samples from newly diagnosed NB with a monoclonal antibody (J173) directed against an epitope common to all CD44 isoforms. CD44 immunoreactivity was detected in 37 of the tumours (71%). CD44 was expressed in all 22 NBs with favourable prognoses (stages 1, 2 or 4S), but only 50% (15/30) of advanced NB (stages 3 and 4) (P < 10(-4)), suggesting that the absence, rather than the overexpression, of CD44 is a signal of tumour aggressiveness. The cumulative progression-free survival was significantly longer in patients with CD44 positive tumours compared with patients with CD44 negative tumours (P < 10(-5)). More importantly, progression-free survival was also significantly higher in CD44 positive patients within the high-risk group (P < 0.01). In univariate analysis, we tested the prognostic value of tumour expression of CD44 in comparison with tumour stage, age, tumour histology, and presence or absence of amplification of the MYCN protooncogene. All five measures had significant prognostic value. The expression of CD44 and the absence of MYCN amplification were the most powerful predictors of a favourable outcome. In a multivariate analysis of these measures, CD44 expression and tumour stage were the only independent prognostic factors for the prediction of patient survival. NB is the first clinical model described in which tumour aggressiveness correlates with repression rather than stimulation of CD44 expression. We recommend the use of CD44 as an additional biological marker in the initial staging of NB.

Adolescent↗
PubMed1995

Is neuroblastoma screening evaluation needed and feasible?

Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity.

Age Factors↗