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Biomedical subjects

O Hartmann

Publications and source records attributed to O Hartmann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas.

BACKGROUND: The role of high dose chemotherapy (HDC) in patients with pediatric brain tumors currently is ill-defined. The purpose of this pilot study was to assess the feasibility and the benefit of HDC after radiotherapy in a group of children with newly diagnosed diffuse pontine gliomas. METHODS: Patients eligible for study were ages 3-18 years with diffuse intrinsic tumors arising in the pons, who were not treated previously with radiotherapy or chemotherapy. Histologic confirmation was not mandatory, provided clinical findings and magnetic resonance imaging were typical. Patients were given focal radiotherapy followed 2-3 months later by HDC. Busulfan (150 mg/m(2) on Days 8, 7, 6, and 5) and thiotepa (300 mg/m(2) on Days 4, 3, and 2) were administered prior to autologous bone marrow transplantation. Survival was the endpoint, and the statistical procedure was based on sequential subgroup analysis. RESULTS: Thirty-six patients were entered on to the study, 12 of whom underwent stereotactic biopsy or open surgery at the time of diagnosis. One patient eventually was excluded due to inappropriate eligibility criteria. All 35 eligible patients received irradiation. Early progression (9 patients) and parental refusal (2 patients) precluded the use of HDC in 11 patients. Three patients died of HDC-related complications. All 21 patients who survived HDC eventually died of disease progression. The median survival time was 10 months for the study group. The median survival time in the subgroup of patients who received HDC was 10 months (range, 3-26 months). Statistical analysis did not suggest any evidence of survival benefit. CONCLUSIONS: For patients with diffuse pontine gliomas, survival using this aggressive treatment modality does not appear to be any better than that reported for conventional radiotherapy.

Adolescent↗
PubMed2000

[Parents' opinions of pediatric oncology day hospitals].

AIM: The aim of this study was to assess parental opinions on the advantages and disadvantages of a pediatric oncology day hospital (DH) so that the structure can be better adapted to the children's needs and parents' expectations, and provide a potentially valid alternative to conventional hospitalization (CH). METHODS: Over a 15-days period, 39 parents of children treated at a DH were approached and asked to fill in a questionnaire on their opinion of the advantages and disadvantages of a DH compared to a CH. RESULTS: The results of this survey were significant. The majority of parents preferred the DH to the CH (69% versus 15%). The illness was perceived as being less severe; and as the child was not continually in the CH context, he/she was able to forget the illness and the hospital to some extent, and was therefore not as anxious. The DH appeared to be better adapted to the child's needs and facilitated the pursuit of normal family life and everyday activities, but imposed constraints on social and professional activities. On the other hand, the CH provided a reassuring treatment context including more comprehensive information, and in particular a better integration of the child and careful monitoring of the disease within the oncology department, and closer relations between the different parents visiting the hospital. In spite of the high preference rate for the DH, in some instances certain disadvantages could outweigh the advantages, e.g., fatigue due to journeys to and from the hospital, or living too far away from the DH; a lack of punctuality, which meant that the parents were unable to plan their day with any certainty; insufficient comfort (noise, a limited number of rooms available); inadequate information; a lack of privacy; and the anxiety connected with having to assume too much responsibility. CONCLUSION: Overall, it was concluded that the parents appeared to appreciate the aims of the DH (i.e., limiting the treatment constraints imposed on the patient and on the parents themselves, thereby maintaining the quality of family life, assuring adequate treatment, reducing cost of treatment). However, the authors consider that the DH has to be organized in such a way that it takes into account the following: the social aspects, i.e., living conditions, parents' social, economic and professional status; parents' and children's psychological traits, expectations; and access to a local care system. The DH should also have sufficient means and staff at its disposal. Without taking these factors into consideration, the DH and other alternatives to the CH will not be able to adequately care for the patients, or meet the parents' expectations, and may even have a negative effect on the family.

Adult↗
PubMed2000

[What is new in pediatric oncology?].

The significant progress made in pediatric oncology during recent years has been due to a major breakthrough in the field of molecular biology and the introduction of new therapeutic strategies that take into account both the quality and the duration of life. Molecular biology has already been instrumental in more fully categorizing the 'small round-cell tumor' group, and in reclassifying the 'Ewing family' tumors. It also provides a valuable tool for the prognostic evaluation of neuroblastomas through the analysis of the N-myc oncogene. In addition, it has permitted the identification of the Li-Fraumeni syndrome of predisposition to cancer in the child, thereby raising the problematical ethical issue of communicating relevant information to subjects at risk. Two examples illustrate innovative strategic concepts: 1) Burkitt's lymphoma, or an example of the successful de-intensification of treatment; and 2) brain tumors in young children, regarding which the desire to improve the quality of life has led to innovative attempts to replace radiotherapy by chemotherapy. Considerable progress has been made in the field of neuropsychology, thereby permitting an improved assessment of disorders and a better management of rehabilitation programs. New anti-cancer agents and also chemo- and radiotherapy that spare healthy tissue are also being developed. Gene therapy and molecular biology will play a major role in future therapeutic strategies; and are now at the preclinical trial stage. This significant overall progress leads to a reconsideration of the organizational approach toward treatment of the pediatric patient population suffering from cancer, and a critical assessment of disease management, which should take into account not only the technical aspects of the disease but also familial and social considerations.

Brain Neoplasms↗
PubMed2000

[Ultimate pre-transfusion control: evaluation of seven appliances].

The transfusion unit of the Institut Gustave Roussy has tested seven pre-transfusion ABO control devices registered at the Agence française de sécurité sanitaire et des produits de santé. Determination of the optimal plan to replace the existing plan in our institution was the primary objective of this study. A significant heterogeneity was observed among tested devices. None of the tested plans fulfilled all the desired quality criteria.

ABO Blood-Group System↗
PubMed2000

Relapses of childhood anaplastic large-cell lymphoma: treatment results in a series of 41 children--a report from the French Society of Pediatric Oncology.

PURPOSE: To study response to chemotherapy and the outcome of children treated for a relapsed anaplastic large-cell lymphoma (ALCL) and to evaluate the role of bone marrow transplantation (BMT) in these patients. PATIENTS AND METHODS: Clinical data concerning the 41 relapses that occurred in 119 patients with ALCL enrolled in 3 consecutive studies since 1975 were analysed. First-line treatment consisted of intensive chemotherapy according to the COPAD protocol for the first series of 12 patients treated between 1975 and 1989 and to the SFOP (French Society of Pediatric Oncology) HM protocols for the 30 patients treated between 1989 and 1997. Twenty-eight patients were treated with CV(B)A (CCNU, vinblastine, ara-C with or without bleomycin), and the others with miscellaneous protocols for recurrent disease. Fifteen patients underwent autologous BMT and 1 allogeneic BMT while in CR2. RESULTS: Thirty-six of forty-one (88%) patients achieved CR2. With a median follow-up of 5 years, 12 patients died, 9 of their disease and 29 patients are alive in CR2 (20 patients), CR3 (5 patients), CR4 (2 patients), CR5 (1 patient) or CR6 (1 patient). Overall and disease-free survival are respectively 69% (53%-82%) and 44% (29%-61%) at three years. In univariate analysis, patients treated with ABMT while in CR2 did not appear to have a better outcome than the other. Remarkably, a long-lasting remission was obtained in 8 of 13 patients treated with weekly vinblastine for a relapse including 6 relapses occurring after ABMT. CONCLUSIONS: Relapsed ALCL are highly chemosensitive but over 40% of the patients experience several relapses. Prolonged conventional chemotherapy based on vinblastine might, in some cases, be as efficient as short intensive treatment with ABMT.

Adolescent↗
PubMed2000

Consolidation with a busulfan-containing regimen followed by stem cell transplantation in infants with poor prognosis stage 4 neuroblastoma.

Although infants with stage 4 neuroblastoma (NB) usually have a good prognosis, metastatic relapses after 1 year of age and amplification of the N-myc oncogene are established poor prognostic factors. In order to improve the survival of patients with such high-risk factors, we performed consolidation with a busulfan (600 mg/m2)-melphalan (140 mg/m2)-containing regimen followed by autologous stem cell transplantation (SCT). From 1986 to 1998, 12 patients were treated according to this strategy. Their median age at diagnosis was 9 months (1-11). Consolidation was performed after a metastatic relapse in five children, because of persistent bone metastases in one and as first-line consolidation in six patients whose tumor exhibited N-myc amplification. The 5-year EFS rate is 64. 5% (36-85%) with a median follow-up of 92 months (20-126). One toxicity-related death occurred in a very heavily pretreated patient. Hepatic veno-occlusive disease was the major side-effect that occurred in nine of 12 children. This busulfan-melphalan combination appears to dramatically improve the prognosis of these high-risk infants with metastatic NB. Given its high toxicity, indications for this consolidation must be restricted to high-risk infants and a lower dose of busulfan (480 mg/m2) is recommended in children weighing less than 10 kg. Bone Marrow Transplantation (2000) 25, 937-942.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Psychotherapeutic practice in paediatric oncology: four examples.

Psychotherapy, often used with children treated for a solid tumour, is seldom described. We present four examples of such therapies: a mother who refused enucleation for her 7-month-old boy; a boy's jealousy towards his sister who was being treated for a brain tumour; a teenager troubled by his scar; a 7-year-old boy embarrassed by the unconscious memory of his treatment when he was 5 months old. All names have been changed, for reasons of privacy. Psychotherapies aim to help children and parents to cope with the violent experience of having cancer, to recover their freedom of thought and decision-making concerning their life, their place in the family, their body image, their self-esteem, their identity. These descriptions of brief psychotherapy could help paediatricians to gain a more thorough understanding of the child's experience, to improve collaboration with psychotherapists and to confront clinical skills of psychotherapists.

Adaptation, Psychological↗
PubMed2000

Adverse outcome of infants with metastatic neuroblastoma, MYCN amplification and/or bone lesions: results of the French society of pediatric oncology.

To assess the relevance of MYCN amplification and bone lesions in stage 4 neuroblastoma (NB) in infants aged <1 year, 51 infants with stage 4 NB were enrolled. Three groups of patients were defined according to the type of metastases and the resectability of the primary tumour. Group I comprised 21 infants with radiologically detectable bone lesions, Group II 22 patients with an unresectable primary tumour and Group III eight patients with only metaiodobenzylguanidine (MIBG) skeletal uptake. MYCN oncogene content was assayed in 47/51 tumours and found to be amplified in 17 (37%). The 5-year event-free survival (EFS) rate of these 51 infants was 64.1% (+/- 7.1%). In a univariate analysis, bone lesions, MYCN amplification, urinary vanillylmandelic/homovanillic acid ratio and serum ferritin levels adversely influenced outcome. In the multivariate analysis, radiologically detectable bone lesions were the most powerful unfavourable prognostic indicator: the EFS rate was 27.2% for these infants compared to 90% for infants without bone lesions (P<0.0001). Our data emphasize the poor prognosis of infants affected by stage 4 NB with bone lesions, especially when associated with MYCN amplification. Given the poor results in this group whatever the treatment, new therapeutic approaches need to be investigated in the future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Phenotypic and genotypic diversity of human neuroblastoma studied in three IGR cell line models derived from bone marrow metastases.

Metastatic stage IV neuroblastoma tumors, as well as cell lines derived from them, are highly malignant and rapidly fatal. To determine whether malignant potential of these cells might be influenced by stromal tissue at sites frequently involved in metastasis, we initiated primary cultures from bone marrow of three patients (331, 337, and 91) with stage IV neuroblastoma. All three explants contained two distinct cell populations, malignant neuroblasts (Nb-type) and substrate adherent stromal-like (Str-type) cells. The cell types were separated at the first passage and studied by cytogenetic, molecular, and immunocytochemical methods. Karyotypic analyses after 3-6 passages in vitro revealed the presence of unique chromosomal abnormalities in Nb-type cells of all three lines: (1) der(1)t(1;7) (p32;q11) and der(5)t(5;17)(q35;q21) in pseudodiploid IGR-N-331 neuroblasts; (2) der(1)t(1;17)(p35;q21-22) x 2 and der(7)t(7;7)(p21;q21) in IGR-N-337 hyperdiploid neuroblasts; and (3) more than six rearranged chromosomes in two related subpopulations of hypodiploid IGR-N-91 neuroblasts. Neuroblastic cells from all three tumors amplified MYCN 25- to 50-fold (with amplified genes visible as dmin or, in one IGR-N-91 subline, as an hsr(14)[q32]) and expressed N-CAM. Str-type cells from tumors 331 and 337 had a normal diploid karyotype, did not express either N-CAM or S-100, and are probably normal bone marrow fibroblasts. By contrast, S-100 negative Str-type IGR-N-91 cells were hypodiploid and shared at least two unbalanced translocations, der(4)t(1;4)(q12;p15) and der(2)t(2;10;17)(p14;q11;q22), with neuroblastic counterparts, indicating that "stromal" cells and malignant neuroblasts had a common tumor cell origin. Thus, the Str-type cells of IGR-N-91 are examples of S-type phenotypic variants frequently described for long-term human neuroblastoma cells lines in vitro, but not previously observed in vivo.

Bone Neoplasms↗
PubMed1999

High-dose chemotherapy in childhood brain tumours.

New therapeutic strategies are required to improve the prognosis of malignant brain tumours in children, in terms of survival and quality of life. During the last 10 years, high-dose chemotherapy (HDCT) with autologous haematopoietic stem cell rescue has been studied in different types of paediatric brain tumours. The most frequently used combined regimens were busulfan-thiotepa and etoposide-thiotepa along with carboplatin or BCNU. High response rates have been reported in medulloblastoma and germ cell tumours, and HDCT has been further developed as salvage therapy or for consolidation in these diseases. Interesting objective tumour responses have been obtained in supratentorial high-grade glioma, but HDCT has not so far been effective either in ependymoma or in diffuse pontine brain stem tumours. This article reviews the rationale for HDCT in brain tumours and the current clinical results obtained in each tumour type. The place of HDCT in the therapeutic strategy for paediatric brain tumours, especially in young children, is discussed.

Antineoplastic Agents↗
PubMed1999

Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations.

High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg(-1)), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 microg h ml(-1)) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 microg h ml(-1)). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens.

Administration, Oral↗
PubMed1999

Prognostic factors in metastatic neuroblastoma in patients over 1 year of age treated with high-dose chemotherapy and stem cell transplantation: a multivariate analysis in 218 patients treated in a single institution.

The purpose of this paper is to study prognostic factors in neuroblastoma patients treated with high-dose chemotherapy and hematopoietic stem cell transplantation. Two hundred and eighteen children over 1 year of age and treated for stage 4 neuroblastoma were enrolled in this study. The median age at diagnosis was 39 months, the sex ratio 1.5 and 84% of patients had an abdominal primary tumor. Skeletal disease was detected in 79% of cases and bone marrow involvement in 93%. N-myc oncogene amplification was present in 27% of the patients studied. The probability of event-free survival at 5 years post-diagnosis was 29% in this series. Three major favorable prognostic factors were significant and independent in the multivariate analysis: age under 2 years at diagnosis (P<0.01), absence of bone marrow metastases at diagnosis (P<0.04) and the high-dose conditioning regimen containing busulfanmelphalan combination (P = 0.001). The quality of response to conventional primary chemotherapy was close to significance (P = 0.053). We conclude that factors related to the patient (age) and extent of disease are predictive of outcome in patients with neuroblastoma treated with conventional chemotherapy followed by surgical excision of the primary and consolidation with high-dose chemotherapy. They should be taken into account in future prospective studies. Moreover, the type of conditioning regimen appears to be the most important prognostic factor. This should encourage new investigations into innovative drug combinations.

Adolescent↗
PubMed1998

CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology.

The purpose of this study was (1) to investigate the efficacy of chemotherapy regimens designed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma (ALCL) and (2) to identify prognostic factors in these children. Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies, HM89 and HM91. The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation. Treatment consisted of 2 courses of COPADM (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisone) and a maintenance treatment of 5 to 7 months. Seventy-eight patients (95%) achieved a complete remission and 21 relapsed. The probability of survival and event-free survival at 3 years was of 83% (72% to 90%) and 66% (54% to 76%), respectively, with a median follow-up of 49 months. In multivariate analysis, visceral involvement, mediastinal involvement, and lacticodeshydrogenase (LDH) level >/=800 UI/L were shown to be predictive of a higher risk of failure. In conclusion, this type of regimen demonstrated efficacy in childhood ALCL. However, therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party.

To determine the incidence and outcome of hepatic veno-occlusive disease (VOD) after blood or marrow transplantation (BMT), we prospectively evaluated all consecutive patients receiving a BMT during a 6-month period in participating EBMT centers. All of them were evaluated for occurrence of VOD according to previously defined clinical criteria. The clinical course, outcome, value of prophylactic and therapeutic interventions, and the influence of previously described risk factors were analyzed. During the study period, 1,652 BMT were performed in 73 centers. VOD was diagnosed in 87 patients (5.3%; 95% confidence interval [CI], 4.2% to 6.4%). Fifty-six of 631 allogeneic BMT (8.9%) and 31 of 1,010 autologous BMT (3.1%) developed this complication (P <.0001). VOD was classified as mild in 7 (8%), moderate in 56 (64.4%), and severe in 24 (27.6%) cases. Sixteen patients died of VOD (corresponding to 1% of the whole series, 18.4% of VOD patients, and 66.7% of severe VOD). The use of unfractionated heparin did not significantly decrease the incidence of VOD. Independent variables associated with an increased risk of VOD were allogeneic BMT (relative risk [RR], 2.8; P <.001), pre-BMT elevation of serum aspartate aminotransferase (RR, 2.4; P =.001), high-dose cytoreductive therapy (RR, 2.3; P =.003), Karnofsky performance score less than 90% (RR, 2.7; P =.006), and prior abdominal radiation (RR, 2.9; P =.03). In conclusion, this prospective study shows that (1) the incidence of VOD is lower than that reported in smaller studies from single centers, (2) about one fourth of cases of VOD progress to severe disease, (3) main risk factors have a major impact on incidence of VOD, and (4) the use of prophylactic unfractionated heparin does not seem to reduce the incidence of VOD.

Adult↗
PubMed1998

A lack of neuroblastoma in Down syndrome: a study from 11 European countries.

An epidemiological investigation in 11 European countries comprising a total childhood population of 54.1 million children and using 8 separate data sources was conducted to evaluate the occurrence of neuroblastoma in Down syndrome (DS). No cases of DS were detected among 6724 infants and children with neuroblastoma, although more than five were expected. This highly significant result (P = 0.0045 according to the Poisson test) is consistent with data in the literature, which contains only two poorly detailed cases in epidemiological studies and one ganglioneuroma in a DS mosaic patient. Like other tumors, such as leukemias, testicular germ cell tumors and lymphomas are in excess in DS patients; the lack of neuroblastomas does not reflect a general decreased incidence of cancer but rather a specific underrepresentation of this precise tumor. S-100 b protein, the gene for which maps to the long arm of chromosome 21, (a) is overproduced in DS patients, (b) produces growth inhibition and differentiation of neural cells in vitro, (c) is abundant in good-prognosis neuroblastomas, and (d) has been shown to induce growth inhibition and differentiation and cell death in several human and murine neuroblastoma cell lines and could be responsible for this variation. Additional epidemiological and experimental studies are warranted to confirm our interpretation of these data.

Adolescent↗
PubMed1998

[Treatment of chemotherapy induced emesis in children].

In recent years, the management of chemotherapy-induced emesis in children has been greatly modified by the introduction of a new therapeutic class: serotonin antagonists. Based on a better knowledge of mechanisms, the treatment now uses combinations of different drugs. These treatments need to be carefully adapted to the patient and to the emetic risk of the chemotherapy, also taking into account the minimal cost. A gradual treatment proposal in five steps is described.

Antiemetics↗