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Biomedical subjects

O Hartmann

Publications and source records attributed to O Hartmann.

At least 163 records · Page 9Linked to original sources
PubMed1990

[Role of high-dose chemotherapy followed by bone marrow autograft in the treatment of metastatic Ewing's sarcoma in children].

Thirty-two children were treated for metastatic Ewing sarcoma by high-dose chemotherapy followed by autologous bone marrow transplantation. Fourteen patients entered phase II studies of high-dose alkylating agents. The response rate observed was 61%. High-dose chemotherapy was used as consolidation in complete remission of 18 patients. Disease free survival appears to be better than that observed under conventional altered chemotherapy. However, with only 4/18 long term survivors, these results remain unsatisfactory, taking into account the recent encouraging results of semi-continuous conventional chemotherapy.

Adolescent↗
PubMed1990

[Neonatal Pepper's syndrome. Apropos of a series of 22 cases].

From 1960 to 1987, 22 neonates were treated at the Institut Gustave-Roussy for a Pepper' syndrome. During this period of time, 83 children were treated for the same syndrome, the neonatal type representing 26% of cases. Twelve of the 22 neonates presented with the rapidly evolving type, requiring an immediate aggressive treatment. In 4 of them death occurred early despite treatment. The 10 other neonates presented with a slowly progressive disease. In 5 of them treatment of the metastatic disease was not necessary to obtain remission. The survival rate of disease without relapses in 77%, with a median follow-up of 8 years. So, despite the high incidence of rapidly progressive forms, the prognosis of this disease remains favorable in neonates, provided an accurate treatment initiated early.

Adrenal Gland Neoplasms↗
PubMed1989

Correlation of MDR1 gene expression with chemotherapy in neuroblastoma.

Forty-one neuroblastoma tumor specimens have been analyzed by Northern and slot blot hybridization techniques with human MDR1 gene probes. Only one of 15 (6%) tumors from patients who had not received chemotherapy exhibited high levels of MDR1 transcripts, while 11 of 26 (42%) treated tumors showed high levels of MDR1 expression (Fisher exact test: P = .03). The results indicate that the level of MDR1 mRNA expression is associated with previous chemotherapy, including drugs that select the multidrug resistance phenotype in vitro regardless of neuroblastoma tissue origin or N-myc content in the genome. For the 26 treated neuroblastomas, the number of nonresponsive tumors was found to be significantly higher among those with high levels of MDR1 mRNA.

Adrenal Gland Neoplasms↗
PubMed1989

Malignant histiocytosis: therapeutic results in 27 children treated with a single polychemotherapy regimen.

Twenty-seven children with histologically proven malignant histiocytosis were treated in the same institution from January, 1975 to December, 1986 with a combination chemotherapy regimen containing vincristine, cyclophosphamide, doxorubicine, and prednisone. Twenty-two patients achieved complete remission, one partial remission, and four no remission. Eight patients relapsed and were treated with Lomustine (CCNU), vinblastine, and bleomycin. In seven cases, a second complete remission was obtained. The overall survival rate is 81% at 5 years and the relapse-free survival rate is 54.5% at 5 years. Prognostic factors were fever and age under 10 at diagnosis, which were correlated with a higher incidence of relapse or no remission.

Adolescent↗
PubMed1989

Pharmacokinetics of high-dose busulfan in children.

The pharmacokinetics of high-dose busulfan given orally at 1 mg/kg every 6 h over 4 days (total dose, 16 mg/kg) in combined chemotherapy followed by autologous bone marrow transplantation was studied in 12 children with a mean age of 7 years (range, 4-14 years). Busulfan levels in biological fluids were measured by a gas chromatographic assay with mass fragmentographic detection, using a deuterated analogue as the internal standard. In a high-dose regimen, busulfan followed one-compartment model kinetics with zero-order absorption. A mean maximal concentration of 803 +/- 228 ng/ml was achieved at 92-255 min after dosing. The mean elimination half-life was 2.33 h, and the mean total clearance was 119 +/- 54 ml/min per m2, with an apparent distribution volume of 27.10 +/- 11.50 l/m2. A mean trough level of 370 ng/ml was found throughout the 4 days of the chemotherapy course. There were no significant variations in pharmacokinetic parameters measured after the first and last doses. Busulfan was monitored in the CSF of nine children at 3.25-7 h after the last dose and was detected in all patients, with a mean CSF-to-plasma concentration ratio of 0.95 (range, 0.5-1.4).

Adolescent↗
PubMed1989

Enhanced cutaneous radiation effects following high-dose busulfan therapy.

Fifteen patients received irradiation after combined chemotherapy with high-dose busulfan followed by autologous or allogeneic bone marrow transplantation. Of nine patients irradiated between day 30 and day 70 after their engraftment, seven developed an increased radiation response in the skin: four showed enhanced reactions during irradiation, and three had a total or severe definitive alopecia more than 16 months after CNS irradiation. Six patients were irradiated after day 70; they had either normal reactions or none at all within the cutaneous radiation portals. The possibility that busulfan might be a radiosensitizer is raised.

Busulfan↗
PubMed1989

Potential therapeutic role of cisplatinum in autologous bone marrow transplantation: in vitro eradication of neuroblastoma cells from bone marrow.

Cisplatinum may prove to be a valuable agent for the elimination of diseased cells in the bone marrow of patients with neuroblastoma. In this study, we measured the efficacy of cisplatinum on human neuroblastoma cell lines and on normal human bone marrow progenitors, GM-CFC and CFU-F. Data indicate that the therapeutic index of cisplatinum is high. We set up an experimental model consisting of a mixture of human bone marrow and human neuroblastoma cells in order to confirm these preliminary results in purging conditions. Results indicate that cisplatinum exhibits a high and specific tumoricidal property and appears to be valid in bone marrow purging.

Bone Marrow↗
PubMed1989

Hemorrhagic cystitis following high-dose chemotherapy and bone marrow transplantation in children with malignancies: incidence, clinical course, and outcome.

Two hundred ninety-one courses of high-dose chemotherapy (HDC) with bone marrow transplantation (BMT) in children with malignancies were reviewed in order to assess the incidence, clinical course, outcome, and predisposing factors of hemorrhagic cystitis. Hemorrhagic cystitis occurred in 19 HDC courses (6.5%). Three patients had grade I hematuria linked to thrombopenia, nine had grade II hematuria despite platelet levels greater than 50 x 10(9)/L, and seven had grade III hematuria with clots and bladder obstruction. Severe complications occurred in grade III patients, but no deaths were directly linked to the cystitis. Fourteen patients recovered within two to 120 days of onset. The other patients died before the cystitis resolved, either of a relapse of the malignancy or of infection. Predisposing factors were age (increased incidence in older children), conditioning regimen containing cyclophosphamide, previous vesical irradiation, association with prolonged aplasia, and hepatic complications. The role of busulfan was also probable. No viral agent was found.

Adolescent↗
PubMed1989

[Clinical, anatomo-pathologic aspects and therapeutic results in 63 malignant ORL non-Hodgkin's lymphomas in children].

Sixty-three children with non Hodgkin's lymphoma involving the ENT zone (Waldeyer's ring) were treated between 1975 and 1985 at the Institut Gustave-Roussy. The tumors were localized in the cavum (32 cases), tonsils (16 cases), mandibles (9 cases) whereas 6 patients had more than one of these sites involved. At the time of diagnosis, 16 (25%) had neuro-meningeal involvement. Distribution, according to stages and histology was as follows: 4 stages I, 27 stages II, 12 stages III, 17 stages IV and 3 were unclassifiable. A Burkitt type of lymphoma was diagnosed in 37 (58%), a convoluted lymphoblastic type in 6 (10%) and 20 (32%) fell in a broad category of "other lymphoblastic variety" (32%). With regard to therapy, two consecutive time periods could be identified: from 1975 to 1980 all patients were given the same treatment and neuro-meningeal prophylaxis consisted of irradiation of the skull and intrathecal injections of methotrexate. Since 1981, the therapeutic regimen is designed according to the histo-immunological classification of the tumors and neuro-meningeal prophylaxis is carried out with the use of high dose methotrexate. With this new approach the survival rate has increased from 45 to 80% and the incidence of neuromeningeal relapses has decreased.

Adolescent↗
PubMed1989

Varicella-zoster virus infections after autologous bone marrow transplantation in children.

We report a retrospective analysis of children who underwent autologous bone marrow transplantation (ABMT) and subsequently developed a varicella-zoster virus (VZV) infection. Among 236 patients transplanted between January 1979 and December 1987, 54 (23%) aged 2 to 18.5 years (mean 7.2) developed 60 VZV infections (25%); there were 10 cases of chicken-pox in 10 patients, 43 zoster infections in 41 patients and seven disseminated zoster infections in seven patients. Eighty-seven percent of VZV infections occurred within the first 6 months after bone marrow transplantation, with a mean interval of 89 days. No significant risk factors for the development of zoster infections were identified. The incidence of VZV infections following ABMT was similar to that observed after allogeneic bone marrow transplant but the onset was earlier after ABMT (3 vs 5 months) and there were fewer complications (2 vs 18%). Acyclovir and/or adenine arabinoside were administered to 46 patients. One child who had had chicken-pox died of interstitial pneumonitis due to VZV despite antiviral therapy. No other symptomatic visceral dissemination was observed.

Adolescent↗
PubMed1989

[Secondary metastatic neuromeningeal localization of neuroblastoma in children].

In order to evaluate the frequency, clinical and radiological aspects and prognosis of central nervous system metastases in children's neuroblastoma, the 258 children presenting with neuroblastoma, and registered from January 1982 to August 1987, were studied. Among them, 7 patients (2.7%), of which 6 had an initially metastatic neuroblastoma, presented with a secondary neuro-meningeal involvement. Parenchyma involvement (4 cases) occurred after a mean period of time of 21 months and marked the relapses. The disease recurs later on, even when locally controlled by surgical excision and local irradiation. Meningeal involvements (3 cases) occurred after a mean delay of 12.7 months, in patients with full tumoral evolutivity, and were responsible for rapid death. The clinical presentation of these metastases differs from that in adults by the rapidity of setting up of the signs and the frequency of intracranial hypertension. CT scan allows approaching diagnosis in the majority of the cases. These data are compared with those in the literature, where 30 cases were reported: they show a high patients' average age and the worse prognosis.

Brain Neoplasms↗
PubMed1989

Role of parenteral antibiotherapy in gastrointestinal tract flora suppression. A study in children treated with high-dose chemotherapy and autologous bone marrow transplantation.

In order to determine the effect of parenteral antibiotherapy on the fecal flora in patients with profound and prolonged granulocytopenia, we initiated a prospective study of 62 cases of autologous bone marrow transplantation following high-dose chemotherapy. All patients were children from 2 to 18 years old, isolated in a protective environment, receiving a diet low in viable microbial content but no oral non-absorbable prophylactic antibiotics to decontaminate the gastrointestinal tract. Bacteriological analysis of fecal flora was conducted at least once a week before and during parenteral antibiotherapy, administered at the first greater than 38 degrees C febrile episode in these granulocytopenic patients (granulocyte count less than 0.5 X 10(9)/l). The 58 evaluable patients fell into three groups with regard to the systemic antibiotherapy: group A (n = 16): moxalactam + mezlocillin; group B (n = 15): moxalactam + tobramycin; and group C (n = 27): cefotaxime plus gentamicin. Fecal flora suppression was observed in 51/58 cases (88%) (group A: 15/16, group B: 13/15, group C: 23/27). It always occurred within 5 days of initiating parenteral antibiotherapy and persisted in 88% of the 51 patients over the whole period of systemic antibiotherapy. During the latter, fecal recolonization was observed in seven cases (12%), always by Enterobacteriaceae sensitive to the prescribed systemic antibiotherapy, never responsible for septicemia. Since parenteral antibiotherapy alone was able to suppress the gastrointestinal tract flora, the effects of this treatment should be considered in all trials of digestive tract decontamination.

Adolescent↗
PubMed1989

Hemopoietic reconstitution after repeated autologous transplantation with mafosfamide-purged marrow.

Twenty-nine children (median age: 41 months) with advanced solid tumors received, as consolidation therapy, two consecutive courses of high-dose chemotherapy (HDC) followed by mafosfamide-purged autologous marrow transplantation (ABMT) with a 3- to 4-month interval between each course. The malignancies were neuroblastoma (n = 22), Ewing's sarcoma (n = 5) and rhabdomyosarcoma (n = 2). Patients received a preparatory regimen consisting of combined high-dose melphalan before each ABMT, with the exception of five patients who received busulfan and cyclophosphamide before the second ABMT. Prior to HDC, bone marrow sufficient for two transplantations was harvested in remission, treated with mafosfamide (50 micrograms/ml) and cryopreserved. Following incubation with the drug, a consistent inhibition (greater than 99%) of granulocyte and macrophage colony-forming units was observed. Despite the elimination of measurable hematopoietic progenitors, all patients underwent engraftment within a similar period of time after the first and the second ABMT. However, peripheral leukocyte and granulocyte recovery was delayed (median 26 and 28 days, respectively, after the first graft; median 27 and 28 days after the second graft). No difference was observed in the bacterial infections following the first and second ABMT. One patient died after the second transplant with diffuse aspergillosis. Recovery to 50 x 10(9) platelets/l occurred after a median 42 days (range 19-71) after the first ABMT and 43 days (range 14-110) after the second. Two patients died of recurrent disease before attaining a normal platelet level. One patient remained thrombocytopenic and died from visceral failure at day 200. These results demonstrate the feasibility of repeated ABMT with mafosfamide-treated marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Malignant histiocytosis in children. Clinical and therapeutic aspects. Apropos of a series of 32 cases].

Thirty-two children with malignant histiocytosis were managed at the Department of Pediatrics of the Gustave-Roussy Institute from January 1975 through December 1987. Clinical presentation included enlarged lymph nodes in all cases, a decline in general health with fever in 74%, skin manifestations in 54%, and visceral involvement in 55%. Twenty-seven patients were treated with the COPAD protocol combining vincristine, cyclophosphamide, adriamycin and prednisone. Twenty-two patients achieved a complete remission, and one a partial remission; there was no remission in four patients. Eight patients had a recurrence and were given a combination of CCNU, vinblastine and bleomycin; seven achieved a second complete remission. Overall survival rate was 72.2% with a median follow up of five years. Survival rate free of disease was 54.5%. Poor prognostic factors included presence of constitutional symptoms upon diagnosis and age under ten years.

Adolescent↗
PubMed1988

Serum neuron-specific/nonneuronal enolase ratio in the diagnosis of neuroblastomas.

Pretreatment samples from 24 children with neuroectodermal tumors (two ganglioneuromas, 22 neuroblastomas) and from 106 others with various tumors were submitted to the enzymatic determination of the serum neuron-specific enolase (NSE). The enzymatic procedure employed in this study allows the systematic determination of the NSE and of the nonneuronal enolase (NNE), thus permitting the calculation of the ratio of the two enolase components. Like results obtained with other procedures, enzymatic determined serum NSE results were raised in a high proportion of Stage IV neuroblastoma (100%) but elevated values also were found in a considerable number of the other tumors (29.2%) like Wilms' tumor, lymphomas, and soft tissue sarcomas. The use of the NSE/NNE ratio which characterizes NSE elevations originating from relative poor or rich sources of NSE, represents an additional index for improving the specificity of the NSE results in the diagnosis of neuroblastomas. With a cutoff value fixed at 7.5%, the specificity of the test is 85.9%. When this limit is fixed at 15%, the specificity reaches 95.3% whereas 81.8% of the results of Stage IV neuroblastomas are still above this value.

Child↗
PubMed1988

[Hepatic complications after high-dose chemotherapy and bone marrow autograft in solid tumors in children].

Two-hundred and thirty-six courses of high-dose chemotherapy with bone marrow transplantation for solid tumors in children were reviewed in order to assess the incidence of hepatic abnormalities and their etiology. Bacterial and fungal hepatitis were excluded from this study. Hepatic complications occurred after 43 courses (20 per cent) in 39 patients. Four patients had hepatic abnormalities after two consecutive courses. Predisposing factors were found to be conditioning regimen including busulfan and previous high dose chemotherapy. Veno-occlusive disease occurred in 11 children and had a fatal outcome in 4. In 9 children, hepatitis was a symptom of diffuse viral infection. In the other 23 courses, hepatitis was isolated but it was difficult to determine whether its etiology was viral (cytomegalovirus, Epstein-Barr virus, adenovirus, HBs, non A non B) or toxic. In these latter forms, the outcome was always good.

Antineoplastic Combined Chemotherapy Protocols↗