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D Valteau-Couanet

Publications and source records attributed to D Valteau-Couanet.

51 records · Page 3Linked to original sources
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

[Humoral immunity and infections during bone marrow transplantation in children: study of 127 transplanted patients successively in a same center].

BACKGROUND: Children with malignant diseases are frequently given high dose chemotherapy plus autologous bone marrow transplants. Infectious complications can lead to morbidity and mortality in this type of treatment. This study was designed to determine whether immunoglobulin deficiency is an additional risk factor for infections. PATIENTS AND METHODS: One hundred and twenty seven children with solid malignant tumors were treated between November 1987 and April 1992 in our Department by chemotherapy followed by autologous bone marrow transplantation. Their serum IgA, IgG and IgM concentrations were measured by nephelometry before chemotherapy, on the day of transplantation and every week thereafter. The frequency and severity of infectious episodes in all the children were recorded using a standard scale. The patients were divided into two subgroups, defined according to their serum IgG concentrations before the transplantation and 7 and 21 days later. RESULTS-Ig deficiency during transplantation was not associated with the occurrence of septicemia or focal infections. It was associated with the course of infection (P = 0.003) and with the occurrence of zoster virus infection during the first 6 months after transplantation (P = 0.003). CONCLUSIONS: Immune replacement during bone marrow transplantation may be indicated in children at risk of Ig deficiency. Fifty percent of the children with solid tumors treated in our institution were at risk of this deficiency.

Adolescent↗
PubMed1993

Chronopharmacology of high-dose busulfan in children.

In bone marrow transplantation, high-dose busulfan is given p.o., usually every 6 h over 4 consecutive days. Since this repeated administration might alter busulfan disposition, fluctuations in busulfan plasma levels were studied over the 4-day treatment period in 21 children (median age, 5 years) with malignant solid tumors. In addition, urinary excretion of unchanged busulfan was measured every 6 h in 4 patients. Busulfan (37.5 mg/m2 for 16 doses) was given on an empty stomach at 12 p.m., 6 p.m., midnight, and 6 a.m. for 4 consecutive days, starting at 12 p.m. Trough plasma levels, i.e., concentration 6 h after each dose and just before the next one, and urinary excretion of busulfan were measured using a gas chromatography-mass spectrometry assay. Busulfan trough plasma levels exhibited a significant circadian rhythm with a higher mean level at 6 a.m. compared to that at 12 p.m., 6 p.m., and midnight. This rhythm was characterized by a double amplitude (mean +/- SD) of 42 +/- 14% and an acrophase (maximum) occurring at 5:48 a.m. +/- 115 min. In addition, once the steady state was reached, no decreasing trend was observed in any patient. Busulfan renal clearance proved to be low since only 5.4 +/- 1.2% of the given dose were excreted unchanged in urine. In the 4 patients studied, busulfan urinary excretion exhibited a significant circadian rhythm which was apparently linked to the physiological circadian rhythm in urinary output. Ten of 20 evaluable patients developed hepatic venoocclusive disease (HVOD). A significant circadian rhythm in the plasma level was found in both HVOD and non-HVOD patients with no difference between the two groups with regard to the 24-h mean, amplitude, or acrophase. Thus, the circadian changes in busulfan trough plasma levels observed at the steady state were not related to the occurrence of HVOD in these children with solid tumors. Moreover, since this rhythm was stable from day 2 to day 4, it should not compromise dose adjustment.

Bone Marrow Transplantation↗
PubMed1993

Systemic Candida infection in pediatric BM autotransplantation: clinical signs, outcome and prognosis.

Of the 393 children who underwent BM autotransplantation in the pediatric oncology unit of the Institut Gustave Roussy between February 1979 and September 1991, 14 (3.56%) developed disseminated Candida infection within 3 months. This incidence was far lower than in other published series. Eleven of the 14 patients recovered from the infection, giving a far higher survival rate (78%) than among adult BM transplant recipients (usually < 30%). All 14 patients had four or more risk factors and persistent BM aplasia (median, 25 days); six had Candida tropicalis infection. Four cases of deep visceral involvement were documented, two of which were lethal. Clinical signs were relatively uniform and included secondary high-grade fever (> 40 degrees C) for 8 days; half the patients developed cardiovascular impairment, respiratory distress, neurological disturbances (altered consciousness or delirium) and severe diarrhoea, within as little as 10 days after transplantation. Blood cultures rapidly became positive after the onset of clinical signs and this permitted prompt treatment with a combination of amphotericin B and 5-fluorocytosine; in addition, central catheters were removed. Blood cultures became sterile within 4 days of treatment in 10 of the 14 cases. The generally favourable outcome in this series could be related to the young age of the patients, the absence of GVHD, the absence of total body irradiation in the conditioning regimen, and early antifungal treatment.

Adolescent↗
PubMed1992

[Residual lymphocytes after specific depletion. Functional study].

We previously demonstrated that, following a 2-day stimulation of T cells by MHC incompatible cells, a ricin A-chain conjugated to a monoclonal anti-IL2 receptor p55 subunit can kill 1.5 log of the activated alloreactive T cells while non specific killing of alloreactive T cells of a third partner does not exceed 0.5 log. This methodology is of potential use for selective alloreactive T cell depletion in MHC incompatible bone marrow transplantation in order to prevent both graft versus host disease and graft rejection. This study shows that this T cell depletion method does not alter T cell reactivity to microorganism antigens encountered in infection following BMT. It was found that T cell proliferation to cytomegalovirus and to candida antigens is not affected as shown in proliferative assays and by limiting dilution analysis for the latter antigen.

Antibodies, Monoclonal↗
PubMed1992

Is 600 mg/m2 the appropriate dosage of busulfan in children undergoing bone marrow transplantation?

Recent studies have reported that the pharmacokinetics of high-dose busulfan in bone marrow transplantation (BMT) are age-dependent: with the usual dosage of 16 mg/kg over 4 days, systemic exposure is two to four times lower in children than in adults. Data suggested that the dose of busulfan should rather be calculated on the basis of the body surface area (BSA). We measured plasma pharmacokinetics of busulfan in 27 children (mean age, 5.4 years) who were administered a new dosage of 600 mg/m2 over 4 days, ie, 17.8 to 29.2 mg/kg (mean, 24.8 mg/kg), using a gas chromatography-mass spectrometry assay. Our results demonstrate that, with this new dosage, systemic exposure is significantly increased in children compared with that achieved with the usual dosage of 16 mg/kg (6,404 +/- 2,378 v 3,918 +/- 1,170 ng.h/mL; P = .003). Moreover, there is no longer a significant difference in systemic exposure between children treated with this new dosage and adults given a dose of 16 mg/kg of busulfan. However, despite the use of a dosage normalized to the BSA, there is still a wide interindividual variation in systemic exposure, ranging from 3,566 to 13,129 ng.h/mL, which may account for the high incidence of venoocclusive disease (VOD) of the liver that we have already reported. The optimal dosage and schedule of busulfan in children requires a more individual approach that could be based on dose adjustment and plasma level monitoring.

Adolescent↗
PubMed1992

Results of the LMT81 protocol, a modified LSA2L2 protocol with high dose methotrexate, on 84 children with non-B-cell (lymphoblastic) lymphoma.

From May 1981 to June 1989, 84 children with non-B-cell lymphoma (82 lymphoblastic, 1 T-cell immunoblastic, 1 unclassified diffuse lymphoma) were treated in the pediatric department of the Institut Gustave Roussy according to a protocol called LMT81, which was derived from the LSA2L2 protocol of Wollner and modified by the adjunction of 10 courses of high dose methotrexate to improve the CNS prophylaxis. No planned irradiation was performed except in cases of initial tests (2 patients) or CNS (5 patients) involvement and residual mass (2 patients). Sixty patients had mediastinal involvement; for the others, primaries were in the head and neck (7), nodes (2), (sub)cutaneous (4), bone (7), and elsewhere (2). According to Murphy's staging system, there were 2 stage I, 6 stage II, 33 stage III, and 43 stage IV. Among the stage IV patients, 41 had bone marrow involvement, 24 of them with more than 25% blast cells in bone marrow and 19 with blast cells in blood; 7 had CNS involvement. Three patients did not achieve complete remission, 4 died in remission (two measles, one post-transfusion AIDS, one unexplained definitive aplasia) and 13 relapsed at 2 to 29 months (median-13 months). Among the 77 patients without initial CNS involvement, there was only one isolated CNS relapse. With a median follow-up of 57 months (10-106 months), the event-free survival is 75% (SE 2.5) for the 84 patients with a plateau at 29 months, 73% (SE 8) for stage I and II patients, 79% (SE 4) for stage III, and 72% (SE 4) for stage IV patients. Survival was similar in each stage group. Reasons for failure of treatment, however, were different, being toxic deaths in stage II; initial therapy resistance, early relapses, and toxic deaths in stage III; and tumor failures in stage IV. In conclusion, this protocol is efficacious on T and non-T, non-B childhood lymphoma with a low incidence of CNS relapse. A future study will seek to diminish toxicity and long-term sequellae while at least maintaining the same cure rate of patients.

Adolescent↗
PubMed1992

Risk factors for hepatic veno-occlusive disease after high-dose busulfan-containing regimens followed by autologous bone marrow transplantation: a study in 136 children.

Risk factors for hepatic veno-occlusive disease (HVOD) were analysed in a population of 136 autografted children who received high-dose busulfan (BU) as part of a conditioning regimen. HVOD was diagnosed according to McDonald's clinical criteria. The incidence of HVOD was particularly high in this series (22%) compared with series with other conditioning regimens but the outcome was favorable in 26 patients (87%). Four deaths occurred (13%), one of which was HVOD related. The clinical presentation of HVOD was similar to that described in previous reports. Although statistical analysis failed to demonstrate any factors predictive of outcome, it did identify risk factors for the occurrence of HVOD: these were (1) a total dose of BU exceeding the standard 16 mg/kg dose; (2) the use of three as opposed to two alkylating agents; (3) the sequence of BU administration when given in the conditioning regimen containing three alkylating agents; and (4) concomitant ketoconazole therapy.

Adolescent↗
PubMed1991

Rhabdomyosarcoma of the larynx in children: a series of five patients treated in the Institut Gustave Roussy (Villejuif, France).

Rhabdomyosarcoma of the larynx is a malignant disease rarely seen in children. We present five cases (3 males, 2 females) observed among 126 patients with rhabdomyosarcoma of the head and neck (excluding the orbit) treated in the Institut Gustave-Roussy between 1955 and 1981. The patients were aged between 5 1/2 years and 13 1/2 years at the time of diagnosis. The presenting symptoms were dysphonia and/or dyspnea; tracheotomy was required in two cases. All five patients received chemotherapy consisting of vincristine, cyclophosphamide, actinomycin D + procarbazine or doxorubicin. Four patients also received radiotherapy (45 Gy during 5 weeks). Laryngectomy was not performed. Treatment sequelae included regional hypoplasia, huskiness, and subclinical thyroid insufficiency; two patients developed a benign thyroid adenoma. One patient presented a bilateral carotid stenosis subsequent to radiotherapy performed on "wide fields" portal designed to provided prophylactic treatment on uninvolved lymph nodes. All the patients are alive and relapse-free with a follow-up of between 13 and 17 years. This small series of RMS of the larynx shows that patients can be cured without laryngectomy, although long-term sequelae associated with radiotherapy are observed.

Adolescent↗
PubMed1991

Nonmetastatic thoracic neuroblastomas: a review of 40 cases.

From 1982 to 1987, 40 children with non-metastatic thoracic neuroblastoma were treated with the same therapeutic regimen. According to TNM staging, there were 11 CS I, 19 CS II, and 10 CS III. All patients underwent surgery; 30 had primary surgical excision; in 10 whose tumors were deemed unresectable, surgery was delayed until after a trial of chemotherapy. Operation was completed by several courses of chemotherapy in case of microscopic residual disease or regional lymph node involvement; radiotherapy was delivered in case of gross residual disease. Using this therapeutic approach, EFS is 92% with a median follow-up of 40 months. Severe complications were rare and sequellae appear to be related to the disease, i.e., neurologic consequences of cord compression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study.

Busulfan is known to be neurotoxic in animals and humans, but its acute neurotoxicity remains poorly characterized in children. We report here a retrospective study of 123 children (median age, 6.5 years) receiving high-dose busulfan in combined chemotherapy before bone marrow transplantation for malignant solid tumors, brain tumors excluded. Busulfan was given p.o., every 6 hours for 16 doses over 4 days. Two total doses were consecutively used: 16 mg/kg, then 600 mg/m2. The dose calculation on the basis of body surface area results in higher doses in young children than in older patients (16 to 28 mg/kg). Ninety-six patients were not given anticonvulsive prophylaxis; 7 (7.5%) developed seizures during the 4 days of the busulfan course or within 24 h after the last dosing. When the total busulfan dose was taken into account, there was a significant difference in terms of neurotoxicity incidence among patients under 16 mg/kg (1 of 57, 1.7%) and patients under 600 mg/m2 (6 of 39, 15.4%) (P less than 0.02). Twenty-seven patients were given a 600-mg/m2 busulfan total dose with continuous i.v. infusion of clonazepam; none had any neurological symptoms. Busulfan levels were measured by a gas chromatographic-mass spectrometry assay in the plasma and cerebrospinal fluid of 9 children without central nervous system disease under 600 mg/m2 busulfan with clonazepam:busulfan cerebrospinal fluid:plasma ratio was 1.39. This was significantly different (P less than 0.02) from the cerebrospinal fluid:plasma ratio previously defined in children receiving a 16-mg/kg total dose of busulfan. This study shows that busulfan neurotoxicity is dose-dependent in children and efficiently prevented by clonazepam. A busulfan dose calculated on the basis of body surface area, resulting in higher doses in young children, was followed by increased neurotoxicity, close to neurotoxicity incidence observed in adults. Since plasma pharmacokinetic studies showed a faster busulfan clearance in children than in adults, this new dose may approximate more closely the adult systemic exposure obtained after the usual 16-mg/kg total dose, with potential inferences in terms of anticancer or myeloablative effects. The busulfan dose in children and infants undergoing bone marrow transplantation should be reconsidered on the basis of pharmacokinetic studies.

Adolescent↗
PubMed1990

Long-term sequelae of conservative treatment by surgery, brachytherapy, and chemotherapy for vulval and vaginal rhabdomyosarcoma in children.

Between 1970 and 1978, 17 girls with rhabdomyosarcoma (RMS) of the vulva or vagina were treated at the Institut Gustave-Roussy (IGR) by conservative treatment including surgery, brachytherapy, and chemotherapy. Twelve pubescent or postpubescent girls were studied for long-term sequelae. Eleven of 12 patients have had a normal puberty, two have a total of three healthy children, 11 have normal menses, and 10 normal menarche (one after hormonal replacement). Only one patient underwent hysterectomy following low-dose brachytherapy. Five girls have no vaginal complications, and three are sexually active. Three have had minimal vaginal sequelae, which required surgical correction to permit sexual intercourse. Four girls sustained serious sequelae (colorectal, vaginal, urethral, and ureteral stenosis). These sequelae, secondary to irradiation, are potentially avoidable in the future given the current advances in brachytherapy and improvements in dosimetry. This conservative treatment is useful and appropriate for girls with RMS of vulvar or vaginal origin when complete remission cannot be obtained with chemotherapy and partial colpectomy.

Adolescent↗
PubMedDate not supplied

Antiinfective prophylaxis with ceftazidime and teicoplanin in children undergoing high-dose chemotherapy and bone marrow transplantation.

Sixty children treated for solid tumors with high-dose chemotherapy followed by bone marrow transplantation were randomly assigned to one of two antibiotic protocols. Group A received prophylaxis consisting of ceftazidime plus teicoplanin beginning before the onset of aplasia and fever; group B received exactly the same antibiotic regimen but beginning at the onset of fever. The two groups were compared in terms of the rate of septicemia, fever of unknown origin, the time-lapse before the appearance of septicemia, the sensitivity of the causative organisms to the antibiotics, the effect of the latter on the intestinal flora, and the rate of fungal infections. The incidence of septicemia was significantly lower in group A (6.6%) than in group B (24.0%), mainly due to the prevention of episodes of early onset. Similarly, the appearance of the first episode of fever was delayed in group A, and the overall duration was reduced. Amphotericin B was prescribed empirically with the same rule in both groups, but three children in group A did not require amphotericin B. The effect on the intestinal flora was similar in the two groups; it must, however, be closely monitored so that the presence of potential pathogens can be dealt with appropriately.

Adolescent↗