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Biomedical subjects

M Ostronoff

Publications and source records attributed to M Ostronoff.

At least 37 records · Page 2Linked to original sources
PubMed1992

Serum levels and receptor expression of tumor necrosis factor-alpha following human allogeneic and autologous bone marrow transplantation.

We have investigated tumor necrosis factor-alpha levels in serum samples of patients before and after allogenic (16 patients) or autologous (8 patients) bone marrow transplantation. A sensitive immunoradiometric assay for monitoring levels of endogenous tumor necrosis factor-alpha was used. The serum levels of tumor necrosis factor-alpha were found to be relatively low (ranging from less than 15 to 77 pg/ml). Among 13 patients having graft-versus-host disease following allogeneic bone marrow transplantation 8 patients did not have detectable tumor necrosis factor-alpha (less than 15 pg/ml) while 4 out of 8 patients undergoing autologous bone marrow transplantation had detectable tumor necrosis factor-alpha levels (15 pg/ml), indicating a lack of correlation between tumor necrosis factor-alpha serum levels and the occurrence of graft-versus-host disease. Because the tumor necrosis factor-alpha levels detected in patient sera could be regulated by TNF-receptor expression, the presence of TNF-receptor on patients' peripheral blood mononuclear cells was also studied using fluorescent liposome-conjugated tumor necrosis factor-alpha and immunofluorescence analysis. Our data indicate that peripheral blood mononuclear cells of some patients receiving either autologous or allogeneic bone marrow transplantation expressed significant levels of TNF-receptors, suggesting a lack of correlation between TNF-receptor expression and graft-versus-host disease development.

Bone Marrow Transplantation↗
PubMed1992

Burkitt's lymphoma in adults: a retrospective study of 46 cases.

The prognosis of Burkitt's lymphoma is generally considered to be poor, particularly in the advanced stages of the disease. Although recent chemotherapy protocols have given high rates of cure in children, there are few such reports concerning adults. We therefore conducted a retrospective analysis of the results for treatment of 46 adults in the Institut Gustave Roussy (IGR) between 1978 and 1987, in order to establish an effective treatment strategy for use in a prospective trial. The median age of the patients was 31 years and the majority were Caucasians of European origin. The clinical symptoms and course of the disease were similar to those in the pediatric situation and corresponded to the so-called non endemic forms observed in Europe and the United States. Presentation was generally extra-nodal, usually with abdominal manifestations. As a rule, the disease progressed rapidly and showed a high affinity for the central nervous system in the absence of specific prophylaxis, despite systemic therapy with highly active agents, particularly in the advanced stages. According to Murphy's classification, there were 6 stage I, 11 stage II, 19 stage III and 10 stage IV patients (3 of whom had CNS involvement). Treatment was heterogenous, although all the patients received polychemotherapy including anthracyclins. The best results were obtained from eleven patients treated according to the French Multicenter Protocols for pediatric Burkitt's lymphoma (LMB-84 and LMB-86). Kaplan-Meier 5-year relapse free survival rate among the 46 patients was 42% (stage I: 83%; stage II: 67%; stage III: 30%; stage IV: 30%). In order to standardize our therapeutic approach, we started a prospective study in 1988 using the unmodified pediatric protocol for our adult patients.

Adolescent↗
PubMed1992

A phase II trial of early intensive chemotherapy with autologous bone marrow transplantation in the treatment of poor prognosis non seminomatous germ cell tumors.

Twenty-eight patients with poor prognosis, advanced metastatic non seminomatous germ cell tumors (NSGCT) were treated with early high dose chemotherapy and autologous bone marrow transplantation (ABMT) rescue. The primary tumor was testicular in 19 patients and extragonadal in nine patients. For 19 patients with a testicular primary, the median probability of complete remission (CR) was 0.05 according to our prognostic mathematical model based on pretreatment levels of serum HCG and AFP. The same prognostic model was used for extragonadal primaries. Treatment consisted of two cycles of a modified double dose of cisplatin, vinblastine, bleomycin, VP-16 regimen (mPVeBV) followed by a high dose cisplatin-etoposide-cyclophosphamide regimen (PEC) followed by ABMT. Of the 28 patients, 17 (61%) achieved CR, one of which was surgical CR (sCR), five died of rapidly progressive disease early during the first cycle of mPVeBV, two had treatment-related deaths, three did not respond and one patient refused treatment. Of the 17 patients initially in CR, three relapsed after 4, 4 and 7 months respectively and have subsequently died. Two other patients died while still in CR: one committed suicide and one died of an infectious complication due to transfusion-related AIDS. Twelve patients are alive in CR after a median follow-up of 66 months (range 7-72 months). The non parametric 3-year survival rate is 40%. To demonstrate the effect of intensive chemotherapy with ABMT, a randomized multicenter French study was set up to evaluate the PVeBV regimen with or without high dose treatment and ABMT in poor risk NSGCT patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer.

Between April 1984 and May 1985, 17 heavily pretreated patients with relapsing or refractory germ cell tumours were treated with cisplatin 40 mg/m2/day, days 1-5; etoposide 350 mg/m2/day, days 1-5; cyclophosphamide 1600 mg/m2/day, days 2-5 and autologous bone marrow transplantation on day 8 as consolidation of conventional salvage chemotherapy. None of the 11 refractory patients and 4 of the 6 responders to prior salvage treatment are long-term survivors at 68, 72, 74 and 74 months. Mean aplasia duration was 17 days and there were 7 documented episodes of septicaemia in 17 febrile patients. 1 patient died of treatment. Among the 4 survivors, 2 patients have a sustained grade II invalidating neuropathy. We conclude that this regimen is not recommended as salvage therapy in refractory patients but may be a useful consolidation treatment in patients responding to conventional salvage chemotherapy.

Adolescent↗
PubMed1990

Salvage therapy with methyl-gag, high-dose Ara-C, M-Amsa, and ifosfamide (MAMI) for recurrent or refractory lymphoma.

Thirty adult patients with relapsed or refractory malignant lymphoma underwent a Phase I-II trial of salvage chemotherapy combining methyl-gag, high-dose Ara-C, M-Amsa, and ifosfamide (MAMI protocol). All patients had been extensively pretreated. At the time of salvage therapy, 21 patients had visceral involvement and 23 patients were refractory. The overall response rate was 50% (11 patients in complete remission and 3 patients in partial remission). The main toxicity was myelosuppression; 4 treatment-related deaths occurred and 17 patients died of tumor progression with a median of 5 months. The MAMI protocol showed similar antitumoral efficacy to that of other salvage chemotherapy regimens used for poor prognosis malignant lymphoma but was more toxic. However, a response rate of 45% in refractory patients should be taken into account and this drug association deserves further investigation with regard to the selection of patients for bone marrow transplants.

Adolescent↗
PubMed1990

[Value of high-dose chemotherapy followed by bone marrow autograft in non-seminomatous germinal tumor with poor prognosis. Results of the combination of cisplatinum, etoposide and cyclophosphamide (PEC protocol)].

In recent years, the prognosis of non-seminomatous germ-cell tumors has been greatly improved by the use of novel chemotherapeutic regimens including platinum derivatives. However, the prognosis remains poor for a certain proportion of these patients. We have therefore developed an intensive chemotherapy protocol (PEC) followed by bone marrow autografting: cisplatin (40 mg/m2/day x 5 d), etoposide (350 mg/m2/day x 5 d), cyclophosphamide (1,600 mg/m2/day x 4 d). Forty-four poor-prognosis patients were thus treated. The results can be stratified into 3 categories, as follows: I: 12 refractory patients: 3 CR, 6 PR, 2 failures, 1 unevaluable. Median survival was short (7 months, range 2-16 months); II: 6 patients with sensitive relapse: 5 CR, 1 unevaluable. Four patients remained in CR at 42, 45, 46 and 48 months; III: 26 patients who received PEC as consolidation therapy in the first CR-PR after courses of conventional chemotherapy and who were selected at the time of diagnosis on the basis of factors of poor prognosis: 16 CR, 3 PR, 7 unevaluable. Two-year disease-free survival (Kaplan-Meier) is 60%. The median duration of neutropenia (less than 0.5 x 10(9)/l) was 15 d (range 6-37) and that of thrombocytopenia (less than 20 x 10(9)/l), 13 d (range 3-32). The most significant non-hematologic toxicity was of the gastrointestinal tract; in particular severe mucositis. Four iatrogenic deaths occurred (2 candidiasis, 1 aspergillosis and 1 hemorrhage). Pharmacokinetic studies were used to determine the optimum time for reinfusing the marrow and provided information on the mechanism of the mucositis. In conclusion, PEC protocol showed a high efficacy with 94% response rate (68.5% CR) among the 35 evaluable pts. Patients refractory to conventional treatment did not appear to benefit from this intensive chemotherapy. However, it appears that it may be useful for patients with relapses sensitive to salvage therapy. Encouraging results were obtained with the PEC protocol administered as early consolidation for patients with identifiable risk factors at diagnosis. A multicenter, randomized trial is currently underway in France to compare this approach with standard conventional chemotherapy.

Adolescent↗
PubMed1990

[Chemotherapeutic intensification in germ cell tumors].

Chemotherapy has dramatically improved the prognosis of non-seminomatous germ cell tumors (NSGCT). However, some patients relapse and others are refractory to first line chemotherapy. We studied a salvage chemotherapeutic regimen with etoposide 75 gm/m2/day, and cisplatin 40 mg/m2/day, days 1-5 and Ifosfamide 3 g/m2/day, days 1 and 2 (VIhP regimen) in 32 patients. We observed 8 complete remissions with 4 long-term NED patients. Hematological, neurological and renal complications were frequent. In 16 other cases, a protocol using high dose chemotherapy, followed by autologous bone marrow rescue was studied. We observed 8 complete remissions with 4 long-term NED patients. These observations support a dose/effect relationship. A French randomized trial testing high dose chemotherapy, followed in some cases by an autologous marrow graft in poor risk advanced NSGCT, has recently been activated.

Adolescent↗
PubMed1989

[Paraneoplastic hypercalcemia and ovarian seminoma. Review of the literature and etiological discussion apropos of a case].

We report a case of hypercalcemia in a 20-year-old woman with an ovarian seminoma. She had neither evidence of bone metastasis nor hyperparathyroidism. Hypercalcemia was well controlled by corticotherapy and chemotherapy, and remained normal after remission was obtained. Different patterns in paraneoplastic hypercalcemia are detailed, with emphasis on PTH-related proteins and vitamin-D metabolites. Eleven cases of neoplasm with hypercalcemia and elevated calcitriol level are reported in the literature. One of them is a seminoma. These elevated levels could be related either to a PTH-like protein, either to 1 alpha-hydroxylase activity in some tumoral cells. Three other cases of seminoma associated with hypercalcemia without dosage of vitamin-D metabolites are reported. Dosage of calcitriol might be performed in paraneoplastic hypercalcemia of seminoma.

Adult↗
PubMed1988

Salvage chemotherapy in refractory germ cell tumors with etoposide (VP-16) plus ifosfamide plus high-dose cisplatin. A VIhP regimen.

Twenty-one patients with refractory germ cell tumors were treated with a chemotherapy regimen containing etoposide (VP-16) (V) 75 mg/m2/day (days 1 to 5), ifosfamide (I) 3 g/m2/day (days 1 and 2) with a 3.6 g/m2 continuous infusion of mesna (days 1 and 2), and high-dose cisplatin (hP) 40 mg/m2/day (days 1 to 5). The regimen is referred to as VIhP. Nineteen patients were evaluable for response. Five patients (26%) achieved a complete remission (CR) with chemotherapy alone, and three patients (16%) were in CR after resection of a residual nonactive tumoral mass (e.g., necrosis and/or fibrosis and/or mature teratoma). Thus, a CR rate of 42% was achieved with the entire treatment. One additional patient achieved a CR after resection of active, bulky disease. Among the responders, five patients (26%) are still alive and disease-free at 6, 7, 9, 10, and 18 months after the initiation of the chemotherapy. However, toxicity was heavy in this protocol. Severe myelosuppression was observed with 10 patients developing aplasia and six patients documented sepsis. Reversible Grade 1-2 renal toxicity occurred in 14 patients, and Grade 2-3 peripheral neurotoxicity occurred in six patients. No hemorrhagic cystitis was encountered. We conclude that a VIhP regimen seems to play an active role in refractory germ cell tumors although the presence of high-dose cisplatin in this regimen does not appear to improve the response rate compared to that of a conventional dose. Toxicity, which seems to be enhanced, is currently under detailed study. However, the contribution of VIhP as a first-line treatment in poor prognosis, advanced germ cell tumors warrants further study.

Adolescent↗
PubMed1988

5-Fluorouracil, doxorubicin, and cisplatin regimen in adrenal cortical carcinoma.

Five patients with metastatic adrenal cortical carcinoma were treated with a combination of 5-fluorouracil (5-FU), doxorubicin, and cisplatin. All patients had a nonhormone producing tumor. A large tumor burden made them unsuitable for mitotane treatment. Treatment could be evaluated in four patients. A complete remission was achieved in one patient and lasted for 38 months: this patient is still alive and free of disease. Furthermore, a minor response and a disease stabilization also were observed. Cardiotoxicity occurred in one patient and myelosuppression in another patient. This regimen appears to be an active combination for the treatment of metastatic adrenal cortical carcinoma.

Adrenal Cortex Neoplasms↗
PubMed1987

Clinical pharmacology of high-dose etoposide associated with cisplatin. Pharmacokinetic and metabolic studies.

Twelve patients were treated with high-dose etoposide give alone or in combination with cisplatin during a clinical trial. We had previously observed, in some subjects who received a combination of high-dose etoposide (350 mg/m2/day X 5 days) and cisplatin (40 mg/m2/day X 5 days), delayed hematological recovery after autologous bone marrow transplantation. Therefore we investigated the pharmacokinetics of etoposide and did not find any drug interaction with cisplatin. In four of these patients we also monitored etoposide salivary excretion and found saliva to plasma ratios in the range 0.003-0.25. The secretion of etoposide into saliva may be of concern if we consider that peroxidases in salivary glands are able to oxidize the drug leading to free radicals. In vitro experiments showed that sulfhydryl compounds are able to inhibit the formation of the etoposide radical. Furthermore, we were able to detect the presence of a new biotransformation product of etoposide in plasma samples of some patients. Fast atom bombardment liquid chromatography-mass spectrometry allowed us to identify this metabolite as the etoposide aglycone. The presence of this derivative in plasma 48 h after the last injection prompted us to delay autologous bone marrow transplantation to 72 h after the end of treatment, since the aglycone is cytotoxic and able to induce DNA strand breaks mediated by topoisomerase II.

Adult↗