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Biomedical subjects

S Bielack

Publications and source records attributed to S Bielack.

13 recordsLinked to original sources
PubMed1991

Transplantation with blood stem cells.

Peripheral blood stem cell transplantation (PBSCT) offers an alternative to autologous bone marrow transplants (A-BMT), especially in malignant diseases with bone marrow contamination. The presence of hemopoietic precursors in peripheral blood has been documented in several animal models and in humans. While many of these precursors might be committed cells with finite renewal capacity, ample evidence suggests that true pluripotent stem cells are circulating in a number sufficient to enable sustained trilineage engraftment after transplantation. Stem cell mobilization is markedly increased in the early recovery phase after intensive chemotherapy and can be promoted by the administration of various cytokines or polyanionic substances. These effects are used to optimize stem cell harvesting by leukapheresis. Clinical trials of PBSCT have been performed in several hundred patients with various hematological and nonhematological malignancies. Recovery was generally more rapid than after A-BMT. However, the envisioned advantage concerning disease control has not been documented so far.

Hematopoietic Stem Cell Transplantation↗
PubMed1991

Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry.

The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable.

Adolescent↗
PubMed1990

Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86).

In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response.

Adolescent↗
PubMed1990

Osteosarcoma.

Explore the source record for details and available documents.

Humans↗
PubMed1988

[Scintigraphic follow-up of osteosarcoma during neoadjuvant chemotherapy. Results of the cooperative osteosarcoma study of the Society for Pediatric Oncology].

The response of osteosarcomas to preoperative chemotherapy as measured by quantitative 99mTc-diphosphonate scintigraphy was compared with the amount of tumor cell destruction found histologically in the resected specimens. 3-phase bone scintigraphy, with determination of tumor/non-tumor (T/NT) ratios, allowed accurate prediction of tumor response in 28 of 30 tumors (accuracy = 93%) after completion and in 10 of 12 osteosarcomas (83%) at the half-way stage of preoperative chemotherapy, when only those tumors were evaluated which showed convergent changes of T/NT ratios in the perfusion and the mineral phase. At the half-way stage, however, evaluation of chemotherapy effects was complicated in 12 of 23 osteosarcomas by diverging T/NT ratios. In contrast, quantification and mapping of the tumor plasma volume and 99mTc-diphosphonate clearance on parametric images predicted correctly the histological tumor response to chemotherapy in 10 of 11 tumors (91%) after completion and in all 11 cases (100%) at the half-way stage.

Adolescent↗
PubMed1986

Determination of 7-hydroxymethotrexate in human plasma by reversed phase high-performance liquid chromatography.

A rapid and sensitive reversed phase HPLC method was developed for the detection of 7-hydroxymethotrexate (7-OHMTX) which is the main metabolite in human plasma after high-dose methotrexate (MTX) therapy. The simple clean-up procedure of plasma samples described allows the measurement of 7-OHMTX during clinical management of MTX infusions. Elimination kinetics of 7-OHMTX are given from 53 drug cycles of 6 patients.

Child↗
PubMed1985

Kinetics of 7-hydroxy-methotrexate after high-dose methotrexate therapy.

Kinetics of 7-hydroxy-methotrexate (7-OH-MTX) excretion after high-dose methotrexate (MTX) (12 g/m2) therapy were monitored in 93 consecutive drug cycles of 19 adolescent patients with osteosarcoma. A reversed-phase HPLC method was used. Serum elimination was found to be monophasic with a mean half-life of 5.5 h. Shortly after the 4-h MTX infusion period 7-OH-MTX levels exceeded those of the parent compound. By 12 h after MTX infusion 7-OH-MTX levels were 16.5 times higher than those of MTX itself. Autostimulation of MTX metabolism leading to enhanced 7-OH-MTX production after repeated drug cycles was not observed. The production of 7-OH-MTX decreased significantly from the first to the last high-dose MTX cycle of the adjuvant chemotherapy protocol.

Adolescent↗
PubMed1985

7-Hydroxy-methotrexate and clinical toxicity following high-dose methotrexate therapy.

7-Hydroxy-MTX production after consecutive high-dose MTX therapy (12 g/m2) was measured in 7 patients with osteosarcoma by HPLC. 7-Hydroxy-MTX serum values in the last cycle were found to be significantly lower compared with the first high-dose MTX treatment of the adjuvant chemotherapy protocol (COSS 80). Moreover, in another patient highly reduced 7-hydroxy-MTX production was correlated with severe clinical toxicity. As 7-hydroxy-MTX is a 200 fold less potent dihydrofolic acid reductase inhibitor compared with MTX decreased production of the metabolite may lead to enhanced clinical toxicity which may not be predictable monitoring MTX serum levels alone.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

[Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study].

The neoadjuvant study COSS-86 was undertaken aiming at (1) improving the cure rate in osteosarcoma by early intensification of chemotherapy in high risk patients and (2) investigating the effect of intraarterial (i.a.) versus intravenous (i.v.) administration of cisplatinum. (1) Ifosfamide was added to the well proven drugs in osteosarcoma such as doxorubicin, high-dose methotrexate and cisplatinum in patients with large tumor size or/and high portion of chondroid groundsubstance or/and scintigraphic nonresponse after 4 weeks of preoperative chemotherapy. It was given in combination with cisplatinum. (2) The same patients were allocated to either the intraarterial study arm or the intravenous control arm of the study. The response rate (greater than 90% tumor necrosis) of all patients was 75% (88/118). No advantage in response rate was achieved by i.a. infusion of cis-platinum within this highly efficient 4-drug regimen (i.a. 75% (33/44) vs. i.v. 74% (35/47)). The significantly improved response rate in this study results in a better metastasis free survival (MFS) of 77% (+/- 4) at 4 years.

Adolescent↗
PubMedDate not supplied

[Cardiomyopathy after osteosarcoma treatment: a contribution to the cardiotoxicity of adriamycin].

The frequency and severity of clinical and subclinical heart damage were studied in patients who had been treated with adriamycin (ADR) as part of the Cooperative Osteosarcoma Studies (COSS). The study charts of 785 patients from 63 participating institutions were reviewed: The overall incidence of drug-induced congestive heart failure was 2.2% (17 cases, 5 fatal). Late left ventricular function was studied in 29 tumor free survivors 81 +/- 41 month after treatment with 342 +/- 113 mg/m2 ADR. A detailed history and physical exam for signs of overt heart disease were obtained. M-mode echocardiography (ECHO, 29 cases) with evaluation of the fractional shortening rate (FS) and radionuclide ventriculography (RNV, 18 cases) with determination of the systolic ejection fraction at rest (EF) were used to screen for subclinical cardiac disease. Impaired cardiac function leading to pathological values was documented in close to one half of these patients. The frequency and severity of clinical and subclinical heart damage increased with cumulative adriamycin and time since cessation of anthracycline therapy.

Adolescent↗
PubMedDate not supplied

[Neoadjuvant chemotherapy of osteosarcoma. Results of the cooperative studies COSS-80 and COSS-82 after 7 and 5 years].

The analysis of the results of two German Pediatric Oncology (GPO) cooperative, neoadjuvant chemotherapy trials after a followup of 7 (COSS-80) and 5 years (COSS-82) allows several conclusions concerning both systemic and local treatment of patients suffering from osteosarcoma. A metastasis free survival rate (MFS) of 59% was reached in the reduced study group of the first study, COSS-80. In addition to size of the primary tumor, the extent of chemotherapy induced devitalisation was very closely related to the probability of survival without systemic recurrence. Following this observation, it was the aim of the next study, COSS-82, to improve the MFS of patients with poorly responding tumors by altering their postoperative chemotherapy regimen. However, this "salvage" approach failed. Moreover, an effort to reduce treatment related toxicity by sparing some patients from the side effects of two particularly toxic drugs, adriamycin (ADR) and cisplatinum (CDDP), by only giving these postoperatively and only after insufficient tumor response to preoperative therapy, failed (MFS of the study arm of COSS-82 45% at 5 years vs. 68% for the control arm with primary use of ADR and CDDP, p less than 0.05). The value of an effective primary chemotherapy is further enhanced by the observation, that en bloc resection of tumors which were poor responders to preoperative therapy was associated with an increased risk of distant metastases when compared with amputation and rotation plasty, while this was not the case for good responders. In conclusion, both systemic tumor control and optimal local therapy require that all effects drugs are to be used as early as possible in the primary treatment of osteosarcoma, in order to enforce maximum tumor cell destruction and hence an optimistic outlook for the individual patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Chemotherapy of osteosarcoma].

Intensified adjuvant chemotherapy increased the 4-year metastasis-free survival probability from 50% (COSS-77) to roughly 80% (COSS-86). Preoperative chemotherapy was found without recognizable hazard and promoting conservative surgery. Following resection the local failure rate ist significantly higher than after demolitive procedures, including rotation plasty (10.5% vs. 2.5%). Local failures bare a very poor prognosis (19/23 DOD). The acute therapy related mortality is less than 3%. Late toxicities like ototoxicity and cardiotoxicity are intriguing and deserve increased attention. The management of the osteosarcoma patient is a complex and difficult interdisciplinary task which is best performed in centers experienced in the treatment of malignant musculo-skeletal tumors.

Antineoplastic Combined Chemotherapy Protocols↗