From December 1979 to August 1982 158 patients were registered for an adjuvant chemotherapy (CT) study COSS -80. To compare the effect of cisplatin (CPL) to that of the drug combination bleomycin, cyclophosphamide, and dactinomycin (BCD), patients were randomized to receive either drug(s) within a course of sequential multidrug CT including doxorubicin and high-dose methotrexate (HDMTX). Definite surgery was done 10-18 weeks after the start of CT. Patients were randomized a second time to receive or not to receive fibroblast interferon in addition to CT beginning at week 16. At a median observation time of 19.5 months (range, 4-34 months), 116 (73%) of 158 patients were continuously disease-free (CDF). After exclusion of 42 patients because of some deviation in history and/or management, 86 (74%) of 116 patients actually were CDF with a 30-month calculated CDF-rate of 68%. There was no difference in CDF rates in the patients receiving BCD versus CPL or receiving interferon versus no interferon. Whereas, in comparison to the previous study COSS -77, the over-all increase in CDF rate does not reach statistical significance, it does, however, for the younger (less than or equal to 12 years) and for male patients, which is assumed to be the effect of increasing the methotrexate dose from 6 to 12 g/m2 in the COSS -80 study.
The clinical presentation of the disease and the results of treatment in 42 patients with malignant peripheral neuroectodermal tumors (MPNT) entered into the Cooperative Ewing's, soft tissue, and neuroblastoma trials of the German Society of Pediatric Oncology were retrospectively analyzed. Within the Ewing's sarcoma trial, patients with chest wall lesions were particularly analysed for MPNT features. The period of observation ranged from 15 to 86 months; the median relapse-free time was 24 months. There were 28 male and 14 female patients, the median age of patients was 15 years (range, 9 months-23 years). Thirty-two patients had l o c a l i i disease (MO), and ten patients presented with primary metastases (Ml). The predominant location of the tumors was the thoracopulmonary region, followed by the extremities, the abdominal/pelvic, and head and neck region. Thirty-one of 42 tumors invohed the adjacent bone. The disease-free survival according to Kaplan-Meier life-table analysis was 56% f 11% for Stage MO patients at 3 years. Nine of ten patients with M1 disease showed progression of their disease. Most patients had combined modality treatment with surgery, chemotherapy and radiation therapy. Best results were obtained with extensive surgery. Radiation doses ranged from 20 to 60 Gy and could not be correlated with the outcome of the disease. Most recurrences occurred at the site of the primary tumor. In patients with primary chemotherapy after biopsy-proven diagnosis, the responsiveness of this disease to chemotherapy could be demonstrated. Combination chemotherapy containing anthracyclines and high doses of alkylating agents appeared superior. Cancer 61:349-357, 1988. ALIGNANT PERIPHERAL neuroectodermal tumors M (MPNT) form a distinct entity from other malignant small round cell tumors such as neuroblastoma, Ewing's sarcoma, rhabdomyosarcoma, and lymphoma and were first distinguished by their light and electron microscopic features. Their neuroectodermal origin was then confirmed by immunohistochemical rnethod~.~" Cytogenetic studies demonstrated a special relation of MPNT to Ewing's sarcoma.'-1° The MPNT arise in soft tissue and bone.
In therapy study ALL-BFM 81 633 previously untreated patients with acute lymphoblastic leukemia (ALL) less than 18 years of age have been recruited from April 1, 1981 to September 30, 1983 and treated in 37 institutions throughout West-Germany and Austria. Here only therapy results of 611 patients with non-B-ALL are presented. Patients with ALL of B-type are described elsewhere. In this fourth consecutive trial of the BFM study group three major questions have been asked: 1. Is it possible to assess the individual risk for relapse more accurately by the use of a risk factor rather than by the risk score which was the discriminator in studies ALL-BFM 76 and ALL-BFM 79? Does this risk factor discriminate more precisely patients at the highest risk for relapse? Offers more intensive risk-adapted therapy to this patient group a better chance for disease-free survival? 2. In patients at a standard risk for relapse with a risk factor below 1.2--approximately 60% of patients with non-B-ALL--can radiotherapy for prevention of CNS disease effectively be replaced by chemotherapy (intermediate dose Methotrexate)? 3. It is possible to reduce duration of maintenance therapy by 6 months to a total duration of 18 months with no unfavorable effect? To assess the radiation problem in standard risk patients and to evaluate the importance of duration of maintenance therapy two randomisations have been utilized. After a median duration of study ALL-BFM 81 of 4 1/2 years and 3 1/4 years after the study had been closed (date of evaluation January 1, 87) the answers are as follows: 1. For the majority of patients risk-adapted therapy had a curative effect. The probability for event-free survival (EFS) in standard risk patients in slightly above 70%, in medium risk patients 67%. In high-risk patients risk-adapted therapy did not improve prognosis, the EFS being still in the order of 50%. A good assessment of the individual risk for relapse is possible by the newly introduced risk factor. This principle is superior to the risk score used in former studies ALL-BFM 76 and ALL-BFM 79 because a low risk group (risk factor below 0.8) could be identified including approximately 25% of all patients with non-B ALL. Selection, quality, and timing of therapy elements remain the decisive prognostic factors, however. 2. Standard risk patients with a risk factor below 0.8 can effectively be protected for CNS relapse by treatment with intermediate dose Methotrexate.(ABSTRACT TRUNCATED AT 400 WORDS)
Twenty-two patients with selective IgA deficiency were studied for the presence of serum precipitins to bovine milk, bovine and fetal calf serum, and circulating immune complexes. Fifty-nine percent had circulating immune complexes, 50% had milk precipitins, 23% had precipitins to bovine serum, and 13% had precipitins to fetal calf serum. All patients with precipitating antibodies against milk or against bovine or fetal calfserum had circulating immune complexes and the precipitin titers correlated with the amount of circulating immune complexes. After one IgA-deficient patient had drunk 100 ml of milk, studies of sequential serum samples showed the presence of casein in the circulation at 60 min and the appearance of increasing amounts of immune complexes for 120 min. These findings are interpreted to indicate that in human beings the IgA system may provide a major barrier to absorption of immunogens from the gastrointestinal tract.
Synaptophysin, an Mr 38,000 integral membrane glycoprotein of neurotransmitter vesicles, has been identified in diverse primary neuroendocrine (NE) tumors of both neural and epithelial origin (Wiedenmann and co-workers, Proc Natl Acad Sci USA 1986; 83: 3500-3504). In the present study, metastases of several types of NE tumors, including medullary thyroid carcinoma, gastrinoma, insulinoma, small (oat) cell carcinoma of the lung, gastrointestinal carcinoid, and neuroblastoma, were examined for the presence of synaptophysin by immunocytochemistry, with the use of tissue sections as well as centrifuged cell suspensions and by immunoblotting of tumor proteins. The results show that expression of synaptophysin can be maintained during formation of metastases. Therefore, the authors propose that synaptophysin antibodies be used for the positive identification of metastatic NE tumors, notably in differential diagnosis. The possible implications of these findings for tumor diagnosis are discussed.
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