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Biomedical subjects

C Sebesta

Publications and source records attributed to C Sebesta.

23 records · Page 2Linked to original sources

[The value of sequential CD 34 measurement for carrying out stem cell pheresis].

The recent significant improvement in disease-free survival in patients with certain haematological malignancies is due to high-dose chemotherapy and subsequent autologous bone marrow and/or stem cell transplantation. The proliferation and egression of stem cells into the peripheral blood must first be stimulated by defined chemotherapy and/or by administration of cytokines. However, the increase of circulating stem cells in peripheral blood is limited to only a few days. By immunologically analysing white blood cells for the expression of the surface antigen CD 34 it is possible to calculate the numbers of haematopoietic progenitor cells. Thus, besides monitoring haematopoietic recovery, the estimation of CD34+ cells in the peripheral blood can be used to indicate the optimal time point for stem cell collection. Two to four stem cell pheresis (one per day) may then yield sufficient stem cells to enable the safe and rapid reconstitution of haematopoiesis following supralethal chemotherapy.

Antigens, CD↗

Prolactin: a possible mediator of graft-versus-host disease following allogeneic bone marrow transplantation in humans.

We have evaluated post-transplant serum levels of prolactin with respect to source of donated bone marrow (BM) and to the occurrence of either acute and/or chronic graft-versus-host disease (GVHD). Forty adult patients underwent allogeneic (n = 35), autologous (n = 4) or syngeneic (n = 1) bone marrow transplantation for haematologic malignancy (n = 32) or aplastic anaemia (n = 8), respectively. Serum prolactin levels measured within 100 days post-transplant were related to patients' sex but otherwise proved unrelated to the occurrence or severity of GVHD and to the source of the BM graft (allogeneic, autologous, syngeneic). Beyond day 100 post-graft, however, serum prolactin levels proved significantly elevated in allogeneic recipients exhibiting chronic GVHD (p = 0.0004) and were unrelated to the patients' sex. In this group of patients, serum prolactin levels were not related to serum cyclosporin levels. In allogeneic recipients exhibiting no GVHD, serum prolactin levels were positively correlated with serum cyclosporin levels (p < 0.05). These data show that serum prolactin levels are significantly elevated beyond day 100 post-graft in recipients exhibiting chronic GVHD. Prolactin, a hormone recently shown also to be released by mononuclear leucocytes and to be involved in lymphocyte activation plays a hitherto unrecognized role in the pathogenesis of GVHD in humans.

Adolescent↗

A phase I-II study of epirubicin, 5-fluorouracil, and leucovorin in advanced adenocarcinoma of the stomach.

BACKGROUND: To determine the maximum tolerated dose of epirubicin for use in combination with 5-fluorouracil (5-FU) and low-dose leucovorin (LV), a Phase I-II trial was conducted in 37 patients with advanced gastric carcinoma. METHODS: The doses of 5-FU (425 mg/m2) and LV (20 mg/m2), both given intravenously on days 1-5, were held constant while the dose of epirubicin was escalated in cohorts of patients (beginning dose, 50 mg/m2 on day 1). Cycles were repeated every 4 weeks. RESULTS: Significant gastrointestinal symptoms and myelosuppression were observed infrequently at the initial dose level. At a dose of 60 mg/m2 of epirubicin on day 1, however, five of eight patients had significant mucosal toxic effects during the first cycle of therapy. In addition, two patients treated at this dose level had Grade 4 granulocytopenia with insufficient recovery to permit a second course by day 28, and one patient each had severe diarrhea and nausea and vomiting. Among 37 patients with assessable disease, there were 3 complete and 11 partial responses (response rate, 38%). CONCLUSIONS: LV modulation of 5-FU can be incorporated safely into combination chemotherapy with epirubicin and provides a relatively active regimen for treatment of disseminated gastric cancer.

Adenocarcinoma↗

Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.

OBJECTIVES: To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care. DESIGN: Randomised study. SETTING: Gastrointestinal oncology departments. PATIENTS: 40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic. INTERVENTIONS: Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle. MAIN OUTCOME MEASURES: Length of survival and quality of life score with an optimised functional living index-cancer scale. RESULTS: Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm. CONCLUSIONS: In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.

Adenocarcinoma↗

Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin.

Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.

Adenocarcinoma↗