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Biomedical subjects

K Pressler

Publications and source records attributed to K Pressler.

17 recordsLinked to original sources
PubMed1998

Multimodality treatment including early high-dose chemotherapy with peripheral blood stem cell transplantation in limited-disease small cell lung cancer.

Combined-modality treatment for limited-disease small cell lung cancer using conventional chemotherapy and chest irradiation achieves high response rates, but most patients relapse over a period of 12 to 16 months. To improve current results, we performed a phase II trial including high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) as part of an early intensification strategy after two cycles of induction therapy. Moreover, to reduce the risk of local recurrence, the protocol included surgical resection in stages I to IIIA patients as well as chest irradiation. Between January 1991 and July 1994, 16 consecutive patients (median age, 50 years; age range, 30 to 59 years) were treated in this single-center trial. The patients received two cycles of conventional chemotherapy consisting of etoposide 500 mg/m2, ifosfamide 4 g/m2, cisplatin 50 mg/m2, and epirubicin 50 mg/m2 plus granulocyte colony-stimulating factor 5 microg/kg at a 3-week interval, followed by PBPC collection and subsequent high-dose etoposide 1,500 mg/m2, ifosfamide 12 g/m2, carboplatin 750 mg/m2, and epirubicin 150 mg/m2 with PBPCT. The duration of the entire chemotherapy program was 9 weeks. Six of 10 patients in stages I to IIIA and one of six patients in stage IIIB received neoadjuvant or adjuvant surgery before high-dose chemotherapy, followed by thoracic (50 Gy) and prophylactic (30 Gy) cranial irradiation. Hematopoietic reconstitution after high-dose chemotherapy occurred within 11 days (range, 9 to 17 days) for both neutrophils (>0.5 x 10(9)/L) and platelets (>20 x 10(9)/L). Oral mucositis (World Health Organization grade 2 to 4) was the predominant nonhematologic toxicity, which was observed in 12 of 16 patients. One patient developed neutropenic septicemia with fatal multiorgan failure. At a median follow-up of 44 months (range, 32 to 77 months) after PBPCT, nine patients are alive and well, resulting in a disease-free and overall survival rate of 56.3% +/- 12.4%. The median overall survival has not yet been achieved. None of the patients who had surgery relapsed or died after therapy. All relapses occurred within the first 12 months after PBPCT. Patients in stages I to IIIA (10 patients) had a 70% +/- 14% overall survival rate at 4 years, while patients in stage IIIB (six patients) had a 33% +/- 19% survival rate at 4 years, with a median survival of 17 months posttransplant. These data demonstrate that a multimodality treatment including early high-dose chemotherapy with PBPCT may lead to a prolonged disease-free survival in the majority of patients. A randomized phase III study has now been initiated to prospectively investigate the role of high-dose chemotherapy, surgery, and chest irradiation in the multidisciplinary approach to limited-disease small cell lung cancer.

Adult↗
PubMed1995

Use of high-dose etoposide/ifosfamide/carboplatin/epirubicin and peripheral blood progenitor cell transplantation in limited-disease small cell lung cancer.

Conventional-dose chemotherapy for limited-disease small cell lung cancer has resulted in high response rates, but rarely in a cure. In an ongoing phase I-II trial, limited-disease small cell lung cancer patients received high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation as part of an early intensification strategy after two cycles of induction chemotherapy. Eligible patients (n = 18) were initially treated with two cycles of etoposide (500 mg/m2), ifosfamide (4 g/m2), cisplatin (50 mg/m2), epirubicin (50 mg/m2) and granulocyte colony-stimulating factor to combine an effective, standard-dose chemotherapy regimen with simultaneous mobilization of PBPCs. Patients who were in partial remission or complete remission after two cycles of induction chemotherapy received high-dose intensification chemotherapy with cumulative doses of 1,500 mg/m2 etoposide, 12 g/m2 ifosfamide, 750 mg/m2 carboplatin, and 150 mg/m2 epirubicin, followed by autologous PBPC transplantation and granulocyte colony-stimulating factor. The duration of the complete chemotherapy program was 9 weeks. All patients received chest irradiation posttransplantation (50 Gy), and those in complete remission received additional prophylactic cranial irradiation (30 Gy). To date, 13 patients with a median age of 49 years (age range, 34 to 62 years) have been treated within this combined-modality treatment protocol. At a median follow-up of 14 months (range, 3 to 45 months) after transplantation, 11 patients were alive and nine were still in complete remission. Nonhematologic toxicity was acceptable; World Health Organization grades 2 to 4 oral mucositis was the most frequently observed (85%) adverse event. No toxic deaths were observed, and hematopoietic reconstitution occurred rapidly after PBPC transplantation; platelet transfusion independence (> 20,000 microL) and neutrophil counts greater than 500 microL were observed at study day 12+. The median survival time was not yet reached. These preliminary data demonstrate that early, high-dose chemotherapy and PBPC transplantation followed by local radiotherapy is safe and may lead to prolonged disease-free survival in some patients. Prospective, randomized studies in a larger series of patients will be required to provide definitive proof of the role of early high-dose chemotherapy in the management of limited-disease small cell lung cancer.

Adult↗
PubMed1993

Peripheral blood progenitor cells mobilized by chemotherapy plus granulocyte-colony stimulating factor accelerate both neutrophil and platelet recovery after high-dose VP16, ifosfamide and cisplatin.

We report on the chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood progenitor cells (PBPCs) and their impact on haematopoietic recovery following high-dose chemotherapy. Twenty-four patients with advanced solid tumours or lymphomas received standard-dose chemotherapy with VP16, ifosfamide and cisplatin (VIP) followed by filgrastim (G-CSF; 5 micrograms/kg s.c. daily for 14 d) for the prevention of chemotherapy induced neutropenia and for the simultaneous mobilization of PBPCs. Maximal numbers of progenitors of different lineages were reached at day 11 (range 9-14) after VIP chemotherapy. A median of 0.415 x 10(9)/l CD34+ cells (range 0.11-1.98), 9000 CFU-GM/ml (range 2800-17,700), 3500 BFU-E/ml (range 400-10,800) and 200 CFU-GEMM/ml (range 0-4400) were recruited. One single apheresis yielded a median of 1.6 x 10(8) mononuclear cells/kg (range 0.2-5.4) or 5.4 x 10(6) CD34+ cells/kg body weight (range 0.2-24.2). Fourteen patients who showed at least a partial remission after two cycles of the standard-dose chemotherapy regimen were subjected to high-dose VIP chemotherapy (cumulative doses of 1500 mg/m2 VP16, 12 g/m2 ifosfamide and 150 mg/m2 cisplatin) with or without PBPC support. The first six patients were treated with growth factors only (IL-3/GM-CSF) and did not receive PBPCs, whereas the following eight patients were supported with PBPCs in addition to IL-3 and GM-CSF. Neutrophil recovery as well as platelet recovery were significantly faster in patients receiving PBPCs with a median of 6.5 d below 0.1 x 10(9) neutrophils/l and 3 d below 20 x 10(9) platelets/l as compared to 10.5 d and 8 d in control patients receiving growth factors only. The accelerated platelet recovery in patients supported with PBPCs might be explained--in the absence of detectable colony-forming units megakaryocyte--by the presence of glycoprotein IIb/IIIa+, non-proliferating endomitotic megakaryocytic precursor cells within G-CSF mobilized PBPCs. Our data demonstrate that chemotherapy plus G-CSF mobilized PBPCs accelerate both neutrophil and platelet recovery after high-dose VIP chemotherapy in patients with solid tumours or lymphomas.

Adult↗
PubMed1992

Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following standard-dose combination chemotherapy with etoposide, ifosfamide, and cisplatin.

PURPOSE: To combine the benefits of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery and recombinant human interleukin-3 (rhIL-3) on platelet recovery, we applied standard-dose chemotherapy with the combined administration of IL-3 and GM-CSF to investigate their efficacy and toxicity. PATIENTS AND METHODS: Thirty-six patients with advanced malignancies were treated with etoposide (VP16) 500 mg/m2, ifosfamide 4 g/m2, and cisplatin 50 mg/m2 (VIP), followed by the sequential administration of IL-3 (days 1 to 5 subcutaneously [SC]) and GM-CSF (day 6 to 15 SC). Control patients received GM-CSF alone or were treated without hematopoietic growth factors. RESULTS: Subcutaneous IL-3 and GM-CSF treatment was well tolerated; low-grade fever (World Health Organization grade 1 to 2) was the only consistent clinical symptom. Neutrophil recovery documented that the duration of neutropenia less than 0.1 x 10(9)/L or less than 0.5 x 10(9)/L was identical in GM-CSF as well as IL-3 and GM-CSF-treated patients, but was shortened significantly when compared with patients who were treated without cytokines. Overall platelet recovery was not different significantly in the three treatment groups. The biologic activity of IL-3 in this cytokine combination was reflected in a variety of effects, which included an increase in basophil and eosinophil counts and the induction of circulating hematopoietic progenitor cells. CONCLUSION: We conclude that after conventional-dose VIP chemotherapy, a shortened treatment course of IL-3 (5 days) sequentially followed by GM-CSF (10 days) combines the benefits of prolonged single GM-CSF treatment on WBC count recovery in all patients and an accelerated platelet recovery only in some intensively pretreated patients.

Adult↗
PubMed1982

Comparison of the antigenicity and tolerance of an influenza aluminium oxide adsorbate vaccine with an aqueous vaccine.

A randomized trial was carried out in 189 adult subjects to test the antigenicity and tolerance of two experimental influenza vaccines, one adsorbed onto aluminium oxide and the other one aqueous, with equal antigen contents. Blood samples for antibody assays, using the haemagglutination inhibition test and the neuraminidase inhibition test, were taken before and 30, 90 and 180 days after vaccination. The results showed that the adsorbate influenza vaccine had a superior immunogenic action to the aqueous vaccine at the same dose rate. There were no significant differences between the tolerances of the two vaccines, which were injected with a needle. About 81% of the vaccinated subjects showed no subjective or objective signs of intolerance. Systemic reactions, which were reported by 9% of the vaccinated subjects, were verified by the doctor in only 2% of cases.

Adolescent↗
PubMed1982

Antibody formation after vaccination with adsorbed and non-adsorbed A/New Jersey/8/76 influenza vaccines.

A study was carried out to determine the titres of haemagglutination inhibiting and neuraminidase antibodies after vaccination of 90 subjects, aged 19 to 35 years, with three aluminium oxide adsorbate and three fluid monovalent influenza A/New Jersey/8/76 vaccines with 54, 108 and 216 IU/dose. Blood samples were taken 1, 3 and 6 months after vaccination. The serological findings showed that adsorbate vaccines induced higher antibody titres than did fluid vaccines with double the antigen content. 'Unprimed persons' reacted to the adsorbate vaccine vaccination with a much higher antibody formation response.

Adsorption↗
PubMed1975

[Vaccination of children against influenza].

In 19 children of 1-7 years of age hemagglutination inhibiting antibodies were measured before and after vaccination against influenza. Before vaccination the serum titers have been markedly lower than in adults. A single vaccination with Alorbat, a vaccine of representative strains of influenza virus inactivated and adsorbed to aluminumoxide, was followed by the same rise of titer as in adults. Therefore with this vaccine a single vaccination is effective in children, and a booster 4 weeks later, as recommended otherwise, is not necessary.

Adult↗
PubMed1975

[On the antigenicity of influenza virus aluminum oxide adjuvant vaccine "Alorbat" in man (author's transl)].

The antihemagglutinin (AH) and antineuraminidase (AN) antibody response in 35 humans to a single vaccination with the aluminum oxide adsorbed influenza virus vaccine "Alorbat" was investigated. The vaccine contained the strains A/Hong Kong/1/68 (H3N2), A/Hong Kong/107/71 (H3N2), A/England/42/72 (H3N2) and B/Iowa/1/69. the rates of significant AH antibody titer increase ranged from 51 percent (against A/Hong Kong/68), 69 (against A/Hong Kong/71), 63 (against A/England/72) to 83 percent (against B/Iowa/69). Persons with high prevaccination titers failed to yield postvaccination antibody titer increase (table 1). Antibody titer increase measured against the neuraminidase of A/England/72 virus was recorded in 60 percent and against the neuraminidase of B/Iowa/69 virus in 31 percent (table 2). Using the neuraminidase of the recombinant strain (A/Bel/42 (H0)-A/Sing/57 (NS) as test antigen a significant titer increase in 32 percent of sera tested was found (table 2). The AN antibody titers against A/England/72 exceeded the titers against the A/Bel-A/Sing recombinant 3,67-5,42 fold. This finding was shown to be caused by additional reaction of anti-H3 antibody with A/England/72 virus resulting in steric hindrance of neuraminidase activity.

Adjuvants, Immunologic↗
PubMedDate not supplied

Serological response to an adsorbed killed trivalent influenza vaccine (including A/New Jersey 8/76 antigen).

The serological evaluation of a trivalent vaccine (A/Victoria 3/75, A/New Jersey 8/76, B/Hong Kong 8/73) has been done by HI and NI tests on 77 paired sera representing all age groups. The percentage of seroconversion induced by the antigens A/Victoria 3/75, A/New Jersey 8/75 and B/Hong Kong 8/73 were 85.95 and 89.6 respectively and the percentage of protective antibodies (greater than 1:40) were 84.4, 72.7 and 80.5 respectively.

Adolescent↗