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  • 1
    Electronic Resource
    Electronic Resource
    High-dose chemotherapy and autologous hematopoieticstem cell transplantation in patients with second primary malignancies (1997)
    Springer
    Hematology and cell therapy 39 (1997), S. 79-83 
    Details
    ISSN: 1279-8509
    Keywords: Autologous bone marrow transplantation ; Autologous peripheral blood stem cell transplantation ; High-dose chemotherapy ; Second primary neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We treated 500 patients with high-dose chemotherapy and autologous bone marrow or autologous peripheral blood stem cell transplantation. Treated conditions included leukemia, lymphoma, breast cancer, lung cancer, germ-cell carcinoma, and other solid tumors. 10/500 (2%) of patients were treated for a second malignancy diagnosed 12 months to 25 years after their initial neoplasm. Four of these ten patients are in complete remission (CR) of both malignancies at a median follow-up of 29+ months after high-dose chemotherapy and autotransplantation. None of these patients would have been eligible for high-dose chemotherapy and autotransplantation by conventional selection criteria which usually exclude patients with a history of prior malignancies. Conclusion. Conventional exclusion criteria for high-dose chemotherapy and autotransplantation may not adequately reflect the prognosis of patients with second or secondary malignancies treated with this therapeutic modality. High-dose chemotherapy and autologous hematopoietic stem cell transplantation may be of true benfit in selected cases of secondary malignancies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s00282-997-0079-3
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  • 2
    Electronic Resource
    Electronic Resource
    Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer (1997)
    Springer
    Annals of oncology 8 (1997), S. 57-64 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; non-small-cell lung cancer ; peripheral blood stem cell transplantation ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I/II trial to assess the feasibilityand activity of combination chemotherapy with etoposide, ifosfamide,cisplatin, and epirubicin in limited-stage (LS, stage I–IIIB) andextensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-pointswere treatment-related morbidity and mortality, response rate, duration ofresponse, and survival. Patients and methods: Chemotherapy followed by granulocytecolony-stimulating factor was given at a dose of etoposide (500mg/m2), ifosfamide (4000 mg/m2), cisplatin (50mg/m2), and epirubicin (50 mg/m2) (VIP-E) to107 patients with NSCLC. Twenty-five patients with qualifying responsesproceeded to high-dose chemotherapy with autologous peripheral blood stem celltransplantation after etoposide (1500 mg/m2), ifosfamide(12,000 mg/m2), carboplatin (750 mg/m2) andepirubicin (150 mg/m2) (VIC-E) conditioning. Results of conventional-dose VIP-E: 35 of 102 (34%) evaluablepatients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed nochange (NC); the remainder of patients progressed with therapy (PD). Objectiveresponse rate was 68% (4% CR, 64% PR) in LS-NSCLC and23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration ofsurvival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-yearsurvival was 26% in LS and 2% in ES-NSCLC. Results of high-dose VIC-E: 23 of 24 evaluable patients improved ormaintained prior responses (92%), 1 patient showed NC. Treatmentmortality was 4%. Median duration of survival was 17 months in LS-NSCLCand 10 months in ES-NSCLC. Two-year survival was 30% in LS and8% in ES-NSCLC. Conclusion: Response-rates and survival after conventional-dose VIP-Echemotherapy are comparable to other published trials of combinationchemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage,but unacceptably high in extensive stage NSCLC. Although better response-rateswere achieved in the high-dose arm, they did not translate into improvedsurvival. Most stage IV NSCLC-patients will neither benefit from VIP-Econventional dose, nor from VIC-E high dose chemotherapy. Whether selectedLS-patients with partial or complete responses to VIP-E induction chemotherapycould benefit from dose intensification in an adjuvant or neo-adjuvant settingremains to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008209713568
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  • 3
    Electronic Resource
    Electronic Resource
    Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer (1997)
    Springer
    Annals of oncology 8 (1997), S. 49-56 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; peripheral blood stem cell transplantation ; small-cell lung cancer ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I/II trial to assess the feasibilityand activity of VIP-E chemotherapy in small-cell lung cancer. End-points weretreatment-related morbidity and mortality, response to treatment, duration ofresponse, and survival. Patients and methods: Two cycles of combination chemotherapy followedby granulocyte colony-stimulating factor (G-CSF) were given at a dose ofetoposide (500 mg/m2), ifosfamide (4000mg/m2), cisplatin (50 mg/m2), and epirubicin(50 mg/m2) to 100 consecutive patients with SCLC. Thirtypatients (19 with LD, and 11 with ED SCLC) proceeded to VIC-E high-dosechemotherapy with autologous peripheral blood stem cell transplantation(PBSCT) at a cumulative dose of etoposide 1500 mg/m2,ifosfamide 12,000 mg/m2, carboplatin 750 mg/m2and epirubicin 150 mg/m2 (VIC-E). Surgical resection ofprimary tumor was attempted at the earliest feasible point. Thoracicirradiation was given after completion of chemotherapy. Results of conventional-dose VIP-E: 97 patients were evaluable forresponse. Objective response rate was 81% in LD-SCLC (33% CR,48% PR; excluding patients in surgical CR) and 77% in ED-SCLC(18% CR, 58% PR). Treatment mortality was 2%. Mediansurvival was 19 months in LD-SCLC and 6 months in ED-SCLC. Two-year survivalwas 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: All 30 patients improved on or maintainedprior responses. Four patients (13%) died of treatment-relatedcomplications. Median survival was 26 months in LD-SCLC and 8 months inED-SCLC. Two-year survival was 53% in LD and 9% in ED SCLC. Conclusion: VIP-E chemotherapy is an effective induction therapy forSCLC. Compared with traditional protocols such as ACO orcarboplatin/etoposide, response rates are slightly improved, while survivalis not different. In the LD SCLC subgroup, high-dose chemotherapy improvedresponse rates and survival, especially for patients in surgical CR prior tohigh-dose therapy. In ED SCLC, however, higher response-rates did nottranslate into improved survival. Selected LD-SCLC patients with good partialor complete remissions after prior therapy may benefit from HDC and PBSCT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008232329498
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  • 4
    Electronic Resource
    Electronic Resource
    Expression of the Fas antigen on primary human leukemia cells (1995)
    Springer
    Annals of hematology 70 (1995), S. 15-17 
    Details
    ISSN: 1432-0584
    Keywords: Fas antigen ; Apoptosis ; Leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antigen defined by the monoclonal antibody anti-Fas can mediate apoptosis, is associated with the receptor for tumor necrosis factor, and is expressed on a limited number of human tissues. In this study we analyzed the expression of Fas on primary human leukemic cells and on mononuclear cells from other hematologic disorders. A total of 95 samples of blood or bone marrow were studied by indirect immunofluorescence. These samples included the normal controls, 47 cases of acute myelogenous leukemia (AML), 11 cases of acute lymphoblastic leukemia (ALL), 21 cases of leukemic lymphoma, seven cases of chronic myelogenous leukemia (CML), five cases of plasma cell leukemia or multiple myeloma, and five cases of myelodysplastic or myeloproliferative syndromes. Normal controls were negative without exception. Among AML, 13/47 cases (28%) were positive; among ALL, 1/11 cases (9%) was positive; among leukemic lymphomas, 3/21 cases (14%) were positive. In a case of plasma cell leukemia which strongly expressed the Fas antigen, we demonstrated that the antibody mediates cell lysis, which was synergistically enhanced by the addition of rabbit complement. In patients with AML, Fas positivity had no obvious clinical relevance. Taken together, our results show that approximately 30% of cases of AML and occasionally other leukemias express the Fas antigens, whereas normal controls are negative in our test system. These findings may be useful in the treatment of refractory leukemias or may permit the purging of autologous transplants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01715376
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  • 5
    Electronic Resource
    Electronic Resource
    Expression of the Fas antigen on primary human leukemia cells (1995)
    Springer
    Annals of hematology 70 (1995), S. 15-17 
    Details
    ISSN: 1432-0584
    Keywords: Key words Fas antigen ; Apoptosis ; Leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary  The antigen defined by the monoclonal antibody anti-Fas can mediate apoptosis, is associated with the receptor for tumor necrosis factor, and is expressed on a limited number of human tissues. In this study we analyzed the expression of Fas on primary human leukemic cells and on mononuclear cells from other hematologic disorders. A total of 95 samples of blood or bone marrow were studied by indirect immunofluorescence. These samples included the normal controls, 47 cases of acute myelogenous leukemia (AML), 11 cases of acute lymphoblastic leukemia (ALL), 21 cases of leukemic lymphoma, seven cases of chronic myelogenous leukemia (CML), five cases of plasma cell leukemia or multiple myeloma, and five cases of myelodysplastic or myeloproliferative syndromes. Normal controls were negative without exception. Among AML, 13/47 cases (28%) were positive; among ALL, 1/11 cases (9%) was positive; among leukemic lymphomas, 3/21 cases (14%) were positive. In a case of plasma cell leukemia which strongly expressed the Fas antigen, we demonstrated that the antibody mediates cell lysis, which was synergistically enhanced by the addition of rabbit complement. In patients with AML, Fas positivity had no obvious clinical relevance. Taken together, our results show that approximately 30% of cases of AML and occasionally other leukemias express the Fas antigens, whereas normal controls are negative in our test system. These findings may be useful in the treatment of refractory leukemias or may permit the purging of autologous transplants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01715376
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  • 6
    Electronic Resource
    Electronic Resource
    Early-onset secondary malignancies after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (1997)
    Springer
    Annals of hematology 74 (1997), S. 73-77 
    Details
    ISSN: 1432-0584
    Keywords: Key words Autologous bone marrow transplantation ; Autologous peripheral blood stem cell transplantation ; High-dose chemotherapy ; Second and secondary primary neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We treated 500 patients with high-dose chemotherapy (HDC) and autologous bone marrow (ABMT) or autologous peripheral blood stem cell transplantation (PBSCT). Treated conditions included leukemia, lymphomas, breast cancer, lung cancer, germ-cell carcinomas, and other solid tumors. In order to assess relapse of primary malignancy or occurrence of new neoplasms, routine screening after ABMT or PBPCT was performed at regular and close intervals. With a total follow-up of 1358 person-years and a median follow-up of 34 months (range 9–91), 10/500 (2%) patients developed second malignancies after PBSCT or ABMT; i.e., one new cancer occurred every 136 person-years. All malignancies were detected at routine follow-up examinations; and 7/10 diagnoses were made in an asymptomatic phase; 6/10 neoplasms were amenable to complete surgical resection, five of which remain in CR at a median of 23+ months after autotransplantation. We conclude that regular and close follow-up examination of patients after autologous hematopoietic stem cell transplantation may be beneficial, since successful treatment of second malignancies is possible in selected cases after early detection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050260
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  • 7
    Electronic Resource
    Electronic Resource
    Untersuchung der DNS-abhängigen RNS-Polymerase aus menschlichen Leukocyten in einem einfachen zellfreien System (1973)
    Springer
    Journal of molecular medicine 51 (1973), S. 730-734 
    Details
    ISSN: 1432-1440
    Keywords: Leukocytes ; Leukemia ; RNA-polymerase ; RNA-metabolism ; Leukocyten ; Leukämie ; RNS-Polymerase ; RNS-Stoffwechsel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Lymphocyten und Leukocyten (Lymphocyten + Granulocyten) werden aus 10–40 ml heparinisiertem Venenblut isoliert, homogenisiert und 15 min bei 1000 g zentrifugiert. In dem aus Zellkernen und Kerntrümmern bestehenden Sediment lassen sich nach Resuspension ca. 70% der DNA-abhängigen RNS-Polymerase-Aktivität des Homogenats nachweisen. Die Reaktion ist von zugesetzter DNS und der Gegenwart aller vier Ribonucleosid-Triphosphate abhängig. Bei chronisch lymphatischer Leukämie, chronisch myeloischer Leukämie und Morbus Hodgkin findet sich unter diesen Bedingungen eine höhere spezifische Aktivität der DNS-abhängigen RNS-Polymerase als bei Normalpersonen.
    Notes: Summary Lymphocytes and leukocytes (lymphocytes + granulocytes), isolated from 10–40 ml of heparinized venous blood, are homogenized, and centrifuged for 15 min at 1000 g. The resuspended pellet, consisting of nuclei and nuclear debris, exhibits ca. 70% of the DNA-depenent RNA polymerase activity of the homogenate. The reaction depends on added DNA template and the presence of all four ribonucleoside triphosphates. In chronic lymphatic leukaemia, chronic myelocytic leukemia, and Hodgkin's disease, the activity of the DNA-dependent RNA polymerase is higher than in normal controls.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468365
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  • 8
    Electronic Resource
    Electronic Resource
    DNS-abhängige RNS-Polymerasen in menschlichen Leukocyten (1975)
    Springer
    Journal of molecular medicine 53 (1975), S. 311-316 
    Details
    ISSN: 1432-1440
    Keywords: DNA-dependent RNA polymerases ; leukemia ; prognostic factors ; DNS-abhängige RNS-Polymerasen ; Leukämie ; prognostische Kriterien
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die spezifischen Aktivitäten der DNS-abhängigen RNS-Polymerasen A und B wurden in von exogener Matrizen-DNS abhängiger Form bei verschiedenen Hämoblastosen bestimmt. Die Aktivitätsbestimmungen erfolgten in Kernhomogenaten isolierter mononucleärer oder segmentkerniger Leukocyten. Eine signifikante Erhöhung der Polymeraseaktivitäten A und B fand sich in den Kernhomogenaten mononucleärer Zellen bei akuter myeloischer Leukämie, während diese bei chronisch-myeloischer Leukämie (signifikant) und chronisch-lymphatischer Leukämie (nicht signifikant) erniedrigt waren. Unter cytostatischer Therapie findet sich eine Angleichung der Polymeraseaktivitäten an den Normbereich. Hiermit ergeben sich möglicherweise neue Kriterien zur Verlaufsbeurteilung von Hämoblastosen unter einer Polychemotherapie.
    Notes: Summary Specific Activities of DNA-dependent RNA polymerases A and B have been determined in nuclei from leukocytes in acute and chronic leukemia. Enzyme activities, dependent on exogenous DNA template, were determined in homogenates of nuclei from isolated mononuclear cells or from isolated granulocytes. Activities of polymerases A and B have been found significantly elevated in homogenates of nuclei from mononuclear cells in acute myelocytic leukemia, while they were found subnormal in corresponding cell fractions from chronic myelocytic leukemia and chronic lymphatic leukemia. During cytostatic treatment polymerase activities were approaching normal values. The prognostic relevance of these data for the course of human leukemia is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01469057
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  • 9
    Electronic Resource
    Electronic Resource
    Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report (1999)
    Springer
    Annals of oncology 10 (1999), S. 561-567 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; hematopoietic growth-factor support ; high-dose chemotherapy ; peripheral blood stem-cell transplantation ; small-cell lung cancer ; treatment toxicity and mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We conducted a phase I–II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I–IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC). Patients and methods: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. Results of standard-dose VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. Results of high-dose VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC. Conclusions: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR 〉2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026453922931
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