SummaryThe majority of the available data on primary central nervous system lymphoma (PCNSL) derive from small unicentric or oligocentric studies. In this multicentre study, we evaluated the response, survival and toxicity in PCNSL patients after carmustine, methotrexate 1·5 g/m2, procarbazine and dexamethasone (BMPD) chemotherapy and searched for prognostic factors. Fifty‐six patients received the BMPD protocol (dexamethasone was given only in course 1). The overall complete response rate to chemotherapy was 61% (34/56). Ten complete responders received whole‐brain irradiation and 24 were not irradiated. Responders to chemotherapy had significantly longer median overall survival than non‐responders (18·2 vs. 9·9 months, P = 0·02). Median survival was significantly longer at institutions accruing at least four patients than at those with fewer patients (31·5 vs. 9·5 months, P = 0·03).

Cyclophosphamide, doxorubicin, vincristine, and prednisone, given every 3 weeks (CHOP-21), is standard chemotherapy for aggressive lymphomas. To determine whether biweekly CHOP (CHOP-14) with or without etoposide is more effective than CHOP-21, 689 patients ages 61 to 75 years were randomized to 6 cycles of CHOP-21, CHOP-14, CHOEP-21 (CHOP plus etoposide 100 mg/m2 days 1-3), or CHOEP-14. Patients in the 2-weekly regimens received granulocyte colony-stimulating factor (G-CSF) starting from day 4. Patients received radiotherapy (36 Gy) to sites of initial bulky disease and extranodal disease. Complete remission rates were 60.1% (CHOP-21), 70.0% (CHOEP-21), 76.1% (CHOP-14), and 71.6% (CHOEP-14). Five-year event-free and overall survival rates were 32.5% and 40.6%, respectively, for CHOP-21 and 43.8% and 53.3%, respectively, for CHOP-14. In a multivariate analysis, the relative risk reduction was 0.66 (P =.003) for event-free and 0.58 (P <.001) for overall survival after CHOP-14 compared with CHOP-21. Toxicity of CHOP-14 and CHOP-21 was similar, but CHOEP-21 and in particular CHOEP-14 were more toxic. Due to its favorable efficacy and toxicity profile, CHOP-14 should be considered the new standard chemotherapy regimen for patients ages 60 or older with aggressive lymphoma.

The combination of cyclophosphamide, doxorubicin, vincristine, and prednisone, given every 3 weeks (CHOP-21) is standard chemotherapy for aggressive lymphomas. To determine whether CHOP given every 2 weeks (CHOP-14) or the addition of etoposide (CHOEP-21, CHOEP-14) can improve results in patients ages 18 to 60 years with good prognosis (normal lactic dehydrogenase [LDH] level), 710 patients were randomized to 6 cycles of CHOP-21, CHOP-14, CHOEP-21 (CHOP plus etoposide 100 mg/m2 days 1-3), or CHOEP-14 in a 2 x 2 factorial study design. Patients in the biweekly regimens received granulocyte colony-stimulating factor (G-CSF) starting from day 4. Patients received radiotherapy (36 Gy) to sites of initial bulky disease and extranodal disease. CHOEP achieved better complete remission (87.6% versus 79.4%; P =.003) and 5-year event-free survival rates (69.2% versus 57.6%; P =.004, primary end point) than CHOP, whereas interval reduction improved overall survival (P =.05; P =.044 in the multivariate analysis). Although the CHOEP regimens induced more myelosuppression, all regimens were well tolerated. CHOEP should be the preferred chemotherapy regimen for young patients with good-prognosis (normal LDH level) aggressive lymphoma.

PURPOSE:This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study.PATIENTS AND METHODS:Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged <or= 60 years with elevated serum lactate dehydrogenase levels were included from 1990 to 1997. Patients with at least a minor response after two cycles of CHOEP (CHOP + etoposide 3 x 100 mg/m(2)) were to receive three further cycles of CHOEP followed by IF radiotherapy (arm A) or one further cycle of CHOEP followed by autologous stem-cell transplantation and IF radiotherapy (arm B).RESULTS:Among 158 patients randomized to arm B, 103 (65%) received HDT. The complete remission rate at the end of treatment was 62.9% in arm A and 69.9% in arm B. With a median observation time of 45.5 months, overall survival for all 312 patients was 63% after 3 years (63% for arm A, 62% for arm B; P =.68). Event-free survival was 49% for arm A versus 59% for arm B (P =.22). Relapse in arm B was associated with a significantly worse survival rate than relapse in arm A (P <.05). Relapse after HDT occurred early (median interval, 3 months). Six patients developed secondary neoplasia, three in arm A and three in arm B.CONCLUSION:Results of the randomized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine, etoposide, cytarabine, and melphalan following shortened standard chemotherapy.

The efficacy of treatment with fotemustine and interferon (IFN) alpha was evaluated in metastatic melanoma. A group of 50 patients with metastatic malignant melanoma were treated with a combination of IFNalpha2b and the nitrosourea fotemustine. The patients received 10 MU IFN three times weekly for 3 weeks and fotemustine at a dose of 100 mg/m2 on days 8, 15 and 22. After a 5-week rest period, patients with stabilized or responding disease received a maintenance therapy consisting of 10 MU IFN three times a week for 1 week followed by administration of fotemustine (100 mg/m2) on day 8. This cycle was repeated every 4 weeks until progression occurred. If there was complete remission (CR), treatment was stopped after an additional three cycles. Toxicity and clinical response were scored according to WHO criteria. Objective response was seen in 14 patients (28%; 95% confidence interval 15.6%-40.4%) with four CR and ten partial responses (PR). The median duration of CR was 73 weeks, that of PR 26 weeks. Toxicity was acceptable, enabling treatment on an outpatient basis. The combination of fotemustine with IFNalpha is effective and well tolerated, but there is no evident advantage over fotemustine monotherapy in the treatment of metastatic melanoma.

The multidrug resistant (MDR) phenotype has been suspected as a major cause of treatment failure in hematologic malignancies. Numerous studies have investigated the expression of the MDR1 gene product, P-glycoprotein, in leukemia, lymphoma and myeloma. Studies in myelogenous leukemia and myeloma have so far provided best evidence for a significant correlation between P-glycoprotein expression and response to chemotherapy, although large discrepancies in the proportion of positive cells limit any definite conclusion. Differences in P-glycoprotein detection techniques and methodology may account for the divergent results thus emphasizing the necessity for standardized methods of detection. Despite this, encouraging clinical results have been obtained using MDR modulators in combination with conventional chemotherapy to inhibit the activity of the P-glycoprotein pump. The paper summarizes currently available clinical data and provides guidelines for future trials aimed to reverse the MDR phenotype. The potential of idarubicin to overcome the MDR phenotype is also discussed.

Summary. The MDRl gene product P‐glycoprotein (P‐gp), a transmembrane efflux pump, is expressed in many normal tissues including subpopulations of normal peripheral blood. To test the potential impact of cigarette smoke and/or a variety of lipophilic industrial solvents present in paint and varnish, P‐gp expression in unsorted peripheral blood cells of 51 healthy volunteers was measured by means of immuno‐cytochemistry and daunorubicin uptake studies. 10 of these volunteers were heavy smokers and 10 were working as painters or sprayers, and consequently in regular and intense contact with industrial solvents. Cigarette smoke had no impact with regard to increased P‐gp expression and function. However, extensive contact with industrial solvents of lipophilic origin was shown to cause a significant increase in the level of P‐gp expression (P<0.001), thus providing new evidence for the broad substrate specificity of the P‐gp pump.

European Journal of HaematologyVolume 48, Issue 2 p. 115-116 A pilot study of recombinant human TNF and interferon-gamma in four patients with refractory AML Walter Fiedler, Corresponding Author Walter FiedlerDept. Oncology/Hematology University Hospital Eppendorf Martinistrasse 52 2000 Hamburg 20 GermanySearch for more papers by this authorHans-Josef Weh, Corresponding Author Hans-Josef WehDept. Oncology/Hematology University Hospital Eppendorf Martinistrasse 52 2000 Hamburg 20 GermanySearch for more papers by this authorDieter K. Hossfeld, Corresponding Author Dieter K. HossfeldDept. Oncology/Hematology University Hospital Eppendorf Martinistrasse 52 2000 Hamburg 20 GermanySearch for more papers by this author Walter Fiedler, Corresponding Author Walter FiedlerDept. Oncology/Hematology University Hospital Eppendorf Martinistrasse 52 2000 Hamburg 20 GermanySearch for more papers by this authorHans-Josef Weh, Corresponding Author Hans-Josef WehDept. Oncology/Hematology University Hospital Eppendorf Martinistrasse 52 2000 Hamburg 20 GermanySearch for more papers by this authorDieter K. Hossfeld, Corresponding Author Dieter K. HossfeldDept. Oncology/Hematology University Hospital Eppendorf Martinistrasse 52 2000 Hamburg 20 GermanySearch for more papers by this author First published: February 1992 https://doi.org/10.1111/j.1600-0609.1992.tb00576.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume48, Issue2February 1992Pages 115-116 RelatedInformation

A case of ALL with +i(13q) as the sole anomaly in a 77-year-old patient is reported. The clinical and cytogenetic findings are discussed.

European Journal of HaematologyVolume 45, Issue 3 p. 183-184 GM-CSF in busulfan overdosage Walter Fiedler, Corresponding Author Walter FiedlerDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this authorGabriele Goetz, Corresponding Author Gabriele GoetzDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this authorHans-J. Weh, Corresponding Author Hans-J. WehDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this authorDieter K. Hossfeld, Corresponding Author Dieter K. HossfeldDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this author Walter Fiedler, Corresponding Author Walter FiedlerDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this authorGabriele Goetz, Corresponding Author Gabriele GoetzDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this authorHans-J. Weh, Corresponding Author Hans-J. WehDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this authorDieter K. Hossfeld, Corresponding Author Dieter K. HossfeldDept. of Oncology/Hematology, University Hospital Eppendorf, Hamburg, West GermanySearch for more papers by this author First published: September 1990 https://doi.org/10.1111/j.1600-0609.1990.tb00452.xCitations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Metcalf D.. The granulocyte-macrophage colony-stimulating factors. Science 1985: 229: 16–22. 10.1126/science.2990035 CASPubMedWeb of Science®Google Scholar 2 Herrmann F., Schultz G., Lindemann A., et al. Hematopoietic responses in patients with advanced malignancy treated with recombinant human granulocyte-macrophage colony-stimulating factor. J Clin Oncol 1989: 7: 159–167. CASPubMedWeb of Science®Google Scholar 3 Groopman JE, Mitsuyasu RT, DeLeo MJ, Oette DH, Golde D-W. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 1987: 317: 593–598. 10.1056/NEJM198709033171003 CASPubMedWeb of Science®Google Scholar 4 Butturini A., de Souza PC, Gale RP, et al. Use of recombinant granulocyte-macrophage colony stimulating factor in the brazil radiation accident. Lancet 1988: II: 471–474. 10.1016/S0140-6736(88)90121-3 CASGoogle Scholar 5 Nemunaitis J., Singer JW, Buckner CD, et al. Use of recombinant human granulocyte-macrophage colony-stimulating factor in autologous marrow transplantation for lymphoid malignancies. Blood 1988: 72: 834–836. CASPubMedWeb of Science®Google Scholar 6 Metcalf D., Begley CG, Johnson GR, et al. Biologic properties in vitro of a recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1986: 67: 37–45. CASPubMedWeb of Science®Google Scholar 7 Fouillard L., Gorin NC, Laporte JP, Douay L., Isnard F., Najman A.. Recombinant human granulocyte-macrophage colony-stimulating factor plus the BEAM regimen instead of autologous bone marrow transplantation. Lancet 1989: I: 1460. 10.1016/S0140-6736(89)90176-1 Google Scholar Citing Literature Volume45, Issue3September 1990Pages 183-184 ReferencesRelatedInformation

European Journal of HaematologyVolume 42, Issue 1 p. 103-103 VEROTOXIN IN THROMBOTIC THROMBOCYTOPENIC PURPURA Friederike Windler, Corresponding Author Friederike Windler Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorHans Josef Weh, Corresponding Author Hans Josef Weh Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorDieter Kurt Hossfeld, Corresponding Author Dieter Kurt Hossfeld Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorHans-Rüdiger Franz, Corresponding Author Hans-Rüdiger Franz Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorHelge Karch, Corresponding Author Helge Karch Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorJürgen Heesemann, Corresponding Author Jürgen Heesemann Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorRainer Laufs, Corresponding Author Rainer Laufs Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this author Friederike Windler, Corresponding Author Friederike Windler Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorHans Josef Weh, Corresponding Author Hans Josef Weh Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorDieter Kurt Hossfeld, Corresponding Author Dieter Kurt Hossfeld Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorHans-Rüdiger Franz, Corresponding Author Hans-Rüdiger Franz Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorHelge Karch, Corresponding Author Helge Karch Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorJürgen Heesemann, Corresponding Author Jürgen Heesemann Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this authorRainer Laufs, Corresponding Author Rainer Laufs Abteilung für Onkologie und Hämatologie, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Transfusionsmedizin, Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. Germany Abteilung für Mikrobiologie Universitäts-Krankenhaus Eppendorf Martinistraße 52 D-2000 Hamburg 20 Fed. Rep. GermanySearch for more papers by this author First published: January 1989 https://doi.org/10.1111/j.1600-0609.1989.tb00256.xCitations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume42, Issue1January 1989Pages 103-103 RelatedInformation

Chronic renal failure heightens the risk of malignancy. We therefore examined lymphocytes from 44 uremic patients and 24 normal controls for chromosome abnormalities and sister chromatid exchange (SCE) rate. This is the first report of SCE in uremia. Uremia was found to increase structurally abnormal chromosomes and elevate the rate of SCE. These cytogenetic changes in uremia may play a role in the heightened risk of cancer.

The analysis of chromosomes of mouse embryos permits detection of transmitted chromosome damage. The protocol involves the treatment of one parent (usually the male) with a clastogen, recovery of embryos and preparation of chromosomes for metaphase analysis.

Es wird ein kurzer Überblick über die derzeit verfügbaren Ergebnisse der Chromosomenanalyse menschlicher Tumoren und Hämoblastosen gegeben. Diese Ergebnisse besagen, daß es mit Ausnahme des Philadelphia-Chromosoms (Ph1) in chronisch myeloischer Leukämie in keiner anderen neoplastischen Erkrankung des Menschen Chromosomenanomalien gibt, die diagnostische und prognostische Bedeutung haben. Die Aneuploidie von Tumorzellen sollte nicht als absolutes Kriterium der Malignität solcher Zellen bewertet werden.