M. Freund H. Link R. E. Schmidt K. Welte (Eds.)
Cytokines in Hemopoiesis, Oncology, and AIDS II
With 208 Figures and 153 Tables
Springer-Verlag Berlin Heidelberg New York London Paris Tokyo HongKong Barcelona Budapest
Priv. Doz. Dr. Mathias Freund Abteilung Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Priv. Doz. Dr. Hartmut Link Abteilung Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Professor Dr. Reinhold E. Schmidt Abteilung Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Professor Dr. Karl Welte Abteilung Padiatrische Hamatologie und Onkologie, Kinderklinik, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Library of Congress Cataloging in Publication Data. Cytokines in hemopoiesis, oncology, and AIDS 111M. Freund ... [et al.] (eds.) "With 208 figures and 153 tables". Includes Index. ISBN 978-3-540-55242-0 1. Cytokines. 2. Hemopoiesis. 3. Cancer - Immunological aspects. 4. AIDS (Disease) 1. Freund, M. (Mathias)
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Preface
In 1989, the First International Symposium on Cytokines in Hemopoiesis, Oncology, and AIDS was held in Hanover, FRG. Since then there has been an explosion of knowledge in this field. New cytokines have been discovered, on which data are presented in this book, and receptors have already been cloned for many cytokines. In clinical application, some cytokines such as TNF have almost completely left the stage, but this may not be for ever. Enormous progress has been made in the field of hemopoietic growth factors, for which clinical studies from phase I to phase III have been conducted, and some of which have even been registered for routine use.
In spite of this rapid development our knowledge of how to clinically exploit the effects of cytokines is very limited and lies far behind the advances made in basic research. Even for the hemopoietic growth factors, questions regarding the effect of adjuvant therapy on survival and or on general outcome in chemotherapy have still not been answered.
Discussion and exchange between those involved in basic science and clinical research is still urgently needed. We hope to successfully contribute to this process by continuing the series proceedings of the International Symposia on Cytokines in Hemopoiesis, Oncology, and AIDS.
Hannover, in July 1992 Mathias Freund Hartmut Link
Reinhold E. Schmidt Karl Welte
List of Contributors
Abbadessa, V. Istituto die Clinica Medica III, Centro Interdipartimenta de Ii Ricerche in Oncologia Clinica, 90100 Palermo, Italy
Abecassis, M. Unidade de Transplante de Medula Ossea, I.P.O.F.G., 1093 Lisboa, Portugal
Aglietta, M. Clinica Medica, Universita di Torino, Via Genova 3, 10126 Torino, Italy
Alegre, A. Hospital de Leganes, Madrid, Spain
Andreesen, R. Medizinische Klinik der Universitat Freiburg, Hugstetter StraBe 55, 7800 Freiburg, Germany
Ansorge, S. Medical School Magdeburg, Department of Internal Medicine, Division of Experimental Immunology, Leipziger StraBe 44, 0-3090 Magdeburg, Germany
Arrighini, A. Department of Pediatrics, University of Brescia, Italy
Asano, S. Department of Medicine, Tokyo University Institute of Medical Science, Tokyo, Japan
Ashman, L.K. Department of Microbiology and Immunology, University of Adelaide, Australia
Attal, M. Toulouse, France
viii List of Contributors
Atzpodien, J. Abteilung fUr Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Auf der Landwehr, Ulrich Division of Hematology-Oncology, Department of Internal Medicine, University of Munster, Albert-Schweitzer-StraBe 33,4400 Munster, Germany
Auf der Landwehr, Ulrike Division of Hematology-Oncology, Department of Internal Medicine, University of Munster, Albert-Schweitzer-StraBe 33, 4400 MUnster, Germany
Baccarini, M. Fraunhofer-Institute for Toxicology and Molecular Biology, Nicolai-Fuchs-StraBe 1, 3000 Hannover 61, Germany
Badea, E. Experimental Department of Cancer, Oncological Institute Bucharest, Sosaaua Fundeni 252, 72435 Bucharest, Romania
Bagnulo, S. 2nd Department of Pediatrics, University of Bari, 70100 Bari, Italy
Baldamus, C.A. Klinik I fUr Innere Medizin der Universitiit zu K61n, Joseph-Stelzmann-StraBe 9, 5000 K61n 41, Germany
Balleisen, L. Medizinische Klinik, Hamatologie/Onkologie, Evangelisches Krankenhaus Hamm, Werler Str. 110, 4700 Hamm, Germany
Bank, U. Medical School Magdeburg, Department of Internal Medicine, Division of Experimental Immunology, Leipziger StraBe 44, 0-3090 Magdeburg, Germany
Barbera, G. Clinical Biochemistry, Hospital de la Princesa, Diego de Leon 62, Madrid 28006, Spain
Bartels, H. Stiidtisches Krankenhaus Sud, Abteilung Hamatologie und Onkologie Kronsforder Allee 71-73, 2400 Lubeck, Germany
BartheIs, M. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Baskurian, A.K. National Research Center for Hematology, Novozykovsky 4a, 125167 Moscow, Russia
List of Contributors ix
Bastion, Y. Service d'Hematologie, Centre Hospitalier Lyon Sud, 69000 Lyon, France
Biitge, R. Department of Hematology, Georg August University, Robert Koch Str. 40, 3400 Gottingen, Germany
Bauer, E. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Baume, D. Institut Paoli Calmettes, 13000 Marseille, France
Baumgarten, E. Universitiitsklinikum Rudolf Virchow, Standort Chari otten burg, Kinderklinik, Heubnerweg 6, 1000 Berlin 19, Germany
Beaujean, F. CDTS du Val de Marne, 51, avenue du Marechal de Lattre de Tassigny, 94010 Creteil Cede x, France
Becker, J.e. Department of Dermatology, University of Wiirzburg, Josef-Schneider-StraBe 2, 8700 Wiirzburg, Germany
Becker, M. Unite de Greffe, H6pital Haut Ceveque, Av. de Magellan, 33604 Pessac, France
Belloc, F. Laboratoire d'Hemobiologie, H6pital Cardiologique, Haut Leveque, 33600 Pessac, France
Benter, T. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Berberana, M. Servicio de Hematologia, Hospital de la Princesa, Diego de Leon 62, Madrid 28006, Spain
Berdel, W.E. Klinikum Steglitz, Med. Klinik und Poliklinik, Abt. Hiimatologie und Onkologie, Freie Universitiit Berlin, Hindenburgdamm 30, 1000 Berlin 45, Germany
Bergmann, L. Department of Hematology and Oncology, Zentrum Innere Medizin, Universitiit Frankfurt, Theodor-Stern-Kai 7, 6000 Frankfurt 70, Germany
x List of Contributors
Bernard, P. Laboratoire d'Hemobiologie, Hopital Cardiologique, Haut Leveque, 33600 Pessac, France
Bernaudin, F. Laboratoire Unite de Greffe (LUG), Hopital Henri Mondor, 54 Av. General de Lattre de Tassigny, 94010 Creteil Cedex, France
BetteIheim, P. Allgemeines Krankenhaus Linz, Krankenhausstr. 9, 4020 Linz, Austria
Bevec, D. Sandoz Research Institute, Vienna, Austria
Bigda, J. Medical School, Department of Histology, Medical School Debinki 1, 80-120 Gdansk, Poland
Bilhou-Nabera, C. Unite De Greffe de Moelle Osseuse, Hopital Haut-Leveque, Avenue Magellan, 3360 Pessac, France
Blaise, D. Service Hematologie. Institut J. Paoli I. Calmettes, 232 Clud. de Sainte Marguerite, 13272 Marseille Cedex 9, France
Blankenstein, T. Institut fur Immunologie, Klinikum Steglitz, Freie Universitiit Berlin, Hindenburgdamm 27, 1000 Berlin 45, Germany
Block, T. Department of Urology, Technische Universitiit Munchen, Klinikum rechts der Isar, Ismaninger Str. 22, 8000 Munchen, Germany
Bodenstein, H. Abteilung fUr Hiimatologie and Onkologie, Klinikum Minden, Portastr. 7-9, 4950 Minden, Germany
Bogliolo, G. Dipartimento di Medicina Interna, Cattedra di Patologia Medica B, Viale Benedetto XV, N. 6, 16132 Genova, Italy
Boguslawska-Jaworska, J. Department of Children's Hematology and Oncology, Medical Academy, ul. Bujwida 44, 50-345 Wrodaw, Poland
Boisseau, M.R. Laboratoire d'Hemobiologie, Hopital Cardiologique, Haut Leveque, 33600 Pessac, France
List of Contributors xi
Boni, L. Department of Hematology/Oncology, "Giannina Gaslini", Children's Research Institute, 16100 Genova, Italy
Bonifer, R. Abteilung fiir Innere Medizin 1, Klinikum der Albert-Ludwigs-Universitiit Freiburg, Hugstetter Stra13e 55, 7800 Freiburg, Germany
Bonnier, S. Laboratoire de Cryobiologie, Centre de Transfusion Sanguine, 1-3, Rue du Vercors, 69007 Lyon, France
Born, J. Abteilung Psychophysiologie, Universitiit Bamberg, 8600 Bamberg. Germany
Bouloux, C. Sanofi Recherche, Montpellier and Labege, France
Brach, M.A. Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Stra13e 55, 7800 Freiburg, Germany
Brack, N. Stiidtisches Krankenhaus Harlaching, 4. Med. Klinik fUr Onkologie, Sanatoriumsplatz 2, 8000 Miinchen 90, Germany
Brado, B. Medizinische Klinik und Poliklinik V, Hiimatologie/Onkologie, Universitiit Heidelberg, Hospitalstra13e 3, 6900 Heidelberg, Germany
Brandely, M. Institut Paoli I. Calmettes, 232, Blvd. de Sainte Marguerite, 13009 Marseille, France
Breidenbach, T. Fraunhofer-Institut/TA, Department of Immunobiology, Nikolai-Fuchs-Stra13e 1, 3000 Hannover 61, Germany
Breul, J. Department of Urology, Technische Universitiit Miinchen, Klinikum rechts der Isar, Ismaninger Str. 22, 8000 Miinchen, Germany
Brieva, J.A. Department of Immunology, Hospital Ramon y Cajal, Carr. Colmenar Viejo, Km. 9,100, 28034 Madrid, Spain
Brockhaus, M. Hoffmann La Roche AG, 4000 Basel, Switzerland
Brzoska, 1. Bioferon GmbH & Co., 7958 Laupheim, Germany
xii List of Contributors
Buchner, T. Division of Hematology-Oncology, Department of Internal Medicine, University of Munster, Albert-Schweitzer-StraBe 33,4400 Munster, Germany
Burg, G. Department of Dermatology, Universitat Wurzburg, losef-Schneider-StraBe 2, 8700 Wurzburg, Germany
Burger, I. Department for Internal Medicine, University Hospital of Zurich, RamistraBe 100, 8091 Zurich, Switzerland
Burger, T. 2nd Department of Medicine, Pecs University of Medicine, Pecs Szechenyi sq. 5, 7621 Hungary
Busch, R. Institute of Statistics and Epidemiology, Technische Universitat Munchen, Klinikum rechts der Isar, 8000 Munchen, Germany
Buscher, D. Fraunhofer-Institute for Toxicology and Molecular Biology, Nicolai-Fuchs-StraBe 1, 3000 Hannover 61, Germany
Busemann, C. Division of Hematology-Oncology, Department of Internal Medicine, University of Munster, Albert-Schweitzer-StraBe 33, 4400 Munster, Germany
Butterfield, I.H. Department of Allergic Diseases, Mayo Clinic, Rochester, MN, USA
Cajozzo, A. Istituto dio Clinica Medica III, Centro Interdipartimenta de la Ricerche in Oncologia Clinica, Via Mazzini 59, 90100 Palermo, Italy
Campos, L. Laboratoire de Cryobiologie, Centre de Transfusion Sanguine, 1 et 3, rue du Vercors, 69007 Lyon, France
Caravello, E. Clinica Medica 'R', University Palermo, Viade1 Vesdro, 129,90100 Palermo, Italy
Carli, M. Department of Pediatrics, University of Padua, 35100 Padova, Italy
Castello, G. Dipartimento di Medicina Interna, Cattedra di Patologia Medica B, Viale Benedetto XV, N. 6, 16132 Genova, Italy
List of Contributors xiii
Cebon, J. Ludwig Institute for Cancer Research, P.O. Royal Melbourne Hospital, Victoria 3050, Australia
Chertkov, J.L. National Research Center for Hematology, Novozykovsky 4a, 125167 Moscow, Russia
Chybicka, A. Department of Children's Hematology and Oncology, Medical Academy, ul. Bujwida 44, 50-345 Wroclaw, Poland
Coelho, R. Unidade de Transplante de Medula Ossea, I.P.O.F.G., 1093 Lisboa, Portugal
Coiffier, B. Service d'Hematologie, Centre Hospitalier Lyon Sud, 69000 Lyon, France
Comis, S. Schering-Plough, S.P.A., via Ripamonti, 89, 20124 Milano, Italy
Cony-Makhoul, P. Laboratoire d'Hemobiologie, H6pital Cardiologique, Haut Leveque, 33600 Pessac, France
Cordero di Montezemolo, L. Clinic of Pediatrics D, University of Torino, 10100 Torino, Italy
Cordonnier, C. Service d'Hematologie, H6pital Henri Mondor, 94010 Creteil Cedex, France
Corneci, I. Experimental Department of Cancer, Oncological Institute Bucharest, Soseaua Fundeni 252, 72425 Bucharest, Romania
Crown, J. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Curigut, A. Experimental Department of Cancer, Oncological Institute Bucharest, Soseaua Fundeni 252, 72425 Bucharest, Romania
Dallmann, I. Abteilung fUr Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraI3e 8, 3000 Hannover 61, Germany
Danhauser-Riedl, S. Department of Medicine, Division of Hematology and Oncology, Technische
xiv List of Contributors
Universitat, Klinikum rechts der Isar, Ismaninger Str. 22, 8000 Munchen 80, Germany
De Bernardi, B. Department of Hematology/Oncology, "Giannina Gaslini", Children's Research Institute, 16100 Genova, Italy
Debost, M. Service de Cryobiologie, Centre de Transfusion Sanguine, 1-3 rue du Vercors, 69007 Lyon, France
Degenhart, C. Medizinische Klinik und Poliklinik V, Hamatologie/Onkologie, Hospitalstraf3e 3, 6900 Heidelberg, Germany
Deicher, H. Abteilung fur Immunologie und Transfusionsmedizin, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-Straf3e 8, 3000 Hannover 61, Germany
Demeocq, F. Clermont Ferrand, France
Deryugina, E.I. National Research Center for Hematology, Novozykovsky 4a, 125167 Moscow, Russia
De Riese, W. Abteilung Urologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Straf3e 8, 3000 Hannover 61, Germany
DelIo Sbarba, P. Institute of General Pathology, University of Florence, V. Morgagni 50, Florence, Italy
del Castillo, S. Hospital Clinico Universitario, Malaga, Spain
de la Camara, R. Servicio de Hematologia, Hospital de la Princesa, Diego de Li:on 62, Madrid 28006, Spain
Diamantstein, T. Institut fUr Immunologie, Klinikum Steglitz, Freie Universitat Berlin, Hindenburgdamm 27,1000 Berlin 45, Germany
Diaz, A. Servicio de Hematologia, Hospital de la Princesa, Diego de Leon 62, Madrid 28006, Spain
List of Contributors xv
Diedrich, H. Abteilung fur Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraI3e 8, 3000 Hannover 61, Germany
Diehl, V. I. Medizinische Klinik, Universitat KOIn, Josef-Stelzmann-StraI3e 9, 5000 Koln 41, Germany
Dima, S. Experimental Department of Cancer, Oncological Institute Bucharest, Soseaua Fundeni 252, 72435 Bucharest, Romania
Di Tullio, M.T. Clinic of Pediatrics, 1st University of Napoli, 80100 Napoli, Italy
Dohmen, M. Abteilung fUr Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraI3e 8, 3000 Hannover 61, Germany
Donne, S. Department of Medicine, Division of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraI3e 8, 3000 Hannover 61, Germany
Darken, B. Medizinische Klinik und Poliklinik V, Universitat Heidelberg, HospitalstraI3e 3, 6900 Heidelberg, Germany
Dormer, P. GSF-Institut fur Experimentelle Hamatologie, MarchioninistraI3e 25, 8000 Munchen 70, Germany
Dorner, M. Department of Internal Medicine V, (Hematology/Oncology and Rheumatology), Universitat Heidelberg, HospitalstraI3e 3, 6900 Heidelberg, Germany
Dorsch, M. Institut fUr Immunologie, KliniKum Steglitz, Freie Universitat Berlin, Hindenburgdamm 27, 1000 Berlin 45, Germany
Drings, P. Thorax-Klinik der L VA Baden, Department of Clinical Oncology, Amalienstra13e 5, 6900 Heidelberg, Germany
Drize, N.J. National Research Center for Hematology, Novozykovsky 4a, 125167 Moscow, Russia
xvi List of Contributors
Duedari, N. CDTS du Val de Marne, 51, avenue du Marechal de Lattre de Tassigny, 94010 Creteil Cedex, France
Dumain, P. Laboratoire d'Hemobiologie, Hopital Cardiologique, Haut Leveque, 33600 Pessac, France
Dummer, R. Dermatologische Klinik, Universitiitsspital Zurich, Gloriastr. 31, Zurich 8091, Switzerland
Dyer, W. Ludwig Institute for Cancer Research, P.O. Royal Melbourne Hospital, Victoria 3050, Australia
Dziadziuszko, R. Medical School, Department of Histology, Debinki 1,80-210 Gdansk, Poland
Ebell, W. Abteilung fUr Piidiatrische Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Eder, M. Department of Haematology, Johann Wolfgang Goethe-Universitiit, Theodor-Stern-Kai 7, 6000 Frankfurt/Main 70, Germany
Elsner, J. Fraunhofer-Institut/T A, Department of Immunobiology, Nikolai-Fuchs-StraBe 8, 3000 Hannover 61, Germany
Emmendorfi"er, A. Fraunhofer-Institute/TA, Department of Immunobiology, Nicolai-Fuchs-Stral3e 1, 3000 Hannover 61, Germany
Evers, P. Eurocetus, Amsterdam, The Netherlands
Exeriede, G. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Falk, W. German Cancer Research Center, Department of Immunogenetics, 1m Neuenheimer Feld 280, 6900 Heidelberg, Germany
Fehm, H.-L. Klinik fUr Innere Medizin, Medizinische Universitiit zu Lubeck, Ratzeburger Allee 160,2400 Lubeck, Germany
List of Contributors xvii
FeIgner, J. Institute of Pathology, MichaelisstraBe 11,2300 Kiel, Germany
Fernandez-Raiiada, J.M. Servicio de Hematologia, Hospital de la Princesa, Diego de Leon 62, Madrid 28006, Spain
Fischer, J.R. Thorax-Klinik der L VA Baden, Department of Clinical Oncology, AmalienstraBe 5, 6900 Heidelberg, Germany
Fischer, M. DRK-Blutspendedienst Niedersachen, Eldagsener StraBe 38, 3257 Springe, Germany
Flego, G. Dipartimento di Medicina Interna, Cattedra di Patologia Medica B, Viale Benedetto XV, N. 6, 16132 Genova, Italy
Fleischer, J. Klinik fUr Innere Medizin der Medizinischen Akademie "c.G. Carus", FetscherstraBe 74, 0-8019 Dresden, Germany
Fonatsch, C. Arbeitsgruppe Tumorcytogenetik, Institut fur Humangenetik, Medizinische Universitiit zu Lubeck, Ratzeburger Allee 160,2400 Lubeck, Germany
Franks, C.R. Eurocetus, B.V., Paasheurelweg 30, 1105 BJ Amsterdam Zuidoost, The Netherlands
Freund, M. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Frickhofen, N. Department of Medicine III, University of Ulm, Robert-Koch-StraBe 8, 7900 Ulm, Germany
Frisch, J. Behringwerke AG, Klinische Forschung Onkologie, E.-V.-Behring StraBe, 3550 Marburg, Germany
Gabrilove, J. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Gabus, R. Institut Paoli Calmettes, 13000 Marseille, France
xviii List of Contributors
Gan, 0.1. National Research Center for Hematology, Novozykovsky 4a, 125167 Moscow, Russia
Ganser, A. Abteilung fiir Hiimatologie, Klinikum der Johann-Wolfgang-Goethe-Universitiit, Theodor-Stern-Kai 7, 6000 Frankfurt 70, Germany
Garaventa, A. Department of Hematology/Oncology, "Giannina Gaslini", Children's Research Institute, 16100 Genova, Italy
Gastaut, J.A. Institut Paoli Calmettes, 13000 Marseille, France
Geissler, K. I. Med. Universitiitsklinik, Lazarettaasse 14, 1090 Wien, Austria
Geissler, R.G. University of Frankfurt/Main, Department of Hematology, Theodor-Stern-Kai 7, 6000 Frankfurt/Main 70, Germany
Gertsmeier, A. DRK-Blutspendedienst Niedersachsen, Eldagsener StraBe 38, 3257 Springe 1, Germany
Gessner, J.E. Abteilung fiir Immunologie und Transfusionsmedizin, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Gilmore, M.J.M.L. Department of Haematology, The Royal Free Hospital and School of Medicine, Pond Street, Hampstead, London NW3 2QG, United Kingdom
Giralt, M. Hospital Miguel Servet, Zaragoza, Spain
Girardin, E. Hopital des Enfants, Unite de Nephrologie Pediatrique, 1211 Geneva 4, Switzerland
Gmur, J. Department for Internal Medicine, University Hospital of Zurich, RiimistraBe 100, 8091 Zurich, Switzerland
Gon~alves, A. Unidade de Transplante de Medula Ossea, I.P.O.F.G., 1093 Lisboa, Portugal
List of Contributors xix
Gonzalez, R. Servicio de Hematologia, Hospital de la Princesa, Diego de Leon 62, Madrid 28006, Spain
Grosse, J. Abteilung Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8 3000 Hannover 61, Germany
GroBmann, A. DRK-Blutspendedienst Niedersachen, Eldagsener StraBe 38, 3257 Springe, Germany
Grote-Metke, A. Medizinische Klinik, Hiimatologie/Onkologie, Evangelisches Krankenhaus Hamm, Werler Str. 110,4700 Hamm, Germany
Grundner-Culemann, E. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
GruB, H.-I. Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter StraBe 55, 7800 Freiburg, Germany
Guyotat, D. Service Hematologie, Hopital Nord avo Albert-Raimond, 42270 St. Priest-En Jarez, France
Haas, R. Department of Internal Medicine V, (Hematology/Oncology and Rheumatology), Universitiit Heidelberg, HospitalstraBe 3, 6900 Heidelberg, Germany
Haase, D. Arbeitsgruppe Tumorcytogenetik, Institut fiir Humangenetik, Medizinische Universitiit zu Liibeck, Ratzeburger Allee 160, 2400 Liibeck, Germany
Halperin, D.S. Hopital des Enfants, Unite d'Onco-hematologie pediatrique, 1211 Geneva 4, Switzerland
Hanauske, A.-R. Department of Medicine, Division of Hematology and Oncology, Technische Universitiit, Klinikum rechts der Isar, Ismaninger Str. 22, 8000 Miinchen 80, Germany
Hanauske, U. Department of Medicine, Division of Dermatology, Medizinische Hochschule Hannover, Ricklinger Str. 5, 3000 Hannover, Germany
xx List of Contributors
Harousseau, 1.L. Department of Hematology, CHR Nantes, Hotel Wien, 1 PI. Alexis Ricordeau, 44035 Nantes Cedex, France
Hartmann, A.A. Department of Dermatology, Universitat Wiirzburg, losef-Schneider-StraBe 2, 8700 Wiirzburg, Germany
Hartung R. Department of Urology, Technische Universitat Miinchen, Klinikum rechts der Isar, 8000 Miinchen, Germany
Hasenclever, D. Klinik I fUr Innere Medizin der Universitat zu KOIn, losef-Stelzmann-StraBe 9, 5000 KOin 41, Germany
Hassan, H.T. Institut fiir Pharmazie, Freie Universitat Berlin, KelchstraBe 31, 1000 Berlin 41, Germany
Haupt, E.A. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Heilig, B. Medizinische Klinik und Poliklinik V, Universitat Heidelberg, HospitalstraBe 3, 6900 Heidelberg, Germany
HeimpeI, H. Department of Medicine III, University of Ulm, Robert-Koch-StraBe 8, 7900 Ulm, Germany
Hein, R. Abteilung fUr Immunologie, Medizinische Hochschule Hannover, KonstantyGutschow-StraBe 8, 3000 Hannover 61, Germany
Henschler, R. Department of Haematology and Oncology, University of Freiburg Medical Center, Hugstetter StraBe 55, 7800 Freiburg, Germany
Henze, G. Universitatsklinikum Rudolf Virchow, Standort Charlottenburg, Kinderklinik, Heubnerweg 6, 1000 Berlin 19, Germany
Hernandez, M. Department of Hematology, Hospital Ramon y Cajal, Carr. Colmenar Viejo, Km. 9,100,28034 Madrid, Spain
List of Contributors xxi
Herrmann, F. Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Stra13e 55, 7800 Freiburg, Germany
Herve, P. Centre Regionale de Transfusion Saguine, 25030 Besanyon, France
Hess, U. Medizinische Klinik C. Abteilung fUr Hamato-Onkologie, Kantonsspital, 9007 St. Gallen, Switzerland
Hiddemann, W. Abt. Hamatologie/Onkologie, Zentrum Innere Medizin, Georg August Universitat, Robert-Koch-Str. 40, 3400 G6ttingen, Germany
Hild, F. Institut fUr Humangenetik, Arbeitsgruppe Tumorcytogenetik, Medizinische Universitiit Lubeck, Ratzeburger Allee 160, 2400 Lubeck, Germany
Himmler, A. Bender & Co GmbH, Dr. Boehringer-Gasse 5-11,1121 Wien, Austria
Hinterberger, W. 1. Med. Univ. Klinik, Lazarettgasse 14, 1050 Wien, Austria
Hintermeier-Knabe, R. Institut fUr Klinische Hamatologie, GSF, MarchioninistraBe 25, 8000 Munchen 70, Germany
Hoelzer, D. Department of Haematology, Johann Wolfgang Goethe-Universitat, Theodor-SternKai 7, 6000 Frankfurt/Main 70, Germany
H6ffken, K. Innere Univ. Klinik und Poliklinik, Tumorforschung, Westdeutsches Tumorzentrum, Hufeland Str. 55,4300 Essen, Germany
Hohaus, S. Department of Internal Medicine V, (Hematology/Oncology and Rheumatology), Universitiit Heidelberg, Hospitalstra13e 3, 6900 Heidelberg, Germany
Holler, E. Medizinische Klinik III, Klinikum GroBhadern, Universitiit Munchen, Marchioninistra13e 15, 8000 Munchen 70, Germany
Huhn, D. Universitiitsklinikum Rudolf Virchow, Innere Medizin und Poliklinik mit Schwerpunkt Hiimatologie und Onkologie, Freie Universitiit Berlin, Spandauer Damm 130, 1000 Berlin 19, Germany
xxii List of Contributors
Hunstein, W. Medizinische Klinik und Poliklinik V, Hiimatologie/Onkologie, HospitalstraBe 3, 6900 Heidelberg, Germany
Hurkuck, F. Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Iaria, J. Ludwig Institute for Cancer Research, P.O. Royal Melbourne Hospital, Victoria 3050, Australia
Iosub, A. Department of Clinical Oncology/Chemo-Immunotherapy, Oncological Institute Bucharest, Soseaua Fundeni 252, 72435 Bucharest, Romania
Jakubowski, A. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Jaquet, K. Institute of Pathology, MichaelisstraBe 11,2300 Kiel, Germany
Jaworski, W. Department of Children's Surgery, Medical Academy, ul. Bujwida 44, 50-345 Wroclaw, Poland
Jucker, M. I. Medizinische Klinik, Universitiit K61n, Josef-Stelzmann-StraBe 9, 5000 Koln 41, Germany
KaItwasser, J.P. Department of Medicine, University of Frankfurt, 6000 Frankfurt/Main 70, Germany
Kanz, L. Med. Universitiitsklinik, Abt. f. Hiimatologie und Onkologie, Hugstetter StraBe 55, 7800 Freiburg i. Br., Germany
Keilholz, U. Medizinische Klinik und Poliklinik V, Hiimatologie und Onkologie, HospitalstraBe 3, 6900 Heidelberg, Germany
Kempeni, J. Knoll AG, 6700 Ludwigshafen, Germany
Kiehl, M. Division of Hematology-Oncology, Department of Internal Medicine, University of Munster, Albert-Schweitzer-StraBe 33, 4400 Munster, Germany
List of Contributors xxiii
Kirchner, H. Abteilung fUr Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Klein, S. I. Medizinische Klinik, Universitiit Kaln, losef-Stelzmann-Stral3e 9, 5000 Kaln 41, Germany
Klein-Struckmeier, A. DRK-Blutspendedienst Niedersachsen, Eldagsener Stral3e 38, 3257 Springe 1, Germany
Kleine, H.D. Abteilung fUr Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Kniiver-Hopf, J. DRK-Blutspendedienst Niedersachen, Eldagsener Stral3e 38, 3257 Springe. Germany
Koch, O. Division of Hematology-Oncology, Department of Internal Medicine, University of M iinster, Albert-Schweitzer-Straf3e 33, 4400 Miinster, Germany
Kojouharoff, G. University of Frankfurt/Main, Department of Hematology, Theodor-Stern-Kai 7, 6000 Frankfurt/Main 70, Germany
Kolb, H.I. Medizinische Klinik III, Klinikum Grof3hadern, Universitiit Miinchen, Marchioninistral3e 15, 8000 Miinchen 70, Germany
Karfer, A. Abteilung fiir Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Kotsch, M. Institut fUr Pathologie der Medizinischen Akademie "CG. Carus", Schubertstral3e 15, 0-8053 Dresden, Germany
Krammer, P.H. German Cancer Research Center, Department of Immunogenetics, 1m Neuenenheimer Feld 280, 6900 Heidelberg, Germany
Kreipe, H. Institute of Pathology, Michaelisstral3e 11, 2300 Kiel, Germany
Kremer, J.-P. GSF-Institut fUr Experimentelle Hiimatologie, Marchioninistral3e 25, 8000 Miinchen 70, Germany
xxiv List of Contributors
Kronke, M. Institut fur Medizinische Mikrobiologie und Hygiene, Technische Universitiit Munchen, TrogerstraBe 4a, 8000 Munchen, Germany
Kubin, T. Medizinische Klinik und Poliklinik V, Universitiit Heidelberg, HospitalstraBe 3, 6900 Heidelberg, Germany
Kuentz, M. Laboratoire Unite de Greffe (LUG), H6pital Henri Mondor, 94010 Creteil Cedex, France
Kuhl, J. Universitiitskinderklinik, Josef-Schneider-StraBe 2, 8700 Wurzburg, Germany
Kyas, U. Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Kyrle, P. I. Med. Universitiitsklinik, Lazarettgasse 14, 1090 Wien, Austria
Lacombe, F. Laboratoire d'Hemobiologie, H6pital Cardiologique, Haut Leveque, 33600 Pessac, France
Lacour, M. H6pital des Enfants, Unite d'Onco-hematologie pediatrique, 1211 Geneva 4, Switzerland
Lahm, H. Swiss Institute for Experimental Cancer Research, Department of Cellular Biology, 1066 Epalinges, Lausanne, Switzerland
Lamana, M.L. Servicio de Hematologia, Hospital de la Princesa, Diego de Leon 62, Madrid 28006, Spain
Lanino, E. Department of Hematology/Oncology, "Giannina Gaslini", Children's Research Institute, 16100 Genova, Italy
Laurent, G. Service des Maladies du Sang, H6pital Purpan, 31000 Toulouse, France
Layton, J. Ludwig Institute for Cancer Research, P.O. Royal Melbourne Hospital, Victoria 3050. Australia
List of Contributors xxv
Le Forestier, C. CDTS du Val de Marne, 51, avenue du Man~chal de Lattre de Tassigny, 94010 Creteil Cedex, France
Lechner, K. 1st Medical Department, University of Vienna, Lazarettgasse 14, 1090 Vienna, Austria
Lemerle, S. Service de Pediatrie, Hopital Intercommunal, 94010 Creteil Cedex, France
Lennert, K. Niemannsweg 26, 2300 Kiel, Germany
Leo, R. Abteilung fur Immunologie, Medizinische Hochschule Hannover, KonstantyGutschow-StraBe 8, 3000 Hannover 61, Germany
Lepeu, G. Institut 1. Paoli-I. Calmettes, 232, Blvd de Sainte Marguerite, Marseille, France
Lerza, R. Dipartimento di Medicina Interna, Cattedra di Patologia Medica B, Viale Benedetto XV, N. 6, 16132 Genova, Italy
Lesslauer, W. Hoffmann La Roche AG, 4000 Basel, Switzerland
Liaiio, F. Department of Nephrology, Hospital Ramon y Cajal, Carr. Colmenar Viejo, Km. 9,100, 28034 Madrid, Spain
Licht, T. Department of Haematology and Oncology, University of Freiburg Medical Center, Hugstetter StraBe 55, 7800 Freiburg, Germany
Liehl, E. I. Med. Universitiitsklinik, Lazarettgasse 14, 1090 Wien, Austria
Liersch, T. Medizinische Universitiitsklinik, Abteilung Hiimatologie/Onkologie, Robert-KochStraBe 40, 3400 Gottingen, Germany
Link, H. Abteilung fUr Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
LotHer, M. Klinik I fur Medizin der Universitiit zu KOln, losef-Stelzmann-StraBe 9, 5000 Koln 41, Germany
xxvi List of Contributors
Lohmann-Matthes, M.-L. Fraunhofer-Institut/TA, Department of Immunobiology, Nikolai-Fuchs-StraBe 1, 3000 Hannover 61, Germany
Lopez, J. Servicio de Hematologia, Hospital de la Princes a, Diego de Leon 62, Madrid 28006, Spain
Lubbert, M. Department <Jf Hematology/Oncology, Medical Center, Albert-Ludwigs-Universitiit, Hugstetter Str. 55, 7800 Freiburg, Germany
Ludwig, W.-D. Department of Hematology and Oncology, Universitiitsklinikum Steglitz, Freie Universitiit Berlin, Hindenburgdamm 30, 1000 Berlin, Germany
Luparello, M. Istituto die Clinica Medica III, Centro Interdipartimenta de la Ricerche in Oncologia Clinica, 90100 Palermo, Italy
Luther, T. Institut fur Pathologie der Medizinischen Akademie "e.G. Carus", SchubertstraBe 15, 0-8053 Dresden, Germany
Majdic, O. Institute of Immunology, University of Vienna, Vienna, Austria
Manakova, T.E. National Research Center for Hematology, Novozykovsky 4a, 125167 Moscow, Russia
Mannoni, P. Institut J. Paoli-I. Calmettes, 232, Blvd de Sainte Marguerite, 13009 Marseille, France
Mapara, M. Medizinische Klinik und Poliklinik V, Universitiit Heidelberg, HospitalstraBe 3, 6900 Heidelberg, Germany
Maraninchi, D. Institut J. Paoli-I. Calmettes, 232, Blvd de Sainte Marguerite, 13009 Marseille, France
Marit, G. Unite de Greffe de Moelle Osseuse, Hopital Haut Leveque, 33604 Pessac, France
Marron, A. Laboratorios Roche, SA
List of Contributors xxvii
Masaoka, T. Department of Internal Medicine, Osaka Adult Disease Center, 563 Ikeda Hata. 1-17-23, Osaka, Japan
Massolo, F. Clinic of Pediatrics, 41100 Modena, Italy
Maureaud, T. Sanofi Recherche, Montpellier and Labege, France
Maurer, A. Department of Haematology, Johann Wolfgang Goethe-Universitat, Theodor-Stern-Kai 7, 6000 Frankfurt/Main 70, Germany
Maurer, D. Institute of Immunology, University of Vienna, Borschkegasse 80, 1090 Vienna, Austria
Maurer, H.R. Institut fUr Pharmazie, Freie Universitat Berlin, Kelchstral3e 31, 1000 Berlin 41, Germany
Mayer, P. I. Med. Universitatsklinik, Lazarettgasse 14, 1090 Wien, Austria
Mazzanti, P. Schering-Plough, S.O.A. Via Ripamonti, 89, 20124, Milano, Italy
Meanwell, CA. Hoffmann La Roche Ltd., Grenzacher Str. 124,4002 Basel, Switzerland
Mencoboni, M. Dipartimento di Medicina Interna, Cattedra di patologia Medica B, Viale Benedetto XV, N. 6, 16132 Genova, Italy
Menzel, T. Abteilung fUr Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Meran, J. Abteilung fUr Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Merteismann, R. Department of Hematology/Oncology, Medical Center, Albert-Ludwigs-Universitat, Hugstetter Str. 55, 7800 Freiburg, Germany
Metha, N. University of Chicago, Department of Medicine, Section of Hematology/Oncology, 5841 S. Maryland, Box 420, Chicago, IL 60637, USA
xxviii List of Contributors
Meuthen, I. Krankenhaus Holweide, 5000 Koln, Germany
Meyer, H.-J. Department of Abdominal Surgery, Medizinische Hochschule Hannover, KonstantyGutschow-Stra13e 8, 3000 Hannover 61, Germany
Miniero. R. Istituti Universitari di Pediatria, Universita di Torino, Piazza Polonia 94, 10126 Torino, Italy
Mohr, H. DRK-Blutspendedienst Niedersachen, Eldagsener StraI3e 38, 3257 Springe, Germany
Moller, A. BASF Bioresearch Co.; Cambridge, MA, USA
Moore, M.A.S. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Morstyn. G. Amgen Inc., 1900 Oaks Terrace Lane, Thousand Oaks, CA 91320, USA
Moter, A. Klinik I fur Innere Medizin der Universitat zu Koln, Josef-Stelzmann-StraI3e 9, 5000 Koln 41, Germany
Mysliwski, A. Medical School, Department of Histology, Debinki 1, 80-210 Gdansk, Poland
Nagabhushan, T.L. Schering Plough Corporation, Schering-Plough Research, 60 Orange Street, Bloomfield, NJ 07003, USA
Nerl, C. I. Medizinische Klinik (HamatologiejOnkologie), Stadtisches Krankenhaus MunchenSchwa bing, 8000 Munchen 40, Germany
Neubauer, v. Department fur Hematology und Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraI3e 8, 3000 Hannover 61, Germany
Neukam, D. Department of Medicine, Division of Dermatology, Medizinische Hochschule Hannover, Ricklinger Str. 5, 3000 Hannover 61, Germany
List of Contributors XXIX
Neumann, C. Hautklinik Linden der Medizinischen Hochschule Hannover, Ricklinger-StraBe 5, 3000 Hannover 91, Germany
Niemeyer, C. Universitatskinderklinik, MathildenstraBe 1, 7800 Freiburg, Germany
Nolasco, I. Unidade de Transplante de Medula Os sea, I.P.O.F.G., 1093 Lisboa, Portugal
Nowak, R. Klinik fUr Innere Medizin der Medizinischen Akademie "c.G. Cams", FetscherstraBe 74, 0-8019 Dresden, Germany
Oberberg, D. Freie Universitat Berlin, Klinikum Steglitz, Abt. Hamatologie und Biologie, Hindenburgdamm 30, 1000 Berlin 45, Germany
Odriozola, 1. Department of Hematology, Hospital Ramon y Cajal, Carr. Colmenar Viejo, Km. 9,100, 28034 Madrid, Spain
Oelke, M. Department of Medicine, Division of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Oelschlagel, U. Klinik fUr Innere Medizin der Medizinischen Akademie "c.G. Cams", FetscherstraBe 74, 0'-8019 Dresden, Germany
Ogniben, E. Department of Internal Medicine V, (Hematology/Oncology and Rheumatology), Universitat Heidelberg, HospitalstraBe 3, 6900 Heidelberg, Germany
Ohno, R. Department of Medicine, Nagoya University Branch Hospital, 20 Daiko-Minami, Higashi-ku Nagoya 461, Japan
Olinescu, R. Laboratory Researcher, Spital Clinic Fundeni, Romania
Olive, D. INSERM Unite 119, 13000 Marseille, France
Oster, W. Behringwerke AG, Postfach 1120, 3550 Marburg, Germany
xxx List of Contributors
Otero, M.J. Servicio de Hematologia, Hospital de la Princesa, Diego de LOOn 62, Madrid 28006, Spain
Ottmann,O.G. Department of Haematology, Johann Wolfgang Goethe-Universitat, Theodor-Stern-Kai 7, 6000 Frankfurt/Main 70, Germany
Plamer, P.A. Eurocetus, B.V. Paasheurelweg 30, 1105-BJ Amsterdam-Zuidoost, The Netherlands
Pannacciulli, I. Dipartimento di Medicina Interna, Cattedra di Patologia Medica B, Viale Benedetto XV, N. 6, 16132 Genova, Italy
Paolucci, P. 3rd Clinic of Pediatrics, 40100 Bologna, Italy
Paras ole, R. Department of Pediatrics, 2nd University of Napoli, 80110 Napoli, Italy
Parwaresch, M.R. Institute of Pathology, MichaelisstraBe 11, 2300 Kiel, Germany
Pascual, J. Department of Nephrology, Hospital Ramon y Cajal, Carr. Colmenar Viejo, Km. 9,100, 28034 Madrid, Spain
Pasino, M. Department of Hematology/Oncology, "Giannina Gaslini", Children's Research Institute, 16100 Genova, Italy
Pauly, J.U. Freie Universitat Berlin, Klinikum Steglitz, Abt. Hamatologie und Onkologie, Hindenburgdamm 30, 1000 Berlin 41, Germany
Paunier, L. Hopital des Enfants, Unite de Nephrologie pediatrique, 1211 Geneva 4, Switzerland
Pavlovic, R. Ludwig Institute for Cancer Research, P.O. Royal Melbourne Hospital, Victoria 3050, Australia
Peest, D. Abteilung fiir Immunologie, Medizinische Hochschule Hannover, KonstantyGutschow-StraBe 8, 3000 Hannover 61, Germany
List of Contributors xxxi
Perricone, R. Istituto die Clinica Medica III, Centro Interdipartimenta de Ii Ricerche in Oncologia Clinica, Paizza Leoni 49, 90100 Palermo, Italy
Pfizenmaier, K. Institut fUr Zellbiologie und Immunologie, Vniversitiit Stuttgart, Pfaffenwaldring 57, 7000 Stuttgart 80, Germany
Pico, J.L. Institut Gustave Roussy, Rue Camille Wemonlins, 94805 Villejuif, France
Pietsch, T. Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Plat, M.T.t Klinik fUr Innere Medizin der Medizinischen Akademie "e.G. Carus", FetscherstraBe 74, 0-8019 Dresden, Germany
Platzer, E. F. Hoffmann-Ia Roche Ltd., International Medicine Hematology, Grenzacher Str. 124, 4002 Basel, Switzerland
Pohl, U. DRK-Blutspendedienst Niedersachen, Eldagsener StraBe 38, 3257 Springe, Germany
Poliwoda, H. Abteilung fiir Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Porzsolt, F. Abteilung Innere Medizin III, Medizinische Klinik und Poliklinik, Vniversitiit Vim, Robert-Koch-StraBe 8, 7900 Vim, Germany
Prentice, H.G. Royal free Hospital, Hampstead, Puot Street, NW3 2Q6, London, England
Puntous, M. Service des Maladies du Sang, Centre Franr;:ois Magendie, Hopital Haut-Leveque, 33600 Pes sac, France
Quesada, S. Abteilung Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Raab, H.-R .. Department of Surgery, Medizinische Hochschule Hannover, Konstanty-GutschowStraBe 8, 3000 Hannover 61, Germany
xxxii List of Contributors
Radzun, H.-J. Institute of Pathology, MichaelisstraBe 11, 2300 Kiel, Germany
Raeder, E. Fraunhofer-Institute/TA, Department of Immunobiology, Nicolai-Fuchs-StraBe 1, 3000 Hannover 61, Germany
Raghavachar, A. Department of Medicine III, University of Ulm, Robert-Koch-StraBe 8, 7900 Uim, Germany
Ramenghi, U. Istituti Universitari di Pediatria, Universita di Torino, Piazza Polonia 94, 10126 Torino, Italy
Ramming, K. University of Chicago, Department of Medicine, Section of Hematology/Oncology, 5841 S. Maryland, Box 420, Chicago, IL 60637, USA
Rastetter, J. Klinikum rechts der Isar der TU, I. Med. Klinik, Abt. Hiimatologie und Onkologie, Ismaninger Str. 15,8000 Munchen 80, Germany
Reiffers, J. Unite de Greffe de Moelle Osseuse, Hopital Haut-Leveque, Avenue Magellan 3360 Pessac, France
Reinhold, D. Medical School Magdeburg, Department of Internal Medicine, Division of Experimental Immunology, Leipziger StraBe 44, 0-3090 Magdeburg, Germany
Reisbach, G. GSF -Institut fUr Experimentelle Hiimatologie, MarchioninistraBe 25, 8000 Munchen 70, Germany
Reiter, A. Abteilung fUr Piidiatrische Hiimatologie und Onkologie, Kinderklinik der Medizinischen Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Resbeut, M. Institut Paoli Calmettes, 232 Blvd. de Sainte Marguerite 13009 Marseille, France
Reuter, C. Division of Hematology-Oncology, Department of Internal Medicine, University of Munster, Albert-Schweitzer-StraBe 33,4400 Munster, Germany
Reutzel, P. University of Frankfurt/Main, Department of Hematology, Theodor-Stern-Kai 7, 6000 Frankfurt/Main 70, Germany
List of Contributors xxxiii
Rice, A. Bone Marrow Transplantat Laboratory, USA CNRS 1456, University of Bordeaux II, 33076 Bordeaux, France
Richards, I.M. University of Chicago, Department of Medicine, Section of Hematology/Oncology, 5841 S. Maryland, Box 420, Chicago, IL 60637, USA
Richter, M. Medizinische Klinik und Poliklinik V, Hamatologie/Onkologie, HospitalstraI3e 3, 6900 Heidelberg, Germany
Riedel, D. Department of Hematology and Oncology, University of Frciburg Medical Center, Hugstetter StraI3e 55, 7800 Freiburg, Germany
Rieder, H. Arbeitsgruppe Tumorcytogenetik, Institut fUr H umangenetik, Medizinische Universitat zu Lubeck, Ratzeburger Allee 160, 2400 Lubeck 1, Germany
Riehm, H. Abteilung fUr Padiatrische Hamatologie und Onkologie, Kinderklinik der Medizinischen Hochschule Hannover, Konstanty-Gutschow-StraI3e 8, 3000 Hannover 61, Germany
Rodrigues, A. Unidade de Transplante de Medula Ossea, I.P.O.F.G., 1093 Lisboa, Portugal
Rodriguez, lM. Hospital Clinico Universitario de Sevilla, Sevilla, Spain
Roldan, E. Department of Immunology, Hospital Ramon y Cajal, Carr. Colmenar Viejo, Km. 9,100, 28034 Madrid, Spain
RosIer, 1. Abteilung fUr Padiatrische Hamatologie und Onkologie, Kinderklinik der Medizinischen Hochschule Hannover, Konstanty-Gutschow-StraI3e 8, 3000 Hannover 61, Germany
Roubi, N. Laboratoire de Cryobiologie, Centre de Transfusion Sanguine, 1,3 rue du Vercors, 69007 Lyon, France
Ruef, C. Hopital Cantonal Universitaire, Division des Maladies Infectieuses, 1211 Geneva 4, Switzerland
xxxiv List of Contributors
Ruszcsysnski, R. Med. Universitatsklinik, Abt. Hamatologie, Hugstetter Str. 55, 7800 Freiburg i. Br., Germany
Sainty, D. Institut Paoli Calmettes, 232, Blvd. de Sainte Marguerite 13009 Marseille, France
Sandner, S. Department of Surgery, Medizinische Hochschule Hannover, Konstanty-GutschowStraBe 8, 3000 Hannover 61, Germany
Sandri, A. Istituti Universitari di Pediatria, Universita di Torino, Piazza Polonia 94, 10126 Torino, Italy
Schedel, I. Abteilung fUr Immunologie und Transfusionsmedizin, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Scheibenbogen, C. Medizinische Klinik und Poliklinik V, Hamatologie/Onkologie, HospitalstraBe 3, 6900 Heidelberg, Germany
Scherrer, R. 1st Medical Department, University of Vienna, Lazarettgasse 14, 1090 Vienna, Austria
Scheurich, P. Fraunhofer-Institut fUr Grenzflachen- und Bioverfahrenstechnik, NobelstraBe 12, 7000 Stuttgart 80, Germany
Schindler, R. Abteilung fiir Nephrologie, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Schlick, E. Knoll AG, KnollstraBe, 6700 Ludwigshafen, Germany
Schmid, F. Department of Urology, Technische Universitat Miinchen, Klinikum rechts der Isar, 8000 Miinchen, Germany
Schmid, H. Universitatsklinikum Rudolf Virchow, Standort Charlottenburg, Kinderklinik, Heubnerweg 6, 1000 Berlin 19, Germany
List of Contributors xxxv
Schmidt, A.G. Abteilung Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Schmidt, E.R. Department of Immunology, Universitat Wiirzburg, losef-Schneider-StraBe 2, 8700 Wiirzburg, Germany
Schmidt, R.E. Abteilung fUr Immunologie und Transfusionsmedizin, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Schmoll, H.J. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
SchneeweiB, A. Department of Internal Medicine V, (Hematology/Oncology and Rheumatology), Universitat Heidelberg, HospitalstraBe 3, 6900 Heidelberg, Germany
Schomburg, A. Abteilung fiir Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Schulz, A. Department of Dermatology, Universitat Wiirzburg, losef-Schneider-StraBe 2, 8700 Wiirzburg, Germany
Schulz, G. Behringwerke AG, 3550 Marburg, Germany
Schiitze, S. Institut fiir Medizinische Mikrobiologie und Hygiene, Technische Universitat Miinchen, TrogerstraBe 4a, 8000 Miinchen, Germany
Schwulera, U. Biotest-Pharma GmbH, Landsteiner StraBe 5, 6072 Dreieich, Germany
Seipelt, G. Abteilung fiir Hamatologie, Klinikum der lohann-Wolfgang-Goethe-Universitat, Theodor-Stern-Kai 7, 6000 Frankfurt 70, Germany
Seither, E. Medizinische Klinik und Poliklinik V, Hamatologie/Onkologie, HospitalstraBe 3, 6900 Heidelberg, Germany
Senekowitsch, R. Freie Universitat Berlin, Klinikum Steglitz, Med. Klinik und Poliklinik, Abt. Hamatologie und Onkologie, Hindenburgdamm 30, 1000 Berlin 45, Germany
xxxvi List of Contributors
Shalitin, C. Department of Biology, Technion City, Haifa 32000, Israel
Siegert, W. Universitatsklinikum Rudolf Virchow, Innere Medizin und Poliklinik mit Schwerpunkt Hamatologie und Onkologie, Freie Universitat Berlin, Spandauer Damm 130, 1000 Berlin 19, Germany
Sillaber, C. 1st Medical Department, University of Vienna, Lazarettgasse 14, 1090 Vienna, Austria
Skosey, P. University of Chicago, Department of Medicine, Section of Hematology/Oncology, 5841 S. Maryland, Box 420, Chicago, IL 60637, USA
Souza, L. Angen Inc., 1900 Oak Terraca Lane, Thousand Oaks, CA 91320, USA
Spaar, H.J. Professor HeB Kinderklinik, Zentralkrankenhaus, St. Jiirgen-StraBe, 2800 Bremen, Germany
Spath-Schwalbe, E. Abteilung Innere Medizin III, Medizinische Klinik und Poliklinik, Universitat Uim, Robert-Koch-StraBe 8, 7900 Ulm, Germany
Stanley, E.R. Albert Einstein College of Medicine, 1300 Morris Park A venue, The Bronx, N.Y. 10461, USA
Stannat-KieBiing, S. Abteilung Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Starnes, H.F. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Steegmann, J.L. Servicio de Hematologia, Hospital de la Princesa, Diego de Leon 62, Madrid 28006, Spain
Stehr, S. Thorax-Klinik der L VA Baden, Department of Clinical Oncology, AmalienstraBe 5, 6900 Heidelberg, Germany
Steiner, M. Abteilung fUr Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
List of Contributors
Steinke, B. Eberhard-Karls-Universitat Tubingen, Med. Universitatsklinik. Abt. II., Otfried Muller StraBe, 7400 Tubingen, Germany
Steinmeier, O. Department of Hematology and Oncology, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Stiller, S. Abteilung fur Hamatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Stoppa, A.M. Institut Paoli Calmettes, 13000 Marseille, France
Sureda, A.
xxxvii
Department of Hematology, Hospital Santa Cren i Sant Pan, San Antonio Maria i Claret, 167, 8025 Barcelona, Spain
Surin, V.L. National Research Center for Hematology, Novozykovsky 4a, 125167 Moscow, Russia
Suttorp, M. Department of Pediatrics, University of Kiel, Schwanenweg 20, 2300 Kiel, Germany
Takaku, F. National Medical Center, Tokyo, Japan
Tamaro, P. "Burlo Garofalo" Institute, 34100 Trieste, Italy
Teichmann, J.V. Fachklinik Erbprinzentanne, Goslarsche StraBe 80, 3392 Clausthal-Zellerfeld, Germany
Teruel, J.L. Department of Nephrology, Hospital Ramon y Cajal, Carr. Colmenar Viejo, Km. 9,100, 28034 Madrid, Spain
Tesch, H. 1. Medizinische Klinik, Universitat K61n, Josef-Stelzmann-StraBe 9, 5000 K6ln 41, Germany
Thiel, E. Department of Hematology and Oncology, Universitatsklinikum Steglitz, Freie Universitat Berlin, Hindenburgdamm 30, 1000 Berlin 45, Germany
Tiberghien, P. Institut Paoli Calmettes, 232, Blvd. de Sainte Marguerite, 13009 Marseille, France
xxxviii List of Contributors
Tilgen, W. Abteilung fur Dermatologie, Universitiit Heidelberg, 6900 Heidelberg, Germany
Timeus, F. Istituti Universitari di Pediatria, Universita di Torino, Piazza Polonia 94, 10126 Torino, Italy
Tolomeo, M. Istituto die Clinica Medica III, Centro Interdipartimenta de Ii Ricerche in Oncologia Clinica, 90100 Palermo, Italy
Tomonaga, M. Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan
T6vari, E. 2nd Department of Medicine, Pecs University of Medicine, Pecs Szechenyi sq. 5, 7621 Hungary
Tremisi, J.P. Service de Cryobiologie, Centre de Transfusion Sanguine, 1-3 rue du Vercors, 69007 Lyon, France
Trotta, P.P. Schering-Plough Research, 60 Orange Street, Bloomfield, N.J. 07003, USA
Tschammler, A. Department of Radiology, Universitiit Wurzburg, Josef-Schneider-Stra13e 2, 8700 Wurzburg, Germany
Tschechne, B. Abteilung fur Immunologie und Transfusionsmedizin, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stra13e 8, 3000 Hannover 61, Germany
Uciechowski, P. Abteilung fUr Immunologie und Transfusionsmedizin, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stra13e 8, 3000 Hannover 61, Germany
Unger, C. Medizinische Universitiitsklinik, Abteilung Hiimatologie/Onkologie, Robert-Koch-Stra13e 40, 3400 Gottingennn, Germany
Valent, P. 1st Medical Department University of Vienna, Lazarettgasse 14, 1090 Vienna, Austria
Vassallo, E. Istituti Universitari di Pediatria, Universita di Torino, Piazza Polonia 94, 10126 Torino, Italy
List of Contributors xxxix
Vehmeyer, K. Medizinische Universitiitsklinik, Abteilung Hiimatologie/Onkologie, Robert-Koch-Stral3e 40, 3400 Gottingen, Germany
Vernant, J.P. Service d'Hematologie, Hopital Henri Mondor, 94010 Creteil Cedex, France
Viens, P. Institut Paoli Calmettes, 13000 Marseille, France
von Wussow, P. Abteilung flir Immunologie und Transfusionsmedizin, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Wacker, P. H6pital des Enfants, Unite d'Onco-hematologie pediatrique, 1211 Geneva 4, Switzerland
Wagner, U. Abteilung flir Hiimatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Wein, A. Medizinische Klinik und Poliklinik V, Hiimatologie/Onkologie, Hospitalstral3e 3, 6900 Heidelberg, Germany
Weiss, C. Department of Internal Medicine V, (Hematology/Oncology and Rheumatology), Universitiit Heidelberg, Hospitalstral3e 3, 6900 Heidelberg, Germany
Welte, K. Abteilung fur Piidiatrische Hiimatologie und Onkologie, Kinderklinik der Hochschule Hannover, Konstanty-Gutschow-Stral3e 8, 3000 Hannover 61, Germany
Wilmanns, W. Medizinische Klinik III, Klinikum Grol3hadern, Universitiit Munchen, Marchioninistral3e 15,8000 Munchen 70, Germany
Witt, B. Department of Internal Medicine V, (Hematology/Oncology and Rheumatology), Universitiit Heidelberg, Hospitalstral3e 3, 6900 Heidelberg, Germany
Wolf, H. Klinik fur Innere Medizin der Medizinischen Akademie "c.G. Carus", Fetscherstra13e 74,0-8019 Dresden, Germany
Woll, E.M. Boehringer Mannheim GmbH, Klinische Forschung und Entwicklung, Sandhoferstral3e 116, 6800 Mannheim, Germany
XL List of Contributors
Wormann, B. Georg August Universitiit Gottingen, Zentrum Innere Medizin, Hiimatologie und Onkologie, Robert-Koch-Str. 40, 3400 Gottingen, Germany
Wyss, M. Hopital des Enfants, Unite d'Onco-hematologie pediatrique, 30, Jd de la Cluse, 1211 Geneva 4, Switzerland
Zafferani, M. Freie Universitiit Berlin, Klinikum Steglitz, Abt. Hiimatologie und Onkologie, Hindenburgdamm 30, 1000 Berlin 45, Germany
Zahn, T. Klinikum Hof, 8670 Hof, Germany
Zeidler, C. Abteilung fur Piidiatrische Hiimatologie und Onkologie, Kinderklinik der Medizinischen Hochschule Hannover, Konstanty-Gutschow-StraBe 8, 3000 Hannover 61, Germany
Ziegler, I. GSF -Institut fUr Experimentelle Hiimatologie, MarchioninistraBe 25, 8000 Munchen 70, Germany
Zuhlsdorf, M. Division of Hematology-Oncology, Department of Internal Medicine, University of Munster, Albert-Schweitzer-StraBe 33, 4400 Munster, Germany
Contents
Introduction and Overview
Cytokine Interactions in Hematopoiesis: An Introduction and Overview M.A.S. Moore..................................................... 3
The Role of Colony-Stimulating Factors in Infection J. Layton, J. Cebon, W. Dyer, J. faria, R. Pavlovic, and G. Morstyn. . . . 15
Physicochemical and Pharmacological Characterization of Interleukin-4: Implications for Clinical Utility P.P. Trotta. . . . . .. . . .. . .. .. . ... .. . . . . . . . . . . . .. .. ... . .. . . . . . . .. ... .. 19
Interleukin-l0: An Overview T.L. Nagabhushan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Preclinical and In Vitro Data
Colony-Stimulating Factors and Hematopoietic Cells. . . . . . . . . . . . . . . . . . 31
In Vitro Modifications Induced by Granulocyte-Macrophage Colony-Stimulating Factor in Human Long-Term Bone Marrow Cultures S. Bonnier, L. Campos, N. Roubi, and D. Guyotat .. .. ... . ... . .. .. .. . . 33
The Addition of Granulocyte-Macrophage Colony-Stimulating Factor to Normal Bone Marrow Enhances Cell Cycle and Clonogenicity Irrespective of Cryopreservation J. Burger, M.l.M.L. Gilmore, J. Gmur, and H.G. Prentice. . . . . . . . . . . . . 39
Effect of Biological Response Modifiers on Human Bone Marrow Progenitor Cells in Human Immunodeficiency Virus Infection R.G. Geissler, O.G. Ottmann, G. Kojouharoff, M. Eder, P. Reutzel, D. Hoelzer, and A. Ganser. ... . .. .. . .. . . .. .. .. .. . . ... . . ... . . . . . ... .. 45
XLii Contents
Plasma Erythropoietic Activity and Hemopoiesis in Murine Postnatal Ontogenesis T.E. Manakova and A.K. Baskurian ................................. 53
In Vitro Modulation of Granulocyte-Macrophage Colony-Stimulating Factor Induced Granulocyte Surface Markers by Pentoxifylline E. Raeder. M.-L. Lohmann-Matthes. and A. EmmendorfJer . . . . . . . . . . . . 59
Myeloperoxidase: Gene Demethylation and Expression in Acute Myeloid Leukemias M. Lubbert. W.-D. Ludwig. R. Ruszczynski. R. Mertelsmann. and F. Herrmann. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Transduction of Neo + Gene into Stromal Precursor Cells of Hematopoietic Microenvironment by Retroviral Gene Transfer N.J. Drize. V.L. Surin. 0.1. Gan. E.I. Deryugina. and J.L. Chertkov. .. . 77
Cytokines in Tumor Development and Suppression. .. ..... ... . ..... ... 85
Cytokine Involvement in Tumor Development and Tumor Suppression M. Dorsch. T. Diamantstein. and T. Blankenstein . . . . . . . . . . . . . . . . . . . . . 87
Modulation of Growth ofaXenotransplanted Human Colon Adenocarcinoma Cell Line in Nude Mice Under the Influence of Systemic Recombinant Human GM-CSF W.E. Berdel. M. ZafJerani. D. Oberberg. and R. Senekowitsch . . . . . . . . . 93
Influence of Interleukin-3, Granulocyte-Macrophage Colony-Stimulating Factor, and Granulocyte Colony-Stimulating Factor on the Proliferation of Human and Murine Urothelial Tumor Cell Lines T. Block. F. Schmid. J. Breul. R. Busch. and R. Hartung.............. 99
Different Cytokines with Autocrine and Immunosuppressive Activities are Secreted by a Small-Cell Lung Cancer Cell Line . J.R. Fischer. S. Stehr. H. Lahm. W. Falk. P. Drings. and P.H. Krammer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Effects of Recombinant Human Erythropoietin on Clonogenic Growth of Primary Human Tumor Specimens in Vitro E. Bauer. S. Danhauser-Riedl. W. De Riese. H.-R. Raab. S. Sandner. H.-J. Meyer. D. Neukam. U. Hanauske. M. Freund. H. Poliwoda. J. Rastetter. and A.-R. Hanauske.... ... ..... ... . ........... .. .... . .. 115
Growth-Modulation Effects of Interleukin-1(l, Interleukin-1B, and Macrophage Colony-Stimulating Factor in Clonogenic Tumor Cells In Vitro S. Donne. W. De Riese. H.-R. Raab. H.-J. Meyer. D. Neukam. U. Hanauske. M. Freund. H. Poliwoda. J. Rastetter. and A.-R. Hanauske 127
Contents XLlll
Effects of Interleukin-4, Interleukin-5, and Interleukin-7 on Clonogenic Growth of Primary Human Tumors In Vitro M. Oelke, W. De Riese, H.-R. Raab, H.-J. Meyer, D. Neukam, U. Hanauske, M. Freund, H. Poliwoda, J. Rastetter, and A.-R. Hanauske 135
Effects of Interleukin-6 on Soft Agar Colony Formation of Primary Solid Tumor Specimens E. Bauer, S. Danhauser-Riedl, K. Welte, W. De Riese, H.-R. Raab, S. Sandner, H.-J. Meyer, D. Neukam, U. Hanauske, M. Freund, H. Polill'oda, J. Rastetter, and A.-R. Hanauske ..... " . . . . . . . . . . . . . . . . 145
Chronic Lymphocytic Leukemia B Cells Express and Secrete Significant Amounts of Transforming Growth Factor-13 J.-P. Kremer, C. Ner!, G. Reisbach, and P. Dormer. .. . . . . . . . . . . . . . . . . 153
In Vitro Tumor Necrosis Factor and Interleukin-l Production in Patients with Chronic Lymphocytic Leukemia E. TOL'ari and T. Burger. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Effects of Tumor Necrosis Factor-ex on Acute Myeloid Leukemia Cells Measured by Flow Cytometric Detection of Bromodeoxyuridine Incorporation H.-D. Kleine, U. Wagner, H. Poliwoda, and M. Freund. . . . . . . . . . . . . . . . 163
Mitogenic Effect of Human Stem Cell Factor Alone or in Combination with G-CSF, GM-CSF, and IL-3 on Fresh Leukemic Blasts from Patients with Stem Cell Factor Receptor-Positive Acute Myeloid Leukemia T. Pietsch, U. Kyas, W.-D. Ludwig, and K. Welte..................... 171
Effect of Interleukin-3 in Human Hematopoietic Progenitor and Precursor Cells in Patients with Myelodysplastic Syndromes U. Hess, A. Ganser, G. Seipelt, O.G. Oltmann, G. Geissler, and D. Hoelzer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Differential Response of Cytogenetically Abnormal Cell Clones in Myelodysplastic Syndromes to Cytokines In Vitro D. Haase, C. Fonatsch, M. Freund, H. Bodenstein, and H. Bartels...... 185
The In Vitro Effect of Interferon-yon Chronic Myeloid Leukemia Cells A. Rice, M. Becker, G. Marit, P. Bernard, F. Belloc, C. Bilhou-Nabera, and J. Reiffers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Simultaneous Measurement of Immunophenotype and DNA Content of Bone Marrow Cells R. Nowak, U. Oelschlagel, T. Luther, M. Kotsch, J. Fleischer, M. Plat, and H. Wolf.......................................................... 205
Cytokines in Hodgkin's Disease H. Tesch, M. Jucker, S. Klein, and V. Diehl ... ..................... ,. 211
XLiv Contents
The Expression Pattern of Cytokine Genes and Cytokine Receptors by Hodgkin's Disease-Derived Cell Lines HDLM-2 and KM-H2 Resembles That of Activated T Cells H.-J. Gruss, M.A. Brach, R. Mertelsmann, and F. Herrmann. . . . . . . . . .. 219
Cytokine Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231
Tumor Necrosis Factor and Lymphotoxin-Induced Signal Pathways K. Pfizenmaier, P. Scheurich, A. Himmler, S. Schutze, and M. Kranke. . 233
Tumor Necrosis Factor Receptor Expression on Human Normal and Malignant B Lymphocytes: Anti-75-kDa Tumor Necrosis Factor Receptor Antibody Inhibits B-Cell Proliferation B. Heilig, M. Mapara, T. Kubin, M. Brockhaus, B. Darken, and W. Hunstein. . . . . . . . . . . . . . . . . . ... .. .. .. . . . . . . . . . . ... . .. . .. . .. . . .. .. 239
Detection of Point Mutations Within the Macrophage ColonyStimulating Factor Receptor Gene in Myelodysplastic Syndromes and Acute Myelomonocytic Leukemias K. Jaquet, H. Kreipe, J. Feigner, H.-J. Radzun, and M.R. Parwaresch . . 247
Interleukin-2 Activates Nuclear Factor kB Binding Activity and Autoregulates Transcriptional Activity of its Own Receptor Gene by Normal Human Monocytes Engaging Nuclear Factor kB M.A. Brach, H.-J. Gruss, D. Riedel, R.H. Mertelsmann, and F. Herrmann. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 255
Interleukin-4 Downregulates Expression of c-kit mRNA and YB5.B8 Antigen (Stem Cell Factor Receptor) in Human Myeloid/Mast Cell Progenitor Cells C. Sillaber, D. Bevec, L.K. Ashman, J.H. Butterfield, R. Scherrer, K. Lechner, D. Maurer, O. Majdic, P. Bettelheim, and P. Valent....... 263
Biochemical Characterization and Regulation of Expression of the Binding Protein for the Granulocyte Colony-Stimulating Factor on Leukemia Cells U. Kyas, T. Pietsch, and K. Welte................................... 269
Tetrahydrobiopterin is a Feedback Modulator of the Interleukin-2 Receptor Complex: Manifestations and Mechanisms I. Ziegler and U. Schwulera. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 277
Receptor Cross-Talk: Protein Kinase C Dependent Down-Modulation of the Colony-Stimulating Factor-l Receptor upon Activation with In terferon-y /Li popol ysaccharide M. Baccarini, D. Buscher, P. Delio Sbarba, and E.R. Stanley. . . . . . . . . . 285
Contents XLV
The Interleukin-2 Receptor (CD25 and p75) in Human Monocytes and Macrophages C. Scheibenbogen, U. Keilholz, M. Richter, B. Brado, R. Andreesen, and W. Hunstein. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 291
Combinations of Cytokines and Cytotoxic Drugs In Vitro. . . . . . . . . . . . . . 297
Synergism of Hematopoietic Cytokines and Cytosine Arabinoside in the Treatment of Acute Myelogenous Leukemia: Experimental Rationales F. Herrmann, M.A. Brach, T. Licht, and R. Mertelsmann.............. 299
Effects of Recombinant Human Cytokines on Cytarabine Activity in K562 Human Myeloid Leukemia Cells H.T. Hassan and H.R. Maurer...................................... 313
Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Increases DNA Polymerase Activity in Acute Myeloid Leukemia Blasts In Vitro and In Vivo C. Reuter, Ulrike Auf der Landwehr, M. Zuhlsdorf, C. Busemann, B. Wormann, T. Buchner, and W. Hiddemann ........................ 321
Kinetic and Genetic Resistance in Acute Leukemia V. Abbadessa, M. Tolomeo, M. Luparello, E. Caravello, R. Perricone, and A. Cajozzo . .. . .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . .. . . . . .. 329
Combination of Hematopoietic Growth Factors Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-1 Reduces Toxicity of Cisplatin, Carboplatin, and Azidothymidine on Normal Human and Murine Hematopoietic Progenitors G. Fiego, G. Castello, R. Lerza, M. Mencoboni, G. Bogliolo, and I. Pannacciulli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
The Susceptibility of Human Leukemia Cells to Allogeneic and Autologous Lymphokine-Activated Killer Cells and Augmentation of the Susceptibility by Exposure of Target Cells to Cytotoxic Drugs In Vitro and In Vivo J. V. Teichmann, W.-D. Ludwig, and E. Thiel. . . . . . . . . . . . . . . . . . . . . . . .. 345
Other Effects and Factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
CD16 Stimulation Induces Stronger Accumulation ofCytokine mRNA in Natural Killer Cells than in Non-MHC-Restricted T Lymphocytes P. Uciechowski, J.E. Gessner, R. Schindler, and R.E. Schmidt. . . . . . . . .. 367
Influence of Chemo- and Radiotherapy on Interleukin-1 Production by Mononuclear Cells of Children with Hematological Malignancies A. Chybicka, W. Jaworski, and J. Boguslawska-Jaworska. . . . . . . . . . . . . . 375
XLvi Contents
Pokeweed Mitogen Induction of Interleukin-2 and Interleukin-6 in Mononuclear Cells: An Alternative Approach to the Combined Phytohemagglutinin/Phorbol Myristrate Acetate Stimulation In Vitro D. Reinhold. U. Bank. and A. Ansorge............................... 381
Immunomodulatory Activity of Hexadecylphosphocholine: Hexadecylphosphochloine-Meidated Enhancement of T-Cell Response K. Vehmeyer. P. Scheurich. T. Liersch. and C. Unger............ ...... 389
Long-Term Culture and Expansion of Adherent Lymphokine-Activated Killer Cells A. Klein-Struckmeier. A. Gertsmeier. and H. Mohr........... ...... ... 397
Bomirski Ab Melanoma as a Model of Tumor-Induced Cachexia J. Bigda. A. Mysliwski. and R. Dziadziuszko ... . . . . . . . . . . . . . . . . . . . . . . 405
Preclinical Evaluation of Cytokines in Animal Models . . . . . . . . . . . . . . . .. 409
In Vivo Effects of Interleukin-6 and Leukemia Inhibitory Factor on Thrombopoiesis in Primates C. Zeidler. L. Kranz. F. Hurkuck. L. Souza. and K. Welte............. 411
In Vivo Synergism of Interleukin-3 and Interleukin-6 on Thrombopoiesis in Primates K. Geissler. P. Valent. P. Bettelheim. C. Sillaber. B. Wagner. P. Kyrle. W. Hinterberger. K. Lechner. E. Liehl. and E. Mayer. . . . . . . . . . . . . . . . . 417
Clinical Data
Cytokines and Their Soluble Receptors in the Serum. . . . . . . . . . . . . . . . . .. 425
Increased Erythropoietin Response After Treatment with Cisplatin, Etoposid, and Bleomycin in Patients with Testicular Cancer A. Moter. C. Pohl. D. Hasenclever. E.M. Woll. M. Loffler. and C.A. Baldamus .................................................... 427
Systemic Release of Tumor Necrosis Factor Alpha in Human Allogeneic Bone Marrow Transplantation: Clinical Risk Factors, Prognostic Significance, and Therapeutic Approaches E. Holler. H.J. Kolb. R. Hintermeier-Knabe. J. Kempeni. P. Herve. A. Moller. and W. Wilmanns........................................ 435
Sequential Release of Tumor Necrosis Factor Alpha and Tumor Necrosis Factor Receptors in Complications of Human Bone Marrow Transplantation R. Hintermeier-Knabe. M. Brockhaus. E. Holler. W. Lesslauer. J. Kempeni. H.J. Kolb. and W. Wi/manns............................ 443
Contents xLvii
Tumor Necrosis Factor CI. in the Course of Allogeneic and Autologous Bone Marrow Transplantation M. Freund, H. Diedrich, W. Ebell, D. Peest, J. Kempeni, A. Muller, and H. Link........................................................... 449
Differences in Stimulated Cytokine Release Between Sleep and Sleep Deprivation E. Spath-Schwalbe, F. Porzsolt, J. Born, and H.-L. Fehm. . . . . .. .. . . . .. 457
Interleukin-5 Expressing Allergen-Specific T Cells in Patients with House Dust Mite Sensitization: Analysis at a Clonal Level R. Bonifer, C. Neumann, R. Mertelsmann, and F. Herrmann. . . . . . . . . .. 465
G-CSF ........................................................... 473
Issues in the Clinical Development of Recombinant Methionyl Human Granulocyte Colony-Stimulating Factor: A Review C.A. Meanwell .................................................... 475
The Use of Recombinant Methionyl Human Granulocyte ColonyStimulating Factor Following High-Dose Chemotherapy and Autologous Bone Marrow Transplantation G. Morstyn. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 483
Recombinant Methionyl Human Granulocyte Colony-Stimulating Factor in High-Risk Non-Hodgkin's Lymphoma Treated with VIM and CHOP: Preliminary Results of a Phase 1/11 Study B. Steinke......................................................... 491
Granulocyte Colony-Stimulating Factor in the Therapy of Myeloid Leukemia R. Ohno, T. Masaoka, S. Asano, M. Tomonaga, and F. Takaku.. . . . . .. 497
Granulocyte Colony-Stimulating Factor Corrects Neutropenia and Associated Clinical Symptoms in Children with Severe Congenital Neutropenia C. Zeidler, A. Reiter, J. Rosier, H. Riehm, and K. Welte.............. 503
Severe Reversible Renal Failure Induced by Recombinant Human Granulocyte Colony-Stimulating Factor in a Child with Chronic Acquired Agranulocytosis D.S. Halperin, M. Lacour, E. Girardin, C. Rue/, L. Paunier, P. Wacker, and M. Wyss...................................................... 511
In Vitro Functions of Granulocyte Colony-Stimulating Factor Induced Neutrophils T. Breidenbach, J. Roesler, J. Elsner, M.-L. Lohmann-Matthes, and K. Welte.......................................................... 521
XLviii Contents
Impaired Calcium Mobilization and Abnormalities in Microfilamentous Cytoskeletal Organization in Granulocyte Colony-Stimulating Factor Induced Neutrophils from Patients with Severe Congenital Neutropenia J. Elsner, J. Roesler, T. Breidenbach, A. Emmendorffer, M.-L. LohmannMatthes, H. Link, and K. Welte..................................... 529
GM-CSF......................................................... 535
Treatment of Poor-Risk Neuroblastoma with Intensive Chemotherapy and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor E. Lanino, R. Parasole, A. Garaventa, A. Arrighini, S. Bagnulo, M. Carli, S. Comis, L. Cordero di Montezemolo, M.T. Di Tullio, F. Massolo, P. Mazzanti, P. Paolucci, M. Pasino, L. Boni, P. Tamaro, and B. De Bernardi. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
Treatment of Relapsed Acute Myeloid Leukemia with GranulocyteMacrophage Colony-Stimulating Factor and Intensive Chemotherapy M. Puntous, F. Lacombe, G. Marit, P. Dumain, P. Cony-Makhoul, F. Belloc, G. Laurent, P. Bernard, M.R. Boisseau, and J. Reiffers. . . . .. . 545
Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Aplastic Anemia: A Phase 1/11 Trial Emphasis on Very Severe Neutropenia and Active Infection A. Raghavachar, W. Hinterberger, J.P. Kaltwasser, K. Hojjken, F. Herrmann, M. Freund, E. Platzer, J. Frisch, H. Heimpel, and N. Frickhofen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555
Successful Third Bone Marrow Transplantation for Severe Aplastic Amimia: Possible In Vivo Synergism of Granulocyte-Macrophage Colony-Stimulating Factor and Erythropoietin M. Abecassis, /. Nolasco, A. Gon(:alves, A. Rodrigues, and R .. Coelho . .. 565
Stimulation of Peripheral Blood Progenitor Cells by Chemotherapy and Granulocyte-Macrophage Colony-Stimulating Factor in Lymphoproliferative Diseases L. Campos, Y. Bastion, N. Roubi, M. Debost, J.P. Tremisi, and B. Coiffier. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 569
Autologous Transplantation of Blood Stem Cells Mobilized with Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Subsequent to Chemotherapy for Relapsed Hodgkin's Disease R. Haas, S. Hohaus, A. SchneeweiB, E. Ogniben, B. Witt, W. Oster, and W. Hunstein ... ..... , ......... , .... .... .. .. . . .. . . ... .. .... .. .. ..... 575
Immunological Characterization of Blood Stem Cell Autografts Collected Under Administration of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor S. Hohaus, R. Haas, E. Ogniben, C. Weiss, and W. Hunstein . . . . . . . . .. 581
Contents xLix
Effect of Recombinant Human Granulocyte-Macrophage ColonyStimulating Factor on Serum Levels of Soluble CD25, CD8, an CD4 in Patients with Hodgkin's Disease in Sensitive Relapse C. Weiss, S. Hohaus, E. Ogniben, M. Dorner, and R. Haas. . . . . . . . . . . . 587
Migration of Neutrophils to the Oral Mucosa During Treatment with Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor W. Ramenghi, R. Min iero , F. Timeus, E. Vassallo, A. Sandri, and M. Aglietta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595
Interleukin-l. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
Clinical Trials of Interleukin-1 ~ A. Jakubowski, J. Gabrilove, J. Crown, and H.F. Starnes... . . . .. . . . ... 603
Interleukin-3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613
Clinical Evaluation of Interleukin-3 A. Ganser, O.G. Ottmann, G. Seipelt, U. Hess, G. Geissler, A. Maurer, M. Eder, and D. Hoelzer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
Response to Interleukin-3 Treatment in Graft Failure After Bone Marrow Transplantation G. Seipelt, A. Ganser, H. Link, M. Suttorp, R. Batge, J. Frisch, G. Schulz, R. Mertelsmann, and Dr. Hoelzer.. . . .... .... .... . . ... .. ... 627
Erythropoietin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633
Erythropietin Treatment in Allogeneic Bone Marrow Transplantation: A Prospective and Randomized Trial J.L. Steegmann, J. Lopez, M. Berberana, M.J. Otero, M.L. Lamana, R. De la Camara, R. Gonzalez, A. Diaz, G. Barbera, and J.M. Fernandez-Ranada........................................................... 635
In Vivo Effects of Recombinant Human Erythropoietin on Circulating CD34+ Cells of Uremic Patients A. Sureda, J. Pascual, J.L. Teruel, E. Roldan, F. Liano, M. Hernandes, and J.A. Brieva. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 641
Interferons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645
Interferon-IX-2b in the Treatment of Chronic Myeloid Leukemia M. Freund, F. Hi/d, P. von Wussow, R. Nowak, W. Hiddemann, B. Wormann, O. Koch, L. Balleisen, A. Grote-Metke, M. Steiner, M. Dohmen, S. Stiller, H.D. Kleine, J. Meran, H. Link, C. Fonatsch, and H. Poliwoda. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647
L Contents
Interferon-ex-2a in the Treatment of Chronic Myeloid Leukemia: Results of the Spanish Group on Interferon-ex-2a in CML 1. Odriozola, 1.L. Steegmann, I.M. Rodriguez, M. Giralt, A. Alegre, S. del Castillo, A. Marron, and I.M. Fernandez Ranada . . .. ... .. . . . . . . 661
Complex Karyotype Evolution Influenced by Interferon Therapy in a Case of Ph-Positive Chronic Myeloid Leukemia F. Hild, H. Rieder, M. Freund, and C. Fonatsch . . . . . . . . . . . . . . . . . . . . .. 667
Treatment of Primary and Relapsed Angioimmunoblastic-Type T-Cell Lymphoma with Recombinant Human Interferon-ex W. Siegert, C. Nerl, I. Meuthen, T. Zahn, N. Brack, K. Lennert, and D. Huhn.......................................................... 673
New Aspects in the Treatment of Human Immunodeficiency Virus Related Koposi's Sarcoma with High-Dose Intralesional Recombinant Interferon ex 2b B. Tschechne, P. von Wussow, I. Schedel, and H. Deicher. . . . . . . . . . . . . . 677
Combination of Interferon-ex and Standard Chemotherapy in Advanced Malignancies A. Iosub, S. Dima, E. Badea, I. Corneci, A. Curigut, and R. Olinescu . .. 683
A 21-kDa Protein as Marker in the Course of Chemotherapy Combined with Cytokines: Interferon-ex or Granulocyte-Macrophase ColonyStimulating Factor T. Benter, E. Grundner-Culemann, H.J. Schmoll, H. Poliwoda, C. Shalitin, and V. Neubauer . ........................... , . .. . . . . . . .. 689
Treatment with Human Recombinant Tumor Necrosis Factor-ex of Patients with Acute Myeloid Leukemia and Chronic Myeloid Leukemia in its Accelerated or Blastic Phase M. Freund, O. Steinmeier, H.-D. Kleine, G. Exeriede, H. Link, J. Kempeni, E. Schlick, M. Barthels, and H. Poliwoda................. 693
Outpatient Therapy of Advanced Malignancies Using Recombinant Interleukin-2 and Recombinant Inteferon-ex With or Without Chemotherapy 1. Atzpodien, A. Korfer, T. Menzel, A. Schomburg, I. Dallmann, 1. Grosse, W. De Riese, H. Poliwoda, and H. Kirchner.. .. ... . . .. . . . .. 707
Treatment of Metastatic Melanoma with Interferon-ex and Interleukin-2: Significant Improvement with a New-Dosing Schedule U. Keilholz, W. Tilgen, L. Bergmann, C. Scheibenbogen, E. Seither, M. Richter, B. Brado, A. Wein, C. Degenhart, and W. Hunstein. . . . . . . . 713
Sequential Chemoimmunotherapy in the Treatment of Metastatic Melanoma I.M. Richards, N. Mehta, K. Ramming, and P. Skosey................ 721
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Interleukin-2 in Combination with Dacarbazine in the Treatment for Malignant Melanoma R. Dummer, J.e. Becker, A. Schulz, A. Tschammler, A.A. Hartmann, and G. Burg........................................................... 729
Characterization of CD3 + and CD56 + Lymphocyte Subsets in Melanoma Patients After In Vivo Recombinant Interleukin-2 Administration J.e. Becker, R. Dummer, R.E. Schmidt, G. Burg, and A.A. Hartmann. . 737
Low-Dose Subcutaneous Interleukin-2 in Human Multiple Myeloma: Current Results of a Phase 1/11 Pilot Study R. Leo, D. Peest, R. Hein, S. Stannat-KieBling, A.G. Schmidt, S. Quesada, J. Atzpodien, H. Kirchner, P. Evers, e.R. Franks, P.A. Palmer, and H. Deicher. . . . .. . . .. . ... . .. . ... ... . .. ... ... .. . . . .. 747
Tolerance and Biological Activity of Bolus Administration of Increasing Doses of Glycosylated Recombinant Interleukin-2 (SR 29009) in Patients with Hematological Malignancy D. Blaise, P. Viens, A.M. Stoppa, e. Bouloux, T. Maureaud, D. Olive, M. Resbeut, G. Lepeu, D. Baume, and D. Maraninchi . . . . . . . . . . . . . . . .. 757
Treatment of Relapsed Acute Leukemias with Systemic Recombinant Interleukin-2 (RU 49637) D. Blaise, A.M. Stoppa, D. Olive, M. Brandely, J.A. Gastaut, D. Sainty, F. Viens, D. Baume, G. Lepeu, P. Mannoni, and D. Maraninchi . . . . . . . . 763
Use of Recombinant Interleukin-2 (RU 49637) After Autologous Bone Marrow Transplantation in Patients with Hematological Disease: Phase I-II Study D. Blaise, D. Olive, M. Brandely, A.M. Stoppa, R. Gabus, P. Tiberghien, M. Altai, J. Rei/fers, F. Demeocq, J.L. Harousseau, J.L. Pico, P. Viens, and D. Maraninchi . ....................... , . . .. . ... . .. . . . . . . . . .. . . . 769
Phase 1/11 Trial with Low-Dose Interleukin-2 and Interferon-Gamma in Children with High-Risk Leukemia and Non-Hodgkin's Lymphoma After Autologous Bone Marrow Transplantation E. Baumgarten, H. Schmid, U. Pohl, J. Kith I, H.J. Spaar, e. Niemeyer, J. Brzoska, W. Siegert, and G. Henze. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775
Autologous Bone Marrow Transplantation with 10-Day-Cultured Bone Marrow Activated by Interleukin-2 in Two Patients with Acute Lymphoblastic Leukemia F. Beaujean, F. Bernaudin, M. Kuentz, e. Le Forestier, e. Cordonnier, S. Lemerle, N. Duedan, and J.P. Vernant . . .. ... . . . .. . . . . .. ... . . . .. .. 783
Antibody Formation in Cancer Patients Treated with Recombinant Interleukin-2 Alone or in Combination with Interferon-ex 2b J. Knuver-Hopf, U. Pohl, M. Fischer, A. GroBmann, 1. Atzpodien, H. Kirchner, and H. Mohr. .. . ... . .. . ... . . . ... . .. . .. . .. . ... .. . .. .. .. 789
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 795