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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ISBN 978-3-540-55242-0 ISBN 978-3-642-48715-6 (eBook)DOI 10.1007/978-3-642-48715-6

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

Contents Ll

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