CYTOKINES AND GROWTH FACTORS IN BLOOD TRANSFUSION

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1 CYTOKINES AND GROWTH FACTORS IN BLOOD TRANSFUSION

2 DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY Volume 32 The titles published in this series are listed at the end of this volume.

3 Cytokines and Growth Factors in Blood Transfusion Proceedings of the Twentyfirst International Symposium on Blood Transfusion, Groningen 1996, organized by the Red Cross Blood Bank Noord Nederland edited by C. Th. SMIT SIBINGA and P. C. DAS Red Cross Blood Bank Noord Nederland, The Netherlands and B. LOWENBERG Erasmus University, Rotterdam, The Netherlands KLUWER ACADEMIC PUBLISHERS DORDRECHT/BOSTON/LONDON

4 A C.I.P. Catalogue record for this book is available from the Library of Congress. ISBN-13: DOl: / e-isbn-13: Published by Kluwer Academic Publishers, P.O. Box 17,3300 AA Dordrecht, The Netherlands. Sold and distributed in the U.S.A. and Canada by Kluwer Academic Publishers, WI Philip Drive, Norwell, MA 02061, U.S.A. In all other countries, sold and distributed by Kluwer Academic Publishers Group, P.O. Box 322, 3300 AH Dordrecht, The Netherlands. Printed on acid-free paper All Rights Reserved 1997 Kluwer Academic Publishers Softcover reprint of the hardcover 1 st edition 1997 No part of the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording or by any information storage and retrieval system, without written permission from the copyright owner.

opening address Baxter Acknowledgement This publication has been

5 Dr. Cees Th. Smit Sibinga Initiator and Organiser Prof. Dr. Bob Lowenberg Chairman Mr. Hans Ouwerkerk Mayor of Groningen. opening address Baxter Acknowledgement This publication has been made possible through the support of Baxter, which is gratefully acknowledged.

6 VII CONTENTS Moderators and Speakers... XI Opening Address... XIII I. Fundamental Aspects of Cytokines and Growth Factors The Role of the Common Gamma Chain of the IL-2, IL-4, IL-7 and IL-15 Receptors in Development of Lymphocytes. Constitutive Expression of Bcl-2 Does Not Rescue the Developmental Defects in Gamma Common-deficient Mice... 3 H. Spits Molecular Mechanisms Involved in the Control of Differential Cytokine Expression in Human Monocytes E. Vellenga Signal Transduction from the Haematopoietic Growth Factor Receptors J.P. Touw Recipient Immune Responses Induced by Allogeneic Whole Blood or Platelet Transfusions: Implications for Immunomodulation J.W. Semple Discussion II. Role and Function of Cytokines and Growth Factors in the Blood Bank Use and Application ofcytokines and Growth Factors in Laboratory Diagnostic Procedures M. Fujihara Ex Vivo Cytokine Production in Blood Components: Relevant or Irrelevant? L. Muylle

7 VlII Haematopoietic Growth Factors for the Expansion of Peripheral Blood Progenitor Cells T.A. Bock Gene Marking and Gene Therapy for Transplantation Medicine D.R. Rill Ex Vivo Culture and Expansion of Haematopoietic Progenitor Cells in Cancer Patients R. Mertelsmann Peripheral Blood Progenitor Grafts Obtained form Healthy Donors P. Dreger Discussion III. Role and Application of Cytokines and Growth Factors in Clinical Medicine Clinical Relevance ofcytokine Levels in Blood Products: Evidence to Correlate with Morbidity N.M. Heddle Ablative Chemotherapy in Solid Tumour Oncology, Technology in Search of an Application? N.H. Mulder Gene Therapy In Malignacies: Development and Clinical Applications of Autologous Tumour Vaccines ll. Drayer Vaccination Strategies to Induce T-cell Immunity against Tumours R.E.M. Toes Cytokines in the Treatment of Infection D.C. Dale Thrombopoietin: Biological Effects Beyond Megakaryopoieses K. Kaushansky Discussion

8 IX IV. Future Potential of Cytokines and Growth Factors in Transfusion Medicine Erythropoietin - Where Do We Go From Here? L.T. Goodnough Ethical Aspects of the Use of Cytokines and Growth Factors in Donors H.M. Dupuis Future Potential of Cytokines and Growth Factors in Transfusion Medicine: What New Horizons Are There to Come? B. Lowenberg Discussion Index

9 XI MODERATORS AND SPEAKERS Moderators B. Lowenberg (chainnan) - Daniel den Hoed Clinic, Rotterdam, NL P.c. Das N.M. Heddle C.Th. Smit Sibinga H.J.C. de Wit lth.m. de Wolf - Red Cross Blood Bank Noord Nederland, Groningen, NL - McMaster University, Hamilton, Ontario, C - Red Cross Blood Bank Noord Nederland, Groningen, NL - Red Cross Blood Bank Noord Nederland, Groningen, NL - Academic Hospital Groningen, Department of Haematology, Groningen, NL Speakers T.A. Bock D.C. Dale - University of Tlibingen, Department of Haematology and Oncology, Tiibingen, D - University of Washington, Seattle, W A, USA H.M. Dupuis - University of Leiden, Department of Metamedica, Leiden, NL M. Fujihara L.T. Goodnough K. Kaushansky R. Mertelsmann N.H. Mulder - Hokkaido Red Cross Blood Centre, Sapporo, J - Washington University School of Medicine, St. Louis, MO, USA - University of Washington, Seattle, WA, USA - Albert-Ludwigs-Universitat, Freiburg, D - Academic Hospital Groningen, Department of Clinical Oncology, Groningen, NL

10 XII L. Muylle D.R. Rill J.W. Semple P. Dreger H. Spits R.E.M. Toes I.P. Touw E. Vellenga - Blood Transfusion Centre Antwerp, Edegem, B - St. Jude Children's Hospital, Division ofbmt, Memphis, T, USA - St. Michael's Hospital, Toronto, Ontario, C - Christian-Albrechts-Universitat zu Kiel, Kiel, D - Netherlands Cancer Institute, Amsterdam, NL - University Hospital Leiden, Department of Immunohaematology, Leiden, NL - Erasmus University Rotterdam, Department of Haematology, Rotterdam, NL - Academic Hospital Groningen, Department of Haematology, Groningen, NL

11 XIII OPENING ADDRESS Ladies and gentlemen, It is a great honour for me as mayor of the city of Groningen to welcome you here. Your visit is part of a commendable tradition on which people with scientific and professional ambitions have been meeting one another here for more than two decades. As a city with ambitions, because that is what we are, we see ourselves in you. The work of the Red Cross Blood Bank in the northern Netherlands under the supervision of its medical director Dr. Cees Smit Sibinga is making a significant contribution to these ambitions. It is putting Groningen on the map as a result of which the northern part of the Netherlands is not only receiving national recognition, but also the recognition it deserves elsewhere in the world, internationally. As one of the large urban centres in the nothern Netherlands we are especially glad to make room for know-how and quality. This, in addition to culture and environment, are two of our trade marks. We have invested a great deal in our city's beauty and quality oflife, but just as you we also know that quality is not something that one attains at anyone point in time. It is actually something that demands ongoing maintenance and the making of adjustments to new challenges. Among other things it is this glimpse into the future that makes your annual gatherings here in Groningen so worthwhile and makes them an example of what the dedication, required to obtain knowledge and know-how, can provide to an activity which is difficult to control. When I call this dedication an important gain from this symposium, I do not do so by chance. In these times too often I feel the lack of a contribution which could be made by scientists and professionals to help solve the problems which cities in the world are increasingly having to face. Naturally, there are signs that the problems of society including health care are being taken seriously. Here and there important contributions are already being made. I am making a plea, here in the midst of so many influential scientists and professionals, for an improvement in the matching together the agendas of city politics and the relevant institutions for research and development. The degree to which we succeed in doing something about the problems oftoday's city as the place, where the gaps in our society make themselves apparent, will be a determining factor in the degree of which we can get to continue to appeal sucessfully for solidarity. Indifference, apathy and aloofuess all form the crux of the symptom to which society must call a halt or be fupt fundamentally of its own strength. Ladies and gentlemen, do not assume from what I am saying however, that

12 XIV I would allow myself to be persuaded by pessimism. I continue to have great confidence in the power of solidarity and in the degree to which we can still appeal to that solidarity. It is for good reason that the donor pool of our blood bank has doubled since 1976 to its present 80,000 registered volunteer blood donors coming from every stratum of the population. To take care of the needs of 1.7 million inhabitants, this is a good percentage, but we can always use more. Ladies and gentlemen, I know that the field of knowledge involving blood banks is continually on the move. Quality, safety and efficiency are key words, that not only involve the scientific and professional value of the work, but also effect its organisation, design and management. Such changes occur in a tempo which for one person might be too fast, but for another could be too slow, but a change is inevitable. I am confident that your scientific and professional curiosity will bring you solutions. Therefore I wish you success with your 21 st international symposium on blood transfusion. May it meet with your high expectations. Welcome in our city of Groningen. Thank you. Hans Ouwerkerk, mayor of Groningen

CELLULAR ENGINEERING AND CELLULAR THERAPIES

CELLULAR ENGINEERING AND CELLULAR THERAPIES DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY Volume 38 The titles published in this series are listed at the end a/this volume. Cellular Engineering and Cellular