Cancer in Organ Transplant Recipients PDF
Preview Cancer in Organ Transplant Recipients
D. Schmahl I. Penn (Eds~) Cancer in Organ Transplant Recipients With 21 Figures Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest Prof. Dr. DIETRICH SCHMAHLt Prof. Dr. ISRAEL PENN Institut fiir Toxikologie University of Cincinnati und Chemotherapie Medical Center Deutsches Krebsforschungszentrum College of Medicine 1m Neuenheimer Feld 280 Department of Surgery W-6900 Heidelberg, FRG 231, Bethesda Avenue Cincinnati OH 45267, USA ISBN-l3: 978-3-540-53020-6 e-ISBN-13: 978-3-642-75991-8 DOl: 10.1007/978-3-642-75991-8 Library of Congress Cataloging-in-Publication Data. Cancer in organ transplant recipients / D. Schmahl. I. Penn (eds.). p. cm. Based on the meeting, held in Heidelberg, May 28-29,1990, sponsored by the German Cancer Research Center. Includes bibliographical references. 1. Cancer Immunological aspects-Congresses. 2. Transplantation of organs, tissues, etc.-Complications and sequelae -Congresses. 3. Immunosuppression-Congresses. 4. Carcinogenesis-Congresses. I. Schmahl, Dietrich. II. Penn, Israel. III. Deutsches Krebsforschungszentrum Heidelberg. [DNLM: 1. Neoplasm Transplantation-congresses. 2. Neoplasmsetiology-congresses. 3. Neoplasms-immunology-congresses. 4. Neoplasms-therapy-congresses. 5. Organ Transplantation-congresses. 6. Transplantation Immunology-congresses. QZ 202 C2153 1990] RC2683.C35 1991 617.9'5-dc20 DNLMIDLC This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its current version, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1991 This use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typesetting: Best-set Typesetter Ltd., Hong Kong 2113130-543210-Printed on acid-free paper In Memoriam The death of Dietrich Schmahl on October 11, 1990, came suddenly, causing great bewilderment and dismay. All of us on the staff of the German Cancer Research Center could hardly believe that someone with the vitality and energy of Dietrich Schmahl was no longer among us. His impulses, criticism, and personal commitment have had a lasting impact, and seemed as natural as they were direct. Meetings with Dietrich Schmahl were unforgettable. My personal recollection is of a conference we both attended in Caracas where I became much better acquainted with him than I had during our previous encounters. I was very impressed by his attentiveness, especially to clinical questions directly affecting the suffering indi vidual, his untiring willingness to discuss issues, even controversial ones, and his power of conviction. For 7 years I had the good fortune of working together with him at the German Cancer Research Center; in his capacity as Institute Director and especially as Deputy Scientific Head of the Center's Foundation, we had contact on numerous issues. During this time I knew Dietrich Schmahl as a colleague who was always ready to help, accessible, and particularly loyal and yet who never hesitated . to make his opinion known. We did not always agree on issues, but he always argued his position in a fair manner and was open to compromise, even if his acceptance of majority decisions in the Center's council meetings was occasionally tinged with resignation. The German Cancer Research Center is very indebted to Dietrich Schmahl for his activities during his 26 years in Heidelberg. Even during difficult times he was committed to the goals of this institution and pursued long-term plans. He always identified with the Center. The Institute he founded in 1964 has made substantial contri butions to the development of new cancer chemotherapy drugs, clinically relevant experimental models, and means of preventing side effects during chemotherapy. A second focus of research was in the field of carcinogenic agents, e.g., nitrosamines, and the study of the interaction of different chemical substances and their dosages. VI In Memoriam Dietrich Schmahl authored more than 600 scientific publications and wrote and edited a number of books. Numerous honors and prizes testify to the international recognition awarded to Dietrich Schmahl. Thanks to his immense experience in the experimental testing of the effects of carcinogenic agents, he was frequently a participant in public discussions of such dangers to man. For Dietrich Schmahl being a physician was a vocation. He was one of the first to undertake specific testing of the long-term side effects of cancer chemotherapy, and always argued in favor of strict indications for the use of cancer medication. The sum of his scientific work, his capacity to bridge the gap between experimental research and the suffering individual, his extreme self-discipline, as well as his definite love for punctuality, his keen interest in the concerns of colleagues, which was always characterized by his willingness to help, and his talent to present matters in a convincing way, even occasionally using biting com ments - all of these qualities molded a personality that simply belonged at the core of the Cancer Research Center. Dietrich Schmahl embodied, as hardly anyone else, an important part of the history of the German Cancer Research Center and decisively contributed to its development. Deutsches Krebsforschungszentrum HARALD ZUR HAUSEN Heidelberg Preface In the early years of this century, cancer researchers experienced difficulty in transplanting tumors from one animal to another. They were using outbred strains of animals and, in the rudimentary state of immunology at that time, initially did not recognize that the major problem was immunologic rejection of the graft. This prob lem was eventually solved by the development of inbred strains of animals. Later still, the use of immunodeficient strains of animals such as nude mice or treatment with immunosuppressive agents greatly expanded the field of tumor transplantation, which to this day remains an important area of cancer research. The situation in animals was inadvertently duplicated in man in the seminal years of transplantation in the early 1960s when kidneys were transplanted from donors who had died of cancer. If the trans planted kidney contained metastatic tumor cells, these were able to survive in the hostile immunologic environment of the recipient under the protection of immunosuppressive therapy, given to pre vent rejection of the renal allograft, and which also prevented rejection of the cancer. Once this problem was recognized the use of such donors was abandoned, but occasional cases of transmitted cancers still occur when organs are transplanted from donors with unsuspected malignancies. Of far greater importance is the development of cancer de novo after transplantation. This was recognized by T.E. Starzl and 1. Penn in Denver in 1968 when they observed two lymphomas after transplantation. One presented with gastrointestinal bleeding caused by a non-Hodgkin's lymphoma involving the stomach and other organs. The second presented with neurologic symptoms caused by a multifocal non-Hodgkin's lymphoma of the brain. Experience with these two patients stimulated enquiries at other transplant centers with reports of one case each from centers in Edinburgh, Minneapolis, and Richmond. These five cases were presented at the 1968 summer meeting of the Transplantation Society in New York and were subsequently published in Trans plantation Proceedings in 1969. At the meeting, Dr. Claude Hitchcock of Minneapolis suggested that Dr. Penn start a registry to VIII Preface collect data on post-transplant malignancies. This led to the establishment of the Denver (now Cincinnati) Transplant Tumor Registry, which collected data from transplant centers throughout the world, and which has provided numerous publications on the subject. Many investigators at other transplant centers have also published data concerning experience with these tumors, gained at their own centers, or gleaned from regional registries. Overall a picture emerged of a group of tumors that are, for the most part, uncommon in the general population, and often exhibit a very dif ferent behavior pattern from similar tumors in the community at large. A third group of tumors involving transplant patients is that where a neoplasm involves a vital organ which can only be treated effectively by removing the entire organ and replacing with a healthy one. A fundamental question that arises is: If any residual tumor cells are left behind, how do they behave when the patient's immune defenses are impaired by immunosuppressive therapy? In the summer of 1989 Prof. D. Schmahl conceived the idea of inviting a small group of experts in various fields - basic cancer research, molecular biology, epidemiology, oncology, virology, nephrology, hematology, immunology, pathology, and transplanta tion surgery - to meet for 2 days for a "brain-storming" session to discuss in depth the field of de novo malignancies after transplanta, tion, and the treatment of pre-existing cancers by organ transplanta tion. He discussed the idea with Dr. 1. Penn, and together they planned the program and a list of invited speakers. The brain storming session was held on May 28-29,1990 in Heidelberg in the Federal Republic of Germany, and was sponsored by the German Cancer Research Center, Heidelberg. This book is the outcome of the presentations and the discussions of all the papers. It represents a detailed examination of the problems of cancers that occur before and after organ transplantation. We are deeply indepted to Dr. B. Bunk and Dr. P. Klein Bauernschmitt for summarizing the discussions and for the scientific organization, and to Mrs. Bielefeld for the technical organization of the brain storming. We would also like to thank Springer-Verlag Heidelberg, especially Dr. Ute Heilmann, for publishing the pre sentations of the meeting. ISRAEL PENN, M.D. DIETRICH SCHMAHL, M.D. Contents Part I De Novo Cancer in Organ Transplant Patients Animal Models of Cancer Caused by Immunosuppression M.R. BERGER. . . . . . . . . . . . . . . . . . . . . . . . . .3 . . . . . . . . . . . . . . . Malignancies in Man After Organ Transplantation L.J. KINLEN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Malignant Lymphoproliferation of Viral Origin in Transplant Patients J.-L. TOURAINE (With 1 Figure). . .. . . . . . . . . .. . . . . . . . . . . . . 27 Clonality of Post-transplant Lymphoproliferative Diseases D. W. HANTO (With 2 Figures) . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Post-transplant Kidney Cancers and Skin Cancers (Including Kaposi's Sarcoma) I. PENN.................... ............................ 46 Discussion ........................................... 54 Part II Treatment of Cancer by Organ Transplantation Liver Transplantation for Malignant Disease N.V. JAMIESON, R. WILLIAMS, and SIR R. CALNE (With 3 Figures) ...................................... 59 Bone Marrow Transplantation B. DORKEN (With 3 Figures) ............................ 68 Transplantation of the Upper Gastrointestinal Organs in Malignant Diseases . G. OTTo (With 1 Figure) ............................... 78 Discussion ........................................... 84 x Contents Part III Possible Causes of Cancer in Transplant Patients The Nordic Project on Renal Transplantation and Cancer S.A. BIRKELAND (With 6 Figures) . . . . . . . . . . . . . . . . . . . . . . . . 89 Human Papillomaviruses E.-M. DE VILLIERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 Immune Response Directed Against Epstein-Barr Virus Carrier B Lymphocytes E. KLEIN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Carcinogenic Effects of Immunosuppressive Drugs in Man D. SCHMAHL and B. BUNK (With 1 Figure) ... . ....... ...... 127 Influence of Blood Transfusions and Immunosuppressive Therapy on Malignancies in Renal Transplant Recipients A. ABRAMCZUK, C.O. KOHLER, A. ENGELMANN, D. BACK, and G. OPELZ ........................................ 132 Possible Causes of Cancer in Transplant Patients I. PENN. . ..... . . . . . . . . . . . . . .. .... .. . ... . ..... . . . . . ... 139 Discussion ........................................... 153 Part IV Possible Prevention of De Novo Cancer in Transplant Patients Post-transplant Malignancies: Clinical Preventive Measures I. PENN.............................................. 157 Immunologic Measures: Unresponsiveness or Tolerance K. ROTHER and P. TERNESS (With 4 Figures) . . . . . . . . . . . . . . . 161 New Immunosuppressive Drugs R. KURRLE and F.R. SEILER...... . . .. ..... ........ . .. ... 169 Cancer Related to Organ Transplantation: Summary and Conclusions I. PENN.............................................. 177 Discussion ........................................... 183 List of Contributors ABRAMCZUK A., Dr., Institut fur Immunologie und Serologie, 1m Neuenheimer Feld 305, W-6900 Heidelberg, FRG BACK D., Dr., Institut fUr Immunologie und Serologie, 1m Neuenheimer Feld 305, W-6900 Heidelberg, FRG BERGER M.R., Dr., Institut fUr Toxikologie und Chemotherapie, Deutsches Krebsforschungszentrum, 1m Neuenheimer Feld 280, W-6900 Heidelberg, FRG BIRKELAND S.A., M.D., Odense University Hospital, DK 5000 Odense, Denmark BUNK B., Dr., Institut fUr Toxikologie und Chemotherapie, Deutsches Krebsforschungszentrum, 1m Neuenheimer Feld 280, W-6900 Heidelberg, FRG DE VILLIERS E.-M., Dr. sc;, Institut fUr Virusforschung, Deutsches Krebsforschungszentrum, 1m Neuenheimer Feld 280, W-6900 Heidelberg, FRG DORKEN B., Dr., Abteilung Innere Medizin V, Medizinische UniversiHitsklinik, Hospitalstr. 3, W-6900 Heidelberg, FRG ENGELMANN A., Dr., Institut fUr Immunologie und Serologie, 1m Neuenheimer Feld 305, W-6900 Heidelberg, FRG HANTO D.W., M.D., Ph.D., Section of Transplantation, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA JAMIESON N.V., M.D., Department of Surgery, Addenbrook's Hospital, Hills Road, Cambridge, CB2 2QQ, UK KIN LEN L.J., M.D., Cancer Research Campaign, Cancer Epidemiology Unit, 15, George Square, Edinburgh, EH8 9JZ, UK KLEIN E., M.D., Department of Tumor Biology, Karolinska Institutet, Box 60400, 104 01 Stockholm, Sweden
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