Post-Transplant Lymphoproliferative Disorders PDF
Preview Post-Transplant Lymphoproliferative Disorders
Post-Transplant Lymphoproliferative Disorders Vikas R. Dharnidharka • Michael Green Steven A. Webber (Eds.) Post-Transplant Lymphoproliferative Disorders Vikas R. Dharnidharka, MD, MPH Steven A. Webber MBChB, MRCP Associate Professor and Chief, Professor of Pediatrics, Fellowship Program Director University of Pittsburgh School Division of Pediatric Nephrology of Medicine University of Florida College of Medicine Chief, Division of Cardiology Medical Director, Pediatric Kidney Co-Director, Heart Center Transplantation, Shands Hospital at UF Medical Director, Pediatric Heart and Gainesville, Florida, USA Heart-Lung Transplantation [email protected] Children’s Hospital of Pittsburgh Pittsburgh, Pennsylvania, USA Michael Green, MD, MPH Professor of Pediatrics and Surgery University of Pittsburgh School of Medicine Division of Infectious Diseases Children’s Hospital of Pittsburgh Pittsburgh, Pennsylvania, USA michael.green@ chp.edu ISBN: 978-3-642-01652-3 e-ISBN: 978-3-642-01653-0 DOI: 10.1007/978-3-642-01653-0 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2009934493 © Springer-Verlag Berlin Heidelberg 2010 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 microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The 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 publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: eStudio Calamar, Figueres/Berlin Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Dedication We dedicate this book to the clinicians and scientists who cared for transplant patients and began the work of understanding the problem of PTLD, to the transplant recipients and their families that we care for who motivate these efforts, and to the colleagues we work with to provide care to our patients. Finally, special thanks to our families who had put up with us and supported our efforts in preparing this book and in all other things: Ramnath, Pushpa, Dimple, Shrey and Ria; Jenny, Dave, Erin, Molly, and Allison; Elizabeth, Hannah, and Katie. v Foreword By the mid 1960s, there was evidence that the loss of tumor surveillance in immunosup- pressed organ recipients could result in (1) accidental engraftment of donor malignancies, (2) accelerated growth of microscopic metastatic neoplasms of either donor or recipient origin, and (3) an increased incidence of de novo malignancies. Although real, the risks from the first two kinds of complications were promptly minimized by appropriate donor and recipient screening. In contrast, the de novo malignancies, most notably those of lymphoid origin (called posttransplantation lymphoproliferative disorders or PTLDs), have been endemic, or at times epidemic, particularly just after the advent of the T-cell-directed agents, cyclosporine, tacrolimus, and the antilymphoid antibodies. The PTLDs resemble the malignancies found in immune deficiency states, including acquired immunodeficiency syndromes. Originally referred to as reticulum cell sarcomas, they constitute a spectrum of lymphopoietic neo- plasms, of which most are B-cell lymphomas that are highly, but not invariably, associated with Epstein–Barr virus infection. Because PTLDs are frequently subject to immune surveillance, the pathogenesis and treatment of these lymphoblastic lesions have been of special interest to tumor biologists as well as to clinicians. Heavy immunosuppression, either applied by protocol or in a man- agement response to rejection, usually precedes the appearance of PTLD. Most of these tumors are of host origin in the organ recipients, whereas almost all are of donor origin after bone marrow transplantation. Although PTLDs occur in all kinds of organ recipients, the highest incidence has been after transplantation of nonrenal organs. Reduction or dis- continuance of immunosuppression in organ recipients allows recovery of tumor surveil- lance and may be followed by tumor regression. The most effective treatment is complete discontinuance of immune suppression. How- ever, this drastic step is usually avoided in kidney recipients and is rarely taken in liver, heart, and lung recipients for whom “treatment rest” and artificial organ support followed by retransplantation are not feasible. Even in such cases, however, stopping immunosup- pression as a last resort has been effective in some nonrenal organ recipients without rejec- tion of their allografts. Such examples of donor-specific, but not tumor-specific, immune nonreactivity and other features of PTLD could not be explained until the mechanisms of leukocyte chimerism-dependent alloengraftment and allogeneic tolerance were elucidated with the discovery that organ recipients had leukocyte microchimerism. vii viii Foreword The resulting fresh insight into mechanisms has suggested treatment options for PTLDs beyond stopping immunosuppression or the use of multiple-agent antilymphoma and anti- viral therapies. In fact, PTLDs have evolved into a free-standing model in which some mysteries of immunology, virology, and tumor biology have been resolved while others await further discoveries that may be exploited. Meanwhile, many books have been writ- ten about transplantation, but none specifically about PTLDs. The three editors of this book are to be commended for their efforts to fill the gap. There is something here for all clinicians, and perhaps for basic scientists who also are looking for new worlds to inves- tigate and conquer. Thomas E. Starzl, MD, PhD Professor of Surgery Thomas Starzl Transplant Institute University of Pittsburgh PA, USA Contents 1 Introduction ........................................................................................................ 1 Vikas R. Dharnidharka, Michael Green, and Steven Webber 2 Historical Perspective on the Early Studies of Posttransplant Lymphoproliferative Disorders (PTLD) ............................ 5 Douglas W. Hanto 3 Epidemiology of PTLD ...................................................................................... 17 Vikas R. Dharnidharka 4 The Biology of Epstein–Barr Virus and Posttransplant Lymphoproliferative Disease ........................................... 29 Olivia M. Martinez 5 Epstein–Barr Viral Load Testing: Role in the Prevention, Diagnosis and Management of Posttransplant Lymphoproliferative Disorders ........... 45 Jutta K. Preiksaitis 6 Clinical Features and Diagnostic Evaluation of Posttransplant Lymphoproliferative Disorder ........................................... 69 Upton D. Allen 7 Pathology ............................................................................................................ 89 Steven H. Swerdlow 8 Prognostic Factors for PTLD ............................................................................ 105 Tapan Maniar and Donald Tsai 9 Treatment of PTLD ............................................................................................ 117 Steven A. Webber ix x Contents 10 Prevention of Epstein–Barr Virus Infection and Posttransplant Lymphoproliferative Disease Following Transplantation ........................... 133 Michael Green and Marian Michaels 11.a Organ Specific Issues of PTLD – Kidney ..................................................... 145 Sophie Caillard 11.b Posttransplantation Lymphoproliferative Disorder (PTLD) in Liver and Small Bowel Transplant Recipients......................................... 153 Jaime Pineda and George V. Mazariegos 11.c Heart and Lung Transplantation .................................................................. 163 Silke Wiesmayr and Steven A. Webber 11.d Posttransplant Lymphoproliferative Disease (PTLD) in Hematopoietic Stem Cell Transplantation (HSCT) ................................. 173 Thomas G. Gross 12 Research Priorities and Future Directions ................................................... 183 Vikas R. Dharnidharka, Michael Green, and Steven A. Webber Index .......................................................................................................................... 187 Contributors Upton D. Allen Douglas W. Hanto Department of Pediatrics, Division of Transplantation, Division of Infectious Diseases, The Transplant Institute, Hospital for Sick Children, Beth Israel Deaconess Medical Center, University of Toronto, Harvard Medical School, Toronto, ON, Canada Boston, MA 02215, USA Sophie Caillard Nephrology-Transplantation Department, Tapan Maniar Hopitaux Universitaires de Strasbourg, University of Pennsylvania, Strasbourg, France Philadelphia, PA, USA Vikas R. Dharnidharka Marian Michaels Division of Pediatric Nephrology, Division of Infectious Diseases, University of Florida College of Medicine, Children’s Hospital of Pittsburgh, Gainesville, FL, USA University of Pittsburgh School of Medicine, Pediatric Kidney Transplantation, Pittsburgh, PA, USA Shands Hospital at UF, University of Florida College of Medicine, Gainesville, FL, USA Olivia M. Martinez Department of Surgery, Michael Green Division of Transplantation Departments of Pediatrics and Surgery, and the Program in Immunology, Division of Infectious Diseases, Stanford University School of Medicine, Children’s Hospital of Pittsburgh, Palo Alto, CA 94305-5492, USA University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA George V. Mazariegos Thomas G. Gross Hillman Center for Department of Pediatrics, Pediatric Transplantation, The Ohio State University School Children’s Hospital of Pittsburgh, of Medicine, Columbus, OH, USA Thomas E. Starzl Transplantation Institute, Division of Hematology/Oncology/BMT, University of Pittsburgh School Nationwide Children’s Hospital, of Medicine, Columbus, OH 43205, USA Pittsburgh, PA 15213, USA xi xii Contributors Jaime Pineda Donald E. Tsai Hillman Center for Division of Hematology/Oncology, Pediatric Transplantation, University of Pennsylvania, Children’s Hospital of Pittsburgh, Philadelphia, PA, USA Pittsburgh, PA, USA Steven A. Webber Department of Pediatrics, Jutta K. Preiksaitis University of Pittsburgh School Division of Infectious Diseases, of Medicine, Pittsburgh, PA, USA University of Alberta, Division of Cardiology, Edmonton, AB, Canada Children’s Hospital of Pittsburgh, Provincial Public Health Laboratory, 3705 5th Avenue, University of Alberta, Edmonton, AB, Pittsburgh, PA 15213, USA Canada T6G 2J2 Silke Wiesmayr Steven H. Swerdlow Division of Cardiology, Division of Hematopathology, Children’s Hospital of Pittsburgh, University of Pittsburgh School University of Pittsburgh School of Medicine, of Medicine, Pittsburgh, PA 15213, USA Pittsburgh, PA, USA
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