Organ Transplantation doc

Organ Transplantation
A Clinical Guide

Organ Transplantation
A Clinical Guide
Edited by
Andrew A. Klein
Consultant, Anaesthesia and Intensive Care, Papworth Hospital, Cambridge, UK
Clive J. Lewis
Consultant Cardiologist and Transplant Physician, Papworth Hospital, Cambridge, UK
JorenC.Madsen
Director of the MGH Transplant Center, Section Chief for Cardiac Surgery, and
W. Gerald and Patricia R. Austen Distinguished Scholar in Cardiac Surgery,
Massachusetts General Hospital, Boston, MA, USA
CAMBRIDGE UNIVERSITY PRESS
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ao Paulo, Delhi, Tokyo, Mexico City
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9780521197533
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Cambridge University Press 2011
is publication is in copyright. Subject to statutory exception

and to the provisions of relevant collective licensing
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take place without the written permission of Cambridge
University Press.
First published 2011
Printed in the United Kingdom at the University Press,
Cambridge
A catalogue record for this publication is available from the
British Library.
Library of Congress Cataloguing in Publication data
Organ transplantation : a clinical guide / edited by
Andrew Klein, Clive J. Lewis, Joren C. Madsen.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-521-19753-3 (hardback)
1. Transplantation of organs, tissues, etc.
2. Transplantation immunology. I. Klein, Andrew.
II. Lewis, Clive J., 1968– III. Madsen, Joren C., 1955–
[DNLM: 1. Organ Transplantation. 2. Transplantation
Immunology. WO 660]
RD120.7.O717 2011
617.9

5 – dc22 2011002165
ISBN 978-0-521-19753-3 Hardback
Cambridge University Press has no responsibility for the
persistence or accuracy of URLs for external or third-party
internet websites referred to in this publication, and does not
guarantee that any content on such websites is, or will remain,
accurate or appropriate.

Every eort has been made in preparing this book to provide
accurate and up-to-date information which is in accord with
accepted standards and practice at the time of publication.
Although case histories are drawn from actual cases, every
eort has been made to disguise the identities of the individuals
involved. Nevertheless, the authors, editors and publishers can
make no warranties that the information contained herein is
totally free from error, not least because clinical standards are
constantly changing through research and regulation. e
authors, editors and publishers therefore disclaim all liability
for direct or consequential damages resulting from the use of
material contained in this book. Readers are strongly advised to
pay careful attention to information provided by the
manufacturer of any drugs or equipment that they plan to use.
Contents
List of contributors vii
Foreword xi
Preface xiii
List of abbreviations xv
Section 1 – General
1 Historical perspectives 1
John Dunning and Sir Roy Calne
2 Immunological principles of acute
rejection 9
FadiG.Issa,RyoichiGoto,andKathrynJ.Wood
3 Immunosuppression: Past, present,
and future 19
Vineeta Kumar and Robert S. Gaston
4A Major complications – cancer 31
Bimalangshu R. Dey and omas R. Spitzer

4B Major complications – pathology of
chronic rejection 38
Yael B. Kushner and Robert B. Colvin
4C Major complications – infection 46
Camille Nelson Kotton
5 Organ donor management and
procurement 53
Edward Cantu III and David W. Zaas
Section 2 – Heart
6 Recipient selection 63
R.V. Venkateswaran and Jayan Parameshwar
7 Donor heart selection 70
KiranK.KhushandJonathanG.Zaro
8 Ventricular assist devices 76
DavidG.HealyandStevenS.L.Tsui
9 Surgical procedure 83
R.V. Venkateswaran and David P. Jenkins
10 Management during surgery 88
Kate Drummond and Andrew A. Klein
11 Postoperative care and early
complications 94
Mandeep R. Mehra
12 Long-term management and
outcomes 102
Hari K. Parthasarathy and Clive J. Lewis
13 Pediatric heart transplantation 112
Jacob Simmonds and Michael Burch
Section 3 – Lung
14 Recipient selection 122
J.S. Parmar

15 Living donor lobar lung
transplantation 128
Hiroshi Date
16 Surgical procedure 133
Faruk
¨
Ozalp, Tanveer Butt, and Stephan
V. B . S c h u e l e r
17 Management during surgery 138
David Ip and Peter Slinger
18 Postoperative care and early
complications 145
Vlad Vinarsky and Leo C. Ginns
19 Long-term management and
outcomes 155
Paul Corris
20 Pediatric lung transplantation 164
Stuart C. Sweet and Samuel Goldfarb
v
Contents
Section 4 – Liver
21 Recipient selection 173
Alex Gimson
22 Living donor liver transplantation 182
Koji Hashimoto, Cristiano Quintini, and
Charles Miller
23 Surgical procedure 190
SimonJ.F.HarperandNevilleV.Jamieson
24 Peri-operative care and early
complications 199

John Klinck and Andrew J. Butler
25 Long-term management and
outcomes 212
William Gelson and Graeme J.M. Alexander
26 Pediatric liver transplantation 220
Hector Vilca-Melendez and Giorgina
Mieli-Vergani
Section 5 – Kidney
27 Recipient selection 231
Ernest I. Mandel and Nina E. Tolko-Rubin
28 Sensitization of kidney transplant
recipients 238
Nick Pritchard
29 Live donor kidney donation 248
Arthur J. Matas and Hassan N. Ibrahim
30 Surgical procedure 253
Paul Gibbs
31 Peri-operative care and early
complications 258
Lorna Marson and John Forsythe
32 Long-term management and
outcomes 265
Sharon Mulroy and John D. Firth
33 Pediatric kidney transplantation 278
Khashayar Vakili and Heung Bae Kim
Section 6 – Other abdominal organs
34 Pancreatic transplantation 286
Dixon B. Kaufman
35 Pancreatic islet transplantation 295
Heidi Yeh and James F. Markmann

36 Intestinal transplantation 303
Stephen J. Middleton, Simon M. Gabe,
Neville V. Jamieson, and Andrew J. Butler
Section 7 – Other
37 Composite tissue allotransplantation:
Face transplantation 313
Maria Siemionow and Can Ozturk
38 Hematopoietic stem cell
transplantation 320
Charles Crawley and omas R. Spitzer
39 Corneal transplantation 330
Yvonne H. Luo and D. Frank P. Larkin
Section 8 – The transplant service
40 UK and European service – legal and
operational framework 335
ChrisJ.RudgeandAxelO.Rahmel
41 US transplant service – legal and
operational framework 347
Walter K. Graham, Richard S. Luskin, and
Francis L. Delmonico
42 Conclusions 355
Clive J. Lewis
Index 357
Color plate section falls between pages 181 and 182.
vi
Contributors
Graeme J.M. Alexander, MA, MD, FRCP
Consultant Hepatologist, Addenbrooke’s Hospital
Cambridge, UK
Heung Bae Kim, MD

Assistant Professor of Surgery, Harvard Medical
School, and Director, Pediatric Transplant Center,
Children’s Hospital Boston, Boston, MA, USA
Michael Burch
Lead Transplant Consultant, Consultant Cardiologist,
Great Ormond Street Hospital for Sick Children,
London, UK
Andrew J. Butler, MD
Consultant, Department of Transplantation Surgery,
Addenbrooke’s Hospital, Cambridge, UK
Tanveer Butt, FRCS
Department of Cardiopulmonary Transplantation,
eNewcastleuponTyneHospitalsNHSFoundation
Trust (NUTH), Freeman Hospital, High Heaton,
Newcastle upon Tyne, UK
Roy Calne, MD
Yeah Ghim Professor of Surgery at the National
University of Singapore, Singapore
Edward Cantu III, MD
Associate Surgical Director of Lung Transplantation,
University of Pennsylvania, Philadelphia, PA, USA
Robert B. Colvin, MD
Department of Pathology, Massachusetts General
Hospital, and Harvard Medical School, Boston,
MA, USA
Paul Corris, MB, FRCP
Professor, Department of Respiratory Medicine,
Freeman Hospital, Newcastle upon Tyne, UK
Charles Crawley
Consultant, Department of Hematology,

Addenbrooke’s Hospital, Cambridge, UK
Hiroshi Date, MD
Professor, Department of oracic Surgery, Kyoto
University Graduate School of Medicine,
Kyoto, Japan
Francis L. Delmonico, MD
Medical Director, New England Organ Bank, and
Professor of Surgery, Harvard Medical School,
Massachusetts General Hospital, Boston, MA, USA
Bimalangshu R. Dey, MD, PhD
Bone Marrow Transplant Program, Department of
Medicine, Massachusetts General Hospital, and
Harvard Medical School, Boston, MA, USA
Kate Drummond, MD
Fellow, Anaesthesia and Intensive Care, Papworth
Hospital, Cambridge, UK
John Dunning, MD
Consultant Cardiothoracic Surgeon, Papworth
Hospital, Cambridge, UK
John D. Firth, DM, FRCP
Consultant Physician and Nephrologist, Cambridge
University Hospitals Foundation Trust,
Cambridge, UK
John Forsythe, MD
Consultant Transplant Surgeon, Royal Inrmary of
Edinburgh, Edinburgh, UK
Simon M. Gabe
Lennard Jones Intestinal Failure Unit, St Mark’s
Hospital, Northwick Park, Harrow,
London, UK

vii
Contributors
Robert S. Gaston, MD, MRCP
Endowed Professor, Transplant Nephrology, and
Medical Director, Kidney and Pancreas
Transplantation, Division of Nephrology,
University of Alabama at Birmingham,
Birmingham, AL, USA
William Gelson, MD, MRCP
Consultant Surgeon, Department of Transplant
Surgery, Addenbrooke’s Hospital, Cambridge, UK
Paul Gibbs
Consultant Surgeon, Department of Transplant
Surgery, Addenbrooke’s Hospital, Cambridge, UK
Alex Gimson
Consultant Physician, Department of Hepatology,
Addenbrooke’s Hospital, Cambridge, UK
Leo C. Ginns, MD
Medical Director, Lung Transplantation,
Massachusetts General Hospital, and Associate
Professor of Medicine, Harvard Medical School,
Boston, MA, USA
Samuel Goldfarb, MD
Attending Physician, Division of Pulmonary
Medicine, Children’s Hospital of Philadelphia;
Medical Director, Lung and Heart/Lung Transplant
Programs, and Assistant Professor of Pediatrics,
University of Pennsylvania School of Medicine,
Philadelphia, PA, USA
Ryoichi Goto, MD

Clinical Research Fellow, Nueld Department
of Surgery, University of Oxford, Oxford, UK
Walter K. Graham, JD
Executive Director, United Network for
Organ Sharing, Richmond, VA, USA
Simon J.F. Harper
Clinical Lecturer in Transplantation, University
of Cambridge and Addenbrooke’s Hospital,
Cambridge, UK
Koji Hashimoto, MD, PhD
Department of Surgery, Cleveland Clinic, Cleveland,
OH, USA
David G. Healy, PhD, FRCSI (C-Th)
Honorary Fellow, Department of Cardiothoracic
Surgery, Papworth Hospital, Cambridge, UK
Hassan N. Ibrahim, MD
Department of Medicine, University of Minnesota,
Minneapolis, MN, USA
David Ip, MBBS, FANZCA
Anaesthesia Fellow, Toronto General Hospital,
Toronto, ON, Canada
Fadi G. Issa, MA, BMBCh, MRCS
Clinical Research Fellow, Nueld Department of
Surgery, University of Oxford, Oxford, UK
Neville V. Jamieson
Consultant Transplantation and HPB Surgeon,
University of Cambridge and Addenbrooke’s
Hospital, Cambridge, UK
David P. Jenkins, MB BS, FRCS (Eng),
MS (Lond), FRCS (CTh)

Consultant Cardiothoracic Surgeon,
Papworth Hospital, Cambridge, UK
Dixon B. Kaufman, MD, PhD
Professor and Chief, Division of Transplantation,
Department of Surgery, University of Wisconsin,
Madison, WI, USA
Kiran K. Khush, MD, MAS
Division of Cardiovascular Medicine, Department of
Medicine, Stanford University, Stanford, CA, USA
Heung Bae Kim, MD
Director, Pediatric Transplant Center, Department of
Surgery, Children’s Hospital Boston, and Associate
Professor of Surgery, Harvard Medical School,
Boston, MA, USA
Andrew A. Klein, MD
Consultant, Cardiothoracic Anaesthesia and
Intensive Care, Papworth Hospital, Cambridge, UK
John Klinck, MD
Consultant Anesthetist, Addenbrooke’s Hospital,
Cambridge, UK
viii
Contributors
Camille Nelson Kotton, MD
Clinical Director, Transplant and Immuno-
compromised Host Infectious Diseases,
Infectious Diseases Division, Massachusetts General
Hospital, Boston, MA, USA
Vineeta Kumar, MD
Assistant Professor of Medicine and Director,
Transplant Nephrology Fellowship Program, Division

of Nephrology, University of Alabama at
Birmingham, Birmingham, AL, USA
Yael B. Kushner, MD
Department of Pathology, Massachusetts General
Hospital, and Harvard Medical School, Boston,
MA, USA
D. Frank. P. Larkin, MD, FRCPI, FRCOphth2
Consultant Surgeon, Moorelds Eye Hospital,
London, UK
Clive J. Lewis, MB, BChir, MRCP, PhD
Consultant, Department of Cardiology, Transplant
Unit, Papworth Hospital,
Cambridge, UK
Yvonne H. Luo, MA, MRCOphth
Specialist Registrar, Moorelds Eye Hospital,
London, UK
Richard S. Luskin
President and CEO, New England Organ Bank,
Waltham, MA, USA
Ernest I. Mandel, MD
Clinical Fellow in Medicine, Brigham and Women’s
Hospital/Massachusetts General Hospital, Boston,
MA, USA
James F. Markmann, MD, PhD
Chief, Division of Transplantation, Department of
Surgery, and Clinical Director, Transplant Center,
Massachusetts General Hospital, and Professor of
Surgery, Harvard Medical School, Boston, MA, USA
Lorna Marson
Senior Lecturer in Transplant Surgery, University of

Edinburgh, Edinburgh, UK
Arthur J. Matas, MD
Department of Surgery, University of Minnesota,
Minneapolis, MN, USA
Mandeep R. Mehra, MBBS, FACP, FACC
Division of Cardiology, Department of Medicine,
University of Maryland School of Medicine,
Baltimore, MD, USA
Stephen J. Middleton, MA, MD, FRCP, FAHE
Consultant Physician, Department of
Gastroenterology, Addenbrooke’s Hospital,
Cambridge University, Cambridge, UK
Giorgina Mieli-Vergani, MD, PhD, FRCP, FRCPCH
Alex Mowat Professor of Paediatric Hepatology,
Institute of Liver Studies, King’s College London
School of Medicine, London, UK
Charles Miller
Director of Liver Transplantation, Cleveland Clinic,
Cleveland, OH, USA
Sharon Mulroy, MD
Locum Consultant Nephrologist, Department of
Renal Medicine, Addenbrooke’s Hospital, Cambridge,
UK
Faruk
¨
Ozalp, MRCS
Department of Cardiopulmonary Transplantation,
eNewcastleuponTyneHospitalsNHSFoundation
Trust, Freeman Hospital, High Heaton, Newcastle
upon Tyne, UK

Can Ozturk, MD
Dermatology and Plastic Surgery Institute, Cleveland
Clinic, Cleveland, OH, USA
Jayan Parameshwar, MD, MPhil, FRCP
Consultant Cardiologist, Advanced Heart Failure and
Transplant Programme, Papworth Hospital,
Cambridge, UK
J.S. Parmar, BM, PhD, FRCP
Consultant Transplant Physician (Respiratory),
Transplant Unit, Papworth Hospital, Papworth
Everard, Cambridge, UK
Hari K. Parthasarathy, MD, MRCP
Transplant Unit, Papworth Hospital,
Cambridge, UK
Nick Pritchard, BSc, MBBS, PhD, FRCP
Consultant Physician, Department of Renal
Medicine, Addenbrooke’s Hospital, Cambridge, UK
ix
Contributors
Cristiano Quintini, MD
Department of General Surgery, Cleveland Clinic,
Cleveland, OH, USA
Axel O. Rahmel
Medical Director, Eurotransplant International
Foundation, Leiden, e Netherlands
Chris J. Rudge, FRCS
National Clinical Director for Transplantation,
Department of Health, London, UK
Stephan V.B. Schueler, MD, PhD, FRCS
Consultant Surgeon, Department of

Cardiopulmonary Transplantation, e Newcastle
upon Tyne Hospitals NHS Foundation Trust,
Freeman Hospital, High Heaton, Newcastle upon
Tyne, UK
Maria Siemionow, MD, PHD, DSC
Professor of Surgery, Dermatology and Plastic
Surgery Institute, Cleveland Clinic,
Cleveland, OH, USA
Jacob Simmonds
Specialist Registrar, Department of Cardiothoracic
Transplantation, Great Ormond Street Hospital,
London, UK
Peter Slinger, MD, FRCPC
Professor of Anesthesia, Toronto General Hospital,
Toronto, ON, Canada
Thomas R. Spitzer, MD
Director, Bone Marrow Transplant Program,
Massachusetts General Hospital, and
Professor of Medicine, Harvard Medical School,
Boston, MA, USA
StuartC.Sweet,MD,PhD
Medical Director, Pediatric Lung Transplant
Program, and Associate Professor of Pediatrics,
Department of Pediatrics, Washington University,
St.Louis,MO,USA
Nina E. Tolkoff-Rubin, MD
Medical Director for Renal Transplantation,
Massachusetts General Hospital, and Professor
of Medicine, Harvard Medical School, Boston,
MA, USA

Steven S.L. Tsui, MA (Cantab), MD, FRCS (Eng),
FRCS (C-Th)
Consultant Surgeon and Director of Transplantation,
Papworth Hospital, Cambridge, UK
Khashayar Vakili, MD
Instructor in Surgery, Harvard Medical School, and
Department of Surgery, Children’s Hospital Boston,
Boston, MA, USA
R.V. Venkateswaran, MS, MD, FRCS-CTh
Fellow, Department of Cardiothoracic Surgery,
Papworth Hospital, Papworth Everard,
Cambridge, UK
Hector Vilca-Melendez, MD, PhD
Consultant Surgeon, Institute of Liver Studies, King’s
College Hospital, London, UK
Vladimir Vinarsky, MD
Clinical Fellow in Medicine, Massachusetts General
Hospital, Boston, MA, USA
Kathryn J. Wood, DPhil
Professor of Immunology, Nueld Department of
Surgery, University of Oxford, Oxford, UK
Heidi Yeh, MD
Assistant in Surgery, Massachusetts General
Hospital, and Instructor in Surgery, Harvard Medical
School, Boston, MA, USA
David W. Zaas
Medical Director, Lung Transplantation, and
Vice-Chair for Clinical Practice, Department
of Medicine, Duke University, Durham, NC,
USA

Jonathan G. Zaroff, MD
Division of Cardiology, Kaiser Permanente,
San Francisco, CA, USA
x
Foreword
e ever expanding nature of transplantation means
that a book aimed at encompassing all aspects of all
transplant subspecialties would be vast. Instead, this
book focuses on the clinical aspects of transplanta-
tion. It provides a concise yet comprehensive guide to
the art and science of caring for transplant patients.
It will undoubtedly provide an excellent resource for
physicians, surgeons, anesthesiologists and, indeed, all
transplant practitioners – medical and non-medical. It
will also be of interest to patients and their families
because it is written and presented in an easy-to-read
format.
is text provides state-of-the-art knowledge from
experts in their respective elds. As such, it will
become an essential companion for anyone involved
in transplantation, especially those at the beginning of
their careers. It will be available as an e-book, and in
the traditional print form. I am sure that you will enjoy,
Organ Transplantation – A Clinical Guide.
omas E. Starzl, MD, PhD
Professor of Surgery and Distinguished Service
Professor, University of Pittsburgh
xi

Preface

e eld of solid organ transplantation has developed
enormously in the last three decades and what was pio-
neering surgery has now become routine. Outcomes
are no longer considered in terms of 1-year survival,
but clinicians and patients are looking to 20 years
and beyond. e current success of transplantation is
based on many dierent factors: developments in sur-
gical technique, better immunosuppression, improved
anesthetic and intensive care, improved microbiology,
and close collaboration between – all those involved in
the transplant pathway have contributed.
However, there are still many problems to be over-
come and success has brought its own challenges.
e adverse impact of immunosuppression – such
as increased risk of some cancers and infections,
increased cardiovascular and cerebrovascular disease,
diabetes and renal failure – have not yet been avoided
by the development of more eective and specic
agents; tolerance remains elusive, although inducing
operational tolerance is perhaps less distant now than
it was a decade ago. In many situations, recurrent
disease is yet to be overcome. Most transplant recip-
ients still have a reduced life expectancy compared
with the normal population and so clinicians are now
focussing on maintaining the quality and length of
life.
Overcoming many of the technical barriers to
transplantation has increased the number of people
who could benet from transplantation and high-
lighted the need for more donors. Donation rates vary

between countries and many factors contribute to this
variation: cultural, logistical, nancial, legal, and med-
ical. e success of initiatives to reduce premature
death from road accidents and cardiovascular and
cerebrovascular disease are of course hugely welcome
buthaveresultedinareductioninthepotentialdonor
pool, and those who are potential donors are becom-
ing older and heavier so that the number and quality of
retrieved organs is falling. e reduction in the tradi-
tional donor pool has encouraged clinicians to look at
additional sources of donors, including living donors
and donors aer circulatory death. ese approaches
will go some way toward mitigating the impact of the
shrinking traditional donor pool; however, the widen-
ing gap between need and supply does bring into focus
the moral, ethical, and legal implications of the intro-
duction of policies for what is, eectively, the rationing
of life-saving organs.
Transplantation remains a high-risk procedure
and its risks have to be balanced against those of
ongoing medical management. Donated organs are
not free of risks of transmission of cancer or infec-
tion and should be considered “second hand” rather
than new. Recipient’s expectations must be managed
appropriately. An excessive focus on outcomes and
avoidance of risk will encourage risk-averse behav-
ior by clinicians and may inhibit some surgeons
from remaining in this challenging eld. erefore,
unless regulation is maintained at an appropriate level,
over-monitoring will ultimately adversely aect the

recipient.
e future of transplantation is, for the moment,
secure and there is little doubt that the need for
transplantation will continue to exceed the supply of
organs.Althoughmanyproblemshavebeenover-
come, many challenges remain. We are encouraged
by the progress in immune tolerance, regenerative
medicine, organ support, and even xenotransplanta-
tion. However, there is much yet to be learned and
then applied to patients. e race between perfect-
ing the process of organ transplantation-fabrication
on one hand and the curing of diseases that lead
xiii
Preface
to organ failure and the need for transplantation
on the other, is on. Fortunately, however, no matter
which side wins, it the patient who is ultimately the
victor.
is book, with contributions from experts in the
broad eld of transplantation from all over the world,
provides an authoritative account of where transplan-
tation has come from, where it is now, and where it
might go in the future. e state-of-the-art knowledge
contained within this volume will help make all who
read it better caregivers to recipients of organ trans-
plants and better prepared to embrace the exciting
future of our eld.
Andrew A. Klein, MD
Consultant, Cardiothoracic Anaesthesia and
Intensive Care, Papworth Hospital, Cambridge, UK

James Neuberger, DM, FRCP
Honorary Professor of Medicine, University of
Birmingham, and Associate Medical Director,
Organ Donation and Transplantation, NHS Blood
and Transplant, Bristol, UK
xiv
Abbreviations
6-MP 6-mercaptopurine
A2ALL Adult-to-Adult Living Donor Liver
Transplantation Cohort Study
ABOi ABO incompatible
ABVC doxorubicin, bleomycin, vinblastine,
and dacarbazine
ACAID Anterior chamber–associated
immune deviation
ACD acquired cystic disease
ACE angiotensin-converting enzyme
ACOT Advisory Committee on
Transplantation
ACR acute cellular rejection
ACT activated clotting time
ADCC antibody-dependent cell-mediated
cytotoxicity
ADH anti-diuretic hormone
AHR acute humoral rejection
aHUS atypical HUS
aICB atraumatic intracranial bleed
AIDS acquired immune deciency
syndrome
AIH autoimmune hepatitis

ALF acute liver failure
ALG anti-lymphocyte globulin
AMR antibody mediated rejection
AP-1 activator protein 1
APC antigen-presenting cell
APOLT auxiliary partial orthotopic liver
transplantation
ARB angiotensin receptor blocker
ARDS acute respiratory distress syndrome
ATC anti-thymocyte globulin
ATG antithymocyte globulin
ATN acute tubular necrosis
ATP adenosine triphosphate production
AV atrioventricular
AZA azathioprine
BASM biliary atresia splenic malformation
BCC basal cell carcinoma
BKV BK virus
BLT bilateral lung transplantation
BMD bone mineral density
BMI body mass index
BNP B-type natriuretic peptide
BODE body mass index, airow obstruction,
dyspnea, and exercise capacity
BOS bronchiolitis obliterans syndrome
BTT bridging to transplant
C3 complement component 3
C4d complement component 4d
CAN chronic allogra nephropathy
CAV cardiac allogra vasculopathy

CAV coronary artery vasculopathy
CBD common bile duct
CBP cardiopulmonary bypass
CD3 cluster of dierentiation (CD) 3
molecule
CDC complement-dependent cytotoxicity
cross-match
CDR chronic ductopenic rejection
CF cystic brosis
CHOP cyclophosphamide, doxorubicin,
vincristine, and prednisone
CHR chronic humoral rejection
CIT cold ischemic time
CKD chronic kidney disease
C
max
maximum concentration
CMV cytomegalovirus
CNI calcineurin inhibitor
CNS central nervous system
CO carbon monoxide
COPD chronic obstructive pulmonary
disease
CPB cardiopulmonary bypass
CPEX cardiopulmonary exercise testing
CR complete remission
CRP C-reactive protein
CRT cardiac resynchronization
therapy
xv

List of abbreviations
c-SMAC central supramolecular activation
cluster
CT computed tomography
CTA composite tissue allotransplantation
CTL cytotoxic T cell
CTLA-4 cytotoxic T-lymphocyte antigen 4
CTTR Cincinnati Transplant Tumor
Registry
CVP central venous pressure
CY cyclophosphamide
CyA cyclosporine
D donor
D– no diarrhea
D+ diarrhea associated
DAG diacylglycerol
DBD donation aer brain death
DC dendritic cell
DCD donation aer cardiac death
DEXA dual-energy X-ray absorptiometry
DGF delayed gra function
DLCO diusing capacity of carbon
monoxide
DLI donor lymphocyte infusion
DM1 type 1 diabetes mellitus
DM2 type 2 diabetes mellitus
DSA donor specic antibodies
DTC donor transplant coordinator
DTH delayed-type hypersensitivity
DVT deep venous thrombosis

EBV Epstein-Barr virus
ECD extended criteria donor
ECMO extracorporeal membrane
oxygenation
EC-MPS enteric-coated mycophenolate
sodium
EF ejection fraction
eGFR estimated glomerular ltration rate
EHBA extra-hepatic biliary atresia
ELITE Ecacy Limiting Toxicity Elimination
ENT ear, nose, and throat
ER endoplasmic reticulum
ESC embryonic stem cell
ESRD end-stage renal disease
ETT endotracheal tube
EVL everolimus
EVLP ex vivo lung perfusion
FasL Fas ligand
FCXM ow cytometry cross-match
FDA US Food and Drug Administration
FEF forced expiratory ow
FEF25–75% forced expiratory ow 25–75%
FEV
1
forced expiratory volume in 1 second
FLR future liver remnant
FRC functional residual capacity
FSGS focal segmental glomerulosclerosis
FVC forced vital capacity
GBM glomerular basement membrane

G-CSF granulocyte colony-stimulating factor
GDA gastroduodenal artery
GERD gastroesophageal reux disease
GFR glomerular ltration rate
GI gastrointestinal
GRWR gra-to-recipient body weight ratio
GvHD gra-versus-host disease
GvL Gra versus leukemia
HAR hyperacute rejection
HARI hepatic artery resistance index
HAT hepatic artery thrombosis
HBV hepatitis B virus
HCC hepatocellular carcinoma
HCV hepatitis C virus
HF heart failure
HFSS Heart Failure Survival Score
HHS Department of Health and Human
Services
HHV human herpes virus
HHV-8 human herpes virus type 8
HIV human immunodeciency virus
HLA human leukocyte antigen
HLAi HLA incompatible
HLT combined heart–lung transplantation
HLT heart–lung transplantation
HMGB-1 high-mobility group box 1 protein
HPC human progenitor cell
HPV human papillomavirus
HRQOL health related quality of life
HRSA Health Resources and Services

Administration
HSC hematopoietic stem cells
HSCT hematopoietic stem cell
transplantation
HSP heat shock protein
HSV herpes simplex virus
HT heart transplant
HT heart transplantation
HTA Human Tissue Authority
HUS hemolytic uremic syndrome
IBMIR immediate blood-mediated
inammatory reaction
ICAM-1 intercellular adhesion molecule 1
xvi
List of abbreviations
ICD implantable cardioverter-debrillator
ICOS inducible T-cell costimulator
ICP intra-cranial pressure
ICU intensive care unit
IE islet equation
IF/TA interstitial brosis and tubular
atrophy
IFN interferon
IFN␥ interferon ␥
Ig immunoglobulin
IgA immunoglobulin A
IgG immunoglobulin G
IHD ischemic heart disease
IL interleukin
IL-2 interleukin-2

IL-2R interleukin-2 receptor
IMP inosine monophosphate
IMV inferior mesenteric vein
iNO inhaled nitric oxide
INR international normalized ratio
INTERMACS International Registry for
Mechanically Assisted Circulatory
Support
IP
3
inositol triphosphate
IPAH idiopathic pulmonary arterial
hypertension
IPEX immune dysregulation,
polyendocrinopathy, enteropathy
X-linked
IPF idiopathic pulmonary brosis
IPTR International Pancreas Transplant
Registry
IRI ischemia/reperfusion injury
ISHLT International Society for Heart and
Lung Transplantation
iTreg inducible Treg
ITU intensive treatment unit
IV intravenous
IVC inferior vena cava
IVIg intravenous immunoglobulin
IVUS intravascular ultrasound
Jak Janus kinase
JCV JC virus

KS Kaposi’s sarcoma
LAS lung allocation system
LCR late cellular rejection
LDH lactate dehydrogenase
LDLLT living donor lobar lung
transplantation
LDLT living donor liver transplantation
LDLT living donor lung transplantation
LFA-1 leukocyte function-associated
antigen 1
LFA-1 lymphocyte-function associated
antigen-1
LT liver transplantation
LT lung transplantation
LV le ventricle
LV le ventricular
LVAD le ventricular assist device
LVEDP le ventricular end-diastolic
pressure
LVH le ventricular hypertrophy
MAC membrane attack complex
MAG3 mercaptoacetyltriglycine
MAP mitogen-activated protein
MAPK MAP kinase
MBD mineral bone disease
MCSD mechanical circulatory support
devices
MELD Model for End-Stage Liver Disease
MHC major histocompatability complex
MHV middle hepatic vein

miH minor histocompatibility
MMF mycophenolate mofetil
MMR measles, mumps, and rubella
MPA mycophenolic acid
MPGN membranoproliferative
glomerulonephritis
MPSC Membership and Professional
Standards Committee
MRI magnetic resonance imaging
MRR medical record review
MRSA methicillin-resistant Staphylococcus
aureus
mTOR mammalian target of rapamycin
NAPRTCS North American Pediatric Renal
Trials and Collaborative Studies
NFAT nuclear factor of activated
Tcells
NF-␬B nuclear factor-␬B
NHL non-Hodgkin’s lymphoma
NHS National Health Service
NHSBT NHS Blood and Transplant
NK natural killer
NKT natural killer T
NO nitric oxide
NOD non-obese diabetic
NODAT new-onset diabetes aer
transplantation
xvii
List of abbreviations
NODAT new-onset diabetes aer

transplantation
NOTA National Organ Transplant Act
NRM non-relapse mortality
nTreg naturally occurring Treg
NYHA New York Heart Association
OB obliterative bronchiolitis
OKT3 muromonab-CD3
OLV one-lung ventilation
OP osteoporosis
OPO organ procurement organization
OPTN Organ Procurement and
Transplantation Network
PA pulmonary arter y
PAK pancreas aer kidney transplant
PAP pulmonary artery pressure
PAS Periodic Acid-Schi
PCA patient-controlled analgesia
PCR polymerase chain reaction
PCWP pulmonary capillary wedge pressure
PDA UK Potential Donor Audit
PDGF platelet-derived growth factor
PEEP positive end expiratory pressure
PGD primary gra dysfunction
PGE2 prostaglandin E2
PGI
2
prostacyclin
PK pharmacokinetic
PKC protein kinase C
PML progressive multifocal

leukoencephalopathy
PMN polymorphonuclear neutrophil
PN parenteral nutrition
ppm parts per million
PRA panel-reactive antibody
PRAISE Prospective Randomized Amlodipine
Survival Evaluation
PRR pattern recognition receptor
PSC primary sclerosing cholangitis
p-SMAC peripheral SMAC
PT prothrombin time
PTA pancreas transplant alone
PTLD post-transplant lymphoproliferative
disease
PTM post-transplant malignancy
P U VA psora l e n and U VA t herapy
PVR pulmonary vascular resistance
PVT portal vein thrombosis
QoL quality of life
Rrecipient
RAD everolimus
RAS renal artery stenosis
rATG rabbit ATG
RBCs red blood cells
RCC renal cell carcinoma
RCT randomized controlled trial
RER respiratory exchange ratio
RIC reduced intensity conditioning
ROS reactive oxygen species
RR relative risk

RSV respiratory syncytial virus
RV right ventricle
RV right ventricular
RVAD right ventricular assist device
RVI respiratory viral infections
SA sinoatrial
SARS severe acute respiratory syndrome
SCC squamouscellcarcinoma
SCID severe combined immunodeciency
SFSS small-for-size syndrome
SIOPEL International Childhood Liver
Tumour Strategy Group of the
International Society of Paediatric
Oncology
SIRS systemic inammatory response
syndrome
SLT single lung transplantation
SMA smooth muscle antibody
SMA superior mesenteric artery
SMV superior mesenteric vein
SOT solid organ transplant
SPK simultaneous pancreas and kidney
transplant
SRL sirolimus
SRTR Scientic Registry of Transplant
Recipients
SRTR US Scientic Registry of Transplant
Recipients
SVC superior vena cava
SVR systemicvascularresistance

T3 triiodothyronine
T4 tetraiodothyronine
TA transplant arteriopathy
TAC tacrolimus
TAH total articial heart
TBBx transbronchial biopsy
TBI total body irradiation
TCD T-cell depleted
TCMR T-cell mediated rejection
TCR T-cell receptor
TEA thoracic epidural anesthesia
xviii
List of abbreviations
TEE transesophageal echocardiography
TEG thromboelastography
TG transplant glomerulopathy
TGF␤ transforming growth factor ␤
helperTcell
TIVA total intravenous anesthesia
TLC total lung capacity
TLCO transfer coecient for carbon
monoxide
TLI total lymphoid irradiation
TLR Toll-like receptor
TMA thrombotic microangiopathy
Tn troponin
TNF tumor necrosis factor
TNF-␣ tumor necrosis factor alpha
TNFR TNF receptor
TPEX therapeutic plasma exchange

TPG transpulmonary gradient
TPG transpulmonary pressure gradient
TR tricuspid regurgitation
Treg regulatory T cell
TSH thyroid-stimulating hormone
UCLA University of California, Los Angeles
UKELD United Kingdom Model for
End-Stage Liver Disease
UNOS United Network for Organ Sharing
UTI urinary tract infection
VA ar t e r i ovenous
VAD ventricular assist device
VBDS vanishing bile duct syndrome
VOD veno-occlusive disease
VRE vancomycin-resistant Enterococcus
faecalis
VTE venous thromboembolism
VV venovenous
VZV varicella zoster virus
WHO World Health Organization
WU Wood units
xix

Section 1 General
Chapter
1
Historical perspectives
John Dunning and Sir Roy Calne
Key points
r

Successful techniques for vascular
anastomoses developed at the end of the
nineteenth century made the transplantation
of internal organs possible.
r
e rst successful human allogra, a
corneal transplant, was performed in 1905.
r
e recognition that the body’s reactions to
foreigntissueledtothefailureofallogra
transplantation gave rise to the new
discipline of immunology.
r
e discovery that cyclosporine, a metabolite
from the fungus Tolypocladium inatum,is
300 times more active against the
proliferation of splenic lymphocytes than
against other cell lines changed the face of
transplantation.
r
As transplantation has become more
successful in terms of survival, quality of life,
and cost benet, the demand for donor
organs has increased so that it is now greater
than supply.
Transplantation of organs represents the pinnacle of
medical achievement in so many dierent ways. It
epitomizes the multi-disciplinary team approach to
patient care. It has a foundation in rened surgical
technique, supported by an understanding of com-

plex immunological events, and requires a complex
approach to pretransplant assessment and postoper-
ativecareofmultipleorgansystems.Yetinsome
respects it also represents a failure: the inability to
repair diseased organs such that the only way forward
is to cast aside the worn out tissue!
e idea of organ and tissue transplantation is
not new, and reference to it may be found in the
ancient literature of China and India. e rst descrip-
tion of a skin transplant is contained in the Sushrutta
manuscripts dating from around 450 BC. e tech-
nique described found use in Europe during the Mid-
dle Ages in the hands of the Italian surgeon Gas-
pare Tagliacozzi. He used it for the reconstruction
of damaged noses, frequently a result of syphilitic
injury, using a skin ap from the forearm. At the time
hewrotethat“thesingularnatureoftheindividual
entirelydissuadesusfromattemptingthisworkon
another person.” Perhaps he had already attempted
the repair using allogeneic donors (transplantation
between genetically disparate individuals) prior to his
successful autogra (transplant of tissue in the same
individual). Although the technique was new to the
people of the time, the concept of tissue transplanta-
tion was well established among Europeans following
the legend of a total leg transplant by Saints Damon
and Cosmos illustrated by artists such as Fra Angelico
and sculpted by Donatello. Such legendary optimism
was not rewarded clinically until much later, but it is
certain that interest in skin graing was revived due

to the substantial need for treatment of the gross leg
ulcers prevalent in the nineteenth century as a result of
injury from syphilis, nutritional deciency, and burns.
Greatadvancesweremadewiththeobservationsof
theFrenchPhysiologistPaulBert,whorecognizedthe
importance of gra neovascularization and described
the success of autograing in comparison with the fail-
ures of allograing.
It was the ophthalmic surgeons who really led the
way to successful allograing with the transplanta-
tion of corneal gras. Samuel Bigger reported what
was probably the rst successful full-thickness corneal
allogra when he performed an operation on a blind
pet gazelle while he was a prisoner in Egypt in 1835.
He replaced the cornea, apparently with good results.
Organ Transplantation: A Clinical Guide, ed. A.A. Klein, C.J. Lewis, and J.C. Madsen. Published by Cambridge University
Press.
C
Cambridge University Press 2011.
1
Section 1: General
Attempts to reproduce this success continued through
the latter part of the nineteenth century, and with tech-
nical improvements and increasing frequency of tri-
als, the results with animal corneal gras improved
steadily. Finally, in 1905, the rst successful human
corneal allogra was performed. Although therapeu-
tic transplantation of the cornea became rmly estab-
lished as part of ophthalmic practice from this time,
there was no theoretical explanation why corneal gra-

ing should be successful whereas the graing of other
organs and tissues was not, nor of the observation that
from time to time corneal gras were rejected.
It was not until Alexis Carrel and Mathieu Jaboulay
developed successful techniques for vascular anasto-
moses at the end of the nineteenth century that the
transplantation of internal organs became possible.
Many dierent animal models were used with attempts
to transplant almost every organ, but the kidney was
the rst organ to which this technique was repeatedly
applied.
Carrel remained a prominent contributor to the
eld of transplant surgery throughout the early 1900s,
moving from France to the United States, where his
collaboration with Guthrie led to signicant contri-
butions to vascular surgery with the development of
techniques for venous patching of arteries and the
use of cold storage to protect tissue for reimplanta-
tion up to 20 hours from its procurement. e result
of their labors was a series of 35 papers describing
their experimental achievements in a wide variety of
animal models for transplantation. However, it was
not until 1908 that survival became extended when
Carrel performed a kidney transplant in a dog with
survival of the gra for several years. With the survival
of gras beyond a few hours, the opportunity to study
tissue histologically emerged, and by 1905, parenchy-
mal inltration by “round cells” and arterial lesions
were recognized.
Of course human donors were not available at

this time, and all organs transplanted were obtained
from animals so that a mixture of pig, goat, mon-
key, and sheep xenogras (transplantation between
species) were undertaken in human patients with acute
renal failure. Although none of these attempts were
successful, the last attempt by Neuhof in 1923 was
particularly encouraging, with the recipient surviv-
ing for 9 days. It demonstrated clearly that throm-
bosis and hemorrhage from vascular anastomoses
was not inevitable. Although most attempts to per-
form organ transplantation were made in animals,
Mathieu Jaboulay attempted the technique in man, and
in 1906 he reported his observations in Lyon Medical.
His attempts used a pig kidney in one patient and a
goat’s kidney in a second, with the organs implanted
in the cubital fossa and anastomosed to the humeral
artery and cephalic vein. Ultimately both attempts
failed as a result of vascular thrombosis, but the kid-
neys did start to diurese initially.
It quickly became apparent that whereas autogras
generally succeeded, allogras and xenogras mostly
failed. Although the technical problems of the oper-
ation had largely been sorted out, it was clear that
“fromabiologicalstandpoint theinteractionsofthe
host and of the new organ are practically unknown.”
e increasing understanding that the resistance to
foreign gras was caused by systemic factors led to
the repeated suggestion that an immune response of
the “anaphylactoid type” was somehow responsible for
gra rejection. It was recognized that research had now

to be directed toward understanding the body’s reac-
tions to foreign tissue, and so from experimental trans-
plantation in the early part of the century, the two
new disciplines of vascular surgery and immunology
emerged.
Other landmarks were reached throughout the
early years of the twentieth century, with growing
understanding of skin gras used to treat burns, and
with Voronoy transplanting the rst cadaveric human
kidney in 1933. His recipient was a 26-year-old woman
who had attempted suicide by swallowing sublimed
mercury. is led to uremic coma. e kidney was pro-
cured from a 60-year-old man who died following a
fracture of the base of the skull. e operation was per-
formed on April 3, 1933, with the renal vessels anas-
tomosed using Carrel’s technique to the femoral ves-
sels and the kidney placed in a subcutaneous pouch,
with externalization of the ureter. Local anesthetic was
used. e donor was known to be blood group B, and
the recipient blood group O. e graed kidney did
diurese for a while, but unfortunately the patient died
2dayslater.
Despite the demonstration of second-set skin gra
rejection in man as early as 1924 and the successful
exchange of skin between identical twins in 1927, no
useful generalizations were made to further elucidate
the immunological mechanisms involved. e prac-
tice of corneal graing continued, but it seemed to be
accepted that the transplantation of other tissues and
organs was impractical, and there was a lull in activ-

ity among surgeons for the next 20 years, with further
2
Chapter 1: Historical perspectives
interruptions to the eld brought about by the Second
World War.
e area of skin graing became of greater impor-
tance for the treatment of war burns and other
injuries, and the death from kidney disease also
provided impetus to focus once more on kidney
transplantation. Short-term success in the late 1940s
was reported by a number of individuals, including
Voronoy, and David Hume working in Boston. Both
transplanted kidneys into patients with uremic coma
that diuresed for a number of days, before stopping and
being removed again. e technique was not seen as
replacement therapy but a method of stimulating a
recovery reex in the native diseased kidney. How-
ever, as the immunological basis of rejection became
established, scientic interest in organ transplanta-
tion waned until eective immunosuppressive regi-
mens were found.
Abdominal organ transplantation
Transplantation of abdominal organs has been a long-
term success story, with patients surviving 40 years
with excellent function in their original graed organs.
e success of clinical allogra transplantation began
with transplantation of kidneys between identical
twins by Murray and colleagues at Peter Bent Brigham
Hospital in Boston in 1956. is was an outstanding
achievement and demonstrated clearly that the kid-

ney would withstand the trauma of removal, periods
of ischemia, and then the procedure of transplanta-
tion into another individual of the same species. e
fact that identical twins would not be able to reject
skin gras and the experimental auto-transplantation
of the kidney in the dog enabled the group in Boston
to proceed with the clinical operation with reasonable
optimism. Unfortunately, a twin donor would not be
available for most patients dying of kidney failure, and
the immunological barrier between individuals proved
to be an enormous biological problem.
For more than a decade, clinical kidney transplan-
tation was the only form of organ graing that was
seriously studied and yielded some success. e identi-
cal twin experience was reproduced, and conditioning
of the recipient with total-body irradiation was applied
to kidney graing between donor and recipient who
were not twins. is was based mainly on experimen-
tal work with bone marrow transplantation; however,
in the clinic the results were disastrous, except in two
cases of kidney graing between non-identical twins.
Patients subjected to total-body irradiation frequently
succumbed to infection, aplasia, and cancer.
e introduction of chemotherapy to supplement
irradiation and allow dose reduction improved the
outcomes further, and in 1960, William Goodwin
introduced methotrexate and cyclophosphamide to
the eld of living related transplantation and treated
an episode of rejection with prednisolone. en, in
London in the mid 1950s, the prolongation of survival

of renal allogras in dogs by the anti-leukemia drug
6-mercaptopurine (6-MP) heralded clinical immuno-
suppression and azathioprine (AZA), a derivative of
6-MP, was found to be slightly better experimentally.
Although 6-MP was used briey with irradiation, it
was rapidly abandoned because of signicant toxic-
ity. e use of AZA in clinical kidney transplanta-
tion was originally disappointing, but when corticos-
teroids were added, this immunosuppressive regimen
resulted in some long-term clinical renal allogra suc-
cesses from the early 1960s.
Further understanding of transplant immunology
was gained with insights into the human leukocyte
antigen (HLA) system and histocompatibility. Cross-
match techniques became established through the
1960s, and understanding of the “transfusion eect”
was also gained (Opelz and Terasaki), whereby previ-
ous transfusion appeared to confer protection for the
transplanted organ.
In the 1960s, experimental transplantation of the
liver, pancreas, intestines, and heart led to a clari-
cation of the technical requirements involved, and
in 1963, Starzl in Denver carried out the rst clini-
cal liver transplant. Unfortunately, the results of this
clinical series were dismal, and Starzl self-imposed a
moratorium until 1967, when he resumed clinical liver
transplantation, having in the meantime improved
the surgical technique and the assessment of gra
function and prevention of rejection. e rst ortho-
topic liver transplant in Europe was performed in

Cambridge by Calne in 1968. For nearly 10 years,
Denver and Cambridge were the only two centers
with regular programs of clinical liver transplantation.
ere were a few outstandingly good results, but many
disappointments. Patients were referred for operation
too late, and anti-rejection therapy was still in the
processofdevelopmentusingmodiedregimensof
AZA, steroids, and polyclonal anti-lymphocyte serum.
In addition to rejection, sepsis, biliary, and vascular
complications and recurrence of the patient’s own dis-
ease oen resulted in failure. During this uncertain
3
Section 1: General
and disappointing phase of development, the vascular-
ized pancreas was also transplanted and shown to be
capable of curing diabetes in a few patients. However,
many patients suered from complications of leakage
of pancreatic enzymes, causing inammation and fatal
sepsis.
A watershed in organ transplantation was the
discovery of the immunosuppressive properties of
cyclosporine (CyA), a metabolite from the fungus
Tolypocladium inatum,byJeanBorelworkingin
the Sandoz laboratories. CyA was 300 times more
active against the proliferation of splenic lymphocytes
than against other cell lines. Experimental and clin-
ical application of CyA transformed the attitude of
previously sceptical clinicians to organ transplanta-
tion. Calne’s paper published in e Lancet in 1979
described its use in 32 kidney transplants, 2 liver

transplants, and 2 pancreatic transplants and showed
improved 1-year functional survival of kidney trans-
plants from below 50% to approximately 80%. It was
introduced to clinical immunosuppressive regimens
worldwide in 1982 and radically improved the sur-
vival of heart, kidney, liver, and pancreas recipients.
About10centershadsoldieredoninthepre-CyAera,
but aer the introduction of CyA, there were soon
more than 1000 centers. e improved results led to an
expanding mismatch of numbers of available donors
to potential recipients seeking a life-saving organ
gra.
Unfortunately, the nephrotoxic side eects of CyA
led to late renal failure in many cases. Hopes that there
might be a dosage window in which rejection could be
controlled and side eects avoided were only realized
in a minority of cases. However, the concept was estab-
lished of combining immunosuppressive drugs with
the objective of obtaining added immunosuppressive
eect but reducing the individual side eects. us
AZA, CyA, and steroids became a standard immuno-
suppressant regimen.
e liver proved to be less susceptible to rejec-
tion than other organs. is had been anticipated by
experimentsinpigsandrats.Inanimportant“patient-
led clinical study,” a group of patients from Denver
stopped taking their maintenance immunosuppres-
sion without telling their doctors. Although lack of
compliance is a common cause of organ gra failure
duetorejection,asurprisingnumberofyoungpatients

with liver transplants did well long-term. A number
of patients, in whom immunosuppression was stopped
for medical indications, usually infection, also did not
require renewal of their immunosuppressive regimen
of drugs. Condence in the surgery and immunosup-
pression gradually increased.
A variety of complicated organ gra procedures
were reported, including small bowel on its own (1988)
and in combination with liver and other organ gras.
e rst combined heart, lung, and liver transplant
was performed by Wallwork and Calne in 1987 at Pap-
worth (Cambridge, United Kingdom), with survival of
thepatientformorethan10years.
ere is now a move toward minimization of
immunosuppression and tolerance. Alemtuzumab
(Campath), an extremely powerful anti-lymphocyte
antibody developed in Cambridge by Waldmann and
colleagues, has induced “prope or almost tolerance”
when used as an induction agent followed by main-
tenance immunosuppression with half-dose CyA,
rather than a full dose of three drugs. Of the original
series of kidney transplantation patients treated in
Cambridge, 80% have never received steroids, and
their quality of life has been excellent aer more
than 10 years of follow-up. is immunosuppressive
regimen has reduced complications of anastomotic
leakageinpancreastransplants,withencouraging
results.
Pancreas graing can never be a treatment for
all diabetics, but when transplanted together with a

kidney in patients with diabetic renal failure, pan-
creas transplantation has produced excellent long-
term results. A move toward islet transplantation to
avoid the major operation has had some early encour-
aging results. is is a eld in which stem cell and/or
gene therapy may well lead to fruitful developments in
the future.
Cardiothoracic transplantation
While the eld of kidney transplantation research and
experimentation moved rapidly into the clinical arena,
progress was not so rapid for the transplantation of
other organs. e rst heart transplant described in
the literature was performed in 1905 by Carrel and
Guthrie. e heart, transplanted from one dog into
a heterotopic position in the neck of another dog,
continued to beat for 2 hours. is model demon-
strated that it was possible to transplant a heart with
all four chambers pumping blood. More importantly,
it demonstrated that the heart could be removed from
its blood supply and sutured into the circulation of a
second animal and still recover its normal organized
4