TRANSPLANTATION TODAY

LILLY BARBA, M.D.MEDICAL DIRECTOR RENAL

TRANSPLANT PROGRAMHARBOR-UCLA MEDICAL CENTER

APRIL 12, 2010

THE HISTORY OF THE HISTORY OF TRANSPLANTATION AS TRANSPLANTATION AS

DEPICTED IN ARTDEPICTED IN ART• The possibility to transplant limbs and organs predates the modern technology of organ transplantation.

• The legend of the “Miracle of the Black Leg” describes two surgeon brothers, who lived during the 3rd century in Asia Minor.

• The legend relates their miraculous removal of the diseased leg of a Caucasian Roman named Justinian and its replacement with the leg of a recently deceased black African. The Miracle of Cosmas & Damian

(15th c.)

SIGNIFICANT EVENTS IN SIGNIFICANT EVENTS IN TRANSPLANTATIONTRANSPLANTATION

AS EARLY AS THE 6TH CENTURY BC THE INDIAN SURGEON SUSHRUTA DESCRIBED RECONSTRUCTION OF DISFIGURING FACIAL WOUNDS BY TRANSPLANTATING SKIN AND CARTILAGE

EARLY INTEREST IN THE POSSIBILITY OF TRANSPLANTATION

TRANSPLANTATION AS A TRANSPLANTATION AS A VIABLE CLINICAL VIABLE CLINICAL

PROCEDUREPROCEDURE 1905 FIRST SUCCESSFUL HUMAN

CORNEAL TRANSPLANT 1930’S HISTOCOMPATIBILITY

ANTIGENS DISCOVERED IN MICE 1954 FIRST SUCCESSFUL KIDNEY

TRANSPLANT PERFORMED BETWEEN IDENTICAL TWINS

1957 AZATHIOPRINE DEVELOPED

TRANSPLANTATION AS A TRANSPLANTATION AS A VIABLE CLINICAL VIABLE CLINICAL

PROCEDUREPROCEDURE 1962 FIRST SUCCESSFUL DECEASED

DONOR KIDNEY TRANSPLANT 1963 DR. HARDY PERFORMS FIRST

SUCCESSFUL LUNG TRANSPLANT 1966 FIRST SUCCESSFUL PANCREAS

TRANSPLANT 1967 DR. BARNARD PERFORMS THE

FIRST SUCCESSFUL HEART TRANSPLANT. DR. STARZL PERFORMS THE FIRST SUCCESSFUL LIVER TRANSPLANT

TRANSPLANTATION AS A TRANSPLANTATION AS A VIABLE CLINICAL VIABLE CLINICAL

PROCEDUREPROCEDURE 1981 DR. SHUMWAY PERFORMS

THE FIRST HEART/LUNG TRANSPLANT

1983 CYCLOSPORINE APPROVED FOR PREVENTION OF REJECTION

1988 FIRST SUCCESSFUL SMALL INTESTINE TRANSPLANT

1990 TACROLIMUS APPROVED FOR PREVENTION OF REJECTION

1995 MYCOPHENOLATE APPROVED

TRANSPLANTATION AS A TRANSPLANTATION AS A VIABLE CLINICAL VIABLE CLINICAL

PROCEDUREPROCEDURE 1996 USE OF SPLIT LIVERS1996 USE OF SPLIT LIVERS 1997 DACLIZUMAB APPROVED 1997 DACLIZUMAB APPROVED

FOR PREVENTION OF ACUTE FOR PREVENTION OF ACUTE REJECTIONREJECTION

1999 SUCCESSFUL ISLET CELL 1999 SUCCESSFUL ISLET CELL TRANSPLANTATION USING THE TRANSPLANTATION USING THE EDMONTON PROTOCOLEDMONTON PROTOCOL

2005 FIRST SUCCESSFUL PARTIAL 2005 FIRST SUCCESSFUL PARTIAL FACE TRANSPLANT PERFORMEDFACE TRANSPLANT PERFORMED

TRANSPLANTATION TRANSPLANTATION TODAYTODAY

THE WAITING LIST SUCCESS RATE OF ORGAN SUCCESS RATE OF ORGAN

TRANSPLANTATIONTRANSPLANTATION REVIEW OF TRANSPLANTATION REVIEW OF TRANSPLANTATION

20092009

THE OPTNTHE OPTN

The Organ Procurement and The Organ Procurement and Transplantation Network Transplantation Network (OPTN)(OPTN) was was established by Congress under the established by Congress under the National Organ Transplant Act (NOTA)National Organ Transplant Act (NOTA) of of 1984 1984

The OPTN is operated by a private, The OPTN is operated by a private, non-profit organization under federal non-profit organization under federal contract.contract.

UNOSUNOSUNITED NETWORK FOR ORGAN UNITED NETWORK FOR ORGAN

SHARINGSHARING UNOS was awarded the first OPTN UNOS was awarded the first OPTN

contract in 1986contract in 1986 UNOS has continued to administer UNOS has continued to administer

the OPTN under contract with the the OPTN under contract with the Health Resources and Services Health Resources and Services Administration of the U.S. Administration of the U.S. Department of Health and Human Department of Health and Human Services (HHS) for more than 20 Services (HHS) for more than 20 years.years.

What is the purpose of the What is the purpose of the OPTN? OPTN?

The OPTN is a public-private The OPTN is a public-private partnership linking all of the partnership linking all of the professionals involved in the donation professionals involved in the donation and transplantation system. and transplantation system.

The primary goals of the OPTN are to:The primary goals of the OPTN are to:1.1. increase and ensure the effectiveness, increase and ensure the effectiveness,

efficiency and equity of organ sharing efficiency and equity of organ sharing in the national system of organ in the national system of organ allocation allocation

2.2. increase the supply of donated organs increase the supply of donated organs available for transplantationavailable for transplantation

THE WAITING LISTTHE WAITING LIST

Initiated on October 25, 1999, UNet Initiated on October 25, 1999, UNet contains data regarding every organ contains data regarding every organ donation and transplant event occurring donation and transplant event occurring in the U.S. since 1986. in the U.S. since 1986.

UNet enables the nation's organ UNet enables the nation's organ transplant institutions to:transplant institutions to:

register patients for transplants register patients for transplants match donated organs to waiting patients match donated organs to waiting patients manage the clinical data of all patients, manage the clinical data of all patients,

before and after their transplants before and after their transplants

Waiting list candidates as of April 11, 2010

All    106,842

Kidney 84,295

Pancreas 1,467

Kidney/Pancreas 2,190

Liver 15,931

Intestine 243

Heart 3,153

Lung 1,831

Heart/Lung 72

   All candidates will be less than the sum due to candidates waiting for multiple organs

UNOS

Total 2,198

Deceased Donor 1,682

Living Donor 516

Based on OPTN data as of 04/02/2010

Transplants performed January Transplants performed January 20102010UNOSUNOS

Donors recovered January 2010

Total 1,139

Deceased Donor 623

Living Donor 516

Based on OPTN data as of 04/02/2010

DONORSDONORSUNOSUNOS

Waitlist and Transplant Activity Waitlist and Transplant Activity for Liver, 1999-2008for Liver, 1999-2008

Waitlist and Transplant Activity Waitlist and Transplant Activity for Kidneys, 1999-2008for Kidneys, 1999-2008

Waitlist and Transplant Activity Waitlist and Transplant Activity for Heart, 1999-2008for Heart, 1999-2008

Waitlist and Transplant Activity Waitlist and Transplant Activity for Lung, 1999-2008for Lung, 1999-2008

TRANSPLANTATION TRANSPLANTATION TODAYTODAY

THE WAITING LIST SUCCESS RATE OF ORGAN

TRANSPLANTATION REVIEW OF TRANSPLANTATION REVIEW OF TRANSPLANTATION

20092009

Patient Survival Until Five Years After Transplant Patients Transplanted 2001-2007

One Year Unadjusted Graft Survival by Year,Living and Deceased Donor Kidney Transplants

One Year Unadjusted Graft Survival by Year, Living and Deceased Donor Liver Transplants

One Year Unadjusted Patient Survival by Year, Living and Deceased Donor Liver Transplants

One Year Unadjusted Graft Survival by Year,Deceased Donor Heart Transplants

One Year Unadjusted Patient Survival by Year,Deceased Donor Heart Transplants

One Year Unadjusted Graft Survival by Year, Deceased Donor Lung Transplants

One Year Unadjusted Patient Survival by Year, Deceased Donor Lung Transplants

SRTRSRTR

Annual Report of the OPTN and SRTR Trends in K and P Transplants

1998 to 2007• The number of patients awaiting transplantation increased

from 40,825 to 76,070 (86%) between 1998 and 2007, reflecting an increase in the number of patients listed “inactive status”. Active patients increased by 4,510 between 2002 and 2007, from 44,263 to 48,773.

• There were 6,037 living donor and 10,082 deceased donor kidney transplants in 2007. Patient and allograft survival was best for recipients of living donor kidneys, least for expanded criteria donor (ECD) deceased donor kidneys, and intermediate for non-ECD kidneys.

• The total number of pancreas transplants peaked at 1,484 in 2004 and has since declined to 1,331. Among pancreas recipients, those with simultaneous pancreas-kidney (SPK) transplants experienced the best pancreas graft survival rates: 86% at one year and 53% at 10 years.

SRTRSRTR

Liver and Intestine Transplantation In the United States, 1998-2007

• Liver transplantation numbers in the United States remained constant from 2004-2007, while the number of waiting list candidates has trended down.

• In 2007, the waiting list was its smallest since 1999, with adults ≥50 years representing the majority of candidates. Most age groups had decreased waiting list death rates, however, children <1 year had the highest death rate.

• Non-cholestatic cirrhosis was most commonly diagnosed. Hepatocellular carcinoma exceptions increased slightly.

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Liver and Intestine Transplantation In the United States, 1998-2007

• Use of liver allografts from donation after cardiac death donors increased in 2007.

• Model for End-stage Liver Disease (MELD)/Pediatric Model for End-stage Liver Disease (PELD) scores <15 accounting for 75% of the waiting list.

• Over the same period, the number of transplants for MELD/PELD <15 decreased from 16.4% to 9.8%.

• The intestine transplantation waiting list decreased from 2006, with the majority of candidates being children <5 years old.

• Death rates remain at about 14 % . Policy changes have been implemented to improve allocation and recovery of intestine grafts to positively impact mortality

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Heart Transplantation in the U.S., 1998-2007

• The number of candidates actively awaiting heart transplantation has declined steadily, from 2,525 in 1998 to 1,408 in 2007, a 44% decrease.

• Despite this decline, a larger proportion of patients are listed as either Status 1A or 1B, likely secondary to increased use of mechanical circulatory support.

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Heart Transplantation in the U.S., 1998-2007

• The overall death rate among patients awaiting heart transplantation fell from 220 to 142 patients per 1,000 patient-years at risk.

• Likely reflects better medical and surgical options for those with end-stage heart failure.

• This trend was noted across all racial groups, both sexes, all disease etiologies (re-transplantation excepted), and all status groups.

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Heart Transplantation in the U.S., 1998-2007

• Recipient numbers were relatively stable over the past decade. In 2007, 2,207 transplants were performed, although the proportion of patients transplanted as Status 1A shifted from 34% to 50%. A trend toward transplanting more patients above 65 years of age was seen.

• Adjusted patient (and graft) survival at three months, one, five, and 10 years after transplantation has gradually, but significantly, improved during the same period.

• Current patient survival estimates are 93%, 88%, 74%, and 55%, respectively (for 3m, 1yr, 5 yr, 10 y).

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Lung Transplantation in the United States,1998-2007

• The most significant change in lung transplantation over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005.

• Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007. There was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007.

• The number of lung transplants performed yearly increased

through the decade to a peak of 1,465 in 2007; the greatest single year increase occurred in 2005.

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Lung Transplantation in the United States,1998-2007

• Despite higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003, and better than in previous years.

• Idiopathic pulmonary fibrosis (IPF) became the most common diagnosis group to receive a lung transplant in 2007. Emphysema was the most common diagnosis in years prior.

• The number of re-transplants and transplants in those >65yrs have increased significantly since 1998, up 295% and 643%, respectively.

• A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n=51).

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TRANSPLANTATION TODAY

• THE WAITING LIST

• SUCCESS RATE OF ORGAN TRANSPLANTATION

• REVIEW OF TRANSPLANTATION 2009

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Review of topics in transplantation

• Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation(NEJM 360:7,2009) : randomized, controlled trial showed machine perfusion associated with a reduced risk of delayed graft function and improved graft survival in the first year post transplant (94 % vs 90 %)

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Review of topics in transplantation

• Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury (AJT 2009:9):The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr

• Calculating Life Years from Transplant (LYFT): Methods for Kidney and Kidney-Pancreas Candidates (AJT 2008:8:997) :Prioritizing candidates with higher LYFT scores for each available kidney could substantially increase total years of life among both transplant candidates and recipients

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Other topics in transplantation

• PAIRED EXCHANGE/CHAIN DONORS

• SURVIVAL OF KIDNEY DONORS

• PREGNANCY IN YOUNG WOMEN AFTER DONATION

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CONCLUSIONS:

• TRANSPLANTATION SAVES LIFES, IMPROVES THE QUALITY OF LIFE

• ALLOGRAFT AND PATIENT SURVIVALS HAVE IMPROVED

• MORE DONORS ARE NEEDED