Basic Immunology Solid Organ Transplantation...Solid Organ Transplantation Daniel Maluf, MD...

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Solid Organ Transplantation

Daniel Maluf, MDAssistant Professor of SurgeryVCU School of Medicine

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Basic Immunology

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Basic Immunology

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Basic Immunology

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History of organ transplantation

First successful heart transplantDr. Norman Shumway, Stanford University Hospital, Stanford, CA

1968

First isolated pancreas transplantDr. Richard Lillehei, University of Minnesota, Minneapolis, MN

1968

First successful liver transplant*Dr. Thomas Starzl, University of Colorado Health Sciences Center, Denver, CO

1967

First successful pancreas/kidney transplantDrs. Richard Lillehei, William Kelly, University of Minnesota, Minneapolis, MN

1966

First successful kidney transplant*Dr. Joseph E. Murray, Brigham & Women's Hospital, Boston, MA

1954

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History of organ transplantation

*Transplant was the first of its kind in the world

First successful living-related lung transplantDr. Vaughn A. Starnes, Stanford University Medical Center, Stanford, CA

1990

First successful living-related liver transplantDr. Christoph Broelsch, University of Chicago Medical Center, Chicago, IL

1989

First successful double lung transplant*Dr. Joel Cooper, Toronto Lung Transplant Group, Toronto General Hospital, Toronto Canada

1986

First successful single lung transplant*Dr. Joel Cooper, Toronto Lung Transplant Group, Toronto General Hospital, Toronto Canada

1983

First successful heart-lung transplantDr. Bruce Reitz, Stanford University Hospital, Stanford, CA

1981

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Cadaveric Donors, Cadaveric Transplants,and Number on Waiting List

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

Source: Donors from OPTN data as of 9/5/00; transplants from Scientific Registry data as of 9/5/00; snapshot of OPTN waiting list on the last day of each year.

Donors

Transplants

Waiting List at Year’s End

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Waiting List Additions 1994-2003: U.S.

0

10,000

20,000

30,000

40,000

50,000

60,000

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003Year

Num

ber

of R

egis

trat

ions

Kidney Liver

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Waiting List Additions 1994-2003: U.S.

0

1000

2000

3000

4000

5000

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003Year

Num

ber o

f Reg

istra

tions

Heart Lung Pancreas Heart-Lung Kidney-Pancreas10

Patients waiting for transplantation

Type of Transplant Patients Waitingkidney 52,216liver 17,546pancreas 1,317pancreas islet 295kidney-pancreas 2,540

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Organ Donor and Recovery

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Percent of Cadaveric DonorsContributing to Each Organ Type

Source: OPTN data as of 9/5/00.

0

1,000

2,000

3,000

4,000

5,000

6,000All Donors N = 5,849

2%

40%

28%

85%92%

KidneyN=5,396

LiverN=4,954

PancreasN=1,627

HeartN=2,316

IntestineN=97

LungN=781

13%

3

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Recovered and Transplanted Cadaveric Organs

1,451

5,012

10,710

2,3161,6271,333

2,2381,298

4,496

9,233

02,0004,0006,000

8,00010,00012,000

Recovered OrgansTransplanted Organs

Kidney Liver Pancreas Heart Lung

Note:Each liver and pancreas segment is counted as an individual organ in this figure.Source:OPTN data as of 9/5/00.

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Organ Disposition (N=21,213) Cadaveric Donors

Not Used9%

Transplanted (Shared)

28%

Used Research3%

Transplanted (Local)

60%

Note: Disposition is shown for 21,213 organs which includes liver and pancreas segments. Source: OPTN data as of 9/5/00.

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Need more organs for transplant!!! Living Donor:

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Deceased and Living Donors1993 - 2003

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Year

Num

ber o

f Don

ors

Deceased DonorLiving Donor

6455

6802

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Using Live-donor Organs:Considerations

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Kidney Transplantation

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1997 National Wait Time– 1099 days

2001 MCVH Wait Time– 845 days

2001 Length of Stay– 7 days

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Kidney Transplantation: Etiology

Europe US Australiaglomerulonephritis 25 17 37diabetes 12 33 13cystic disease 8 4 7HTN 10 29 8analgesic 2 1 11interstitial nephritis 17 ? 11UNK 26 15 13

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Kidney Transplantation:Severity of renal failure

Severity GFR (ml/min) Signsmild 30-50 HTNmoderate .10-29 HTN, anemiasevere <10 pericarditis, osteodystrophyend-stage <5 pruritis,edema, dyspnea

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Kidney TransplantationMCV Evaluation: The Listing process– history and physical, financial and social

support system evaluation– blood typing, CXR, EKG, TB, Hep C, Hep

B, HIV testing and dental clearance – Women must have a pap smear &

mammogram– Diabetics:VCUG & gallbladder u/s &

cardiac clearance – Colonoscopy mandatory for age>50

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Contraindications– Active Infection– Cancer w/in 5 years– Morbid Obesity– Active Substance Abuse– Severe Coronary Artery or Peripheral

Vascular Disease– Medical Non-Compliance

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Kidney transplant Operation

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25


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National Data. UNOS.ORG

(83.2, 86.5)84.913175 YearAB

(84.2, 86.2)85.235365 YearB

(84.3, 85.4)84.9113935 YearA

(84.9, 85.9)85.4131175 YearO

(88.4, 91.0)89.717833 YearAB

(90.0, 91.5)90.748313 YearB

(90.3, 91.1)90.7150953 YearA

(90.5, 91.3)90.9172323 YearO

(94.4, 96.4)95.417951 YearAB

(95.1, 96.3)95.747651 YearB

(95.1, 95.8)95.4147861 YearA

(95.4, 96.0)95.7174511 YearO

95% ConfidenceIntervalSurvival Rate# AliveYears Post TransplantBlood Type

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Kidney Graft SurvivalOne- and Five-Year by Level of HLA Mismatch

91% 92% 90% 85%

68% 64% 61%55%

0

20

40

60

80

100

0 MM 1 MM 3 MM 6 MM

Perc

enta

ge

One-YearFive-Year

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Renal Transplant Patient Survival VCUHS vs National Average

0

0.2

0.4

0.6

0.8

1

0 365 730 1095

Days

PatientSurvival

United States VCUHS

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Using Live-donor Organs: Considerations

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Living-Donor Liver Transplantation in the U.S.

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Kidney Transplantation At VCUHS Living Donor Transplants

0

5

10

15

20

25

30

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

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Kidney Transplantation: Complication - rejection

T cell

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Kidney Transplantation: Complication - infection

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Post-Transplantation Cancer

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Post-Transplantation Cancer (by age)

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Incidence of Skin Cancer in Organ Transplant Recipients

Squamous cell carcinoma– 65-fold

Squamous cell carcinoma of the lip– 20-fold

Basal cell carcinoma– 10-fold

Melanoma– 3.4-fold

Kaposi’s sarcoma– 8.4-fold

Other: – lung, – prostate, – colon, – PTLD, etc.

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Kidney-Pancreas Transplantation

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0

20

40

60

80

100

Kidney-Pancreas

Kidney-Liver Kidney-Heart Intestine-Liver

Perc

ent

1st Organ Graft 2nd Organ Graft Patient

1-Year Graft and Patient Survival RatesMultiple Organ Transplants1997-1998 Transplant Cohort

Source: Scientific Registry data as of 9/5/00.

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5-Year Graft and Patient Survival Rates1990-1998 Transplant Cohort

0

20

40

60

80

100

CadavericKidney

Living DonorKidney

Liver Pancreas Heart Lung Heart-Lung

Perc

ent

Graft Patient

Source: Scientific Registry data as of 9/5/00.

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Pancreas TransplantationIndications– Pancreas alone

• Retransplant/Graft Failure • Diabetes Mellitus – Type I• Diabetes Mellitus – Type II Diabetes

– Chronic Pancreatitis – Cystic Fibrosis

– Pancreas after kidney• DM

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Pancreas Transplantation

Arterial inflow provided by ‘y graft’Splenic attachment preserved to decrease graft hyperperfusionSpleen is removed and exocrine secretions drained via duodeno-ileostomy or duodeno-cystostomy

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Success rates– Patient Survival (1995-1999)

MCV National• 30 day 100% 98.4%• 1 year 95.6% 94.5%• 5 years 83.8% 90%

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Kidney-Pancreas Transplantation: success rates

82.5%82.5%90.2%75.7%5 years

91.4%91.4%95.7%82.6%1 year

96.2%95.8%97.9%90%30 day

KidneyPancreasKidneyPancreas

NationalMCV

Graft Survival (1995 – 1999)

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1997 National Wait Time - 335 days 2000 MCVH Wait Time - 238 days 2000 MCV Length of Stay- 9 days

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Etiology of early renal graft dysfunction– Donor issues

• Hypotension/pressor agent usage• age• oliguria

– Preservation issues• prolonged warm ischemia• prolonged cold ischemia

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Etiology of early renal graft dysfunction– Immunologic issues

• ABO incompatibility• high PRA• african-american descent• hyperacute rejection (preformed antibodies)• accelerated rejection (second set exposure)• Acute and chronic rejection

– Drug toxicity

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Early complications– Vascular thrombosis

• venous/ arterial– Ureteral issues

• leakage/stenosis– Lymphocele– Incisional issues

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Contraindications– Active Infection– Cancer w/in 5 years– Morbid Obesity/Type II diabetes– Active Substance Abuse– Severe Coronary Artery or Peripheral

Vascular Disease– Medical Non-Compliance– age >50 years

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Liver Transplantation

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Liver TransplantationSeverity, Signs and Symptoms

• quality of life issues– recurrent cholangitis, intractable ascites or

pruritis, severe lethargy or bone disease• severe hepatic dysfunction & complications

– hyperbilirubinemia / jaundice– severe coagulopathy– marked hypoalbuminemia / ascites– variceal hemorrhage– spontaneous bacterial peritonitis

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Etiology– Hepatitis C 23%– Alcohol 20%– Cryptogenic 12%– PSC 10%– PBC 11%– Autoimmune 5%– Fulminant failure 5%

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Contraindications– HIV– Extrahepatic malignancy– Uncontrolled sepsis– On going substance abuse– Advanced cardiopulmonary disease– Severe pulmonary hypertension– Noncompliance

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Liver TransplantationMCV evaluation– multidisciplinary team assessment

• surgical (alternative or adjunct procedures)• hepatologist (intensive medical management)• cardiologist (catheterization/stenting/ P-Thal)• pulmonologist (PFT, bubble echo, ABGs)• psychologist (organic brain

syndromes/dependency)• social work (support system analysis)• financial (can it be done)

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Cadaveric liver– National 1997 Wait Time - 439 days– MCVH 2000 Wait Time - 178 days– Average 2000 Length of Stay- 9 days

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Success rates– Cadaveric liver patient survivals

MCV National• 30 day 93.2% 94%• 1 year 83.8% 85.6%• 5 years 78.5% 75.9% (3yr)

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Success rates– Cadaveric liver graft survivals

MCV National• 30 day 89.8% 90%• 1 year 79.5% 79.8%• 5 years 73.7% 68.8% (3yr)

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Liver Transplants by Donor Type1997-1999

0500

10001500200025003000350040004500

Cadaveric 3929 4270 4367Living 76 86 219

1997 1998 1999

Source: Scientific Registry data as of 9/5/00. 66

Living Donor Relationship To Recipient1990, 1995, 1999

2 511

53

29

126

15

45

23 20

7

18

37

18

0

10

20

30

40

50

60

Parent Sibling Offspring OtherRelated

Unrelated

Perc

ent

199019951999

Source: OPTN data as of 9/5/00.

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Live donor liver– 2000 Wait Time- 108 days– Recipient Length of Stay- 10.5 days– Donor Length of Stay- 6.5 days

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Live donor liver-Survival 1999-2000

Patient Graft 30 day 95% 92%1 year 83% 81%

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Liver Transplant

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Liver Transplant

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Graft loss etiology– Sepsis– MI– CVA– Recurrent disease

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Early complications– primary graft dysfunction– hepatic artery thrombosis– bile duct leakage– rejection

• acute cellular• chronic

– infection

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Liver Transplant Graft SurvivalVCUHS vs National Average

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0.2

0.4

0.6

0.8

1

0 365 730 1095

Days

GraftSurvival

United States VCUHS

Source: www.ustransplant.org 76

Liver Transplant Patient SurvivalVCUHS vs National Average

0

0.2

0.4

0.6

0.8

1

0 365 730 1095

Days

PatientSurvival

United States VCUHS

Source: www.ustransplant.org

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Living Donor Liver Transplant At VCUHS Graft Survivals

0

0.2

0.4

0.6

0.8

1

0 365 730 1095

Days

GraftSurvival

Living Cadaveric

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Living Donor Liver Transplant At VCUHS Patient Survivals

0

0.2

0.4

0.6

0.8

1

0 365 730 1095

Days

PatientSurvival

Living Cadaveric

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Solid Organ Transplantation

Daniel Maluf, MDAssistant Professor of SurgeryVCU School of Medicine

Basic Immunology Solid Organ Transplantation...Solid Organ Transplantation Daniel Maluf, MD...

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