Optimizing lung transplant outcomes in the adult and pediatric patient

Optimizing lung transplant outcomes in the adult and pediatric

patient.

Cynthia S. Herrington, MDAssociate Professor of Surgery

Keck School of MedicineUniversity of Southern California

Optimizing Lung Transplant Outcomes

Holy SRTR

International practices and outcomes and where the pitfalls exist --ISHLT

How to asses a program when the wheels fall off the bus

The Adults


AGE DISTRIBUTION OF ADULT LUNG TRANSPLANT RECIPIENTS BY ERA

0

5

10

15

20

25

18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 66+

% o

f tra

nspl

ants

.

1985-1994 (N=4,426)1995-1999 (N=6,691)2000-6/2009 (N=20,099)

p < 0.0001Mean age by era1985-1994 = 44.6 years1995-1999 = 47.3 years2000-6/2009 = 50.1 years

2010ISHLT

J Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival (Transplants: January 1994 - June 2008)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13Years

Bilateral/Double Lung (N=14,055)Single Lung (N=10,869)All Lungs (N= 24,936)

Double lung: 1/2-life = 6.6 Years; Conditional 1/2-life = 9.1 YearsSingle lung: 1/2-life = 4.6 Years; Conditional 1/2-life = 6.4 YearsAll lungs: 1/2-life = 5.3 Years; Conditional 1/2-life = 7.5 Years

P < 0.0001

Surv

ival

(%)

2010ISHLT


ADULT LUNG TRANSPLANTATIONProcedure Type within Indication, by Year

0

10

20

30

40

50

60

70

80

90

100

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

% o

f tra

nspl

ants

Bilateral/Double Lung Transplant Single Lung Transplant

AT Def COPD IPF IPAH

2010ISHLT


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: January 1988 – June 2008)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12Years

Surv

ival

(%)

1988-1994 (N=4,318)1995-1999 (N=6,558)2000-6/2008 (N=17,227)

1988-1994: 1/2-life = 4.0 Years; Conditional 1/2-life = 7.0 Years1995-1999: 1/2-life = 4.6 Years; Conditional 1/2-life = 7.3 Years2000-6/2008: 1/2-life = 5.7 Years; Conditional 1/2-life = 7.9 Years

N at risk = 129

N at risk = 406

N at risk = 577

Survival comparisons by era1988-94 vs. 1995-99: p = 0.00021988-94: vs. 2000-6/08: p <0.0001 1995-99 vs. 2000-6/08: p <0.0001

2010ISHLT


ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2008)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years

18-34 (N = 4,819)35-49 (N = 7,127)50-59 (N = 10,069)60-65 (N = 4,929)66+ (N = 907)

Survival comparisonsAll p-values significant at p < 0.0001 except 18-34 vs. 35-49: p =0.4955; 60-65 vs. 66+: p = 0.0001

HALF-LIFE 18-34: 5.9 Years; 35-49: 6.3 Years; 50-59: 5.1 Years; 60-65: 4.3 Years; 66+: 3.3 Years

Surv

ival

(%)

2010ISHLT


ADULT LUNG TRANSPLANTATION Kaplan-Meier Survival by Gender (Transplants: January 1990 – June 2008)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years

Surv

ival

(%)

Male (N=14,799)

Female (N=13,050)

HALF-LIFE Male: 5.0 years; Female: 5.4 Years

p = 0.0003 N at risk at 10 years=928

N at risk = 154N at risk at 10 years=910

N at risk = 127

2010ISHLT


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2008)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13Years

Surv

ival

(%)

Alpha-1 (N=2,187) CF (N=4,144) COPD (N=9,616)IPF (N=5,459) IPAH (N=1,123) Sarcoidosis (N=660)

HALF-LIFE Alpha-1: 6.1 Years; CF: 7.1 Years; COPD: 5.2 Years; IPF: 4.3 Years; IPAH: 4.9 Years; Sarcoidosis: 5.1 Years

Survival comparisonsAll comparisons with Alpha-1 and CF are statistically significant at 0.01

IPAH vs. IPF: p = 0.0210COPD vs. IPF: p < 0.0001

2010ISHLT


ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival By Diagnosis Conditional on Survival to 1 Year

(Transplants: January 1990 – June 2008)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13Years

Surv

ival

(%)

Alpha-1 (N=1,630) CF (N=3,085)COPD (N=7,214) IPF (N=3,618)IPAH (N=720) Sarcoidosis (N=439)

HALF-LIFE Alpha-1: 8.5 Years; CF: 9.4 Years; COPD: 6.6 Years;IPF: 6.7 Years; IPAH: 9.3 Years; Sarcoidosis: 8.5 Years

Survival comparisonsAll comparisons with Alpha-1 and COPD are statistically significant at 0.01 except Alpha-1 vs. Sarcoidosis p = 0.6576 and COPD vs. IPF p = 0.7539

CF vs. IPF: p < 0.0001IPAH vs. IPF: p < 0.0001IPF vs. Sarcoidosis: p = 0.0028

2010ISHLT


ADULT LUNG TRANSPLANTS (1996-6/2008) Risk Factors for 1 Year Mortality

DIAGNOSIS Procedure type N

Relative Risk P-value

95% conf. Interval

IPAH All 406 2.19 <0.0001 1.63 - 2.95

Retransplant All 424 2.01 <0.0001 1.62 - 2.49

Other* All 724 1.82 <0.0001 1.50 - 2.20

Sarcoidosis Double 264 1.78 <0.0001 1.34 - 2.37

Alpha-1 antitrypsin deficiency Single 356 1.77 <0.0001 1.40 - 2.22

Pulmonary Fibrosis (not IPF) All 149 1.75 0.0018 1.23 - 2.49

Alpha-1 antitrypsin deficiency Double 448 1.47 0.0022 1.15 - 1.88

IPF Double 1,219 1.47 0.0002 1.20 - 1.80

IPF Single 1,890 1.35 0.0011 1.13 - 1.62

Cystic fibrosis All 1,783 1.32 0.0197 1.04 - 1.66

COPD/Emphysema Double 1,765 1.19 0.0250 1.02 - 1.39

(N=13,079) *Other = All diagnoses other than COPD, IPAH, IPF, cystic fibrosis, pulmonary fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, retransplant and LAM.

Reference group = COPD/Emphysema, Single lung

2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141


TRANSPLANT CHARACTERISTICS N Relative Risk P-value

95% Confidence

Interval

Transplant year = 1996/1997 vs. 2007/2008 1,546 1.86 <0.0001 1.59 - 2.18



Donor CMV +/ Recipient CMV - 2,643 1.21 <0.0001 1.10 - 1.33

Transplant year = 2002/2003 vs. 2007/2008 2,053 1.17 0.0468 1.00 - 1.37

(N=13,079)



DONOR CHARACTERISTICS N Relative Risk P-value

95% Confidence

Interval

Donor history of diabetes 479 1.45 <0.0001 1.20 - 1.75

RECIPIENT CHARACTERISTICS

Recipient on dialysis 49 1.81 0.0097 1.16 - 2.85

IV inotropes 54 1.73 0.0051 1.18 - 2.54

Hospitalized (including ICU) 1,316 1.65 <0.0001 1.44 - 1.88

Ventilator 390 1.54 <0.0001 1.26 - 1.88

Chronic steroid use 6,170 1.11 0.013 1.02 - 1.21

(N=13,079)


ADULT LUNG TRANSPLANTS (1996-6/2008) Borderline Significant Risk Factors for 1 Year Mortality

RECIPIENT CHARACTERISTICS N Relative Risk P-value

95% Confidence

Interval

Diagnosis = sarcoidosis, single lung 135 1.41 0.0752 0.97 - 2.07

Prior pulmonary embolism 126 1.33 0.0812 0.96 - 1.84

Recipient prior malignancy 515 1.20 0.0584 0.99 - 1.44

Anoxia 901 0.87 0.0983 0.73 - 1.03

(N=13,079)


ADULT LUNG TRANSPLANTS (1/1996-6/2008) Risk Factors for 1 Year Mortality

Recipient Age

0

0.5

1

1.5

2

25 30 35 40 45 50 55 60 65

Recipient Age

p < 0.0001

Rel

ativ

e R

isk

of 1

Yea

r Mor

talit

y

2010ISHLT



TRANSPLANT CHARACTERISTICS N Relative Risk P-value

95% Confidence

Interval

Transplant year = 1998/1999 vs. 2002-2004 1,589 1.44 <0.0001 1.31 - 1.58



Donor CMV +/ Recipient CMV - 1,435 1.14 0.0014 1.05 - 1.24

0-3 HLA mismatches vs. 4-6 mismatches 1,033 0.90 0.0430 0.82 - 1.00

(N=7,609)



DIAGNOSIS Procedure type N

Relative Risk P-value

95% conf. Interval

Alpha-1 antitrypsin deficiency Single 303 1.34 0.0008 1.13 - 1.59

Retransplant All 182 1.31 0.0154 1.05 - 1.62

Cystic fibrosis All 1,091 0.79 0.0140 0.65 - 0.95

LAM All 71 0.52 0.0069 0.32 - 0.84

(N=7,609)

Reference group = COPD/Emphysema, Single lung



DONOR CHARACTERISTICS N Relative Risk P-value 95% Confidence

Interval

Donor history of diabetes 214 1.32 0.0037 1.09 - 1.58

Donor cause of death = anoxia 406 0.77 0.0015 0.65 - 0.90

RECIPIENT CHARACTERISTICS

IV inotropes 54 2.02 <0.0001 1.45 - 2.83

Recipient on dialysis 22 1.81 0.0166 1.11 - 2.93

Prior sternotomy 348 1.27 0.0013 1.10 - 1.47

Hospitalized (including ICU) 548 1.25 0.0018 1.09 - 1.44

Recipient history of diabetes 605 1.21 0.0023 1.07 - 1.37

Chronic steroid use 3,548 1.10 0.0091 1.02 - 1.18

(N=7,609)


ADULT LUNG TRANSPLANTS (1996-6/2004) Borderline Significant Risk Factors for 5 Year Mortality

RECIPIENT CHARACTERISTICS N Relative Risk

P-value

95% Confidence

Interval

Diagnosis = IPAH 292 1.40 0.0866 0.95 - 2.06

Prior pulmonary embolism 72 1.32 0.0693 0.98 - 1.79

Ventilator 156 1.27 0.0548 1.00 - 1.62

Diagnosis = other* 343 1.17 0.0686 0.99 - 1.40

Female recipient/female donor vs. male recipient/male donor 2,143 0.88 0.0953 0.76 - 1.02

(N=7,609)*Other = All diagnoses other than COPD, IPAH, IPF, cystic fibrosis, pulmonary fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, retransplant and LAM.

Reference diagnosis group = COPD/Emphysema, Single lung



Recipient Age

0

0.5

1

1.5

2

20 25 30 35 40 45 50 55 60 65

Recipient Age

Rel

ativ

e R

isk

of 5

Yea

r Mor

talit

y

p < 0.0001

2010ISHLT


ADULT LUNG RECIPIENTSLongitudinal Analysis

Functional Status of Surviving Recipients(Follow-ups: April 1994 – June 2009)

For the Same Patients

0%

20%

40%

60%

80%

100%

1 Year (N = 1,632) 3 Year (N = 1,632) 5 Year (N = 1,632)

No Activity Limitations Performs with Some Assistance Requires Total Assistance

2010ISHLT


ADULT LUNG RECIPIENTSEmployment Status of Surviving Recipients

(Follow-ups: April 1994 – June 2009)

0%

20%

40%

60%

80%

100%

1 Year (N=9,787) 3 Year (N=6,090) 5 Year (N=3,777) 10 year (N=702)

Working (FT/PTStatus unknown)Working Part Time

Working Full Time

Retired

Not Working

2010ISHLT


ADULT LUNG RECIPIENTS: Rehospitalization Post-transplant of Surviving Recipients

(Follow-ups: April 1994 - June 2009)

0%

20%

40%

60%

80%

100%

1 Year (N = 12,933) 3 Year ( N = 8,059) 5 Year (N = 4,988) 10 Year (N=894)

No Hospitalization Hosp: No Rej/No Inf Hosp: RejectionHosp: Infection Hosp: Rej/Inf

2010ISHLT


POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 Year Post-Transplant


Follow-ups: April 1994 – June 2000

Follow-ups: July 2000 – June 2009

Outcome Within 1 Year Total number with known response

Within 1 Year Total number with known response

Hypertension 49.1% (N = 3,757) 54.10% (N = 8,040)

Renal Dysfunction 23.20% (N = 3,675) 24.80% (N = 9,057)

Abnormal Creatinine < 2.5 mg/dl 12.9% 18.40%

Creatinine > 2.5 mg/dl 8.6% 4.80%

Chronic Dialysis 1.8% 1.50%

Renal Transplant 0.0% 0.10%

Hyperlipidemia 13.1% (N = 3,897) 29.20% (N = 8,624)

Diabetes 16.8% (N = 3,718) 30.30% (N = 8,976)

Bronchiolitis Obliterans Syndrome 10.7% (N = 3,450) 9.10% (N = 8,547)

2010ISHLT


POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 1 and 5 Years

Post-Transplant (Follow-ups: April 1994 - June 2009)

Outcome Within 1 Year Total number with known response

Within 5 Years Total number with known response

Hypertension 52.5% (N = 11,797) 84.4% (N = 3,271)

Renal Dysfunction 24.40% (N = 12,732) 34.7% (N = 3,834)

Abnormal Creatinine < 2.5 mg/dl 16.8% 23.1%

Creatinine > 2.5 mg/dl 5.9% 8.3%

Chronic Dialysis 1.6% 2.8%

Renal Transplant 0.1%

0.5%

Hyperlipidemia 24.2% (N = 12,521) 56.5% (N = 3,600)

Diabetes 26.3% (N = 12,694) 38.0% (N = 3,551)

Bronchiolitis Obliterans Syndrome 9.6% (N = 11,997) 36.9% (N = 2,965)

2010ISHLT


POST-LUNG TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence in Survivors within 10 Years Post-Transplant


Outcome Within 10 Years Total number with known response

Hypertension 97.3% (N = 337)

Renal Dysfunction 41.5% (N = 612)

Abnormal Creatinine < 2.5 mg/dl 26.5% Creatinine > 2.5 mg/dl 5.9% Chronic Dialysis 6.9% Renal Transplant 2.3%

Hyperlipidemia 68.5% (N = 410)

Diabetes 37.4% (N = 374)

Bronchiolitis Obliterans Syndrome 54.1% (N = 379)

2010ISHLT


FREEDOM FROM BRONCHIOLITIS OBLITERANS SYNDROME For Adult Lung Recipients (Follow-ups: April 1994-June 2009)

Conditional on Survival to 14 days

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11Years

Freedom from Bronchiolitis ObliteransSyndrome (N = 12,058)

N at risk at 5 years = 1,575

N at risk = 90

% F

reed

om fr

om B

ronc

hiol

itis

Obl

itera

ns S

yndr

ome

2010ISHLT


FREEDOM FROM BRONCHIOLITIS OBLITERANS SYNDROME STRATIFIED BY INDUCTION USE

For Adult Lung Recipients (Follow-ups: April 1994-June 2009)Conditional on Survival to 14 days

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11Years

No induction (N=6,189)Induction (N=4,978)

p = 0.0019

N at risk at 5 years = 583


N at risk = 48

N at risk = 25

% F

reed

om fr

om B

ronc

hiol

itis

Obl

itera

ns S

yndr

ome

2010ISHLT


FREEDOM FROM MALIGNANCYFor Adult Lung Recipients (Follow-ups: April 1994-June 2009)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13Years

% F

ree

from

Mal

igna

ncy

All malignancy Lymph Skin Other

2010ISHLT


ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (Deaths: January 1992- June 2009)

CAUSE OF DEATH0-30 Days (N = 1,966)

31 Days – 1 Year

(N = 3,387)

>1 Year – 3 Years

(N = 3,073)

>3 Years – 5 Years

(N = 1,737 )


(N = 2,014)

>10 Years (N = 483)

BRONCHIOLITIS 6 (0.3%) 159 (4.7%) 781 (25.4%) 508 (29.2%) 507 (25.2%) 95 (19.7%)

ACUTE REJECTION 74 (3.8%) 61 (1.8%) 48 (1.6%) 10 (0.6%) 15 (0.7%) 1 (0.2%)

LYMPHOMA 1 (0.1%) 86 (2.5%) 63 (2.1%) 28 (1.6%) 46 (2.3%) 23 (4.8%)

MALIGNANCY, OTHER 4 (0.2%) 100 (3.0%) 202 (6.6%) 151 (8.7%) 219 (10.9%) 47 (9.7%)

CMV 0 96 (2.8%) 29 (0.9%) 5 (0.3%) 4 (0.2%) 0

INFECTION, NON-CMV 396 (20.1%) 1,205 (35.6%) 710 (23.1%) 329 (18.9%) 363 (18.0%) 81 (16.8%)

GRAFT FAILURE 557 (28.3%) 589 (17.4%) 591 (19.2%) 327 (18.8%) 379 (18.8%) 87 (18.0%)

CARDIOVASCULAR 213 (10.8%) 144 (4.3%) 118 (3.8%) 82 (4.7%) 99 (4.9%) 36 (7.5%)

TECHNICAL 162 (8.2%) 76 (2.2%) 18 (0.6%) 8 (0.5%) 12 (0.6%) 6 (1.2%)

OTHER 553 (28.1%) 871 (25.7%) 513 (16.7%) 289 (16.6%) 370 (18.4%) 107 (22.2%)

2010ISHLT


Children


AGE DISTRIBUTION OF PEDIATRIC LUNG RECIPIENTS

By Year of Transplant

1 3 4 6

20

48 51 48

8274

87 89

68 6863

71 75 7887 87

95102

43

0102030405060708090

100110

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

12-17 Years1-11 Years<1 Year

Num

ber o

f Tra

nspl

ants

Analysis includes living donor transplants

NOTE: This figure includes only the pediatric lung transplants that are reported to the ISHLT Transplant Registry. Therefore, these numbers should not be interpreted as the rate of change in pediatric lung procedures performed worldwide.


NUMBER OF CENTERS REPORTING PEDIATRIC LUNG TRANSPLANTS BY CENTER VOLUME

0

10

20

30

40

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

Transplant Year

Num

ber o

f Cen

ters

Rep

ortin

g Pe

diat

ric T

rans

plan

ts

20+ transplants10-19 transplants5-9 transplants1-4 transplants

Analysis includes living donor transplants 2010ISHLTJ Heart Lung Transplant. 2010 Oct; 29 (10): 1083-1141

0%

20%

40%

60%

80%

100%

Europe (N=211) North America (N=498) Other (N=37)

% o

f Tra

nspl

ants

-

Cystic Fibrosis IPAH IPF OB Other Congenital heart disease Re-TX

PEDIATRIC LUNG TRANSPLANTS:DIAGNOSIS DISTRIBUTION BY LOCATION

Transplants between January 2000 and June 2009

NOTE: Unknown diagnoses were excluded from this tabulation.

Total number of transplants reported:Europe = 237North America = 498Other = 41

Analysis includes living donor transplants


LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group

(Transplants: January 1990 - June 2008)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Years

Surv

ival

(%)

Adult (N=27,851)

Pediatric (N=1,174)

HALF-LIFE Adult = 5.2 Years; Pediatric = 4.6 Years

P = 0.9423

2010ISHLT


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Procedure Type


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14Years

Surv

ival

(%)

Single Lung (N=73)

Bilateral/Double Lung (N=1,101)

HALF-LIFE Single Lung: 2.2 Years; Bilateral/double Lung: 4.9 Years

P < .0001

2010ISHLT


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Age Group


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years

Surv

ival

(%)

<1 Year (N=84)1-11 Years (N=334)12-17 Years (N=756)

<1 year vs. 1-11 years: p = 0.3124<1 year vs. 12-17 years: p = 0.83871-11 years vs. 12-17 years: p = 0.0395

HALF-LIFE<1 Year: 6.4 Years1-11 Years: 6.0 Years12-17 Years: 4.3 Years

N at risk = 10N at risk = 17

N at risk = 20

2010ISHLT


PEDIATRIC LUNG TRANSPLANTATIONConditional Kaplan-Meier Survival by Age Group


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years

Surv

ival

(%)

<1 Year (N=50)1-11 Years (N=231)12-17 Years (N=524)

<1 year vs. 1-11 year: p = 0.6485<1 year vs. 12-17 years: p = 0.13861-11 years vs. 12-17 years: p =0.0696

N at risk = 10

N at risk = 17

N at risk = 20

CONDITIONAL HALF-LIFE<1 Year: 8.8 Years1-11 Years: 8.7 Years12-17 Years: 6.1 Years

2010ISHLT


PEDIATRIC LUNG TRANSPLANTATIONKaplan-Meier Survival by Donor Type for Recipients Age 12-17 Years


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10Years

Surv

ival

(%)

Deceased Donor (N = 756)

Living Donor (N = 77)

p = 0.3570

N at risk = 7

N at risk = 35

HALF-LIFEDeceased: 4.3 YearsLiving: 3.7 Years

2010ISHLT


0

5

10

15

20

25

0-<1 month 1-<12 months 12-<36 months 36+ months Not reported

Num

ber o

f R

e-Tr

ansp

lant

s

Time Between Previous and Current Transplant

PEDIATRIC LUNG RE-TRANSPLANTS Between January 1994 and June 2009

2010ISHLT


0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5

Years

Surv

ival

(%)


PEDIATRIC LUNG RETRANSPLANTSSurvival for Transplants Performed Between January 1994 and June 2008

2010ISHLT


PEDIATRIC LUNG RECIPIENTSLongitudinal Analysis

Functional Status of Surviving RecipientsFor the Same Patients

(Follow-ups: April 1994-June 2009)

0%

20%

40%

60%

80%

100%

1 Year (N = 82) 3 Years (N = 82) 5 Years (N = 82)

No Activity Limitations Performs with Assistance Total Assistance

2010ISHLT


PEDIATRIC LUNG RECIPIENTS Rehospitalization Post-transplant of Surviving Recipients


0%

20%

40%

60%

80%

100%

Up to 1 Year (N =578)

Between 2 and 3Years (N = 346)



No Hospitalization Hospitalized, Not Rejection/Not InfectionHospitalized, Rejection Hospitalized, Infection OnlyHospitalized, Rejection + Infection

2010ISHLT


POST-LUNG TRANSPLANT MORBIDITY FOR PEDIATRICS Cumulative Prevalence in Survivors within 1 Year Post-Transplant


Outcome Within 1 Year

Total number with known response

Hypertension 43.0% (N = 561)

Renal Dysfunction 10.7% (N = 571) Abnormal Creatinine < 2.5 mg/dl 7.5% Creatinine > 2.5 mg/dl 2.1% Chronic Dialysis 0.7% Renal Transplant 0.4%

Hyperlipidemia 5.0% (N = 579)

Diabetes 25.7% (N = 571)

Bronchiolitis Obliterans Syndrome 13.6% (N = 536)

2010ISHLT


Optimizing the outcomes…..evaluate program vulnerabilities by doing root cause analysis on each death

Take risks proportional to the stability of the program


ADULT LUNG TRANSPLANT RECIPIENTS: Cause Of Death (Deaths: January 1992- June 2009)

CAUSE OF DEATH0-30 Days (N = 1,966)

31 Days – 1 Year

(N = 3,387)

>1 Year – 3 Years

(N = 3,073)


(N = 1,737 )


(N = 2,014)

>10 Years (N = 483)

BRONCHIOLITIS 6 (0.3%) 159 (4.7%) 781 (25.4%) 508 (29.2%) 507 (25.2%) 95 (19.7%)

ACUTE REJECTION 74 (3.8%) 61 (1.8%) 48 (1.6%) 10 (0.6%) 15 (0.7%) 1 (0.2%)

LYMPHOMA 1 (0.1%) 86 (2.5%) 63 (2.1%) 28 (1.6%) 46 (2.3%) 23 (4.8%)

MALIGNANCY, OTHER 4 (0.2%) 100 (3.0%) 202 (6.6%) 151 (8.7%) 219 (10.9%) 47 (9.7%)

CMV 0 96 (2.8%) 29 (0.9%) 5 (0.3%) 4 (0.2%) 0

INFECTION, NON-CMV 396 (20.1%) 1,205 (35.6%) 710 (23.1%) 329 (18.9%) 363 (18.0%) 81 (16.8%)

GRAFT FAILURE 557 (28.3%) 589 (17.4%) 591 (19.2%) 327 (18.8%) 379 (18.8%) 87 (18.0%)

CARDIOVASCULAR 213 (10.8%) 144 (4.3%) 118 (3.8%) 82 (4.7%) 99 (4.9%) 36 (7.5%)

TECHNICAL 162 (8.2%) 76 (2.2%) 18 (0.6%) 8 (0.5%) 12 (0.6%) 6 (1.2%)

OTHER 553 (28.1%) 871 (25.7%) 513 (16.7%) 289 (16.6%) 370 (18.4%) 107 (22.2%)

2010ISHLT


0

20

40

60

80

100

CyA TAC Rapamycin MMF AZA CyA TAC Rapamycin MMF AZA

% o

f Pat

ient

s

1-Year Follow-Up 5-Year Follow-Up

Consecutive bars within each drug type represent follow-ups in 2002, 2003, 2004, 2005, 2006, 2007, 2008 & 2009.

ADULT LUNG RECIPIENTSMaintenance Immunosuppression at Time of Follow-up

For follow-ups between January 2002 through June 2009 Analysis limited to patients receiving prednisone

NOTE: Different patients are analyzed in Year 1 and Year 5

Analysis is limited to patients who were alive at the time of the follow-up


ADULT LUNG RECIPIENTSKaplan-Meier Survival by Maintenance Immunosuppression

Combinations Conditional on Survival to 1 Year (Transplants: January 2000-June 2008)

Analysis limited to patients receiving prednisone

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

Years

Surv

ival

(%)

Tacrolimus + MMF use at discharge and 1 year (N=1,986)Tacrolimus + AZA use at discharge and 1 year (N=1,068)Cyclosporine + MMF use at discharge and 1 year (N=415)Cyclosporine + AZA use at discharge and 1 year (N=474)

p = 0.0046

2010ISHLT


ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: January 1995 - June 2009)

*Other includes:Sarcoidosis: 2.0%Bronchiectasis: 0.4%Congenital Heart Disease: 0.3%LAM: 0.9%OB (non-ReTx): 0.5%Miscellaneous: 5.3%

48%

31%

9%

6%

2%

1%3%

Alpha-1 COPD CF IPF IPAH Re-Tx Other*


ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1995 - June 2009)

26%

16% 2%5%

26%

7%

17%

Alpha-1 COPD CF IPF IPAH Re-Tx Other*

*Other includes:Sarcoidosis: 3.0%Bronchiectasis: 4.4%Congenital Heart Disease: 1.3%LAM: 1.2%OB (non-ReTx): 1.2%Miscellaneous: 5.8%

2010ISHLT



Continuous Factors (see figures) Recipient age

Transplant center volume

Cardiac output

Recipient FVC % predicted (borderline)

Bilirubin

Recipient oxygen required at rest

Height difference

Recipient FEV1 % predicted (borderline)

2010ISHLT



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50

Center Volume (cases per year)

p < 0.0001

Rel

ativ

e R

isk

of 1

Yea

r Mor

talit

y

2010ISHLT



Continuous Factors (see figures) Recipient age

Transplant center volume

Cardiac output

Bilirubin

Recipient oxygen required at rest

Donor age

Recipient FEV1 % predicted

Recipient height (borderline)

2010ISHLT



Donor Age

0

0.5

1

1.5

2

15 20 25 30 35 40 45 50 55

Donor Age

Rel

ativ

e R

isk

of 5

Yea

r Mor

talit

y

p = 0.0063

2010ISHLT



Center Volume

0

0.5

1

1.5

2

5 10 15 20 25 30 35 40 45 50

Center Volume (cases per year)

Rel

ativ

e R

isk

of 5

Yea

r Mor

talit

y

p < 0.0001

2010ISHLT


Documents

Optimizing lung transplant outcomes in the adult and pediatric patient