future trends in hematopoietic cell transplantation (hct) · 21 11/2007 improving survival: adults...
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![Page 1: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/1.jpg)
Creating Connections. Saving Lives.™
NATIONAL MARROW DONOR PROGRAM®
Future Trends in Hematopoietic Cell Transplantation (HCT)
Dennis Confer, MDNMDP Chief Medical OfficerNovember 1, 2007
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1 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Current and Future Trends
Registries of adult donors and cord blood units are growing larger
Transplant numbers are increasing
Patient populations are changing
Transplant survival is improving
![Page 3: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/3.jpg)
2 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
World Marrow Donor Association -WMDA
Association of adult donor registries and public cord blood banks engaged in international delivery of HCs
Annual member survey assesses worldwide donor numbers and transplantation activity
www.worldmarrow.org
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
3 11/2007
Adult Donor Registries Reporting to WMDA
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
4 11/2007
Adult Donors Worldwide
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
5 11/2007
Cord Blood Banks Reporting to WMDA
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
6 11/2007
Cord Blood Units Worldwide
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
7 11/2007
1,000,000
2,000,000
3,000,000
4,000,000
5,000,000
6,000,000
7,000,000
8,000,000
1988 1993 1998 2003 2008
Adu
lt D
onor
s
0
10,000
20,000
30,000
40,000
50,000
60,000
70,000
Cor
d B
lood
Uni
tsAdult Donors6,856,150
National Marrow Donor Program Adult Donors & CBUs– Sept 30, 2007
CBUs69,081
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
8 11/2007
NMDP Transplants Facilitatedby Fiscal Year 1987–2007
0
400
800
1200
1600
2000
2400
2800
3200
3600
400019
87
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year of Transplant
Num
ber o
f Tra
nspl
ants
Bone marrow
Peripheral blood stem cells
Cord blood
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
9 11/2007
Worldwide Transplants Facilitatedby Calendar Year 1997–2006
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
1100019
87
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Year of Transplant
Num
ber o
f Tra
nspl
ants
Bone marrow
Peripheral blood stem cells
Cord blood
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
10 11/2007
NMDP Grafts as a Percent of the WMDA Totalby Calendar Year 1997–2006
0%
10%
20%
30%
40%
50%
60%
70%
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Year of Transplant
Perc
ent o
f Tot
al
Bone marrow
Peripheral blood stem cells
Cord blood
All HCT grafts
![Page 12: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/12.jpg)
Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
11 11/2007
Adult Donor Registries Reporting to WMDA
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12 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Current and Future Trends
Registries of adult donors and cord blood units are growing larger
Transplant numbers are increasing
Patient populations are changing
Transplant survival is improving
![Page 14: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/14.jpg)
13 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
NMDP Transplant Recipients by Diagnosis
0
200
400
600
800
1000
1200
1400
AML ALL MDS NHL CML
2001 2002 2003 2004 2005 2006 2007
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14 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
NMDP Transplant Recipients by Diagnosis
0
200
400
600
800
1000
1200
1400
AML ALL MDS OL CML NHL HL IIS SAA Other
2006 2007
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
15 7/2007
More Transplant Recipients are Older
Transplant Patients ≥ 55 Years
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
Year of Transplant
Perc
enta
ge o
f All
Tran
spla
nts
0
100
200
300
400
500
600
Num
ber o
f Tra
nspl
antsPercentage
Number
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
16 7/2007
Transplant Recipients by Age Group FY 2006 and FY 2007
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
17 7/2007
Transplant Recipients > 50 years Account for Most of the Growth
239 287
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18 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Current and Future Trends
Registries of adult donors and cord blood units are growing larger
Transplant numbers are increasing
Patient populations are changing
Transplant survival is improving
![Page 20: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/20.jpg)
Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
19 11/2007
Improving Survival: All Adults with Malignant Diseases
These curves show statistically significant improvements in overall survival comparing 4 time periods with similar numbers of patients
– 1987 – 94: n = 1674
– 1995 – 97: n = 1958
– 1998 – 2000: n = 2185
– 2001 – 2004: n = 1811
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
20 11/2007
Improving Survival: Adults with High-Risk Malignant Diseases
Similar results with a more dramatic impact of recent years are seen restricting the analysis to only High-risk adults
– 1987 – 94: n = 807
– 1995 – 97: n = 910
– 1998 – 2000: n = 1011
– 2001 – 2004: n = 948
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
21 11/2007
Improving Survival: Adults Aged 18 – 54 with Malignant Diseases
Excluding patients over age 54 modestly improves survival compared the first set of curves, but note the rise in older patient numbers
– 1987 – 94: n = 1666, excluded 8
– 1995 – 97: n = 1897, excluded 61
– 1998 – 2000: n = 2057, excluded 128
– 2001 – 2004: n = 1550, excluded 261
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
22 11/2007
Improving Survival: Adults with Non-Malignant Diseases
These curves show statistically significant improvements in overall survival comparing 4 time periods with similar, but smaller numbers of patients with non-malignant diseases
– 1987 – 94: n = 81
– 1995 – 97: n = 56
– 1998 – 2000: n = 70
– 2001 – 2004: n = 82
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
23 11/2007
Improving Survival: Pediatrics with Malignant Diseases
These curves show statistically significant improvements in overall survival comparing 4 time periods with pediatric patients
– 1987 – 94: n = 646
– 1995 – 97: n = 666
– 1998 – 2000: n = 638
– 2001 – 2004: n = 657
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
24 11/2007
Improving Survival: Pediatrics with Non-Malignant Diseases
These curves show statistically significant improvements in overall survival comparing 4 time periods of pediatric patients with non-malignant diseases
– 1987 – 94: n = 225
– 1995 – 97: n = 228
– 1998 – 2000: n = 234
– 2001 – 2004: n = 253
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25 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Further Evidence of Improving Survival
Center-specific analysis – Evaluates one-year survival at all US transplant centers
Employs a rolling 5-year window
Report Year Period 1-Year Survival
2003 1996-2001 42.2%
2006 2000-2004 48.8%
2007 2001-2005 51.5%
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26 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Monitoring Survival over Time -PART: Program Assessment Rating Tool
Initiative of the President’s Office of Management and Budget (OMB)
Evaluates government programs on multiple measures
Must include a Health Outcome Measure
We proposed:
– Aggregate 1-year survival for a defined subset of patients evaluated over time
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27 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
PART: Program Assessment and Rating Tool
Restricted to patients <50 years age
Myeloablative regimens only
Acute leukemias in any remission
Chronic Myelogenous Leukemia
MDS – RA or RARS only
First analysis completed in May 2006
– 5,432 recipients through December 31, 2003
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28 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Factors Considered in the Modeling for the PART Analysis
Recipient age
Recipient sex
Recipient race
Recipient CMV status
Recipient BMI
Disease and Stage
Time from Dx to Tx
Disease Risk
Karnofsky/Lansky
Coexisting disease
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29 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Adjusted 1-year Survivals over Time: Part Analysis – 1988 - 2003
0
10
20
30
40
50
60
70
1988
- 90
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
Adjusted Survival
Linear (AdjustedSurvival)Pe
rcen
t Aliv
e at
1 Y
ear
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30 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Current and Future Trends
Registries of adult donors and cord blood units are growing larger
Transplant numbers are increasing
Patient populations are changing
Transplant survival is improving
![Page 32: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/32.jpg)
31 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
How Many Transplants Should We Be Doing?
Approaches to an Answer:
– Infer from the Matched Sibling Transplants
– Infer from the Search Activity
– Infer from knowledge of diseases
These numbers are U.S.A. only!
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
32 11/2007
The Likelihood of a Match Between Two Siblings is 25%
Mother Father
I II A B
I A I B II A II B
Mother Father
I II A B
Mother Father
I II A B
Mother Father
I II A B
![Page 34: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/34.jpg)
33 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Either you do or you don’t- Probability of a match = 1 – Probability of no match
One sibling– Probability of a match = 1 – 0.75 = 25%
Two siblings– Probability of a match = 1 – (0.75*0.75) = 44%
Six siblings– Probability of a match = 1 – (0.75)6 = 82%
1.3 siblings– Probability of a match = 1 – (0.75)1.3 = 31%
Probability of a Sibling Match
![Page 35: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/35.jpg)
34 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Either you do or you don’t- Probability of a match = 1 – Probability of no match
One sibling– Probability of a match = 1 – 0.75 = 25%
Two siblings– Probability of a match = 1 – (0.75*0.75) = 44%
Six siblings– Probability of a match = 1 – (0.75)6 = 82%
1.3 siblings– Probability of a match = 1 – (0.75)1.3 = 31%
Probability of a Sibling Match
![Page 36: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/36.jpg)
35 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
How Many Transplants Should We Be Doing?
Infer from the Matched Sibling Transplants
– CIBMTR estimates 3,500 matched sibling transplants annually in the U.S.
– 3,500/0.3 = 11,667 is the “Total Need”
– 11,667 – 3,500 = 8,167 are candidates for unrelated transplants
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36 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
How Many Transplants Should We Be Doing?
Infer from the Unrelated Donor Search Activity
– NMDP received 7,249 U.S. preliminary searches in the past 12 months
![Page 38: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/38.jpg)
37 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
NMDP Transplant Recipients by Diagnosis
0
500
1000
1500
2000
2500
AML ALL MDS OL CML NHL HL IIS SAA Other
2006 2007
![Page 39: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/39.jpg)
38 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
How Many Transplants Should We Be Doing?
Infer from the Knowledge of Diseases– Estimate the incidence of disease by age
group– Calculate the number of new cases
annually– Estimate those who are candidates for
transplantation– Partition between sibling and unrelated
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39 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
NMDP Transplant Recipients by Diagnosis and Estimated Candidates
0
500
1000
1500
2000
2500
AML ALL MDS OL CML NHL HL IIS SAA Other
2006 2007 0 - 64 y/o 0 - 74 y/oActual Actual Candidates Candidates
![Page 41: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/41.jpg)
40 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
How Many Transplants Should We Be Doing?
Approaches to an Answer:
– Infer from the Matched Sibling Transplants = 8,167
– Infer from the Search Activity = 7,249
– Infer from knowledge of diseases = 8,500 – 10,000
![Page 42: Future Trends in Hematopoietic Cell Transplantation (HCT) · 21 11/2007 Improving Survival: Adults Aged 18 – 54 with Malignant Diseases ... MDS – RA or RARS only First analysis](https://reader034.vdocuments.us/reader034/viewer/2022051815/6040ce49483a213474133e66/html5/thumbnails/42.jpg)
41 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
How Many Transplants Should We Be Doing?
Approaches to an Answer:
– Infer from the Matched Sibling Transplants = 8,167
– Infer from the Search Activity = 7,249
– Infer from knowledge of diseases = 8,500 – 10,000
None of these considers emerging indications
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42 Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM ®
Future Trends
Registries of adult donors and cord blood units continue to grow
Transplant numbers will increase, approaching 10,000 in the U.S. alone
Patient populations will continue to evolve
Successful transplantation will be the expectation
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Creating Connections. Saving Lives.™NATIONAL MARROW DONOR PROGRAM®
43 11/2007
Worldwide Transplants Facilitatedby Calendar Year 1997–2006
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Year of Transplant
Num
ber o
f Tra
nspl
ants
Bone marrow
Peripheral blood stem cells
Cord blood