Dr. Sullivan - American Society for Blood and Marrow Transplantation

Report
Hematopoietic Cell
Transplant (HCT)
in Older Individuals
Keith M. Sullivan, MD
Duke University Medical Center
ASBMT Corporate Retreat
September 2012
Record female life expectancy from 1840 to the present
Oeppen & Vaupel. Science 296: 1029, 2002.
Projected number of cancer cases for 2000 through 2050
Edwards, BK, et al. Cancer 94: 2786, 2002.
Decline in Deaths from Cardiovascular Disease in Relation to Scientific Advances.
Nabel EG, Braunwald E. N Engl J Med 2012;366:54-63.
Trends in transplantation,
by transplant type and recipient age*
1999-2008
100
Transplants, %
80
 20 yrs
21-40 yrs
41-50 yrs
51-60 yrs
> 60 yrs
60
40
20
0
1999-2003
2004-2008
Allogeneic Transplants
1999-2003
2004-2008
Autologous Transplants
* Transplants for AML, ALL, NHL, Hodgkin Disease, Multiple Myeloma
Slide 7
SUM10_9.ppt
Trends in transplantation,
by transplant type and recipient age*
1999-2008
100
< 50 years
 50 years
< 60 years
 60 years
Transplants, %
80
60
40
20
0
1988-1994 1995-2001 2002-2008
1988-1994 1995-2001 2002-2008
Allogeneic Transplants
Autologous Transplants
* Transplants for AML, ALL, NHL, Hodgkin Disease, Multiple Myeloma
Slide 8
SUM10_29.ppt
Allogeneic transplantations by conditioning
regimen intensity and patient age,
registered with CIBMTR 1999-2008
11,000
Number of Transplants
10,000
9,000
Reduced Intensity Conditioning, Age  50 years
Reduced Intensity Conditioning, Age < 50 years
Standard Myeloablative Conditioning
8,000
7,000
6,000
5,000
4,000
3,000
2,000
1,000
0
1999
2000
2001
2002
2003
2004
2005
2006
2007 *
2008 *
* Data incomplete
Slide 21
SUM10_23.ppt
Older Patients Eligible
 Transplants for patients over age 50 now account
for 35% of all NMDP-facilitated transplants
National Marrow Donor Program® © 2008
CIBMTR: Survival Analysis of Patientws with
Multiple Myeloma treated with HCT
(1990-2004)
Age group
N=
100-day TRM
(probability)
5 yr OS
(probability)
40-49
3291
4%
50%
50-59
6410
4%
47%
60-69
4370
4%
42%
>70
514
5%
37%
CIBMTR: Center for International Blood and Bone Marrow Transplant Research
Patients with MM receiving Autologous HCT
Duke Experience
Age group
<65
>65
Total
2009
50
12 (20%)
62
2010
62
18 (22%)
80
2011
67
29 (30%)
96
No difference in toxicity and TRM in comparison to
younger population of patients
Conclusions:
 Is age per se a negative prognostic factor?
 Age has a negative impact on prognosis mainly because
Referral bias
Under-treatment
 And should age impact on treatment decision?
 We need a better risk stratification in older patients
based on:
Comorbidity
Performance status
Social support
Not on age
Factors Determining Outcome
after HCT
• Stage of Malignant Disease
• Functional Performance Status
• Other CoMorbid Conditions
Relapse Risk in Nonmyeloablative
Allogeneic HCT
(834 pts prepared with 2 Gy TBI +/- Flu, 1997-2006)
Low Risk
CLL in CR
Low Grade NHL (CR or Not)
MM in CR
Mantle cell NHL (CR or not)
MPD
High grade NHL in CR
ALL in CR-1
High Risk_________
MDS: RAEB, RAEBT
MDS after chemotherapy
AML after MDS
AML not in CR
High Grade NHL not in CR
Hodgkins
CML in CR2 or AP/BC
CMML
ALL in CR-2+
3 year Survival: 60%
2 year Relapse: 0-0.24 per pt yr
3 year Survival: 26%
2 year Relapse: 0.52 per pt yr
Kahl, et al
Blood 110: 2744, 2007
Karnofsky Functional Performance
Normal activity and hard work; no special care
100 Normal
90 Normal activity; minor symptoms/signs of disease
80 Normal activity with effort
Unable to work; lives at home with varying assistance
70
60
50
Cares for self, unable to carry on normal activity
Needs occasional assistance
Needs considerable assistance and frequent medical care
Unable to care for self; institutional care
40
30
20
10
0
Disabled, requires special care
Hospital admission
Hospital admission, supportive care
Moribund
Dead
CoMorbid Conditions at HCT
Figure 3. Kaplan-Meier probabilities of survival among patients with
hematologic malignancies treated with allo-NMA-HCT as stratified into
four risk groups based on a consolidated HCT-CI and KPS scale. Group
I (solid black line) includes patients with HCT-CI scores of 0 to 2 and a
KPS of 80%; group II (dotted black line) includes patients with
HCT-CI scores of 0 to 2 and a KPS of 80%; group III (solid blue line)
includes patients with HCT-CI scores of 3 and a KPS of 80%; group
IV (dotted blue line) includes patients with HCT-CI scores of 3 and a
KPS of 80%. Survival rates at 2 years were 68%, 58%, 41%, 32%
for risk groups I, II, III, and IV, respectively. (From Sorror et al., 2008.45
Reprinted with permission. ©2008, Wiley InterScience.)
Nonmyeloablative (NMA)
Allogeneic HCT for
Older Patients
(JAMA 2011)
NMA Allografts for Older Patients
(Study Design)
Patients and Centers
• 372 patients age 60-75 years
• Enrolled in 18 centers between 1998-2008
Regimen and Transplant
• 2 Gy TBI +/- Fludarabine (30 mg/m2 x 3)
• Allogeneic donors (related and unrelated, HLA-matched and
mismatched), unmodified PBMCT
• Post-transplant MMF and CNI
Protocol Exclusion
• DLCO < 50% to < 70%
• Cardiac EF < 35% to < 40%
• KPS < 50% to < 70%
• Cirrhosis with portal hypertension
Sorror et al
JAMA 306:1874,2011
Patient Characteristics by Age
60-64 years
65-69 years
218
121
33
19
49
31
16
48
34
15
36
48
Donor (%)
HLA-match sibling
HLA-match URD
HLA-mismatch
48
40
10
46
46
7
63
30
6
HCT-CI (%)
0
1-2
3-4
>5
22
30
33
13
20
35
26
17
21
24
42
12
Number pts
Relapse Risk (%)
Low
Standard
High
70-75 years
5-year Outcomes by Age
(Percent)
Outcomes (%)
60-64 years
(N = 218)
Non relapse Mortality
Relapse
Overall Survival
PFS
Hospitalized
Acute GVHD (II-IV)
Chronic GVHD
Graft rejections
27
38
38
34
54
54
42
4
65-69 years
70-75 years
(N = 121)________ N = 33)
26
45
33
29
36
50
41
4
31
42
25
27
55
52
49
3
Survival by Relapse Risk and HCTCoMorbidity Index (CI)
(Patients 60-75 years)
Relapse Risk
HCT – CI Scores
0
1-2
>3
Low
69%
Standard
45% 44% 23%
High
41%
56%
56%
15% 23%
Conclusions
1. Older age (60-75 yrs), per se, is not a
risk factor for adverse outcome
following NMA allogeneic HCT
2. Among older allograft recipients,
overall survival is decreased with:


High-Risk Malignancy (HR2.22)
HCT-CI  3 (HR 1.97)
Blommestein et al, Ann
Hematol 2012; E-pub
Life But At What Cost?
QALY* Cost
$50,000
US Medicare Renal Dialysis Coverage (1982)
($121,000, 2008 inflation adjusted)
$30,000-50,000 UK NICE2
$109,000
Lower bound ($109K-297K) plausible range QALY
saved on base case analysis of expenditures
$113,000
WHO: 3x per capita GDP4
???
Public discourse needed to decide on worthwhile services5
*QALY, Quality-Adjusted Life-Year
1. Health Affairs 2000; 19: 92-109
2. www.nice.org.uk/media/B52/A7/Methods Guide Updated June2008.pdf
3. Medical Care 2008; 46: 349-356
4. Health Econ 2000; 9: 235-251
5. Medical Care 2008; 46: 343-345
What Services Are Worthwhile?
Cost
High
Net Benefit
High
Value
Example
Depends on Cost & Benefits
ICD, HAART
for HIV
_______________________________________________________________
Low
High
High
HIV screening
_______________________________________________________________
High
Low
Low
MRI for low back pain
Owens DK et al, Ann Intern Med 2011; 154: 178-80
Cost of Chronic Transfusion
for Stroke Prevention in SCD
• Data were collected on 21 patients for 296
•
•
•
patient months
Charges ranged from $9828 to $50,852 per
patient per year
Charges for patients who required chelation
therapy ranged from $31,143 to $50,852 per
patient per year (median, $38 607)
Charges are approx. $400 000 per patient
decade for patients who require deferoxamine
chelation
Wayne, Schoenike, and Pegelow; Blood 96:2369, 2000
Cost of BMT – Stroke Indication
BMT
• Matched related donor
• $260,000 hosp. charges
• supportive care after
•
•
BMT is 9-fold lower
than for SCA patients
avg. lifespan of male
survivors is 72 years
age at BMT: 10 years
Supportive care
• Mean medical costs in
•
•
Bilenker JH, et al J Ped Hem/Onc 1998; 20:528
SCA patients receiving
12 transfusions/year
and regular DFO
(2008) - $59,233
DFO $10,899 and DFO
admin $8,722
average lifespan for
HbSS males is 42 years
Delea TE et al Am J Hematol 2008; 83:263
Cost of BMT
Incremental cost-effectiveness
(cost of treatment per year of life gained)
ICE =Cost (BMT-supportive care)
ICE =
# years survival (BMT-supportive care)
Cost of BMT – stroke patient
Incremental cost-effectiveness
[59,000x10]+[260,000]+[6550x62]-[59,000x32]
ICE =
72-42
ICE = - $21,063 per YOL gained
ICE of moderate HTN in middle aged men:
$13,500 per YOL gained
•
National Policy to Eliminate:
– Procedures without evidence of benefit
• Local Innovations to Discover:
– Care that is Faster, Cheaper, Better

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