What have the transplant
registries taught us?
Bo Björkstrand, MD, PhD
Karolinska University Hospital Huddinge
Stockholm, Sweden
EBMT Myeloma Registry ­ Autologous SCT
EBMT myeloma registry studies
· Allogeneic BMT
1991, 1995
· Prognostic factors in autologous SCT
1994 etc
· TBI vs chemo conditioning in autologous SCT
1999
· Allogeneic vs autologous SCT
1996, 2001
· Syngeneic SCT
1999
· Single vs tandem autologous SCT
1999
· Interferon maintenance post autologous SCT
2001
· Impact of allogeneic graft type (BM, PBSC)
2001
· Timing of second autograft
2004
March 2005
EBMT Myeloma Registry ­ Autologous SCT
EBMT myeloma registry studies ­ recent and present
· Impact of donor gender
2005
· SCT (auto, allo) in plasma cell leukemia
2005
· SCT (auto, allo) in rare myeloma types
2005
· SCT in amyloidosis
2005
· Allogeneic RIC- vs full-dose conditioning SCT
2005
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT - Current Status
· EBMT Multiple Myeloma registry ­
established in the early 1980ies
· Total: 19,562 reported patients
transplanted from 1986 through 2003
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Patient Characteristics
· Sex (M / F)
­ Males
11,521 (59%)
­ Females
8,041
(41%)
· Age at transplantation
<60 years
14,473 (74%)
>60 years
5,089
(26%)
· Time from diagnosis to transpl.
­ <1 year
14,022
(72%)
­ >1 year
5,254
(28%)
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Myeloma isotype
· IgG
55% (10,719)
· IgA
20% (3,955)
· Light chain
15% (2,991)
· Non-secretory
3% (619)
· IgD
1% (258)
· Others
<1% (87)
· Unknown
5% (933)
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
(N=19562)
1.00
.80
.60
.40
.20
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
PFS
(N=19562)
1.00
.80
.60
.40
.20
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
CR achievement
Total Population (N=19562)
1.00
.80
.60
Incidence
.40
.20
Cumulative 0.00
0
365
730
1095
1460
DAYS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
RELAPSE
Total Population (N=19562)
1.00
.80
Incidence .60
.40
.20
Cumulative 0.000 12 24 36 48 60 72 84 96 108 120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
NRM
Total Population (N=19562)
1.00
.80
.60
Incidence
.40
.20
FIRST TWELVE MONTHS
Cumulative 0.00
0
1
2
3
4
5
6
7
8
9
10
11
12
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
Patient Sex
1.00
.80
.60
female (N= 8041)
.40
.20
male (N=11521)
p<0.01
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
Age at Transplant
1.00
.80
.60
< 60 yrs (N=14473)
.40
.20 p<0.01
>= 60 yrs (N=5089)
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
Number of Pre-treatment Lines
1.00
.80
.60
0-1 line (N=6413)
.40
.20 p<0.01
2-3 lines (N=2054)
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
Stage at Transplant
1.00
.80
stage I (N=1710)
.60
stage II (N=2907)
.40
.20
p<0.01
stage III (N=8415)
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
2 microglobulin
1.00
.80
.60
low (<=4) N=3035
.40
.20 p<0.01
high (> 4) N=1462
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
Response Status at Transplant
1.00
.80
.60
CR or PR (N=5693)
.40
.20 p<0.01
non-responsive (N=1090)
0.00
0
12
24
36
48
60
72
84
96
108
120
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
Survival
Cytogenetics (N=706)
1.00
normal (N=473)
.80
.60
.40
abnormal (N=233)
.20
p<0.01
0.00
0
12
24
36
48
60
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
PFS
Cytogenetics (N=706)
1.00
.80
normal (N=473)
.60
.40
.20
p<0.01
abnormal (N=233)
0.00
0
12
24
36
48
60
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous Transplants in Multiple Myeloma
NRM
Cytogenetics
.50
FIRST TWELVE MONTHS
.40
.30
Incidence
.20
abnormal (n=233)
.10
Cumulative 0.00
normal (N=473)
0
1
2
3
4
5
6
7
8
9
10
11
12
MONTHS
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Comments
· Very high autotransplant activity in multiple myeloma
· Several factors of statistically significant prognostic
importance for outcome
· Most apparent unfavourable prognostic factors
­ Abnormal karyotype
­ Disease stage III
­ High beta-2-mcgb at diagnosis
­ Unresponsive prior to transplantation (progressive disease in
particular)
­ More than 1 line of conventional therapy
­ Higher age
­ Male gender
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Comments
· Low non-relapse mortality
· A handful of patients alive and disease free after 10-14
years - cured?
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT in plasma cell leukemia
Retrospective registry study, transplants from 1980-2001
n
Plasma cell leukemia
135
Multiple myeloma 'common' type,
9,887
single autograft
IgG 54%, IgA 20%, light chain 26%
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT in plasma cell leukemia
Prognostic factors
Groups comparable for gender, level of S-Ig, S-Ca, S-Alb
PCL
MM
p
Hemoglobin
8.75
10.9
0.0001
S-creatinin
114
91
0.021
Beta-2-mcb at diagnosis
6.1
2.5
0.0001
B2m > 4.0
72%
31%
0.0001
Abnormal bone x-ray
46%
68%
0.025
March 2005
Plasma cell leukemia vs MM ­ CR after auto-SCT
1.0
.8
.6
remission
p=0.04
.4
PCL, n=135
Complete
.2
Myeloma, n=9887
0.0
0
24
48
72
96
Months
CR at 12 mo
32% for PLC
Drake et al, EBMT 2005
24% for MM
EBMT Myeloma Registry ­ Autologous SCT
Plasma cell leukemia vs MM ­ OS after autologous SCT
1.0
.8
Myeloma, n=9887
.6
p=0.0001
Survival
.4
PCL, n=135
.2
0.0
0
24
48
72
96
120
144
168
192
Months
Median OS
21 mo for PLC
55 mo for MM
Drake et al, EBMT 2005
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Plasma cell leukemia vs MM ­ NRM after autologous SCT
.30
.20
Mortality
PCL, n=135
p=0.04
Related
.10
Transplant
Myeloma, n=9887
0.00
0
24
48
72
96
120
144
168
192
Months
TRM at 6 mo
10% for PLC
4% for MM
Drake et al, EBMT 2005
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT in plasma cell leukemia
Conclusions
· Poorer prognosis in plasma cell leukemia
­ Higher TRM
­ Poorer survival
­ in spite of higher CR-rate before and after ASCT in plasma cell leukemia
Drake et al, EBMT 2005
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT in 'rare myelomas'
· Retrospective registry study, transplants 1980-2001
Myeloma type
n
IgD
149
Non-secretory
415
'Common' type
9,887
Morris et al, EBMT 2004
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT in IgD-myeloma
IgD
'Common'
p
Median OS post-transpl.
43 mo
55 mo
0.003
TRM at 1 year
9%
4%
0.23
CR-rate at 1 year
36%
24%
0.01
Morris et al, EBMT 2004
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT in non-secretory MM
Non-secr.
'Common'
p
Median OS post-transpl
50 mo
55 mo
N.S.
TRM at 1 year
3%
4%
N.S.
Morris et al, EBMT 2004
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Autologous SCT in 'rare'MM
Conclusions
·IgD-myeloma
­ only 149 transplants during a 21 year period
­ apparently poorer survival than 'common' MM, in spite of higher CR-rate
­ TRM comparable to 'common' MM
· Non-secretory myeloma
­ survival and TRM similar to 'common' MM,...
­ ... in spite of higher rate of stage III disease in NS (data not shown)
Morris et al, EBMT 2004
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Transplant registries ­ what for?
· Continuous monitoring of transplant activity ­ What are we
doing?
· Information about trends and changes in methodology and
indications
· Retrospective analyses of matched groups ­ to precede or
substitute (?) randomised trials
· Studies of "rare events" (disease type, twin donors,
complications, etc)
March 2005
EBMT Myeloma Registry ­ Autologous SCT
Acknowledgements
Curly Morris
Belfast City Hospital, Northern Ireland, UK
Mary Drake
"
Charles Crawley
Addenbrookes Hospital, Cambridge, UK
Anja van Biezen
EBMT Statistics Centre, Leiden, Netherlands
Simona Iacobelli
"
Gösta Gahrton
Karolinska University Hospital Huddinge,
Stockholm, Sweden
All physicians and data managers in the EBMT centres
March 2005

Document Outline