Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...
Unrelated Cord Blood Transplantation In Adults with Hematological Malignancies Eurocord Results
1. Vanderson Rocha, MD, PhD
Professor of Haematology- Oxford University
BMT unit, Churchill Hospital
Oxford, UK
Scientific Director of Eurocord
Paris, France
Unrelated Cord Blood Transplantation
In adults with Hematological Malignancies
Eurocord Results
2. UCBT for adults with Malignancies
• Eurocord Registry update
• Indications
• Survey on outcomes for specific diseases
• Survey on outcomes of elderly patients in Europe and USA
• Conditioning regimen
• Complications (engraftment)
3. UCBT for adults with Malignancies
• Eurocord Registry update
• Indications
• Survey on outcomes for specific diseases
• Survey on outcomes of elderly patients in Europe and USA
• Conditioning regimen
• Complications (engraftment)
4. Eurocord Registry Update
• 12.066 CBU shipped for transplantation (283, 2%, not used):
11.783 CBU used for:
• 9.883 CBT from 1988 to 2012 in 51 countries and 577 centres
293 EBMT 6958 cases (75%)
267 Non-EBMT 2379 cases (25%)
54%
46%
Children n=5071 (54%)
Adult n=4265 (46%)
8%
92%
Related n=708 (8%)
Unrelated n=8618 (92%)
5. Eurocord Registry
N°of European CBUs shipped by year*
* 215 CBUs not infused are included in the bar chart
0
100
200
300
400
500
600
700
800
900
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Year of
shipment
N of
CBUs
1990 3
1991 1
1992 2
1993 1
1994 5
1995 15
1996 30
1997 58
1998 92
1999 123
2000 145
2001 192
2002 167
2003 187
2004 298
2005 440
2006 590
2007 695
2008 823
2009 813
2010 878
2011 817
2012 813
N=7188
6. Eurocord Registry
Unrelated European CBT by recipient’s age and graft type
Children Adults
* Still collecting 2012 data
0
50
100
150
200
250
300
1990
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Double CBT
Single CBT
*
0
50
100
150
200
250
300
350
400
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Double CBT
Single CBT *
In children: 92% single CBT In adults: 47% double CBT
8. Children, n=2354 Adult, n=1337
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
TNC (x10^7) of CBU Used for Single Transplants
9. UCBT for adults with Malignancies
• Eurocord Registry update
• Indications
• Survey on outcomes for specific diseases
• Survey on outcomes of elderly patients in Europe and USA
• Conditioning regimen
• Complications (engraftment)
11. Age distribution for adult patients
0 200 400 600 800 1000 1200
16- 30 y
30- 39 y
40- 49 y
50- 59 y
>60 y
1103
736
790
752
433
N=1185
12. UCBT for adults with Malignancies
• Eurocord Registry update
• Indications
• Survey on outcomes for specific diseases
• Survey on outcomes of elderly patients in Europe and USA
• Conditioning regimen
• Complications (engraftment)
14. 2 Years Survival in Adults (single and double unrelated CBT)
with Acute Leukemia (n=1552) by disease status
CR1 (n= 636)- 48%
CR2 (n= 557)- 41%
More advanced (n= 359)-12%
16. Clinical Results of Unrelated CBT in Adults
n Median
FU (m/y)
Outcomes Favourable Risk
Factors
Ref
Lymphoid
malignancies
104 18 m DFS: 41% Chemosensitive disease
Low-dose TBI
Cell dose>2x107/Kg
JCO, 2009
MDS
108 25 m DFS: 30% low-risk disease Leukemia,
2010
Acute leukemia-
KIR
218 14 m LFS:
KIR-MM: 55%
KIR-M: 31%
KIR-ligand incompatibility
HLA 0/1 mismatch
Leukemia
2009
Acute leukemia-
RIC
155 18 m LFS: 51% Disease Status
HLA 0/1 mismatch
Not
published
ALL 421 24 m LFS
CR1: 39%
CR2: 31%
Adv: 8%
Disease Status, age<35
No use of ATG
Submitted
2013
AML 604 24 m LFS:
CR1: 43%
CR2: 38%
Adv: 11%
Disease Status, no previous
autologous transplant, TBF
(MAC)
Disease status, age<48 years
Not
published
17. Clinical Results of Unrelated CBT in Adults
n Median
FU (m/y)
Outcomes Favourable Risk
Factors
Ref
Lymphoid
malignancies
104 18 m DFS: 41% Chemosensitive disease
Low-dose TBI
Cell dose>2x107/Kg
JCO, 2009
MDS
108 25 m DFS: 30% low-risk disease Leukemia,
2010
Acute leukemia-
KIR
218 14 m LFS:
KIR-MM: 55%
KIR-M: 31%
KIR-ligand incompatibility
HLA 0/1 mismatch
Leukemia
2009
Acute leukemia-
RIC
155 18 m LFS: 51% Disease Status
HLA 0/1 mismatch
Not
published
ALL 421 24 m LFS
CR1: 39%
CR2: 31%
Adv: 8%
Disease Status, age<35
No use of ATG
Submitted
2013
AML 604 24 m LFS:
CR1: 43%
CR2: 38%
Adv: 11%
Disease Status, no previous
autologous transplant, TBF
(MAC)
Disease status, age<48 years
Not
published
18. Outcomes of unrelated cord blood transplant
for adults with acute lymphoblastic
leukemia: a survey conducted by Eurocord
and the ALWP/EBMT
L Tucunduva, A Ruggeri , G Sanz, S Furst, B Rio, G Socié, W Arcese, M
Michallet, I Yakoub-Agha, J Cornelissen, J Sanz, P Montesinos, D Purtill, E
Gluckman, M Mohty and V Rocha
BMT Tandem Meetings CIBMTR / ASBMT
Salt Lake City 13-17 February/2013
No conflict of interest to disclose
19. Patient and disease characteristics n=421
Characteristics
CR1,
n=195
CR2,
n= 136
Not CR
n= 90
Median age at UCBT, years (range) 35 (18-64) 26 (18-76) 30 (18-60)
Age ≥35 years at diagnosis 48% 25% 31%
Immunophenotype
B 71% 74% 63%
T 20% 21% 35%
Other 9% 5% 2%
WBC count at diagnosis
median (range) 16 (0.6-456) 11 (0.2-624) 13 (0.7-515)
≥30x109
/L 40% 32% 39%
≥100x109
/L 14% 14% 24%
Cytogenetics
very high risk 57% 23% 28%
high risk 5% 2% 8%
standard risk 38% 75% 63%
Median time from diagnosis to UCBT,
months (range)
7 (3-39) 31 (2-96) 16 (3-113)
Median time from diagnosis to first
relapse, months (range) na 27 (3-140) 13 (2-138)
20. Transplant characteristics
Characteristics
CR1,
n=195
CR2,
n= 136
Not CR
n= 90
Type of UCB graft
single 57% 54% 70%
double 43% 46% 30%
TNC x107
/Kg; median (range) 4.0 (1.8-9.4) 4.1 (1.5-9.0) 3.8 (1.8-9.2)
HLA matching
No mismatch 4% 1% 0%
1 mismatch 32% 23% 26%
2-3 mismatches 64% 76% 74%
Type of conditioning
RIC 28% 24% 18%
MAC 72% 76% 82%
23. Results - 2y LFS all patients
CR1 39±4%(n=195)
CR2 31±4% (n=136)
not in CR 8±3% (n=90)
p<0.0001
24. Results - 2y LFS all patients
no ATG 42±4% (n=132)
ATG 23±3% (n=239)
p<0.0001
25. Results - 2y LFS
MAC RIC
no ATG 39±6% (n=72)
ATG 23±3% (n=212)
no ATG 47±6% (n=62)
ATG 33±10% (n=25)
p=0.02 p=0.04
26. Multivariate analysis for LFS
• Variables tested in the model:
-- age (≥35 vs <35 years)
-- remission status (CR1 and CR2 vs advanced)
-- median collected TNC (equal or superior vs inferior 4.0x107/kg)
-- conditioning (RIC vs MAC)
-- type of graft (single vs double)
-- use of ATG in conditioning regimen (yes vs no)
Variable HR 95% IC p value
age ≥35 y 1.3 1.1-1.7 0.03
not in CR at UCBT 2.5 2.0-3.3 <0.0001
ATG 1.5 1.1-2.0 0.009
Factors associated with decreased LFS
27. Clinical Results of Unrelated CBT in Adults
n Median
FU (m/y)
Outcomes Favourable Risk
Factors
Ref
Lymphoid
malignancies
104 18 m DFS: 41% Chemosensitive disease
Low-dose TBI
Cell dose>2x107/Kg
JCO, 2009
MDS
108 25 m DFS: 30% low-risk disease Leukemia,
2010
Acute leukemia-
KIR
218 14 m LFS:
KIR-MM: 55%
KIR-M: 31%
KIR-ligand incompatibility
HLA 0/1 mismatch
Leukemia
2009
Acute leukemia-
RIC
155 18 m LFS: 51% Disease Status
HLA 0/1 mismatch
Not
published
ALL 421 24 m LFS
CR1: 39%
CR2: 31%
Adv: 8%
Disease Status, age<35
No use of ATG
Submitted
2013
AML 604 24 m LFS:
CR1: 43%
CR2: 38%
Adv: 11%
Disease Status, no previous
autologous transplant, TBF
(MAC)
Disease status, age<48 years
Not
published
28. Cord blood transplantation for adult
with acute myeloid leukaemia:
a survey on behalf of Eurocord and ALWP-EBMT
Annalisa Ruggeri, William Arcese, Guillermo Sanz, Bernard Rio,
Noel Milpied, Sabine Furst, Josep Ribera, Alberto Bosi, Emmanouel Nikiforakis,
Eliane Gluckman, Mohamad Mohty, Myriam Labopin and Vanderson Rocha
16th Congress of the European Hematology Association (EHA)
London - 11/06/2011
No conflict of interest to disclose
29. UCBT for AML
Patients and disease characteristics, n= 604
60% single and 40% adults
CR1, n=229 CR>=2, n=228 Adv, n=147
Median age at UCBT (years) 40 (18-66) 42 (18-68) 41 (22-67)
Male 109 (49%) 109 (48%) 71 (48%)
Positive pts CMV serology 130 (63%) 133 (64%) 74 (64%)
High risk cytogenetic n=192 n=190 n=114
115 (60%) 94 (49%) 63 (55%)
Interval diagnosis-UCBT 6 months 22 months 13 months
Previous HSCT (auto/allo) 12 (5%) 77 (34%) 44 (32%)
Median Follow-up 24 (range 3-120) months
30. UCBT for AML
Transplant characteristics, n=604
• MAC • RIC
MAC: TBI dose > 6Gy, Busulfan dose >8 mg/Kg or IV BU>9.6 mg/kg
CyFluTBI-
2Gy
72%
Other Flu-
Based
15%
Other
13%BuFluTT
34%
BuCy
10%BuCyTT
5%
CYTBI-12Gy
16%
CyFluTBI-
12Gy
11%
Other Bu-
Based
12%
Other
12%
31. UCBT for AML- MAC
LFS
MAC- 2y LFS by disease status, n=293
Disease Status
(Remission)
HR 2,11- 95%CI 1,56- 2,87, p=<0,0001
No Previous HSCT HR 2,19 -95%CI 1,58- 3,04, p=<0,0001
Multivariate analysis (LFS- MAC)
CR1: 51%
CR2 and CR3:37%
Adv: 14%
p<0.0001
33. UCBT for adults with Malignancies
• Eurocord Registry update
• Indications
• Survey on outcomes for specific diseases
• Survey on outcomes of elderly patients in Europe and USA
• Conditioning regimen
• Complications (engraftment)
34. Changing trends of UCBT for hematological malignancies
in patients older than 50 years:
a Eurocord- CIBMTR survey
Annalisa Ruggeri, Mary Eapen,
Luciana Tucunduva, Fernanda Volt, Mary Horowitz,
Vanderson Rocha, Daniel Weisdorf and Eliane Gluckman
No conflict of interest to disclose
36. Single and double UCBT:
distribution of age for adult patients
0 200 400 600 800 1000 1200
16- 30 y
30- 39 y
40- 49 y
50- 59 y
>60 y
1171
780
719
805
477
1103
736
790
752
433
Eurocord
CIBMTR
37. Study Objective
Survey of patients more than 50 years of age
reported to Eurocord and CIBMTR
• Period 2005 - 2011
• Hematologic malignancies
N = 1529
n = 848 (N. America)
n= 681 (Europe)
Median follow up:
24 months 0
100
200
300
400
500
600
50- 59 y 60- 69 y 70+ y
Eurocord
CIBMTR
64%
36%
60%
37%
3%
Age distribution
42. Overall Survival
-AML by disease status and conditioning-
Eurocord, n=257
46±4%
33±10%
30±12%
6±4%
■ CR and MAC, n=29
■ CR and RIC, n=176
■ Rel and MAC, n=17
■ Rel and RIC, n=35
43. Overall Survival
- Acute Myeloid Leukemia –
Probability,%
Years
0
100
0
20
40
60
80
90
10
30
50
70
0
100
20
40
60
80
90
10
30
50
70
1 2
CR and MAC (N=112)
CR and RIC (N=191)
Rel and MAC (N=49)
Rel and RIC (N=31)
CIBMTR, n=373
46. UCBT for adults with Malignancies
• Eurocord Registry update
• Indications
• Survey on outcomes for specific diseases
• Survey on outcomes of elderly patients in Europe and USA
• Conditioning regimen
• Complications (engraftment)
48. No Flu Based (n=1471) 86 %
Fludarabine based MAC (n=384) 91%
6050403020100
1,0
,8
,6
,4
,2
0,0
Neutrophil recovery after single UCBT for patients with malignant
disorders after myeloablative conditioning regimen (n=1946)
p< 0.0001
49. Conditioning regimen
Myeloablative
Analyze the impact of TT, iv BU, F+ATG (TBF-ATG) on long
term outcomes after single unit UCBT compared to other
MAC regimens in adults with leukemias in remission
H Bittencourt et al. # 377, Oral session EBMT
51. Early Stage (n=147)
Characteristics
Group 1, sUCBT
Cy-based
n=93
Group 2, sUCBT
Bu+Flu+TT
n=54
Age (years) 33(18-54) 32 (19-51)
HLA match – 4/6 51(56%) 28(53%)
Acute Leukemia* 79(85%) 52 (96%)
Median TNC after thawing
(107
Kg)
2.5 (0.6-7.6) 2.3 (1.4-4.9)
GVHD Prophylaxis:
CSA+Steroids
ATG
78(84%)
83(89%)
38 (70%)
48(89%)
Year of UCBT* 2003 (2000-2007) 2006 (2005-2008)
* P<0.05
Besides ABO major incompatibility (P=0.02), there was no other differences among the 2 groups for patients disease and UCBT
characteristics (gender, weight, CMV status, previous autologous HSCT, CD34+ infused cells)
52. EFS at 5 years
Early Stage
Group 1: sUCBT-Cy-based: 28%
Group 2: sUCBT-BuFluTT: 41%
BuFluTT associated with better event-free survival in multivariate analysis
HR 0.64 (CI95%:0.41-0.99 – P=0.04)
P=0.07
DFS: 32%
54. p=0.03
Group 1: sUCBT-CyTBI12: 30±7%, n=68 (Cell dose 2.9)
Group 2: sUCBT-BuFluTT+ATG: 46±6%, n=88 (Cell dose 3.1)
Group 3: dUCBT-CyFluTBI12: 48±6%, n=83 (Cell dose 3.7)
LFS at 2 years
MAC sUCBT and dUCBT in adults with AL in CR1
56. Disease Free Survival according to conditioning
after single and double UCBT for malignancies in
adults ( n=155)
Months
28% others
51% CY+TBI 2GY+FLU (n=101)
P= 0.0002
57. 0 10 20 30
0.00.20.40.60.81.0
Months
Probability Relapse
2 year estimate: 46%
Phase II trial in France on the use of TCF–RIC in UCBT for
AML ( n=79)
Cumulative Incidence of Relapse
Rio B et al
Should we include Thiotepa or increase TBI
in the RIC ?
58. UCBT for adults with Malignancies
• Eurocord Registry update
• Indications
• Survey on outcomes for specific diseases
• Survey on outcomes of elderly patients in Europe and USA
• Conditioning regimen
• Complications (engraftment)
59. PROBABILITY OF ENGRAFTMENT
• The Probability Density to engraft describes the
probability to engraft at each time point from CBT, also
considering competing events (ie early deaths)
• The engraftment probability peaks at +21, the median
halves at +31 (20%) and drops to 5% at day 42
-0.0050
0.0000
0.0050
0.0100
0.0150
0.0200
0.0250
0.0300
0.0350
0.0400
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90
20% 5%
The area under the
curve beyond each
time points represents
the residual probability
to engraft
60.
61. Conclusions
Single and unrelated cord blood with myeloablative or
reduced intensity conditioning regimens are feasible
procedures and have extented the use of allo transplants
for patients without a HLA matched donor
Graft failure and delayed neutrophil recovery are still
problems to be circumvent in the field of UCBT
Analysis of risk factors in specific diseases are important with
the aim to improve final outcomes.