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
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Unrelated Cord Blood Transplantation In Adults with Hematological Malignancies Eurocord Results
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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
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)
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)
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%)
Eurocord Registry
N°of European CBUs shipped by year*
* 215 CBUs not infused are included in the bar chart
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)
Transplant characteristics
Characteristics CR1,
n=195 CR2,
n= 136Not CRn= 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%
Other n=30 (29%)
Cy+Flu+TBI
n=73 (71%)
Conditioning
MAC n=314 RIC n=103
Cy+TBIn=80(44%)
Cy+Flu+TBIn=63 (35%)
Othern=36
Cy+Bu n=10 (8%)
Cy+Bu+Thio n=27 (21%)
Bu+Flu+Thio n=78 (62%)
Other n=11 (9%)
Cy+Thio n=1
Cy+Bu+Thio n=1
Cy+Flu n=3
Flu+Mel n= 1
Cy+Flu+Mel n=2
Cy+Flu+Thio n=1Bu+Flu n=1
Cy+Bu+Flu n= 2
Bu+Flu+Thio n=8
Flu+other n=4
Cy+Bu+Flu+ARAC+amsa
crine n=1
GVHD prophylaxis
MAC RIC
0
10
20
30
40
50
60
70
80
0
20
40
60
80
100
120
• Use of ATG in conditioning regimen
p<0.0001
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
Results - 2y LFS all patients
no ATG 42±4% (n=132)
ATG 23±3% (n=239)
p<0.0001
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
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)
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%
TBF Single UCBT vs
other MAC single UCBT vs
TBI+CY+Flu double UCBT
What are the results ?
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
Which is the “best” RIC for UCBT?
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
0 10 20 30
0.0
0.2
0.4
0.6
0.8
1.0
Months
Pro
babi
lity
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 ?
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)
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