Glomerular Filtration and determinants of glomerular filtration .pptx
Outcomes of Double Unit Cord Blood Transplantation in Patients with Malignant Disorders: Eurocord Registry Analysis
1. Vanderson Rocha, MD, PhD
Professor of Haematology- Oxford University
BMT unit, Churchill Hospital
Oxford, UK
Scientific Director of Eurocord
Paris, France
Outcomes of Double Unit
Cord Blood Transplantation in patients with
malignant disorders: Eurocord Registry analysis
2. Eurocord Registry
General data base* overview
*Eurocord Registry status as off December, 31st, 2012
Eurocord registry database N or %
Cord blood units / European CB units % 12 066 / 58%
CBT cases / single% / double% 9 883 / 63% / 23%
European CBT cases 65%
Countries / Centres / EBMT centres 51 / 577 / 297
Unrelated CBT cases 93%
Children CBT cases 54%
3. Eurocord Registry at ABM
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. Characteristic range
Conditioning MAC 76%
RIC 24%
GvHD prophylaxis CsA+MMF 48%
CsA+steroids 30%
CsA+MMF+other 5%
FK506+other 4%
Other 13%
Use of ATG Yes 68%
No 32%
Number of HLA mismatches 0 5%
1 37%
≥2 58%
Median collected TNC, x105/kg 5.1 2.15-44.29
Median infused TNC, x107/kg 5.1 0.98-34.2
Transplant and graft characteristics
9. Neutrophil Engraftment
at 60 days: 87%, n=218
Malignant disease: 90%, n=178, Non Malignant disease: 67%, n=40, p=0.001
Chimerism at 100 days available for 146/182 patients who engrafted,
Mixed 10%,
Full donor 90% (17 patients had long term persistance of both CBU)
10. Non engraftment
• 36 patients experienced primary graft failure
– 27 died in a median time of 72 days after CBT. 5
had received a 2nd Tx (2 haplo, 2 dUCBT, 1 PBSC)
– 9 are alive with a median FU of 18 months. 3 with
available information, had a subsequent Tx (2 CBT
and 1 UD-BMT).
16. Patient characteristics
Patient Characteristics Range
Median age, years
46 y 18-76
Median weight, kg
71 kg 40-171
Median year of transplant
2009 1999-2012
Median follow-up
23 months 3-98
From 1999 to 2012, 1118 adult patients
were transplanted with
double UCBT In 32 EBMT countries
18. Transplantation and graft characteristics
(n= 1118)
Characteristic range
Conditioning RIC 67%
MAC 33%
GvHD prophylaxis CsA+MMF 73%
CsA+steroids 13%
CsA+MMF+other4%
FK506+other 3%
Other 7%
Use of ATG Yes 38%
No 62%
Number of HLA mismatches 0/1 28%
≥2 72%
Median collected TNC, x105/kg 4.9 1.5-14.8
Median infused TNC, x107/kg 3.8 0.33-14.6
19. Neutrophil Engraftment
(n= 1118)
Neutophil Engraftment at 60 days: 87+1%, n=1118
Chimerism at 100 days available for 881/1053 patients who engrafted,
Mixed 14%, Full donor 86%
Lymphoid Mal, n=219: 89+2%
Ac Leukemia, n=820: 87+2%
MDS/MPS, n=239: 82+3%
21. Relapse
(n= 1118)
ACUTE LEUKEMIA OTHER
MALIGNANCIES
N CI N CI
EARLY 267 21% 34 21%
INTERMEDIATE 242 29% 43 21%
ADVANCED 114 39% 281 30%
22. Mortality and causes of death
(n= 681 out 1118)
Among 395 patients transplanted with advanced disease, 267 died in a median
time of 108 days after CBT, of those 106, of the original disease
24. DFS at 2 year by type of disease and
conditioning regimen
MAC, n=388 RIC, n=711
Lymphoid Mal, n=26:40+11%
Ac Leukemia, n=286: 34+2%
MDS/MPS, n=72: 25+3%
Lymphoid Mal, n=181: 41+3%
Ac Leukemia, n=371: 41+3%
MDS/MPS, n=151: 23+4%
25. DFS at 2 year by disease status and conditioning
regimen
MAC, n=388 RIC, n=711
Early , n=147: 44+5%
Intermediate, n=115: 36+5%
Advanced n=120: 18+4%
Early , n=224 46+5%
Intermediate, n=215: 44+4%
Advanced n=264: 27+4%
26. DFS- Multivariate analysis
HR 95%CI p value
Diagnosis: MDS vs acute
leukemia
1.4 1.5- 1.95 0.02
Diagnosis:
Lymphoid malignancies vs
acute leukemia
1.2 0.88- 1.7 0.22
Disease Status
Remission vs not remission
0.51 0.38- 0.68 0.0001
27. Disease free Survival for acute leukemia
(n=811)
• DFS at 2 year by type of disease
p=0.48
AML, n=499: 40+2%
ALL, n=313: 37+2%
28. Disease free Survival for acute leukemia
(n=811)
DFS at 2 year by disease
status, CR1
DFS at 2 year by disease
status, CR2
AML, n=196: 50+4%
ALL, n=136: 48+2%
AML, n=175: 48+4%
ALL, n=129: 38+2%
29. Which are the risk factors associated with
the double graft that can change one or
two units selection in dCBT ?
30. Risk factors of engraftment in dBCT
• Winner unit
dose of CD3 cells?
order of infusion?
CD34 viable cells?
HLA?
others?
• Engraftment
Disease status?
Conditioning regimen?
Cell dose? TNC? CD34? CFU-GM?
31. Is there a number of nucleated cells or
CD34 associated with outcomes in double
UCBT?
32. Patients and disease characteristics
n= 430
Median (range) n
Children 41 (9%)
430
Adult 389 (91%)
Age (years)
Children 15 (4-18) 41
Adult 45 (18-67) 389
Weight (Kg)
Children 52 (14-88) 41
Adult 70 (40-120) 389
Positive CMV serology 205 (49%) 413
Diagnosis 241 (56%) 430
Acute leukemia 58 (13%)
MDS 131 (31%)
Other malignancies
Advanced Diseases 168 (40%) 419
Median Follow up (months) 12 (3-70)
34. Double UCBT (n=430) - Neutrophil Engraftment at 60 days
Number of pfCD34+
• CI Neutrophil Engraftment (NE): 81±2%
• 346 pts (80%) achieved engraftment in a median time of 23 days
0 10 20 30 40 50 60
Days
0.00.20.40.60.81.0
Cumulativeincidenceofneutrophilengraftment
pf CD34 <1.7x105/kg 79+3%
pf CD34 >1.7x105/kg 83+3%
p = 0.03
35. Double UCBT (n=430)- Neutrophil Engraftment at 60 days
Number of ptCD34+ Number of ptCD34+
0 10 20 30 40 50 60
Days
0.00.20.40.60.81.0
Cumulativeincidenceofneutrophilengraftment
ptCD34 < 1.2x05/kg 76+3%
ptCD34 > 1.2x05/kg 85+2%
p = 0.04
0 10 20 30 40 50 60
Days0.00.20.40.60.81.0
Cumulativeincedenceofneutrophilengraftment
p = 0.006
ptCD34 < 0.9x05/kg 74+4%
ptCD34 > 0.9 and < 1.8 x05/kg 81+3%
ptCD34 > 1.8x105/kg 87+3%
36. 0 20 40 60 80 100
Days
0.00.20.40.60.81.0
Cumulativeincidenceoftransplantation-relatedmortality
Double UCBT – TRM at 100 days
CI 12 months of TRM: 16+2 %
pfCD34 > 1.2x05/kg 11+2%
pfCD34 <1.2x05/kg 18+3%
p = 0.02
Number of pfCD34+
0 20 40 60 80 100
Days
0.00.20.40.60.81.0
Cumulativeincidenceoftransplantantion-relatedmortality
37. Multivariate analysis -Double UCBT
Summary
pf TNC pfCD34+ pt TNC pt CD34+ Others variables
Overall survival
- - - -
Disease status
at transplantation
Disease free survival
- - - - Disease status
at transplantation
Neutrophil engraftment
-
1.7x105
/kg
(median)
-
1.2x105
/kg
(4th percentile)
No other factor
p=0.04 p=0.015
Transplantation-related mortality
-
1.2X105
/kg
(4th percentile)
-
HLA, MAC, age
p=0.004
38. Conclusions
• Double Cord Blood Transplantation has extended the use
of Cord Blood Cells for Adults for whom the number of
cells is not sufficient.
• Need of more data and follow-up
• However despite a higher cell dose, graft failure is
around 10-15% (a higher CD34+ cell dose of both units seems to be an
important factor to increase engraftment and decrease mortality)
• Acute GVHD seems to be increased
• Mortality is associated with infections (delayed engraftment?,
delayed immune recovery?), GVHD and toxicity
• MDS and advanced disease are factors associated with
decreased DFS rates