should we expand cord blood? - comtecgroup rocha.pdf · 8/8 matched bm 246 177 139 99 82 7/8...
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Should we expand cord blood?
Vanderson Rocha, MD, PhDSirio Libanes Hospital and Children’s Cancer Hospital,
University of Sao Paulo, Brazil Eurocord Office, Paris , France
Single CBT (>2.5x10e7/kg)compared to PB and BM in Single CBT (>2.5x10e7/kg)compared to PB and BM in adults with ALadults with AL
LeukemiaLeukemia--free Survivalfree Survival--Transplantation in Remission Transplantation in Remission ––
Pro
bab
ilit
y,
%
100
0
20
40
60
80
90
10
30
50
70
Months 0 6 12 18 248/8 matched BM 246 177 139 99 82 7/8 matched BM 106 69 46 35 31
8/8 matched PBPC 452 316 220 143 112 7/8 matched PBPC 166 89 66 45 36
4/6-6/6 matched UCB 123 77 47 30 24
8/8 BM, 52%
7/8 BM, 41%
8/8 PBPC, 50%
PBPC 7/8 39%
4-6/6 UCB, 44%
Eapen M, Rocha V et al; Lancet Oncol 2010
100,
0
100,
0
99,6
96,0
86,1
71,2
53,4
100,
0
99,6
92,1
71,2
45,5
27,4
15,0
100,
0
96,0
71,2
38,8
18,6
8,2
3,4
0
20
40
60
80
100
120
10 20 30 40 50 60 70
Weight (Kg)
% CB units > 2E+07 CNT/Kg% CB units > 3E+07 CNT/Kg% CB units > 4E+07 CNT/Kg
Perc
enta
ge (%
)% of available French CBU according to TNC/Kg RFSP: French Network of CBB (Besançon, Bordeaux, Paris, Marseille)
Decision to freeze >80 ml Utilization of almost 3% of the inventory
Comparative Retrospective
Registry Based Analysis
Selection criteria
• First single (s) or double (d) cord blood transplants performed from 1998 to 2009 in
transplant centers in Europe
• Adults ≥
18 years old with AML or ALL in complete remission
• Myeloablative or reduced intensity conditioning regimen
sUCBT dUCBT
P
N
377
230
Age
(y)
Median
35
37
0.06Range
18‐67
18‐66
Weight (Kg) Median
65
68 <0.001 Range
30‐112
40‐110
Female Gender
49%
43% 0.15
CMV + 68% 60% 0.06
Patients characteristics
N
377
230
AML
229 (61%)
145 (63%) 0.64ALL
148 (39%)
85 (37%)
Poor risk (cytogenetics)
36%
32% 0.02
Status at transplant
0.17CR1
203 (54%)
114(50%)
CR2
141 (37%) 102(44%)
CR3
33 (9%)
14 (6%)
Previous autologous transplant 15%
12% 0.17
Median year of transplantation 2006 2007 <0.001
Disease and Transplant characteristics
sUCBT dUCBT
P
N
377
230
Conditioning
Myeloablative
68% 45%
<0.001
Reduced intensity
32% 55%
ATG/ALG
69%
29% <0.001
GVHD Prophylaxis
<0.001
CsA +
Corticosteroids
50%
18%MMF containing 48% 75%
Median follow‐up time (mo) 20 (1‐133) 14 (1‐49)
Transplant Characteristics
sUCBT dUCBT
P
N
377
230
HLA match (HLA‐A,‐B by serology and DRB1 low resolution)
HLA Matched
0.13 6/6 or 5/6
37%
30%
4/6 or 3/6
63
%
70%
Nucleated cells infusedx107/kg 2.6
3.7
<0.001
Range
0.6‐16
1.1‐10
Donor characteristics
sUCBT dUCBT
P
Results
6 12 18 24 30 36 42 48 54 60
0.0
0.2
0.4
0.6
0.8
1.0
sUCBT versus dUCBT for adults with AL Neutrophil recovery
82 ± 2%
82 ± 3%dUCBT
sUCBT
P=0.12
days
sUCBT versus dUCBT for adults with AL 100 day CI of Acute GVHD II‐IV
30 60 90 120
0.0
0.2
0.4
0.6
0.8
21 ± 2%
39 ± 3%dUCBT
sUCBT
P<0.0001
days
sUCBT versus dUCBT for adults with AL Acute GVHD II‐IV
months
sUCBT versus dUCBT for adults with AL 2 years Relapse incidence
0 6 12 18 24 30 36
0.0
0.2
0.4
0.6
0.8
1.0
29 ± 3%
23 ± 3%dUCBT
sUCBT
P=0.24
2 years‐
Leukemia Free survival after sUCBT and dUCBT in adults with AL transplanted in remission
35 ± 3%
44 ± 4%dUCBT
sUCBT
P=0.13
months
In a multivariate analysis adjusted for differences and risk factors Double CBT was associated with improved LFS rates [p=0.04 HR=0.67 (0.45‐0.97)]
2 years‐
Leukemia Free survival after sUCBT and dUCBT in adults with AL transplanted in first complete remission
(CR1)
sUCBT 39±4%
dUCBT 53±5%
months
Favorable3% 3%
Intermediate54% 41%
Unfavorable43% 56%
sUCBT dUCBT
0 6 12 18 24 30 36
0.0
0.2
0.4
0.6
0.8
2 years‐
incidence of relapase after sUCBT and dUCBT in adults with AL transplanted in first complete remission
(CR1)
25 ± 3%
15± 4%dUCBT
sUCBT
P=0.03
In a multivariate analysis adjusted for differences and risk factors Double CBT was associated with decreased relapse [p=0.01 HR=0.74
(0.58‐0.93)]
months
2 years-Leukemia Free Survival after sUCBT and dUCBT in adults with AL in second (CR2) and third complete remission (CR3)
months
sUCBT 31±4%
dUCBT 35±5%
Summary• Double
CBT
have
extended
the
indication
of
allogeneic
hematopoietic
transplantation
to
adults
who
could
not find a single CBT unit.
• We
confirmed
lower
relapse
and
improved
LFS
rates after
dUCBT
compared
to
sUCBT
for
patients
transplanted in CR1.
• Higher
incidence
of
grade
II‐IV
aGVHD
in
dUCBT,
but not higher mortality compared to sUCBT
• Cost might be a limiting factor.
• Randomized
studies
are
on
going
in
the
US
and
in France comparing s and d UCBT
Acknowledgments Participating Centers
Pierre and Marie Curie Center, Alger - AlgeriaRoyal Perth Hospital, Perth - AustraliaMedical University, Graz - AustriaSt. Anna Kinderspital, Vienna - AustriaUniversity Hospital Gasthuisberg, Leuven - Belgium University Ziekenhuis, Brussels - Belgium University of Liege, Liege - Belgium Turku University, Turku - FinlandUniversity Central Hospital, Helsinki - FinlandCentre Hospitalier Angers - FranceHôpital Saint-Jacques, Besançon - FranceHôpital Haut-Lévêque (CHU), Bordeaux - FranceHôpital Augustin Morvan, Brest - FranceCentre Hospitalier Universitaire (CHU), Caen - FranceHôpital Percy, Clamart - FranceCHU Henri Mondor, Créteil - FranceCHU Hôtel-Dieu, Centre Jean Perrin, Clermont-Ferrand - FranceCHU Albert Michallon La Tronche, Grenoble - FranceHôpital Claude Huriez, Lille - France Centre Hospitalier Universitaire, Limoges - FranceHôpital Edouard Herriot, Lyon - FranceHôpital La Timone, Marseille - FranceInstitut Paoli-Calmettes, Marseille - FranceHôpital Lapeyronie, Montpellier - FranceHôpital Brabois, Nancy - FranceCentre Hospitalier Universitaire Hôtel-Dieu, Nantes - FranceGroupe Hospitalier l’Archet, Nice - FranceHôpital Necker, Paris - FranceHôpital Saint-Louis, Paris - France Hôpital Saint-Antoine, Paris - FranceHôtel Dieu, Paris - FranceHôpital de la Pitié-Salpêtrière, Paris - France Hôpital Jean Bernard, Poitiers - FranceHôpital Pontchaillou (CHU), Rennes - FranceHôpital Charles Nicolle, Rouen - FranceHôpital Nord/Institut de Cancérologie de la Loire, Saint-Etienne - FranceHôpital Hautepierre, Strasbourg - FranceHôpital Purpan, Toulouse - FranceHôpital Bretonneau, Tours - FranceInstitut Gustave-Roussy (IGR), Villejuif – France
Heinrich Heine University, Düsseldorf – GermanyUniversitaetsklinikum, Düsseldorf – GermanyGrosshadern Clinic, Munich - GermanyFriedrich-Schriller University, Jena – GermanyUniversity Regensburg, Regensburg - GermanyUniversity Medical School, Patras – GreeceEvangelismos Hospital, Athens – GreeceHadassah University Hospital, Jerusalem – IsraelBeilinson Hospital, Petach-Tikva – IsraelChaim Sheba Medical Center, Tel-Hashomer – IsraelRikshospitalet, Oslo - NorwayCentral Clinic Hospital, Warsaw - PolandSan Gerardo Hospital, Monza - ItalyAz. S. Croce e Carle Hospital, Cuneo - ItalyRiuniti Hospital, Bergamo - ItalyUniversity Hospital, Udine - ItalyLa Sapienza University, Roma - ItalyAz. Riuniti Hospital, Ancona - ItalyA. Businco Hospital , Cagliari - ItalyFerrarotto Hospital, Catania - ItalySan Martino Hospital, Genova - ItalyHospital University San Giovanni Battista, Torino - ItalyBologna University, S.Orsola-Malpighi Hospital, Bologna - ItalyHospital Maggiore, Milano - ItalyPoliclinico San Matteo, Pavia - ItalyHospital S. Camillo, Roma - ItalyHospital San Maurizio, Bolzano - ItalyCareggi Hospital, Firenze - ItalyAz. Hospital University Senese, Siena - ItalyV. Cervello Hospital, Palermo - Italy
Institut Portugues Oncologia, Porto – PortugalKing Faisal Hospital & Research Centre, Riyadh - Saudi ArabiaHospital Clinic, Barcelona – SpainHospital Reina Sofia, Córdoba – SpainHospital Santa Creu & Sant Pau, Barcelona – SpainHospital University Germans Trias i Pujol, Barcelona – SpainHospital Vall d’Hebron, Barcelona – SpainHospital Duran i Reynals, Barcelona – SpainHospital Clinic University, Valencia – SpainHospital University La Fe, Valencia – SpainHospital University Virgen de las Nieves, Granada – SpainHospital Carlos Hay, Málaga – SpainHospital Ramon y Cajal, Madrid – SpainNiño Jesus Children`s Hospital, Madrid - SpainHospital Gregorio Marañón, Madrid - Spain Clinic Hospital, Salamanca - Spain Hospital University Virgen del Rocío, Sevilla - Spain Huddinge University Hospital, Stockholm - Sweden
Umea University Hospital, Umea - Sweden University Hospital, Linköping - Sweden University Hospital, Zürich - Switzerland University Hospital, Geneva - Switzerland University Hospital, Bern - Switzerland Radboud University, Medical Centre, Nijmegen - The Netherlands Leiden University Hospital, Leiden - The Netherlands University Medical Center, Utrecht - The Netherlands Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam - The Netherlands Imperial College, London - United Kingdom GKT School of Medicine, London - United Kingdom Royal Marsden Hospital, London - United Kingdom University College London Hospital, London - United Kingdom Gartnaval General Hospital, Glasgow - United Kingdom Churchill Hospital, Oxford - United Kingdom Heartlands Hospital, Birmingham - United Kingdom Queen Elizabeth Hospital, Birmingham - United Kingdom Royal Hospital, Bristol - United Kingdom Nottingham City Hospital, Nottingham - United Kingdom Sheffield Children`s Hospital, Sheffield - United Kingdom
Acknowledgments Participating Centers