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, PhD Sirio Libanes Hospital and Children’s Cancer Hospital, University of Sao Paulo, Brazil Eurocord Office, Paris , France

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Page 1: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 2: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 3: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 4: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 5: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 6: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 7: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 8: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 9: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

Results 

Page 10: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 11: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 12: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

sUCBT versus dUCBT for adults with AL  Acute GVHD II‐IV

Page 13: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 14: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 15: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 16: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 17: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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%

Page 18: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 19: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 20: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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

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

Page 21: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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
Page 22: Should we expand cord blood? - Comtecgroup rocha.pdf · 8/8 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