Trasplante de Células Madre Hemopoyéticas.

Dos décadas de progreso

A. Urbano IspizuaHospital Clinic, Universidad de Barcelona

Noviembre de 2011

Al comienzo, estaba la médula ósea

Al comienzo, estaba la médula ósea

1957 Thomas y Mathe

Al comienzo, estaba la médula ósea

1957 Thomas y Mathe

1970 Bortin inicia el IBMTR n=200

Actividad de TPH en Europa N

úmer

o de

TP

H

0

5000

10000

15000

20000

25000

30000

1990 20092000

Piel

Hígado

Intestino

L LL L

Células T del receptor

Células inmunes donante

Microorganismos

Alo-TPH

QT/RT CMH

Fuente de PH

MO SP CU

Fuente de PH

The European Group for Blood and Marrow Transplantation

0

20

40

60

80

100

1990 1992 1994 1996 1998 2000 2002 2004 2006

auto PB

allo PB

cord

EBMT Activity Survey on HSCT 1990-2006 changes in PBSC and Cord

%

Stromal-cell

Stemcell

CXCR4

SDF-1

Lapidot T, Experimental Hematology 30 (2002) 973-981

Homing and Movilization

Osteoblasts

CXCL12

12

Stromal-cell

Stemcell

CXCR4

SDF-1

AMD3100

Liles WC, Blood 102 (2003) 2728-2730 Burroughs L, Blood 106 (2005) 4002-4008Larochelle A, Blood 107 (2006) 3772-3778

AMD3100 and movilization of HPC

Osteoblasts

CXCL12

Stromal-cell

Stem Cell

CXCR4

SDF-1

ElastasesCathepsin GMMPs

G-CSF(-)(+)

Larochelle A, Blood 107 (2006) 3772-3778

G-SCF and movilization of HPC

CXCL12

Osteoblasts

14Méndez-Ferrer Simón, Nature 2008

Early stage disease

Advanced disease

Survival

The European Group for Blood and Marrow TransplantationH.B. 3.2011

EBMT Activity Survey on HSCT 1990–2009:

Cord blood HSCT

18

Number of stem cell productsreleased for unrelated transplantation

3,08

215

5

3,55

228

2

3,70

065

336

8

3,51

51,

127

390

3,23

81,

679

540

3,39

22,

485

617

3,18

73,

198

963

3,13

34,

133

1,12

6

3,12

54,

796

1,79

1

3,00

25,

416

2,07

5

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

10,000

11,000N

umbe

r of

don

atio

ns

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006Cord Blood Units ProvidedPBSC donationsBM donations

UC 13%

PB 62%

BM 25%

Alo-TPH

Evolution of URD SCT in Spain

12 29 43 45 60 65 51 53 50 43 43 3050 48 55

78 8252 7

11 9 26 36 46 56

87115 117

145178

814

1720 29 35

40 51 46 62

104

116137

133

142

0

50

100

150

200

250

300

350

400

1994 1996 1998 2000 2002 2004 2006 2008 2010

BM PB CB

UC 35%

20

1 2 4 1 7 3 9 10 9 7 2 7 1 5 41 1 9 12 10 21 14 17

510 19 9

22 15 1533

57

82 95

123

16

0

20

40

60

80

100

120

140

160

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

UCPBBM

International transplants from SpanishDonations

Total number of donations*: 655

* Excluding Lymphocyte donation

Export

AL in remission

DFS

CR vs. REL: RR 2.40, p<0.001

CBT vs. BMT/PBSCT URD 7/8 or 8/8 HREapen et al. Lancet Oncology 2010

CUMULATIVE INCIDENCE OF TRM AFTER UNRELATED DONOR UCB TRANSPLANTATION (N = 102). EFFECT OF CD34 DOSE. Wagner et al. Blood 2002;100:1611

CD34+ threshold: 1.7 × 105/kg

A: Spheres obtained from theCD146+CD105+ fraction from the samplesorted on the 21/07/11 (14 days)

B: Spheres obtained from the CD146-CD105+ fraction from the sample sortedon the 21/07/11 (14 days)

C. Spheres obtained from the CD105+ fractionfrom the sample sorted on the 21/07/11 (22days)

Figure. Spheres expansion after 2weeks (A and B) and after 3 w (C)

HUMAN MESENCHYMAL STEM CELL NICHE FOR HAEMATOPOIETIC STEM CELLS EXPANSION

Simón Méndez-Ferrer, Joan Isern, Beatriz Martín-Antonio, Ana M. Martín, Pedro Marín, Álvaro Urbano-Ispizua

Relación Donante-Receptor

Actividad de TPH en Europa

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

Núm

ero

de T

PH

1990 20092000

Auto

Alo

The European Group for Blood and Marrow TransplantationH.B. 3.2011

Evolution of Non MyeloAblative Allo HSCT in

Europe 1990-2009

HSCT

The European Group for Blood and Marrow TransplantationH.B. 3.2011

EBMT Activity Survey on HSCT 1990-2009:

donor origin

HSCT

Proporción de Alo-TPH DNE

0

2

4

6

8

10

12

14

Periodo analizado

%

95-99 00-03 04-07

“Mismatched”

“Matched”

CIBMTR 2011

Resultados

Recaídas post alo-TPHNuevas estrategias de Tto

• No inmunológicos– Acondicionamientos más específicos– Tto postrasplante

• Inmunológicos– Modificaciones de la composición del inóculo– Infusión de linfocitos del donante– Reeducación de linfocitos T– Uso de células dendríticas

36

Genetically modified T cells expressing first-, second and third-generation scFv receptors

Tissue Antigens ISSN 0001-2815

Muchas gracias por vuestra atención

The European Group for Blood and Marrow TransplantationH.B. 3.2011

EBMT Activity survey on HSCT in 2009: main indication - allogeneic

Baldomero H et al. BMT 2011 Feb 28. [Epub]

The European Group for Blood and Marrow TransplantationH.B. 3.2011

EBMT Activity survey on HSCT in 2009: main indication - autologous

Baldomero H et al. BMT 2011 Feb 28. [Epub]

The European Group for Blood and Marrow TransplantationH.B. 3.2011

EBMT Activity survey on HSCT in 2009: Donor type

Baldomero H et al. BMT 2011 Feb 28. [Epub]

Severe events in donors

Adverse effect Event Bone Marrow(n= 24,099)

PBSC(n=15,111)

Severe Cardiovascular 6 4Thromboembolic 1 7Pulmonary comp. 1 1Haemorrhage 1 3Seizures 1Spleen rupture 5Other 3 5

Died (within 30 days) 1 4Malignancies Hematologic malignancies 7 12

3 cardiac arrest1 Haemorrhage

PTE

Halter et al. Haematologica 2009;94:94-101.

Less aggressive method

Indicaciones

The European Group for Blood and Marrow TransplantationH.B. 3.2011

EBMT Activity Survey on HSCT 1990-2009:Haematological Malignancies: allogeneic HSCT

HSCT

The European Group for Blood and Marrow TransplantationH.B. 3.2011

EBMT Activity Survey on HSCT 1990-2009:Haematological Malignancies: autologous HSCT

HSCT