Trasplante de Células Madre Hemopoyéticas. Dos décadas de ... · Trasplante de Células Madre...
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Trasplante de Células Madre Hemopoyéticas. Dos décadas de progreso A. Urbano Ispizua Hospital Clinic, Universidad de Barcelona Noviembre de 2011
Transcript of Trasplante de Células Madre Hemopoyéticas. Dos décadas de ... · Trasplante de Células Madre...
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
