Trasplante de Células Madre Hemopoyéticas. Dos décadas de progreso

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

2 Al comienzo, estaba la médula ósea

3 Al comienzo, estaba la médula ósea 1957 Thomas y Mathe

4 Al comienzo, estaba la médula ósea 1957 Thomas y Mathe 1970 Bortin inicia el IBMTR n=200

5

6 Actividad de TPH en Europa Número de TPH

7 Alo-TPH QT/RT CMH Piel Hígado Intestino Células inmunes donante L L L L Células T del receptor Microorganismos

8 Fuente de PH

9 Fuente de PH MO SP CU

10 EBMT Activity Survey on HSCT changes in PBSC and Cord % auto PB allo PB cord The European Group for Blood and Marrow Transplantation

11 Homing and Movilization Osteoblasts Stromal-cell CXCL12 SDF-1 CXCR4 Stem cell Lapidot T, Experimental Hematology 30 (2002)

12 AMD3100 and movilization of HPC Osteoblasts Stromal-cell CXCL12 SDF-1 AMD3100 CXCR4 Stem cell Liles WC, Blood 102 (2003) Burroughs L, Blood 106 (2005) Larochelle A, Blood 107 (2006)

13 G-SCF and movilization of HPC G-CSF (+) (-) Osteoblasts Stromal-cell CXCL12 SDF-1 Elastases Cathepsin G MMPs Stem Cell CXCR4 Larochelle A, Blood 107 (2006)

14 Méndez-Ferrer Simón, Nature

15

16 Survival Early stage disease Advanced disease

17 EBMT Activity Survey on HSCT : Cord blood HSCT The European Group for Blood and Marrow Transplantation H.B

18 Number of stem cell products released for unrelated transplantation 18 3, , , ,515 1, ,238 1, ,392 2, ,187 3, ,133 4,133 1,126 3,125 4,796 1,791 3,002 5,416 2,075 11,000 10,000 9,000 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000 Number of donations Cord Blood Units Provided PBSC donations BM donations Alo-TPH UC 13% PB 62% BM 25%

19 Evolution of URD SCT in Spain UC 35% BM PB CB

20 International transplants from Spanish Donations Total number of donations*: UC PB BM Export * Excluding Lymphocyte donation

21 CBT vs. BMT/PBSCT URD 7/8 or 8/8 HR Eapen et al. Lancet Oncology 2010 AL in remission DFS CR vs. REL: RR 2.40, p<0.001

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

23 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 A: Spheres obtained from the CD146+CD105+ fraction from the sample sorted on the 21/07/11 (14 days) B: Spheres obtained from the CD146- CD105+ fraction from the sample sorted on the 21/07/11 (14 days) Figure. Spheres expansion after 2 weeks (A and B) and after 3 w (C) C. Spheres obtained from the CD105+ fraction from the sample sorted on the 21/07/11 (22 days)

24 Relación Donante-Receptor

25 Actividad de TPH en Europa Número de TPH Auto Alo

26 Evolution of Non MyeloAblative Allo HSCT in Europe H S C T The European Group for Blood and Marrow Transplantation H.B

27

28 EBMT Activity Survey on HSCT : donor origin H S C T The European Group for Blood and Marrow Transplantation H.B

29 Proporción de Alo-TPH DNE % Mismatched Matched Periodo analizado CIBMTR 2011

30

31 Resultados

32

33

34

35 No inmunológicos Recaídas post alo-tph Nuevas estrategias de Tto 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 36

37 Genetically modified T cells expressing first-, second and third-generation scfv receptors Tissue Antigens ISSN

38 Muchas gracias por vuestra atención

39 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 Transplantation H.B

40 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 Transplantation H.B

41 EBMT Activity survey on HSCT in 2009: Donor type Baldomero H et al. BMT 2011 Feb 28. [Epub] The European Group for Blood and Marrow Transplantation H.B

42 Less aggressive method Severe events in donors Adverse effect Event Bone Marrow (n= 24,099) PBSC (n=15,111) Severe Cardiovascular 6 4 Thromboembolic 1 7 Pulmonary comp. 1 1 Haemorrhage 1 3 Seizures 1 Spleen rupture 5 Other PTE 3 5 Died (within 30 days) 1 4 Malignancies Hematologic malignancies cardiac arrest 1 Haemorrhage Halter et al. Haematologica 2009;94:

43

44 Indicaciones

45 EBMT Activity Survey on HSCT : Haematological Malignancies: allogeneic HSCT H S C T The European Group for Blood and Marrow Transplantation H.B

46 EBMT Activity Survey on HSCT : Haematological Malignancies: autologous HSCT H S C T The European Group for Blood and Marrow Transplantation H.B

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