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Beneficio terapeutico de la interaccion materno filial

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Banc de Sang i Teixits
Banc de Sang i Teixits

This document summarizes the development of the Anthony Nolan Register, which was established in 1974 to recruit donors for bone marrow transplants. It has since grown to over 1 million donors and provided transplants to over 10,000 recipients. The document also discusses Anthony Nolan's cord blood program established in 2007, the use of cord blood as an alternative transplant source, and ongoing research into selecting optimal cord blood units based on immunogenetic factors to improve transplant outcomes.

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BENEFICIO TERAPEUTICO DE LA INTERACCION MATERNO FILIAL JORNADA ANUAL DEL PROGRAMA DE CONCORDIA 25 Mayo 2017
ANTHONY NOLAN PANEL 1974
Beneficio terapeutico de la interaccion materno filial
Development of The Anthony Nolan Register 1971 - Anthony Nolan born suffering from Wiskott-Aldrich Syndrome 1974 - Donor recruitment commenced to establish a panel of donors 1979 - Anthony died without receiving a transplant 2017 - Number of donors on Reg = 1,000,000 2017- Number of donors provided for transplant = > 10,000 ANTHONY NOLAN
ANTHONY NOLAN CORD BLOOD PROGRAMME 2007-2017 Register Cell Pharmacy CORD BLOOD BANK CORD BLOOD PHARM
Beneficio terapeutico de la interaccion materno filial
ANTHONY NOLAN CORD BLOOD PROGRAM SERGI QUEROL SUSANA G GOMEZ
A DONOR FOR EVERYONE ? Related Donors ? Unrelated Donors ? Cord blood ? Haploidenticals ? +Cell therapy
¡°Among patients with pretransplantation minimal residual disease, the probability of overall survival after receipt of a transplant from a cord-blood donor was at least as favorable as that after receipt of a transplant from an HLAmatched unrelated donor and was significantly higher than the probability after receipt of a transplant from an HLA-mismatched unrelated donor. Furthermore, the probability of relapse was lower in the cord-blood group than in either of the other groups.¡±
Scientific evidence for a new ¡°personalised¡± CB selection 1. NIMA virtual match (maternal, cord blood T regs) (van Rood et al, PNAS 2009) ¨C Improving engraftment ¨C Decreasing TRM 2. IPA (maternal cell microchimerism) (van Rood et al, PNAS 2012) ¨C Decreasing relapse 3. KIR genomics and function (CB NK alloreactivity) (Sekine et al, Blood 2016) ¨C Decreasing relapse 4. PIRCHE (Bioinformatic prediction of indirect recognition, beneficial mismatching) (Thus et al, Biol Blood Marrow Transpl 2016) ¨C Decreasing relapse (class I) ¨C Decreasing GVHD (class II) 5. CTLA4, Previous pregnancies (in study), others
Beneficio terapeutico de la interaccion materno filial
Beneficio terapeutico de la interaccion materno filial
NIMA y IPA
FUNCION DE LA PLACENTA Flujo sanguineo: Para el fin del embarazo el flujo sangu¨ªneo en la placenta llega 500ml/min La divisiones de la placenta dan gran superficie, lo que permite mayores intercambios (unos 10 metros cuadrados al termino del embarazo Funci¨®n de transferencia Funci¨®n Respiraci¨®n Funci¨®n Endocrina Funci¨®n de Barrera
NIMA y IPA
Beneficio terapeutico de la interaccion materno filial
A1, 24 HLA-A HLA-B HLA-DRHLA-C HLA-DPHLA-DQ B7, 27 !!!!! MATCH !!!!! Cw1, 6 DR1, 8 DQ3,7 DP2,4 ?Alejandro Madrigal 2015
HLA Mismatch and Outcome of BMT P CB 3, 24 3, 24 3503, 3801 3501, 3801 1203 1203 GVHD died HLA-A HLA-B HLA-C Outcome
HLA-B*3501 VS B*3503 (S-116 -F) B*3501 P Y, F, M B*3503 P M, L (F) 2 9
B*3503 B*3501
MIMA Match and Outcome of BMT P CB 3, 24 3, 24 3503, 3801 3501, 3801 1203 1203 No GVHD ALIVE HLA-A HLA-B HLA-C Outcome 3503 MIMA Match
NIMA: Probability of transplant-related mortality (TRM) for patients 10 years of age or older Jon J. van Rood et al. PNAS 2009;106:19952-19957 ?2009 by National Academy of Sciences
Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation (PNAS 2012; 109 (7): 2509) IPA: Maternal cell microchimerism in CB
Estudio de la influencia de embarazos previos de la donante en el resultado de los trasplantes alog¨¦nicos no emparentados de sangre de cord¨®n Anthony Nolan Banc de Sang i Teixits EUROCORD FASE I DR OLGA NIKOLAJEVA MD
Maternal previous pregnancy Characteristics All patients Patients (N) 639 Maternal number of previous pregnancies None, n (%) One, n (%) ¡Ý2, n (%) 320 (50.1) 218 (34.1) 101 (15.8)
Difference in between the groups from 1st, 2nd 3rd and more deliveries Characteristics 1st pregnancy (n=320) 2nd pregnancy (n=218) ¡Ý 3 pregnanci es (n=101) p-value Maternal age Median(range), years 29.7 (18.4-43.1) 31.2 (18.4-43.5) 33.7 (19-42.5) <0.0001 Maternal gestational age Full-term,n (%) Premature,n(%) Missing, n (%) 180 (56.3) 80 (25) 60 (18.8) 105 (48.2) 70 (32.1) 43 (19.7) 43 (42.6) 33 (32.7) 25 (24.8) 0.04
Effect of maternal previous pregnancy to 5-y OS and 5-y DFS 5-y OS No - 36.3% (95%CI, 31-41.9) Yes ¨C 45.7% (95%CI, 40-51) 5-y DFS No - 34.4% (95%CI, 29-40) Yes ¨C 44.1% (95%CI, 38.3 -50)
A B C p=0.02 p=0.03
Outcomes and unfavourable risk factor Hazard ratio (95% CI) p-value Relapse Advanced disease 2.5 (1.8-2.6) <0.0001 Overall survival Advanced disease Older recipient¡¯s age (¡Ý18 y) Maternal previous pregnancies Maternal number of previous pregnancies 2.8 (2.2-3.7) 1.3 (1.0-1.6) 0.4 (0.2-0.7) 1.4 (1.0-1.9) <0.0001 0.01 0.04 0.03 Non-relapse mortality Recipient¡¯s CMV seropositivity Advanced disease ¡Ý2 HLA mismatched grafts 1.6 (1.4-1.9) 1.8 (1.5-2.2) 1.6 (1.2-1.9) 0.0003 0.0004 0.001 Disease-free survival Advanced disease Maternal previous pregnancies Maternal number of previous pregnancies 3.0 (2.3-3.6) 0.4 (0.2-0.8) 1.4 (1.0-1.9) <0.0001 0.005 0.04 Multivariate analysis of risk factors for the main outcomes after UCBT for 639 children and adults with AL
Conclusions ? CBUs from 2nd pregnancy superior in UCBT outcomes , like NRM and OS ? Biological mechanism is yet to be established
Discussion ? Role of NIMA and IPA ? Role of previous pregnancy sex ? Role of birth order ? Role of MiHA ? Future larger studies capturing previous pregnancy sex and parental/maternal haplotypes are required
Estudio de la influencia de embarazos previos de la donante en el resultado de los trasplantes alog¨¦nicos no emparentados de sangre de cord¨®n Anthony Nolan Banc de Sang i Teixits EUROCORD FASE II
Estudio de la influencia de embarazos previos de la donante en el resultado de los trasplantes alog¨¦nicos no emparentados de sangre de cord¨®n FASE II 560 Pacientes registrados en EUROCORD quienes recibieron un CB del BST
AGRADECIMIENTOS Marta Torrabadella Reynoso Mar Sanchez Martinez Jesus Maroto Alamo Silvia Tuset Guillen Emma Enrich Rande Francesc Rudilla Salvador Susana G Gomez Sergio Querol Giner
560 BUSQUEDAS DE INFORMACION EN 50 MATERNIDADES: DE LA DONANTE: o fecha de nacimiento (en el caso de que no dispongamos de ella) DEL EMBARAZO OBJETO DE ESTUDIO: o APGAR del reci¨¦n nacido (1-10) o tipo de parto categorizado (vaginal eut¨®cico, vaginal instrumental, ces¨¢rea electiva, ces¨¢rea urgente, aborto) SI HA HABIDO EMBARAZOS ANTERIORES, DE CADA UNO DE ELLOS: o Si ha habido donaci¨®n de cord¨®n (Si, No) o En caso de que s¨ª: fecha de la colecta cord¨®n o sexo del reci¨¦n nacido o APGAR del reci¨¦n nacido (1-10) o tipo de parto categorizado (vaginal eut¨®cico, vaginal instrumental, ces¨¢rea electiva, ces¨¢rea urgente, aborto)
560, los embarazos previos que han tenido
De las donantes llamadas las que se han contactado (naranja) y las que no se ha podido contactar (azul) clasificadas por el a?o de la donaci¨®n. 106 donantes: ? 71 exito de contacto ? 35 no contactadas
- Tiempo desde la donaci¨®n vs. ?xito de contactarlas - N¨²mero de embarazos previos por a?o o por comunidad aut¨®noma - Correlaci¨®n entre las madres contactadas y las que no se han podido contactar ESTUDIO SOCIO-DEMOGRAFICO
FUTURE STEPS Identification of novel immunogenetic factors for the optimal cord blood selection to improve survival after transplantation NovoCord
Beneficio terapeutico de la interaccion materno filial
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Beneficio terapeutico de la interaccion materno filial

  • 1. BENEFICIO TERAPEUTICO DE LA INTERACCION MATERNO FILIAL JORNADA ANUAL DEL PROGRAMA DE CONCORDIA 25 Mayo 2017
  • 4. Development of The Anthony Nolan Register 1971 - Anthony Nolan born suffering from Wiskott-Aldrich Syndrome 1974 - Donor recruitment commenced to establish a panel of donors 1979 - Anthony died without receiving a transplant 2017 - Number of donors on Reg = 1,000,000 2017- Number of donors provided for transplant = > 10,000 ANTHONY NOLAN
  • 5. ANTHONY NOLAN CORD BLOOD PROGRAMME 2007-2017 Register Cell Pharmacy CORD BLOOD BANK CORD BLOOD PHARM
  • 7. ANTHONY NOLAN CORD BLOOD PROGRAM SERGI QUEROL SUSANA G GOMEZ
  • 8. A DONOR FOR EVERYONE ? Related Donors ? Unrelated Donors ? Cord blood ? Haploidenticals ? +Cell therapy
  • 9. ¡°Among patients with pretransplantation minimal residual disease, the probability of overall survival after receipt of a transplant from a cord-blood donor was at least as favorable as that after receipt of a transplant from an HLAmatched unrelated donor and was significantly higher than the probability after receipt of a transplant from an HLA-mismatched unrelated donor. Furthermore, the probability of relapse was lower in the cord-blood group than in either of the other groups.¡±
  • 10. Scientific evidence for a new ¡°personalised¡± CB selection 1. NIMA virtual match (maternal, cord blood T regs) (van Rood et al, PNAS 2009) ¨C Improving engraftment ¨C Decreasing TRM 2. IPA (maternal cell microchimerism) (van Rood et al, PNAS 2012) ¨C Decreasing relapse 3. KIR genomics and function (CB NK alloreactivity) (Sekine et al, Blood 2016) ¨C Decreasing relapse 4. PIRCHE (Bioinformatic prediction of indirect recognition, beneficial mismatching) (Thus et al, Biol Blood Marrow Transpl 2016) ¨C Decreasing relapse (class I) ¨C Decreasing GVHD (class II) 5. CTLA4, Previous pregnancies (in study), others
  • 14. FUNCION DE LA PLACENTA Flujo sanguineo: Para el fin del embarazo el flujo sangu¨ªneo en la placenta llega 500ml/min La divisiones de la placenta dan gran superficie, lo que permite mayores intercambios (unos 10 metros cuadrados al termino del embarazo Funci¨®n de transferencia Funci¨®n Respiraci¨®n Funci¨®n Endocrina Funci¨®n de Barrera
  • 17. A1, 24 HLA-A HLA-B HLA-DRHLA-C HLA-DPHLA-DQ B7, 27 !!!!! MATCH !!!!! Cw1, 6 DR1, 8 DQ3,7 DP2,4 ?Alejandro Madrigal 2015
  • 18. HLA Mismatch and Outcome of BMT P CB 3, 24 3, 24 3503, 3801 3501, 3801 1203 1203 GVHD died HLA-A HLA-B HLA-C Outcome
  • 19. HLA-B*3501 VS B*3503 (S-116 -F) B*3501 P Y, F, M B*3503 P M, L (F) 2 9
  • 21. MIMA Match and Outcome of BMT P CB 3, 24 3, 24 3503, 3801 3501, 3801 1203 1203 No GVHD ALIVE HLA-A HLA-B HLA-C Outcome 3503 MIMA Match
  • 22. NIMA: Probability of transplant-related mortality (TRM) for patients 10 years of age or older Jon J. van Rood et al. PNAS 2009;106:19952-19957 ?2009 by National Academy of Sciences
  • 23. Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation (PNAS 2012; 109 (7): 2509) IPA: Maternal cell microchimerism in CB
  • 24. Estudio de la influencia de embarazos previos de la donante en el resultado de los trasplantes alog¨¦nicos no emparentados de sangre de cord¨®n Anthony Nolan Banc de Sang i Teixits EUROCORD FASE I DR OLGA NIKOLAJEVA MD
  • 25. Maternal previous pregnancy Characteristics All patients Patients (N) 639 Maternal number of previous pregnancies None, n (%) One, n (%) ¡Ý2, n (%) 320 (50.1) 218 (34.1) 101 (15.8)
  • 26. Difference in between the groups from 1st, 2nd 3rd and more deliveries Characteristics 1st pregnancy (n=320) 2nd pregnancy (n=218) ¡Ý 3 pregnanci es (n=101) p-value Maternal age Median(range), years 29.7 (18.4-43.1) 31.2 (18.4-43.5) 33.7 (19-42.5) <0.0001 Maternal gestational age Full-term,n (%) Premature,n(%) Missing, n (%) 180 (56.3) 80 (25) 60 (18.8) 105 (48.2) 70 (32.1) 43 (19.7) 43 (42.6) 33 (32.7) 25 (24.8) 0.04
  • 27. Effect of maternal previous pregnancy to 5-y OS and 5-y DFS 5-y OS No - 36.3% (95%CI, 31-41.9) Yes ¨C 45.7% (95%CI, 40-51) 5-y DFS No - 34.4% (95%CI, 29-40) Yes ¨C 44.1% (95%CI, 38.3 -50)
  • 29. Outcomes and unfavourable risk factor Hazard ratio (95% CI) p-value Relapse Advanced disease 2.5 (1.8-2.6) <0.0001 Overall survival Advanced disease Older recipient¡¯s age (¡Ý18 y) Maternal previous pregnancies Maternal number of previous pregnancies 2.8 (2.2-3.7) 1.3 (1.0-1.6) 0.4 (0.2-0.7) 1.4 (1.0-1.9) <0.0001 0.01 0.04 0.03 Non-relapse mortality Recipient¡¯s CMV seropositivity Advanced disease ¡Ý2 HLA mismatched grafts 1.6 (1.4-1.9) 1.8 (1.5-2.2) 1.6 (1.2-1.9) 0.0003 0.0004 0.001 Disease-free survival Advanced disease Maternal previous pregnancies Maternal number of previous pregnancies 3.0 (2.3-3.6) 0.4 (0.2-0.8) 1.4 (1.0-1.9) <0.0001 0.005 0.04 Multivariate analysis of risk factors for the main outcomes after UCBT for 639 children and adults with AL
  • 30. Conclusions ? CBUs from 2nd pregnancy superior in UCBT outcomes , like NRM and OS ? Biological mechanism is yet to be established
  • 31. Discussion ? Role of NIMA and IPA ? Role of previous pregnancy sex ? Role of birth order ? Role of MiHA ? Future larger studies capturing previous pregnancy sex and parental/maternal haplotypes are required
  • 32. Estudio de la influencia de embarazos previos de la donante en el resultado de los trasplantes alog¨¦nicos no emparentados de sangre de cord¨®n Anthony Nolan Banc de Sang i Teixits EUROCORD FASE II
  • 33. Estudio de la influencia de embarazos previos de la donante en el resultado de los trasplantes alog¨¦nicos no emparentados de sangre de cord¨®n FASE II 560 Pacientes registrados en EUROCORD quienes recibieron un CB del BST
  • 34. AGRADECIMIENTOS Marta Torrabadella Reynoso Mar Sanchez Martinez Jesus Maroto Alamo Silvia Tuset Guillen Emma Enrich Rande Francesc Rudilla Salvador Susana G Gomez Sergio Querol Giner
  • 35. 560 BUSQUEDAS DE INFORMACION EN 50 MATERNIDADES: DE LA DONANTE: o fecha de nacimiento (en el caso de que no dispongamos de ella) DEL EMBARAZO OBJETO DE ESTUDIO: o APGAR del reci¨¦n nacido (1-10) o tipo de parto categorizado (vaginal eut¨®cico, vaginal instrumental, ces¨¢rea electiva, ces¨¢rea urgente, aborto) SI HA HABIDO EMBARAZOS ANTERIORES, DE CADA UNO DE ELLOS: o Si ha habido donaci¨®n de cord¨®n (Si, No) o En caso de que s¨ª: fecha de la colecta cord¨®n o sexo del reci¨¦n nacido o APGAR del reci¨¦n nacido (1-10) o tipo de parto categorizado (vaginal eut¨®cico, vaginal instrumental, ces¨¢rea electiva, ces¨¢rea urgente, aborto)
  • 36. 560, los embarazos previos que han tenido
  • 37. De las donantes llamadas las que se han contactado (naranja) y las que no se ha podido contactar (azul) clasificadas por el a?o de la donaci¨®n. 106 donantes: ? 71 exito de contacto ? 35 no contactadas
  • 38. - Tiempo desde la donaci¨®n vs. ?xito de contactarlas - N¨²mero de embarazos previos por a?o o por comunidad aut¨®noma - Correlaci¨®n entre las madres contactadas y las que no se han podido contactar ESTUDIO SOCIO-DEMOGRAFICO
  • 39. FUTURE STEPS Identification of novel immunogenetic factors for the optimal cord blood selection to improve survival after transplantation NovoCord